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36374874
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33197716
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36512043
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Graph Transformer Geometric Learning of Brain Networks Using Multimodal MR Images for Brain Age Estimation.
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Accurate brain age prediction with lightweight deep neural networks.
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Cardiac MRI in patients with COVID-19 infection.
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Brain age is considered as an important biomarker for detecting aging-related diseases such as Alzheimer's Disease (AD). Magnetic resonance imaging (MRI) have been widely investigated with deep neural networks for brain age estimation. However, most existing methods cannot make full use of multimodal MRIs due to the difference in data structure. In this paper, we propose a graph transformer geometric learning framework to model the multimodal brain network constructed by structural MRI (sMRI) and diffusion tensor imaging (DTI) for brain age estimation. First, we build a two-stream convolutional autoencoder to learn the latent representations for each imaging modality. The brain template with prior knowledge is utilized to calculate the features from the regions of interest (ROIs). Then, a multi-level construction of the brain network is proposed to establish the hybrid ROI connections in space, feature and modality. Next, a graph transformer network is proposed to model the cross-modal interaction and fusion by geometric learning for brain age estimation. Finally, the difference between the estimated age and the chronological age is used as an important biomarker for AD diagnosis. Our method is evaluated with the sMRI and DTI data from UK Biobank and Alzheimer's Disease Neuroimaging Initiative database. Experimental results demonstrate that our method has achieved promising performances for brain age estimation and AD diagnosis.</AbstractText
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Deep learning has huge potential for accurate disease prediction with neuroimaging data, but the prediction performance is often limited by training-dataset size and computing memory requirements. To address this, we propose a deep convolutional neural network model, Simple Fully Convolutional Network (SFCN), for accurate prediction of brain age using T1-weighted structural MRI data. Compared with other popular deep network architectures, SFCN has fewer parameters, so is more compatible with small dataset size and 3D volume data. The network architecture was combined with several techniques for boosting performance, including data augmentation, pre-training, model regularization, model ensemble and prediction bias correction. We compared our overall SFCN approach with several widely-used machine learning models. It achieved state-of-the-art performance in UK Biobank data (N = 14,503), with mean absolute error (MAE) = 2.14y in brain age prediction and 99.5% in sex classification. SFCN also won (both parts of) the 2019 Predictive Analysis Challenge for brain age prediction, involving 79 competing teams (N = 2,638, MAE = 2.90y). We describe here the details of our approach, and its optimisation and validation. Our approach can easily be generalised to other tasks using different image modalities, and is released on GitHub.</AbstractText
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COVID-19 infection is a systemic disease with various cardiovascular symptoms and complications. Cardiac MRI with late gadolinium enhancement is the modality of choice for the assessment of myocardial involvement. T1 and T2 mapping can increase diagnostic accuracy and improve further management. Our study aimed to evaluate the different aspects of myocardial damage in cases of COVID-19 infection using cardiac MRI.</AbstractText This descriptive retrospective study included 86 cases, with a history of COVID-19 infection confirmed by positive RT-PCR, who met the inclusion criteria. Patients had progressive chest pain or dyspnoea with a suspected underlying cardiac cause, either by an abnormal electrocardiogram or elevated troponin levels. Cardiac MRI was performed with late contrast-enhanced (LGE) imaging, followed by T1 and T2 mapping.</AbstractText Twenty-four patients have elevated hsTnT with a median hsTnT value of 133 ng/L (IQR: 102 to 159 ng/L); normal value < 14 ng/L. Other sixty-two patients showed elevated hsTnI with a median hsTnI value of 1637 ng/L (IQR: 1340 to 2540 ng/L); normal value < 40 ng/L. CMR showed 52 patients with acute myocarditis, 23 with Takotsubo cardiomyopathy, and 11 with myocardial infarction. Invasive coronary angiography was performed only in selected patients.</AbstractText Different COVID-19-related cardiac injuries may cause similar clinical symptoms. Cardiac MRI is the modality of choice to differentiate between the different types of myocardial injury such as Takotsubo cardiomyopathy and infection-related cardiomyopathy or even acute coronary syndrome secondary to vasculitis or oxygen-demand mismatch.</AbstractText • It is essential to detect early COVID-related cardiac injury using different cardiac biomarkers and cardiac imaging, as it has a significant impact on patient management and outcome. • Cardiac MRI is the modality of choice to differentiate between the different aspects of COVID-related myocardial injury.</AbstractText
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Graph Transformer Geometric Learning of Brain Networks Using Multimodal MR Images for Brain Age Estimation. Brain age is considered as an important biomarker for detecting aging-related diseases such as Alzheimer's Disease (AD). Magnetic resonance imaging (MRI) have been widely investigated with deep neural networks for brain age estimation. However, most existing methods cannot make full use of multimodal MRIs due to the difference in data structure. In this paper, we propose a graph transformer geometric learning framework to model the multimodal brain network constructed by structural MRI (sMRI) and diffusion tensor imaging (DTI) for brain age estimation. First, we build a two-stream convolutional autoencoder to learn the latent representations for each imaging modality. The brain template with prior knowledge is utilized to calculate the features from the regions of interest (ROIs). Then, a multi-level construction of the brain network is proposed to establish the hybrid ROI connections in space, feature and modality. Next, a graph transformer network is proposed to model the cross-modal interaction and fusion by geometric learning for brain age estimation. Finally, the difference between the estimated age and the chronological age is used as an important biomarker for AD diagnosis. Our method is evaluated with the sMRI and DTI data from UK Biobank and Alzheimer's Disease Neuroimaging Initiative database. Experimental results demonstrate that our method has achieved promising performances for brain age estimation and AD diagnosis.</AbstractText
|
Accurate brain age prediction with lightweight deep neural networks. Deep learning has huge potential for accurate disease prediction with neuroimaging data, but the prediction performance is often limited by training-dataset size and computing memory requirements. To address this, we propose a deep convolutional neural network model, Simple Fully Convolutional Network (SFCN), for accurate prediction of brain age using T1-weighted structural MRI data. Compared with other popular deep network architectures, SFCN has fewer parameters, so is more compatible with small dataset size and 3D volume data. The network architecture was combined with several techniques for boosting performance, including data augmentation, pre-training, model regularization, model ensemble and prediction bias correction. We compared our overall SFCN approach with several widely-used machine learning models. It achieved state-of-the-art performance in UK Biobank data (N = 14,503), with mean absolute error (MAE) = 2.14y in brain age prediction and 99.5% in sex classification. SFCN also won (both parts of) the 2019 Predictive Analysis Challenge for brain age prediction, involving 79 competing teams (N = 2,638, MAE = 2.90y). We describe here the details of our approach, and its optimisation and validation. Our approach can easily be generalised to other tasks using different image modalities, and is released on GitHub.</AbstractText
|
Cardiac MRI in patients with COVID-19 infection. COVID-19 infection is a systemic disease with various cardiovascular symptoms and complications. Cardiac MRI with late gadolinium enhancement is the modality of choice for the assessment of myocardial involvement. T1 and T2 mapping can increase diagnostic accuracy and improve further management. Our study aimed to evaluate the different aspects of myocardial damage in cases of COVID-19 infection using cardiac MRI.</AbstractText This descriptive retrospective study included 86 cases, with a history of COVID-19 infection confirmed by positive RT-PCR, who met the inclusion criteria. Patients had progressive chest pain or dyspnoea with a suspected underlying cardiac cause, either by an abnormal electrocardiogram or elevated troponin levels. Cardiac MRI was performed with late contrast-enhanced (LGE) imaging, followed by T1 and T2 mapping.</AbstractText Twenty-four patients have elevated hsTnT with a median hsTnT value of 133 ng/L (IQR: 102 to 159 ng/L); normal value < 14 ng/L. Other sixty-two patients showed elevated hsTnI with a median hsTnI value of 1637 ng/L (IQR: 1340 to 2540 ng/L); normal value < 40 ng/L. CMR showed 52 patients with acute myocarditis, 23 with Takotsubo cardiomyopathy, and 11 with myocardial infarction. Invasive coronary angiography was performed only in selected patients.</AbstractText Different COVID-19-related cardiac injuries may cause similar clinical symptoms. Cardiac MRI is the modality of choice to differentiate between the different types of myocardial injury such as Takotsubo cardiomyopathy and infection-related cardiomyopathy or even acute coronary syndrome secondary to vasculitis or oxygen-demand mismatch.</AbstractText • It is essential to detect early COVID-related cardiac injury using different cardiac biomarkers and cardiac imaging, as it has a significant impact on patient management and outcome. • Cardiac MRI is the modality of choice to differentiate between the different aspects of COVID-related myocardial injury.</AbstractText
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33839631
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30616875
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33451816
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Innumerable hemorrhagic brain metastases from a neuroendocrine tumor grade-1 with prolonged natural history.
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Surgical treatment of an asymptomatic giant supratentorial cavernous hemangioma. Case report.
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Large-Volume Hyperthermia for Safe and Cost-Effective Targeted Drug Delivery Using a Clinical Ultrasound-Guided Focused Ultrasound Device.
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Neuroendocrine tumors (NET) are rare tumors with a low incidence of brain metastasis, especially in grade 1 NET. The most common source of brain metastasis is the lung. We present an unusual case of NET grade 1 with multiple hemorrhagic brain metastases.</AbstractText A 46-year-old woman, who initially presented with a seizure, was diagnosed with multiple brain and lung lesions. She was offered a biopsy for diagnosis, but she refused and lost to follow up. Eighteen years later, she developed progressive quadriparesis and confusion. A biopsy of the left frontal lobe lesions showed NET grade 1. A lung biopsy of the left upper lobe was consistent with the same diagnosis. The patient's functional status was poor with Eastern Cooperative Oncology Group (ECOG) grade 4. She only received palliative whole-brain radiation therapy (WBRT) and died 3 months after discharge.</AbstractText NET is a spectrum that encompasses benign to malignant cells. There is a female predominance in lower grades and male predominance in higher grades. No effective management for brain metastases was described, and the prognosis remains poor.</AbstractText Multiple brain metastases can be the first presentation of patients with NET. Early diagnosis and treatment may have a more favorable impact on the outcome of this disease. The longstanding numerous hemorrhagic NET brain metastases is exceedingly rare. The neuroimaging appearance is similar to other neoplastic and non-neoplastic lesions. An important differential diagnosis to consider is metastatic melanoma and choriocarcinoma, familial cavernous malformation, diffuse axonal injury, cerebral vasculitis, and amyloid angiopathy.</AbstractText
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A case is reported of a 19-year old patient with a supratentorial giant cavernous malformation (GCM). This was an incidental finding in the context of acute head trauma. Brain computed tomography (CT) scan and magnetic resonance imaging (MRI) revealed a giant supratentorial right mass. Surgical excision was performed, and histopathology findings were consistent with a cavernous malformation (CM). The patient had a complete neurological recovery. To our knowledge, this is the first case of a GCM in an asymptomatic patient with total surgical excision.</AbstractText
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Lyso-thermosensitive liposomes (LTSLs) are specifically designed to release chemotherapy agents under conditions of mild hyperthermia. Preclinical studies have indicated that magnetic resonance (MR)-guided focused ultrasound (FUS) systems can generate well-controlled volumetric hyperthermia using real-time thermometry. However, high-throughput clinical translation of these approaches for drug delivery is challenging, not least because of the significant cost overhead of MR guidance and the much larger volumes that need to be heated clinically. Using an ultrasound-guided extracorporeal clinical FUS device (Chongqing HAIFU, JC200) with thermistors in a non-perfused ex vivo bovine liver tissue model with ribs, we present an optimised strategy for rapidly inducing (5-15 min) and sustaining (>30 min) mild hyperthermia (ΔT <+4°C) in large tissue volumes (≤92 cm<sup
|
Innumerable hemorrhagic brain metastases from a neuroendocrine tumor grade-1 with prolonged natural history. Neuroendocrine tumors (NET) are rare tumors with a low incidence of brain metastasis, especially in grade 1 NET. The most common source of brain metastasis is the lung. We present an unusual case of NET grade 1 with multiple hemorrhagic brain metastases.</AbstractText A 46-year-old woman, who initially presented with a seizure, was diagnosed with multiple brain and lung lesions. She was offered a biopsy for diagnosis, but she refused and lost to follow up. Eighteen years later, she developed progressive quadriparesis and confusion. A biopsy of the left frontal lobe lesions showed NET grade 1. A lung biopsy of the left upper lobe was consistent with the same diagnosis. The patient's functional status was poor with Eastern Cooperative Oncology Group (ECOG) grade 4. She only received palliative whole-brain radiation therapy (WBRT) and died 3 months after discharge.</AbstractText NET is a spectrum that encompasses benign to malignant cells. There is a female predominance in lower grades and male predominance in higher grades. No effective management for brain metastases was described, and the prognosis remains poor.</AbstractText Multiple brain metastases can be the first presentation of patients with NET. Early diagnosis and treatment may have a more favorable impact on the outcome of this disease. The longstanding numerous hemorrhagic NET brain metastases is exceedingly rare. The neuroimaging appearance is similar to other neoplastic and non-neoplastic lesions. An important differential diagnosis to consider is metastatic melanoma and choriocarcinoma, familial cavernous malformation, diffuse axonal injury, cerebral vasculitis, and amyloid angiopathy.</AbstractText
|
Surgical treatment of an asymptomatic giant supratentorial cavernous hemangioma. Case report. A case is reported of a 19-year old patient with a supratentorial giant cavernous malformation (GCM). This was an incidental finding in the context of acute head trauma. Brain computed tomography (CT) scan and magnetic resonance imaging (MRI) revealed a giant supratentorial right mass. Surgical excision was performed, and histopathology findings were consistent with a cavernous malformation (CM). The patient had a complete neurological recovery. To our knowledge, this is the first case of a GCM in an asymptomatic patient with total surgical excision.</AbstractText
|
Large-Volume Hyperthermia for Safe and Cost-Effective Targeted Drug Delivery Using a Clinical Ultrasound-Guided Focused Ultrasound Device. Lyso-thermosensitive liposomes (LTSLs) are specifically designed to release chemotherapy agents under conditions of mild hyperthermia. Preclinical studies have indicated that magnetic resonance (MR)-guided focused ultrasound (FUS) systems can generate well-controlled volumetric hyperthermia using real-time thermometry. However, high-throughput clinical translation of these approaches for drug delivery is challenging, not least because of the significant cost overhead of MR guidance and the much larger volumes that need to be heated clinically. Using an ultrasound-guided extracorporeal clinical FUS device (Chongqing HAIFU, JC200) with thermistors in a non-perfused ex vivo bovine liver tissue model with ribs, we present an optimised strategy for rapidly inducing (5-15 min) and sustaining (>30 min) mild hyperthermia (ΔT <+4°C) in large tissue volumes (≤92 cm<sup
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36411785
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34476184
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36343534
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Feasibility study of 2D Dixon-Magnetic Resonance Fingerprinting (MRF) of breast cancer.
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Repeatability of MR fingerprinting in normal cervix and utility in cervical carcinoma.
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Comparison of response properties of the electrically stimulated auditory nerve reported in human listeners and in animal models.
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Application of MRF to evaluate the feasibility of 2D Dixon blurring-corrected MRF (2DDb-cMRF) to differentiate breast cancer (BC) from normal fibroglandular tissue (FGT).</AbstractText Prospective study on 14 patients with unilateral BC on 1.5 T system/axial T2w-TSE sequence, 2DDb-cMRF, B1 map, dynamic contrast-enhanced (DCE) T1-w GE-series. Mean T1 and T2 values and standard deviations were computed in the BC-/FGT-ROI on pre-/post-contrast MRF-maps and their differences were tested by two-tailed student t-test.Accuracy and repeatability of MRF were evaluated in a phantom experiment with gelatin with Primovist surrounded by fat.The T1 reduction between pre-/post-contrast MRF-maps was correlated to DCE signal enhancement in the last image post-contrast through the Pearson´s correlation coefficient (r) and for the phantom validation experiment through the Lin's concordance correlation coefficient (CCC).Visual evaluation of cancers on MRF-Maps was performed by rating each MRF-Map by 3 radiologists.</AbstractText T1- and T2-MRF values of BC vs. FGT were for T1 and T2 pre-contrast respectively: 1147 ± 1 ms vs. 1052 ± 9 ms (p = 0.007) and 83 ± 1 ms vs. 73 ± 1 ms (p = 0.03); post-contrast respectively: 367.3 ± 121.5 ms vs. 690.3 ± 200.3 ms (p = 0.0005) and 76.9 ± 11.5 ms vs. 69.8 ± 15.2 ms (p = 0.12). r was positive (FGT r = 0.7; BC r = 0.6). CCC was 0.999 for T1 and 0.994 for T2. In the T1- and T2-MRF-Maps before contrast respectively (7,7,8)/14 and (5,9,8)/14 cancers were visible to the readers; afterwards, (11,12,12)/14 and (5,6,11)/14.</AbstractText MRF is promising for distinction between BC and FGT as well as for analyzing pre-/post-contrast T1 changes. However, its potential for differential diagnosis warrants further studies.</AbstractText
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Magnetic resonance fingerprinting (MRF) is a fast-imaging acquisition technique that generates quantitative and co-registered parametric maps. The aim of this feasibility study was to evaluate the agreement between MRF and phantom reference values, scan-rescan repeatability of MRF in normal cervix, and its ability to distinguish cervical carcinoma (CC) from normal cervical tissues.</AbstractText An International Society of Magnetic Resonance in Medicine/National Institute of Standards and Technology (ISMRM/NIST) phantom was scanned using MRF 15 times over 65 days. Agreement between MRF and phantom reference T1 and T2 values was assessed by linear regression. Healthy volunteers and patients with suspected CC were prospectively recruited. MRF was repeated twice for healthy volunteers (MRF1 and MRF2). Volumes of interest of normal cervical tissues and CC were delineated on T1 and T2 maps. MRF scan-rescan repeatability was evaluated by Bland-Altman plots, within-subject coefficients of variation (wCV), and intraclass correlation coefficients (ICC). T1 and T2 values were compared between CC and normal cervical tissues using Mann-Whitney U test. Receiver operating characteristic (ROC) analysis was performed to evaluate diagnostic efficiency.</AbstractText Strong correlations were observed between MRF and phantom (R<sup Excellent agreement was observed between MRF and phantom reference values. MRF exhibited excellent scan-rescan repeatability in normal cervix with potential value in differentiating CC from normal cervical tissues.</AbstractText
|
Cochlear implants (CIs) provide acoustic information to implanted patients by electrically stimulating nearby auditory nerve fibers (ANFs) which then transmit the information to higher-level neural structures for further processing and interpretation. Computational models that simulate ANF responses to CI stimuli enable the exploration of the mechanisms underlying CI performance beyond the capacity of in vivo experimentation alone. However, all ANF models developed to date utilize to some extent anatomical/morphometric data, biophysical properties and/or physiological data measured in non-human animal models. This review compares response properties of the electrically stimulated auditory nerve (AN) in human listeners and different mammalian models. Properties of AN responses to single pulse stimulation, paired-pulse stimulation, and pulse-train stimulation are presented. While some AN response properties are similar between human listeners and animal models (e.g., increased AN sensitivity to single pulse stimuli with long interphase gaps), there are some significant differences. For example, the AN of most animal models is typically more sensitive to cathodic stimulation while the AN of human listeners is generally more sensitive to anodic stimulation. Additionally, there are substantial differences in the speed of recovery from neural adaptation between animal models and human listeners. Therefore, results from animal models cannot be simply translated to human listeners. Recognizing the differences in responses of the AN to electrical stimulation between humans and other mammals is an important step for creating ANF models that are more applicable to various human CI patient populations.</AbstractText
|
Feasibility study of 2D Dixon-Magnetic Resonance Fingerprinting (MRF) of breast cancer. Application of MRF to evaluate the feasibility of 2D Dixon blurring-corrected MRF (2DDb-cMRF) to differentiate breast cancer (BC) from normal fibroglandular tissue (FGT).</AbstractText Prospective study on 14 patients with unilateral BC on 1.5 T system/axial T2w-TSE sequence, 2DDb-cMRF, B1 map, dynamic contrast-enhanced (DCE) T1-w GE-series. Mean T1 and T2 values and standard deviations were computed in the BC-/FGT-ROI on pre-/post-contrast MRF-maps and their differences were tested by two-tailed student t-test.Accuracy and repeatability of MRF were evaluated in a phantom experiment with gelatin with Primovist surrounded by fat.The T1 reduction between pre-/post-contrast MRF-maps was correlated to DCE signal enhancement in the last image post-contrast through the Pearson´s correlation coefficient (r) and for the phantom validation experiment through the Lin's concordance correlation coefficient (CCC).Visual evaluation of cancers on MRF-Maps was performed by rating each MRF-Map by 3 radiologists.</AbstractText T1- and T2-MRF values of BC vs. FGT were for T1 and T2 pre-contrast respectively: 1147 ± 1 ms vs. 1052 ± 9 ms (p = 0.007) and 83 ± 1 ms vs. 73 ± 1 ms (p = 0.03); post-contrast respectively: 367.3 ± 121.5 ms vs. 690.3 ± 200.3 ms (p = 0.0005) and 76.9 ± 11.5 ms vs. 69.8 ± 15.2 ms (p = 0.12). r was positive (FGT r = 0.7; BC r = 0.6). CCC was 0.999 for T1 and 0.994 for T2. In the T1- and T2-MRF-Maps before contrast respectively (7,7,8)/14 and (5,9,8)/14 cancers were visible to the readers; afterwards, (11,12,12)/14 and (5,6,11)/14.</AbstractText MRF is promising for distinction between BC and FGT as well as for analyzing pre-/post-contrast T1 changes. However, its potential for differential diagnosis warrants further studies.</AbstractText
|
Repeatability of MR fingerprinting in normal cervix and utility in cervical carcinoma. Magnetic resonance fingerprinting (MRF) is a fast-imaging acquisition technique that generates quantitative and co-registered parametric maps. The aim of this feasibility study was to evaluate the agreement between MRF and phantom reference values, scan-rescan repeatability of MRF in normal cervix, and its ability to distinguish cervical carcinoma (CC) from normal cervical tissues.</AbstractText An International Society of Magnetic Resonance in Medicine/National Institute of Standards and Technology (ISMRM/NIST) phantom was scanned using MRF 15 times over 65 days. Agreement between MRF and phantom reference T1 and T2 values was assessed by linear regression. Healthy volunteers and patients with suspected CC were prospectively recruited. MRF was repeated twice for healthy volunteers (MRF1 and MRF2). Volumes of interest of normal cervical tissues and CC were delineated on T1 and T2 maps. MRF scan-rescan repeatability was evaluated by Bland-Altman plots, within-subject coefficients of variation (wCV), and intraclass correlation coefficients (ICC). T1 and T2 values were compared between CC and normal cervical tissues using Mann-Whitney U test. Receiver operating characteristic (ROC) analysis was performed to evaluate diagnostic efficiency.</AbstractText Strong correlations were observed between MRF and phantom (R<sup Excellent agreement was observed between MRF and phantom reference values. MRF exhibited excellent scan-rescan repeatability in normal cervix with potential value in differentiating CC from normal cervical tissues.</AbstractText
|
Comparison of response properties of the electrically stimulated auditory nerve reported in human listeners and in animal models. Cochlear implants (CIs) provide acoustic information to implanted patients by electrically stimulating nearby auditory nerve fibers (ANFs) which then transmit the information to higher-level neural structures for further processing and interpretation. Computational models that simulate ANF responses to CI stimuli enable the exploration of the mechanisms underlying CI performance beyond the capacity of in vivo experimentation alone. However, all ANF models developed to date utilize to some extent anatomical/morphometric data, biophysical properties and/or physiological data measured in non-human animal models. This review compares response properties of the electrically stimulated auditory nerve (AN) in human listeners and different mammalian models. Properties of AN responses to single pulse stimulation, paired-pulse stimulation, and pulse-train stimulation are presented. While some AN response properties are similar between human listeners and animal models (e.g., increased AN sensitivity to single pulse stimuli with long interphase gaps), there are some significant differences. For example, the AN of most animal models is typically more sensitive to cathodic stimulation while the AN of human listeners is generally more sensitive to anodic stimulation. Additionally, there are substantial differences in the speed of recovery from neural adaptation between animal models and human listeners. Therefore, results from animal models cannot be simply translated to human listeners. Recognizing the differences in responses of the AN to electrical stimulation between humans and other mammals is an important step for creating ANF models that are more applicable to various human CI patient populations.</AbstractText
|
37987558
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28710580
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38393608
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Assessment of myocardial injuries in ischaemic and non-ischaemic cardiomyopathies using magnetic resonance T1-rho mapping.
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Assessment of acute kidney injury with T1 mapping MRI following solid organ transplantation.
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Post-stroke Chinese pure alexia: linguistic features and neuropsychological profiles.
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To identify clinical correlates of myocardial T1ρ and to examine how myocardial T1ρ values change under various clinical scenarios.</AbstractText A total of 66 patients (26% female, median age 57 years [Q1-Q3, 44-65 years]) with known structural heart disease and 44 controls (50% female, median age 47 years [28-57 years]) underwent cardiac magnetic resonance imaging at 1.5 T, including T1ρ mapping, T2 mapping, native T1 mapping, late gadolinium enhancement, and extracellular volume (ECV) imaging. In controls, T1ρ positively related with T2 (P = 0.038) and increased from basal to apical levels (P < 0.001). As compared with controls and remote myocardium, T1ρ significantly increased in all patients' sub-groups and all types of myocardial injuries: acute and chronic injuries, focal and diffuse tissue abnormalities, as well as ischaemic and non-ischaemic aetiologies (P < 0.05). T1ρ was independently associated with T2 in patients with acute injuries (P = 0.004) and with native T1 and ECV in patients with chronic injuries (P < 0.05). Myocardial T1ρ mapping demonstrated good intra- and inter-observer reproducibility (intraclass correlation coefficient = 0.86 and 0.83, respectively).</AbstractText Myocardial T1ρ mapping appears to be reproducible and equally sensitive to acute and chronic myocardial injuries, whether of ischaemic or non-ischaemic origins. It may thus be a contrast-agent-free biomarker for gaining new and quantitative insight into myocardial structural disorders. These findings highlight the need for further studies through prospective and randomized trials.</AbstractText
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To evaluate T1 mapping as a non-invasive, functional MRI biomarker in patients shortly after solid organ transplantation to detect acute postsurgical kidney damage and to correlate T1 times with renal function.</AbstractText 101 patients within 2 weeks after solid organ transplantation (49 kidney transplantation, 52 lung transplantation) and 14 healthy volunteers were examined by MRI between July 2012 and April 2015 using the modified Look-Locker inversion recovery (MOLLI) sequence. T1 times in renal cortex and medulla and the corticomedullary difference were compared between groups using one-way ANOVA adjusted for multiple comparison with the Tukey test, and T1 times were correlated with renal function using Pearson's correlation.</AbstractText Compared to healthy volunteers T1 times were significantly increased after solid organ transplantation in the renal cortex (healthy volunteers 987 ± 102 ms; kidney transplantation 1299 ± 101 ms, p < 0.001; lung transplantation 1058 ± 96 ms, p < 0.05) and to a lesser extent in the renal medulla. Accordingly, the corticomedullary difference was diminished shortly after solid organ transplantation. T1 changes were more pronounced following kidney compared to lung transplantation, were associated with the stage of renal impairment and significantly correlated with renal function.</AbstractText T1 mapping may be helpful for early non-invasive assessment of acute kidney injury and renal pathology following major surgery such as solid organ transplantation.</AbstractText • Renal cortical T1 relaxation times are prolonged after solid organ transplantation. • Cortical T1 values increase with higher stages of renal function impairment. • Corticomedullary difference decreases with higher stages of renal function impairment. • Renal cortical T1 relaxation time and corticomedullary difference correlate with renal function. • T1 mapping may be helpful for non-invasive assessment of post-operative renal pathology.</AbstractText
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Very few cases of Chinese pure alexia have been reported to date. We aim to summarize the linguistic features and neuropsychological profiles of Chinese pure alexia through a case series study.</AbstractText 11 consecutive patients with post-stroke Chinese pure alexia and 11 healthy controls were included. The Aphasia Battery of Chinese (ABC) and 68-Chinese character oral reading test (68-character test) were used to evaluate the reading and writing ability. Reading errors were classified based on the performance of 68-character test. Neuropsychological profiles were evaluated with corresponding scales. The possible correlation between the reading ability and the writing ability or neuropsychological performance was analyzed.</AbstractText The patients had a correct rate of 43.7 ± 23.2% in the 68-character test, significantly lower (P < 0.001) than that of controls. Shape-similar error was the most common type of reading error (101/209, 48.3%). The ABC total writing score rate of the patients ranged from 68.9% to 98.7% (median, 90.5%), significantly lower (P < 0.001) than that of the controls. The patients also showed worse performance in MMSE, auditory verbal learning test, Boston naming test, intersecting pentagons copying and clock-drawing test (all P < 0.05). In the patient group, the correct rate of 68-character test was significantly correlated with the ABC total writing score rate (P = 0.008), the score rate of Boston naming test (P = 0.017), and the clock-drawing test score (P = 0.010).</AbstractText Shape-similar errors may be a characteristic of Chinese pure alexia. The correlation between visuospatial dysfunction and pure alexia might explain the frequent occurrence of shape-similar errors in Chinese pure alexia.</AbstractText
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Assessment of myocardial injuries in ischaemic and non-ischaemic cardiomyopathies using magnetic resonance T1-rho mapping. To identify clinical correlates of myocardial T1ρ and to examine how myocardial T1ρ values change under various clinical scenarios.</AbstractText A total of 66 patients (26% female, median age 57 years [Q1-Q3, 44-65 years]) with known structural heart disease and 44 controls (50% female, median age 47 years [28-57 years]) underwent cardiac magnetic resonance imaging at 1.5 T, including T1ρ mapping, T2 mapping, native T1 mapping, late gadolinium enhancement, and extracellular volume (ECV) imaging. In controls, T1ρ positively related with T2 (P = 0.038) and increased from basal to apical levels (P < 0.001). As compared with controls and remote myocardium, T1ρ significantly increased in all patients' sub-groups and all types of myocardial injuries: acute and chronic injuries, focal and diffuse tissue abnormalities, as well as ischaemic and non-ischaemic aetiologies (P < 0.05). T1ρ was independently associated with T2 in patients with acute injuries (P = 0.004) and with native T1 and ECV in patients with chronic injuries (P < 0.05). Myocardial T1ρ mapping demonstrated good intra- and inter-observer reproducibility (intraclass correlation coefficient = 0.86 and 0.83, respectively).</AbstractText Myocardial T1ρ mapping appears to be reproducible and equally sensitive to acute and chronic myocardial injuries, whether of ischaemic or non-ischaemic origins. It may thus be a contrast-agent-free biomarker for gaining new and quantitative insight into myocardial structural disorders. These findings highlight the need for further studies through prospective and randomized trials.</AbstractText
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Assessment of acute kidney injury with T1 mapping MRI following solid organ transplantation. To evaluate T1 mapping as a non-invasive, functional MRI biomarker in patients shortly after solid organ transplantation to detect acute postsurgical kidney damage and to correlate T1 times with renal function.</AbstractText 101 patients within 2 weeks after solid organ transplantation (49 kidney transplantation, 52 lung transplantation) and 14 healthy volunteers were examined by MRI between July 2012 and April 2015 using the modified Look-Locker inversion recovery (MOLLI) sequence. T1 times in renal cortex and medulla and the corticomedullary difference were compared between groups using one-way ANOVA adjusted for multiple comparison with the Tukey test, and T1 times were correlated with renal function using Pearson's correlation.</AbstractText Compared to healthy volunteers T1 times were significantly increased after solid organ transplantation in the renal cortex (healthy volunteers 987 ± 102 ms; kidney transplantation 1299 ± 101 ms, p < 0.001; lung transplantation 1058 ± 96 ms, p < 0.05) and to a lesser extent in the renal medulla. Accordingly, the corticomedullary difference was diminished shortly after solid organ transplantation. T1 changes were more pronounced following kidney compared to lung transplantation, were associated with the stage of renal impairment and significantly correlated with renal function.</AbstractText T1 mapping may be helpful for early non-invasive assessment of acute kidney injury and renal pathology following major surgery such as solid organ transplantation.</AbstractText • Renal cortical T1 relaxation times are prolonged after solid organ transplantation. • Cortical T1 values increase with higher stages of renal function impairment. • Corticomedullary difference decreases with higher stages of renal function impairment. • Renal cortical T1 relaxation time and corticomedullary difference correlate with renal function. • T1 mapping may be helpful for non-invasive assessment of post-operative renal pathology.</AbstractText
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Post-stroke Chinese pure alexia: linguistic features and neuropsychological profiles. Very few cases of Chinese pure alexia have been reported to date. We aim to summarize the linguistic features and neuropsychological profiles of Chinese pure alexia through a case series study.</AbstractText 11 consecutive patients with post-stroke Chinese pure alexia and 11 healthy controls were included. The Aphasia Battery of Chinese (ABC) and 68-Chinese character oral reading test (68-character test) were used to evaluate the reading and writing ability. Reading errors were classified based on the performance of 68-character test. Neuropsychological profiles were evaluated with corresponding scales. The possible correlation between the reading ability and the writing ability or neuropsychological performance was analyzed.</AbstractText The patients had a correct rate of 43.7 ± 23.2% in the 68-character test, significantly lower (P < 0.001) than that of controls. Shape-similar error was the most common type of reading error (101/209, 48.3%). The ABC total writing score rate of the patients ranged from 68.9% to 98.7% (median, 90.5%), significantly lower (P < 0.001) than that of the controls. The patients also showed worse performance in MMSE, auditory verbal learning test, Boston naming test, intersecting pentagons copying and clock-drawing test (all P < 0.05). In the patient group, the correct rate of 68-character test was significantly correlated with the ABC total writing score rate (P = 0.008), the score rate of Boston naming test (P = 0.017), and the clock-drawing test score (P = 0.010).</AbstractText Shape-similar errors may be a characteristic of Chinese pure alexia. The correlation between visuospatial dysfunction and pure alexia might explain the frequent occurrence of shape-similar errors in Chinese pure alexia.</AbstractText
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30470988
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23418584
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31203463
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Homophone Advantage in Sentence Acceptability Judgment: An Experiment with Japanese Kanji Words and Articulatory Suppression Technique.
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The effects of aging on conflict detection.
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Skeletal Muscle Wasting and Its Relationship With Osteoarthritis: a Mini-Review of Mechanisms and Current Interventions.
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The purpose of this study was to examine the role and nature of phonology in silent reading of Japanese sentences. An experiment was conducted using a Japanese sentence acceptability judgment task. One important finding was that participants more rapidly rejected homophonic sentences in which one two-kanji compound word was replaced by its homophone word than non-homophonic sentences. In the latter, the word was replaced by a non-homophone spelling control; that is, we observed a homophone advantage. Participants were able to identify the correct word easily through foil's homophonic mate. This indicated that activated phonology played a role in the Japanese sentence acceptability judgment task and it contributed to the error detection/recovery process. Another important finding was that the homophone facilitation effect remained under articulatory suppression. It confirmed that phonology was activated at an early stage as abstract, non-articulatory phonology.</AbstractText
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Several cognitive changes characterize normal aging; one change regards inhibitory processing and includes both conflict monitoring and response suppression. We attempted to segregate these two aspects within a Go/No-go task, investigating three age categories. Accuracy, response times and event-related potentials (ERPs) were recorded. The ERP data were analyzed, and the Go and No-go trials were separated; in addition, the trials were organized in repeat trials (in which the subjects repeated the action delivered in the previous trial) and switch trials (in which the subjects produced a response opposite to the previous response). We assumed that the switch trials conveyed more conflict than the repeat trials. In general, the behavioral data and slower P3 latencies confirmed the well-known age-related speed/accuracy trade-off. The novel analyses of the repeat vs. switch trials indicated that the age-related P3 slowing was significant only for the high conflict condition; the switch-P3 amplitude increased only in the two older groups. The 'aging switch effect' on the P3 component suggests a failure in the conflict conditions and likely contributes to a generalized dysfunction. The absence of either a switch effect in the young group and the P3 slowing in middle-aged group indicate that switching was not particularly demanding for these participants. The N2 component was less sensitive to the repeat/switch manipulation; however, the subtractive waves also enhanced the age effects in this earlier time window. The topographic maps showed other notable age effects: the frontal No-go N2 was nearly undetectable in the elderly; in the identical time window, a large activity in the posterior and prefrontal scalp regions was observed. Moreover, the prefrontal activity showed a negative correlation with false alarms. These results suggest that the frontal involvement during action suppression becomes progressively dysfunctional with aging, and additional activity was required to reach a good level of accuracy.</AbstractText
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Osteoarthritis (OA) is a subset of joint disorders resulting in degeneration of synovial joints. This leads to pain, disability and loss of independence. Knee and hip OA are extremely prevalent, and their occurrence increases with ageing. Similarly, loss of muscle mass and function, sarcopenia, occurs during ageing.</AbstractText Little is known about the impact of muscle wasting on OA progression; nevertheless, it has been suggested that muscle wasting directly affects the stability of the joints and loss of mobility leads to gradual degeneration of articular cartilage. The molecular mechanisms underlying muscle wasting in OA are not well understood; however, these are probably related to changes in gene expression, as well as epigenetic modifications. It is becoming clear that skeletal muscle wasting plays an important role in OA development and/or progression. Here, we discuss mechanisms, current interventions, such as exercise, and potentially novel approaches, such as modulation of microRNAs, aiming at ameliorating OA symptoms through maintaining muscle mass and function.</AbstractText
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Homophone Advantage in Sentence Acceptability Judgment: An Experiment with Japanese Kanji Words and Articulatory Suppression Technique. The purpose of this study was to examine the role and nature of phonology in silent reading of Japanese sentences. An experiment was conducted using a Japanese sentence acceptability judgment task. One important finding was that participants more rapidly rejected homophonic sentences in which one two-kanji compound word was replaced by its homophone word than non-homophonic sentences. In the latter, the word was replaced by a non-homophone spelling control; that is, we observed a homophone advantage. Participants were able to identify the correct word easily through foil's homophonic mate. This indicated that activated phonology played a role in the Japanese sentence acceptability judgment task and it contributed to the error detection/recovery process. Another important finding was that the homophone facilitation effect remained under articulatory suppression. It confirmed that phonology was activated at an early stage as abstract, non-articulatory phonology.</AbstractText
|
The effects of aging on conflict detection. Several cognitive changes characterize normal aging; one change regards inhibitory processing and includes both conflict monitoring and response suppression. We attempted to segregate these two aspects within a Go/No-go task, investigating three age categories. Accuracy, response times and event-related potentials (ERPs) were recorded. The ERP data were analyzed, and the Go and No-go trials were separated; in addition, the trials were organized in repeat trials (in which the subjects repeated the action delivered in the previous trial) and switch trials (in which the subjects produced a response opposite to the previous response). We assumed that the switch trials conveyed more conflict than the repeat trials. In general, the behavioral data and slower P3 latencies confirmed the well-known age-related speed/accuracy trade-off. The novel analyses of the repeat vs. switch trials indicated that the age-related P3 slowing was significant only for the high conflict condition; the switch-P3 amplitude increased only in the two older groups. The 'aging switch effect' on the P3 component suggests a failure in the conflict conditions and likely contributes to a generalized dysfunction. The absence of either a switch effect in the young group and the P3 slowing in middle-aged group indicate that switching was not particularly demanding for these participants. The N2 component was less sensitive to the repeat/switch manipulation; however, the subtractive waves also enhanced the age effects in this earlier time window. The topographic maps showed other notable age effects: the frontal No-go N2 was nearly undetectable in the elderly; in the identical time window, a large activity in the posterior and prefrontal scalp regions was observed. Moreover, the prefrontal activity showed a negative correlation with false alarms. These results suggest that the frontal involvement during action suppression becomes progressively dysfunctional with aging, and additional activity was required to reach a good level of accuracy.</AbstractText
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Skeletal Muscle Wasting and Its Relationship With Osteoarthritis: a Mini-Review of Mechanisms and Current Interventions. Osteoarthritis (OA) is a subset of joint disorders resulting in degeneration of synovial joints. This leads to pain, disability and loss of independence. Knee and hip OA are extremely prevalent, and their occurrence increases with ageing. Similarly, loss of muscle mass and function, sarcopenia, occurs during ageing.</AbstractText Little is known about the impact of muscle wasting on OA progression; nevertheless, it has been suggested that muscle wasting directly affects the stability of the joints and loss of mobility leads to gradual degeneration of articular cartilage. The molecular mechanisms underlying muscle wasting in OA are not well understood; however, these are probably related to changes in gene expression, as well as epigenetic modifications. It is becoming clear that skeletal muscle wasting plays an important role in OA development and/or progression. Here, we discuss mechanisms, current interventions, such as exercise, and potentially novel approaches, such as modulation of microRNAs, aiming at ameliorating OA symptoms through maintaining muscle mass and function.</AbstractText
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35851275
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24875392
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35720298
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Meta-analytic evidence that mindfulness training alters resting state default mode network connectivity.
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Test-retest reliabilities of resting-state FMRI measurements in human brain functional connectomics: a systems neuroscience perspective.
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Upper Gastrointestinal Tract IrAEs: A Case Report About Sintilimab-Induced Acute Erosive Hemorrhagic Gastritis.
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This meta-analysis sought to expand upon neurobiological models of mindfulness through investigation of inherent brain network connectivity outcomes, indexed via resting state functional connectivity (rsFC). We conducted a systematic review and meta-analysis of rsFC as an outcome of mindfulness training (MT) relative to control, with the hypothesis that MT would increase cross-network connectivity between nodes of the Default Mode Network (DMN), Salience Network (SN), and Frontoparietal Control Network (FPCN) as a mechanism of internally-oriented attentional control. Texts were identified from the databases: MEDLINE/PubMed, ERIC, PSYCINFO, ProQuest, Scopus, and Web of Sciences; and were screened for inclusion based on experimental/quasi-experimental trial design and use of mindfulness-based training interventions. RsFC effects were extracted from twelve studies (mindfulness n = 226; control n = 204). Voxel-based meta-analysis revealed significantly greater rsFC (MT > control) between the left middle cingulate (Hedge's g = .234, p = 0.0288, I<sup
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Resting-state functional magnetic resonance imaging (RFMRI) enables researchers to monitor fluctuations in the spontaneous brain activities of thousands of regions in the human brain simultaneously, representing a popular tool for macro-scale functional connectomics to characterize normal brain function, mind-brain associations, and the various disorders. However, the test-retest reliability of RFMRI remains largely unknown. We review previously published papers on the test-retest reliability of voxel-wise metrics and conduct a meta-summary reliability analysis of seven common brain networks. This analysis revealed that the heteromodal associative (default, control, and attention) networks were mostly reliable across the seven networks. Regarding examined metrics, independent component analysis with dual regression, local functional homogeneity and functional homotopic connectivity were the three mostly reliable RFMRI metrics. These observations can guide the use of reliable metrics and further improvement of test-retest reliability for other metics in functional connectomics. We discuss the main issues with low reliability related to sub-optimal design and the choice of data processing options. Future research should use large-sample test-retest data to rectify both the within-subject and between-subject variability of RFMRI measurements and accelerate the application of functional connectomics.</AbstractText
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Immune checkpoint inhibitors (ICIs) have now become the standard therapy for malignancies like non-small cell lung cancer and classical Hodgkin's lymphoma. ICIs are associated with unique immune-related adverse events (irAEs) caused by dysregulated immune activation. Treatment of lower gastrointestinal (GI) tract irAEs, such as colitis, is more common. However, for upper gastrointestinal tract irAEs, there is a lack of consensus in terms of globally standardized disease classification and treatment guidelines. Here, we report a case of sintilimab-induced acute erosive hemorrhagic gastritis.</AbstractText A 54-year-old man with metastatic NSCLC (PT2N2M1 stage IV) underwent treatment with eight courses of sintilimab + bevacizumab, followed by maintenance therapy with sintilimab alone. However, he presented with epigastric pain and melena at the end of the first sintilimab treatment, and the symptoms occurred repeatedly after regular treatment with acute erosive hemorrhagic gastritis. Repeat esophagogastroduodenoscopy (EGD) showed severe hemorrhagic gastritis; symptomatic relief and improvement in EGD images were noted for as long as he was being treated with steroids, methylprednisolone sodium.</AbstractText As far as we are aware, we here describe the first case of sintilimab-associated acute erosive hemorrhagic gastritis, an upper gastrointestinal toxicity event. Throughout the treatment progression, differential diagnosis, multidisciplinary discussion, and the use of immunosuppressants were instrumental in clarifying the diagnosis and were crucial to the prognosis of the patient and continued treatment with ICIs.</AbstractText
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Meta-analytic evidence that mindfulness training alters resting state default mode network connectivity. This meta-analysis sought to expand upon neurobiological models of mindfulness through investigation of inherent brain network connectivity outcomes, indexed via resting state functional connectivity (rsFC). We conducted a systematic review and meta-analysis of rsFC as an outcome of mindfulness training (MT) relative to control, with the hypothesis that MT would increase cross-network connectivity between nodes of the Default Mode Network (DMN), Salience Network (SN), and Frontoparietal Control Network (FPCN) as a mechanism of internally-oriented attentional control. Texts were identified from the databases: MEDLINE/PubMed, ERIC, PSYCINFO, ProQuest, Scopus, and Web of Sciences; and were screened for inclusion based on experimental/quasi-experimental trial design and use of mindfulness-based training interventions. RsFC effects were extracted from twelve studies (mindfulness n = 226; control n = 204). Voxel-based meta-analysis revealed significantly greater rsFC (MT > control) between the left middle cingulate (Hedge's g = .234, p = 0.0288, I<sup
|
Test-retest reliabilities of resting-state FMRI measurements in human brain functional connectomics: a systems neuroscience perspective. Resting-state functional magnetic resonance imaging (RFMRI) enables researchers to monitor fluctuations in the spontaneous brain activities of thousands of regions in the human brain simultaneously, representing a popular tool for macro-scale functional connectomics to characterize normal brain function, mind-brain associations, and the various disorders. However, the test-retest reliability of RFMRI remains largely unknown. We review previously published papers on the test-retest reliability of voxel-wise metrics and conduct a meta-summary reliability analysis of seven common brain networks. This analysis revealed that the heteromodal associative (default, control, and attention) networks were mostly reliable across the seven networks. Regarding examined metrics, independent component analysis with dual regression, local functional homogeneity and functional homotopic connectivity were the three mostly reliable RFMRI metrics. These observations can guide the use of reliable metrics and further improvement of test-retest reliability for other metics in functional connectomics. We discuss the main issues with low reliability related to sub-optimal design and the choice of data processing options. Future research should use large-sample test-retest data to rectify both the within-subject and between-subject variability of RFMRI measurements and accelerate the application of functional connectomics.</AbstractText
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Upper Gastrointestinal Tract IrAEs: A Case Report About Sintilimab-Induced Acute Erosive Hemorrhagic Gastritis. Immune checkpoint inhibitors (ICIs) have now become the standard therapy for malignancies like non-small cell lung cancer and classical Hodgkin's lymphoma. ICIs are associated with unique immune-related adverse events (irAEs) caused by dysregulated immune activation. Treatment of lower gastrointestinal (GI) tract irAEs, such as colitis, is more common. However, for upper gastrointestinal tract irAEs, there is a lack of consensus in terms of globally standardized disease classification and treatment guidelines. Here, we report a case of sintilimab-induced acute erosive hemorrhagic gastritis.</AbstractText A 54-year-old man with metastatic NSCLC (PT2N2M1 stage IV) underwent treatment with eight courses of sintilimab + bevacizumab, followed by maintenance therapy with sintilimab alone. However, he presented with epigastric pain and melena at the end of the first sintilimab treatment, and the symptoms occurred repeatedly after regular treatment with acute erosive hemorrhagic gastritis. Repeat esophagogastroduodenoscopy (EGD) showed severe hemorrhagic gastritis; symptomatic relief and improvement in EGD images were noted for as long as he was being treated with steroids, methylprednisolone sodium.</AbstractText As far as we are aware, we here describe the first case of sintilimab-associated acute erosive hemorrhagic gastritis, an upper gastrointestinal toxicity event. Throughout the treatment progression, differential diagnosis, multidisciplinary discussion, and the use of immunosuppressants were instrumental in clarifying the diagnosis and were crucial to the prognosis of the patient and continued treatment with ICIs.</AbstractText
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29371852
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23288627
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28523468
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Devising a Method to Study if Wernicke's Aphasia Patients are Aware That They Do Not Comprehend Language or Speak It Understandably.
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Defining language networks from resting-state fMRI for surgical planning--a feasibility study.
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Development of a novel radiotherapy motion phantom using a stepper motor driver circuit and evaluation using optical surface scanning.
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Wernicke's Aphasia (WA) is characterized by an individual speaking fluent gibberish without the ability to understand anything that is said to them or anything they attempt to read. It is caused by damage to the left posterior temporoparietal cortex, also known as Wernicke's area. An additional intriguing symptom of WA patients is their apparent obliviousness to their own lack of understanding despite their intact reasoning or other cognitive abilities. Their only deficit seems to be in the basic rules of language that define word meaning, also known as phonology. Growing out of a project in an undergraduate class, we devised a phonology-free approach to communicating with WA patients that attempts to answer the questions of whether WA patients know that they do not understand what is said to them, that others do not understand what they have said, and if these patients are distressed by this lack of communication. We here describe the process and the resulting method.</AbstractText
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Presurgical language mapping for patients with lesions close to language areas is critical to neurosurgical decision-making for preservation of language function. As a clinical noninvasive imaging technique, functional MRI (fMRI) is used to identify language areas by measuring blood-oxygen-level dependent (BOLD) signal change while patients perform carefully timed language vs. control tasks. This task-based fMRI critically depends on task performance, excluding many patients who have difficulty performing language tasks due to neurologic deficits. On the basis of recent discovery of resting-state fMRI (rs-fMRI), we propose a "task-free" paradigm acquiring fMRI data when patients simply are at rest. This paradigm is less demanding for patients to perform and easier for technologists to administer. We investigated the feasibility of this approach in right-handed healthy control subjects. First, group independent component analysis (ICA) was applied on the training group (14 subjects) to identify group level language components based on expert rating results. Then, four empirically and structurally defined language network templates were assessed for their ability to identify language components from individuals' ICA output of the testing group (18 subjects) based on spatial similarity analysis. Results suggest that it is feasible to extract language activations from rs-fMRI at the individual subject level, and two empirically defined templates (that focuses on frontal language areas and that incorporates both frontal and temporal language areas) demonstrated the best performance. We propose a semi-automated language component identification procedure and discuss the practical concerns and suggestions for this approach to be used in clinical fMRI language mapping.</AbstractText
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Recent developments in radiotherapy have focused on the management of patient motion during treatment. Studies have shown that significant gains in treatment quality can be made by 'gating' certain treatments, simultaneously keeping target coverage, and increasing separation to nearby organs at risk (OAR). Motion phantoms can be used to simulate patient breathing motion and provide the means to perform quality control (QC) and quality assurance (QA) of gating functionality as well as to assess the dosimetric impact of motion on individual patient treatments. The aim of this study was to design and build a motion phantom that accurately reproduces the breathing motion of patients to enable end-to-end gating system quality control of various gating systems as well as patient specific quality assurance. A motion phantom based on a stepper motor driver circuit was designed. The phantom can be programmed with both real patient data from an external gating system and with custom signals. The phantom was programmed and evaluated with patient data and with a square wave signal to be tracked with a Sentinel™ (C-Rad, Uppsala, Sweden) motion monitoring system. Results were compared to the original curves with respect to amplitude and phase. The comparison of patient curve data showed a mean error value of -0.09 mm with a standard deviation of 0.24 mm and a mean absolute error of 0.29 mm. The square wave signals could be reproduced with a mean error value of -0.03 mm, a standard deviation of 0.04 mm and a mean absolute error of 0.13 mm. Breathing curve data acquired from an optical scanning system can be reproduced accurately with the help of the in-house built motion phantom. The phantom can also be programmed to follow user designed curve data. This offers the potential for QC of gating systems and various dosimetric quality control applications.</AbstractText
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Devising a Method to Study if Wernicke's Aphasia Patients are Aware That They Do Not Comprehend Language or Speak It Understandably. Wernicke's Aphasia (WA) is characterized by an individual speaking fluent gibberish without the ability to understand anything that is said to them or anything they attempt to read. It is caused by damage to the left posterior temporoparietal cortex, also known as Wernicke's area. An additional intriguing symptom of WA patients is their apparent obliviousness to their own lack of understanding despite their intact reasoning or other cognitive abilities. Their only deficit seems to be in the basic rules of language that define word meaning, also known as phonology. Growing out of a project in an undergraduate class, we devised a phonology-free approach to communicating with WA patients that attempts to answer the questions of whether WA patients know that they do not understand what is said to them, that others do not understand what they have said, and if these patients are distressed by this lack of communication. We here describe the process and the resulting method.</AbstractText
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Defining language networks from resting-state fMRI for surgical planning--a feasibility study. Presurgical language mapping for patients with lesions close to language areas is critical to neurosurgical decision-making for preservation of language function. As a clinical noninvasive imaging technique, functional MRI (fMRI) is used to identify language areas by measuring blood-oxygen-level dependent (BOLD) signal change while patients perform carefully timed language vs. control tasks. This task-based fMRI critically depends on task performance, excluding many patients who have difficulty performing language tasks due to neurologic deficits. On the basis of recent discovery of resting-state fMRI (rs-fMRI), we propose a "task-free" paradigm acquiring fMRI data when patients simply are at rest. This paradigm is less demanding for patients to perform and easier for technologists to administer. We investigated the feasibility of this approach in right-handed healthy control subjects. First, group independent component analysis (ICA) was applied on the training group (14 subjects) to identify group level language components based on expert rating results. Then, four empirically and structurally defined language network templates were assessed for their ability to identify language components from individuals' ICA output of the testing group (18 subjects) based on spatial similarity analysis. Results suggest that it is feasible to extract language activations from rs-fMRI at the individual subject level, and two empirically defined templates (that focuses on frontal language areas and that incorporates both frontal and temporal language areas) demonstrated the best performance. We propose a semi-automated language component identification procedure and discuss the practical concerns and suggestions for this approach to be used in clinical fMRI language mapping.</AbstractText
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Development of a novel radiotherapy motion phantom using a stepper motor driver circuit and evaluation using optical surface scanning. Recent developments in radiotherapy have focused on the management of patient motion during treatment. Studies have shown that significant gains in treatment quality can be made by 'gating' certain treatments, simultaneously keeping target coverage, and increasing separation to nearby organs at risk (OAR). Motion phantoms can be used to simulate patient breathing motion and provide the means to perform quality control (QC) and quality assurance (QA) of gating functionality as well as to assess the dosimetric impact of motion on individual patient treatments. The aim of this study was to design and build a motion phantom that accurately reproduces the breathing motion of patients to enable end-to-end gating system quality control of various gating systems as well as patient specific quality assurance. A motion phantom based on a stepper motor driver circuit was designed. The phantom can be programmed with both real patient data from an external gating system and with custom signals. The phantom was programmed and evaluated with patient data and with a square wave signal to be tracked with a Sentinel™ (C-Rad, Uppsala, Sweden) motion monitoring system. Results were compared to the original curves with respect to amplitude and phase. The comparison of patient curve data showed a mean error value of -0.09 mm with a standard deviation of 0.24 mm and a mean absolute error of 0.29 mm. The square wave signals could be reproduced with a mean error value of -0.03 mm, a standard deviation of 0.04 mm and a mean absolute error of 0.13 mm. Breathing curve data acquired from an optical scanning system can be reproduced accurately with the help of the in-house built motion phantom. The phantom can also be programmed to follow user designed curve data. This offers the potential for QC of gating systems and various dosimetric quality control applications.</AbstractText
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38845969
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35304554
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39253727
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Methodology exploration and reproducibility evaluation of TAI and TSI for quantitative ultrasound assessment of hepatic steatosis.
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T1 reduction rate with Gd-EOB-DTPA determines liver function on both 1.5 T and 3 T MRI.
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Potential roles of voltage-gated ion channel disruption in Tuberous Sclerosis Complex.
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New quantitative ultrasound techniques can be used to quantify hepatic steatosis, including tissue attenuation imaging (TAI), tissue scatter -distribution imaging (TSI), and the hepatorenal index (HRI). However, the measurement norms and the effects of fasting on these measurements remain unclear. The present study performed a methodological exploration and investigated the reliability of these measurements.</AbstractText In total, 103 participants were prospectively recruited for ultrasonography and magnetic resonance imaging (MRI) scans. For the TAI and TSI data, the upper (2 cm), middle (4 cm) and lower (6 cm) areas determined according to the depth of the region of interest from the liver capsule, were sampled three times. Correlation analyses were performed to compare the measurements of TAI, TSI, and HRI with the controlled attenuation parameter (CAP) or MRI-proton density fat fraction (MRI-PDFF). Intra- and inter-operator repeatability was assessed using intraclass correlation coefficients. The effects of fasting on these measurements were then compared.</AbstractText The TAI and TSI measurements obtained from the upper and middle depths exhibited stronger correlations with the CAP measurements than those obtained from the lower depth. Specifically, the mean TAI had a significant positive correlation with MRI-PDFF (r = 0.753, P < 0.0001). TAI and TSI measurements exhibited excellent intra- (0.933 and 0.925, respectively) and inter- (0.896 and 0.766, respectively) examiner reliability. However, the correlation between HRI and CAP measurements was only 0.281, with no significant correlation with MRI-PDFF, and intra- and inter-examiner reproducibility of 0.458 and 0.343, respectively. Fasting did not affect these measurements.</AbstractText TAI and TSI measurements demonstrated good intra- and interobserver reliability and correlated well with CAP and MRI-PDFF measurements. However, in practice-based clinical applications, the sampling depth should be controlled within 2-4 cm of the hepatic capsule; no fasting is required before the examination.</AbstractText
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Magnetic resonance T1 mapping before and after Gd-EOB-DTPA administration allows quantification of the T1 reduction rate as a non-invasive surrogate marker of liver function. A major limitation of T1 relaxation time measurement is its dependency on MRI field strengths. Since T1 reduction rate is calculated as the relative shortening of T1 relaxation time before and after contrast administration, we hypothesized that the T1 reduction rate is comparable between 1.5 and 3 T. We thus compared liver T1 relaxation times between 1.5 and 3 T in a total of 243 consecutive patients (124, 1.5 T and 119, 3 T) between 09/2018 and 07/2019. T1 reduction rates were compared between patients with no cirrhosis and patients with cirrhosis Child-Pugh A-C. There was no significant difference of T1 reduction rate between 1.5 and 3 T in any patient group (p-value 0.126-0.861). On both 1.5 T and 3 T, T1 reduction rate allowed to differentiate between patients with no cirrhosis and patients with liver cirrhosis Child A-C (p < 0.001). T1 reduction rate showed a good performance to predict liver cirrhosis Child A (AUC = 0.83, p < 0.001), Child B (AUC = 0.83, p < 0.001) and Child C (AUC = 0.92, p < 0.001). In conclusion, T1 reduction rate allows to determine liver function on Gd-EOB-DTPA MRI with comparable values on 1.5 T and 3 T.</AbstractText
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Tuberous Sclerosis Complex (TSC) is a lynchpin disorder, as it results in overactive mammalian target of rapamycin (mTOR) signaling, which has been implicated in a multitude of disease states. TSC is an autosomal dominant disease where 90% of affected individuals develop epilepsy. Epilepsy results from aberrant neuronal excitability that leads to recurring seizures. Under neurotypical conditions, the coordinated activity of voltage-gated ion channels keep neurons operating in an optimal range, thus providing network stability. Interestingly, loss or gain of function mutations in voltage-gated potassium, sodium, or calcium channels leads to altered excitability and seizures. To date, little is known about voltage-gated ion channel expression and function in TSC. However, data is beginning to emerge on how mTOR signaling regulates voltage-gated ion channel expression in neurons. Herein, we provide a comprehensive review of the literature describing common seizure types in patients with TSC, and suggest possible parallels between acquired epilepsies with known voltage-gated ion channel dysfunction. Furthermore, we discuss possible links toward mTOR regulation of voltage-gated ion channels expression and channel kinetics and the underlying epileptic manifestations in patients with TSC.</AbstractText
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Methodology exploration and reproducibility evaluation of TAI and TSI for quantitative ultrasound assessment of hepatic steatosis. New quantitative ultrasound techniques can be used to quantify hepatic steatosis, including tissue attenuation imaging (TAI), tissue scatter -distribution imaging (TSI), and the hepatorenal index (HRI). However, the measurement norms and the effects of fasting on these measurements remain unclear. The present study performed a methodological exploration and investigated the reliability of these measurements.</AbstractText In total, 103 participants were prospectively recruited for ultrasonography and magnetic resonance imaging (MRI) scans. For the TAI and TSI data, the upper (2 cm), middle (4 cm) and lower (6 cm) areas determined according to the depth of the region of interest from the liver capsule, were sampled three times. Correlation analyses were performed to compare the measurements of TAI, TSI, and HRI with the controlled attenuation parameter (CAP) or MRI-proton density fat fraction (MRI-PDFF). Intra- and inter-operator repeatability was assessed using intraclass correlation coefficients. The effects of fasting on these measurements were then compared.</AbstractText The TAI and TSI measurements obtained from the upper and middle depths exhibited stronger correlations with the CAP measurements than those obtained from the lower depth. Specifically, the mean TAI had a significant positive correlation with MRI-PDFF (r = 0.753, P < 0.0001). TAI and TSI measurements exhibited excellent intra- (0.933 and 0.925, respectively) and inter- (0.896 and 0.766, respectively) examiner reliability. However, the correlation between HRI and CAP measurements was only 0.281, with no significant correlation with MRI-PDFF, and intra- and inter-examiner reproducibility of 0.458 and 0.343, respectively. Fasting did not affect these measurements.</AbstractText TAI and TSI measurements demonstrated good intra- and interobserver reliability and correlated well with CAP and MRI-PDFF measurements. However, in practice-based clinical applications, the sampling depth should be controlled within 2-4 cm of the hepatic capsule; no fasting is required before the examination.</AbstractText
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T1 reduction rate with Gd-EOB-DTPA determines liver function on both 1.5 T and 3 T MRI. Magnetic resonance T1 mapping before and after Gd-EOB-DTPA administration allows quantification of the T1 reduction rate as a non-invasive surrogate marker of liver function. A major limitation of T1 relaxation time measurement is its dependency on MRI field strengths. Since T1 reduction rate is calculated as the relative shortening of T1 relaxation time before and after contrast administration, we hypothesized that the T1 reduction rate is comparable between 1.5 and 3 T. We thus compared liver T1 relaxation times between 1.5 and 3 T in a total of 243 consecutive patients (124, 1.5 T and 119, 3 T) between 09/2018 and 07/2019. T1 reduction rates were compared between patients with no cirrhosis and patients with cirrhosis Child-Pugh A-C. There was no significant difference of T1 reduction rate between 1.5 and 3 T in any patient group (p-value 0.126-0.861). On both 1.5 T and 3 T, T1 reduction rate allowed to differentiate between patients with no cirrhosis and patients with liver cirrhosis Child A-C (p < 0.001). T1 reduction rate showed a good performance to predict liver cirrhosis Child A (AUC = 0.83, p < 0.001), Child B (AUC = 0.83, p < 0.001) and Child C (AUC = 0.92, p < 0.001). In conclusion, T1 reduction rate allows to determine liver function on Gd-EOB-DTPA MRI with comparable values on 1.5 T and 3 T.</AbstractText
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Potential roles of voltage-gated ion channel disruption in Tuberous Sclerosis Complex. Tuberous Sclerosis Complex (TSC) is a lynchpin disorder, as it results in overactive mammalian target of rapamycin (mTOR) signaling, which has been implicated in a multitude of disease states. TSC is an autosomal dominant disease where 90% of affected individuals develop epilepsy. Epilepsy results from aberrant neuronal excitability that leads to recurring seizures. Under neurotypical conditions, the coordinated activity of voltage-gated ion channels keep neurons operating in an optimal range, thus providing network stability. Interestingly, loss or gain of function mutations in voltage-gated potassium, sodium, or calcium channels leads to altered excitability and seizures. To date, little is known about voltage-gated ion channel expression and function in TSC. However, data is beginning to emerge on how mTOR signaling regulates voltage-gated ion channel expression in neurons. Herein, we provide a comprehensive review of the literature describing common seizure types in patients with TSC, and suggest possible parallels between acquired epilepsies with known voltage-gated ion channel dysfunction. Furthermore, we discuss possible links toward mTOR regulation of voltage-gated ion channels expression and channel kinetics and the underlying epileptic manifestations in patients with TSC.</AbstractText
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32765286
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35075810
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31847650
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Acute Low Dose of Trazodone Recovers Glutamate Release Efficiency and mGlu2/3 Autoreceptor Impairments in the Spinal Cord of Rats Suffering From Chronic Sciatic Ligation.
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Serotonin receptors in epilepsy: Novel treatment targets?
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Spinal cord stimulation modulates complexity of neural activities in patients with disorders of consciousness.
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We investigated whether chronic sciatic ligation modifies the glutamate release in spinal cord nerve endings (synaptosomes) as well as the expression and the function of presynaptic release-regulating mGlu2/3 autoreceptors and 5-HT<sub
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Despite the availability of over 30 antiseizure medications (ASMs), there is no "one size fits it all," so there is a continuing search for novel ASMs. There are divergent data demonstrating that modulation of distinct serotonin (5-hydroxytryptamine, 5-HT) receptors subtypes could be beneficial in the treatment of epilepsy and its comorbidities, whereas only a few ASM, such as fenfluramine (FA), act via 5-HT. There are 14 different 5-HT receptor subtypes, and most epilepsy studies focus on one or a few of these subtypes, using different animal models and different ligands. We reviewed the available evidence of each 5-HT receptor subtype using MEDLINE up to July 2021. Our search included medical subject heading (MeSH) and free terms of each "5-HT subtype" separately and its relation to "epilepsy or seizures." Most research underlines the antiseizure activity of 5-HT<sub
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<b
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Acute Low Dose of Trazodone Recovers Glutamate Release Efficiency and mGlu2/3 Autoreceptor Impairments in the Spinal Cord of Rats Suffering From Chronic Sciatic Ligation. We investigated whether chronic sciatic ligation modifies the glutamate release in spinal cord nerve endings (synaptosomes) as well as the expression and the function of presynaptic release-regulating mGlu2/3 autoreceptors and 5-HT<sub
|
Serotonin receptors in epilepsy: Novel treatment targets? Despite the availability of over 30 antiseizure medications (ASMs), there is no "one size fits it all," so there is a continuing search for novel ASMs. There are divergent data demonstrating that modulation of distinct serotonin (5-hydroxytryptamine, 5-HT) receptors subtypes could be beneficial in the treatment of epilepsy and its comorbidities, whereas only a few ASM, such as fenfluramine (FA), act via 5-HT. There are 14 different 5-HT receptor subtypes, and most epilepsy studies focus on one or a few of these subtypes, using different animal models and different ligands. We reviewed the available evidence of each 5-HT receptor subtype using MEDLINE up to July 2021. Our search included medical subject heading (MeSH) and free terms of each "5-HT subtype" separately and its relation to "epilepsy or seizures." Most research underlines the antiseizure activity of 5-HT<sub
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Spinal cord stimulation modulates complexity of neural activities in patients with disorders of consciousness. <b
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40210657
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28148640
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39589160
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Children engage neural reward structures for creative musical improvisation.
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The role of the hippocampus in navigation is memory.
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Copper homeostasis and neurodegenerative diseases.
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Children spontaneously engage in creative behaviors. However, little is known about the biological underpinnings of creativity in children. We identified neural substrates associated with musical improvisation in children aged 9-11. Participants played a non-ferromagnetic piano keyboard in a functional magnetic resonance imaging (fMRI) scanner using a musical paradigm that required no prior musical experience, in which they played a rote pattern from memory or improvised melodies using those same notes. fMRI analysis of children's brains during musical improvisation revealed (1) heightened functional connectivity between emotion and reward brain areas and (2) deactivation of auditory, limbic, and parietal structures, particularly the middle temporal gyrus, angular gyrus, precuneus, and cingulate cortex. Importantly, improvisation engaged reward structures more than the control condition. Neural results suggest that children possess nascent creativity networks that form the roots for later adult creativity networks.</AbstractText
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There is considerable research on the neurobiological mechanisms within the hippocampal system that support spatial navigation. In this article I review the literature on navigational strategies in humans and animals, observations on hippocampal function in navigation, and studies of hippocampal neural activity in animals and humans performing different navigational tasks and tests of memory. Whereas the hippocampus is essential to spatial navigation via a cognitive map, its role derives from the relational organization and flexibility of cognitive maps and not from a selective role in the spatial domain. Correspondingly, hippocampal networks map multiple navigational strategies, as well as other spatial and nonspatial memories and knowledge domains that share an emphasis on relational organization. These observations suggest that the hippocampal system is not dedicated to spatial cognition and navigation, but organizes experiences in memory, for which spatial mapping and navigation are both a metaphor for and a prominent application of relational memory organization.</AbstractText
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Copper, one of the most prolific transition metals in the body, is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations. Copper homeostasis is meticulously maintained through a complex network of copper-dependent proteins, including copper transporters (CTR1 and CTR2), the two copper ion transporters the Cu -transporting ATPase 1 (ATP7A) and Cu-transporting beta (ATP7B), and the three copper chaperones ATOX1, CCS, and COX17. Disruptions in copper homeostasis can lead to either the deficiency or accumulation of copper in brain tissue. Emerging evidence suggests that abnormal copper metabolism or copper binding to various proteins, including ceruloplasmin and metallothionein, is involved in the pathogenesis of neurodegenerative disorders. However, the exact mechanisms underlying these processes are not known. Copper is a potent oxidant that increases reactive oxygen species production and promotes oxidative stress. Elevated reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial dysfunction. Reactive oxygen species serve as key signaling molecules in copper-induced neuroinflammation, with elevated levels activating several critical inflammatory pathways. Additionally, copper can bind aberrantly to several neuronal proteins, including alpha-synuclein, tau, superoxide dismutase 1, and huntingtin, thereby inducing neurotoxicity and ultimately cell death. This study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases, with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease pathogenesis. By synthesizing the current findings on the functions of copper in oxidative stress, neuroinflammation, mitochondrial dysfunction, and protein misfolding, we aim to elucidate the mechanisms by which copper contributes to a wide range of hereditary and neuronal disorders, such as Wilson's disease, Menkes' disease, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. Potential clinically significant therapeutic targets, including superoxide dismutase 1, D-penicillamine, and 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline, along with their associated therapeutic agents, are further discussed. Ultimately, we collate evidence that copper homeostasis may function in the underlying etiology of several neurodegenerative diseases and offer novel insights into the potential prevention and treatment of these diseases based on copper homeostasis.</AbstractText
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Children engage neural reward structures for creative musical improvisation. Children spontaneously engage in creative behaviors. However, little is known about the biological underpinnings of creativity in children. We identified neural substrates associated with musical improvisation in children aged 9-11. Participants played a non-ferromagnetic piano keyboard in a functional magnetic resonance imaging (fMRI) scanner using a musical paradigm that required no prior musical experience, in which they played a rote pattern from memory or improvised melodies using those same notes. fMRI analysis of children's brains during musical improvisation revealed (1) heightened functional connectivity between emotion and reward brain areas and (2) deactivation of auditory, limbic, and parietal structures, particularly the middle temporal gyrus, angular gyrus, precuneus, and cingulate cortex. Importantly, improvisation engaged reward structures more than the control condition. Neural results suggest that children possess nascent creativity networks that form the roots for later adult creativity networks.</AbstractText
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The role of the hippocampus in navigation is memory. There is considerable research on the neurobiological mechanisms within the hippocampal system that support spatial navigation. In this article I review the literature on navigational strategies in humans and animals, observations on hippocampal function in navigation, and studies of hippocampal neural activity in animals and humans performing different navigational tasks and tests of memory. Whereas the hippocampus is essential to spatial navigation via a cognitive map, its role derives from the relational organization and flexibility of cognitive maps and not from a selective role in the spatial domain. Correspondingly, hippocampal networks map multiple navigational strategies, as well as other spatial and nonspatial memories and knowledge domains that share an emphasis on relational organization. These observations suggest that the hippocampal system is not dedicated to spatial cognition and navigation, but organizes experiences in memory, for which spatial mapping and navigation are both a metaphor for and a prominent application of relational memory organization.</AbstractText
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Copper homeostasis and neurodegenerative diseases. Copper, one of the most prolific transition metals in the body, is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations. Copper homeostasis is meticulously maintained through a complex network of copper-dependent proteins, including copper transporters (CTR1 and CTR2), the two copper ion transporters the Cu -transporting ATPase 1 (ATP7A) and Cu-transporting beta (ATP7B), and the three copper chaperones ATOX1, CCS, and COX17. Disruptions in copper homeostasis can lead to either the deficiency or accumulation of copper in brain tissue. Emerging evidence suggests that abnormal copper metabolism or copper binding to various proteins, including ceruloplasmin and metallothionein, is involved in the pathogenesis of neurodegenerative disorders. However, the exact mechanisms underlying these processes are not known. Copper is a potent oxidant that increases reactive oxygen species production and promotes oxidative stress. Elevated reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial dysfunction. Reactive oxygen species serve as key signaling molecules in copper-induced neuroinflammation, with elevated levels activating several critical inflammatory pathways. Additionally, copper can bind aberrantly to several neuronal proteins, including alpha-synuclein, tau, superoxide dismutase 1, and huntingtin, thereby inducing neurotoxicity and ultimately cell death. This study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases, with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease pathogenesis. By synthesizing the current findings on the functions of copper in oxidative stress, neuroinflammation, mitochondrial dysfunction, and protein misfolding, we aim to elucidate the mechanisms by which copper contributes to a wide range of hereditary and neuronal disorders, such as Wilson's disease, Menkes' disease, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. Potential clinically significant therapeutic targets, including superoxide dismutase 1, D-penicillamine, and 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline, along with their associated therapeutic agents, are further discussed. Ultimately, we collate evidence that copper homeostasis may function in the underlying etiology of several neurodegenerative diseases and offer novel insights into the potential prevention and treatment of these diseases based on copper homeostasis.</AbstractText
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32525133
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30287460
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32576849
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A Novel Metallic Artifact Reduction Technique When Using a Computed Tomography-Guided Percutaneous Metallic Antenna to Ablate Malignant Pulmonary Nodules: A Qualitative and Quantitative Assessment.
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Subtraction CTA: An Alternative Imaging Option for the Follow-Up of Flow-Diverter-Treated Aneurysms?
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The Contribution of Oculomotor Functions to Rates of Visual Information Processing in Younger and Older Adults.
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BACKGROUND Metallic microwave ablation (MWA) antenna-related artifacts are usually created in conventional CT images, and these artifacts can influence the effect of ablation. The aim of this study was to evaluate a new type of metal artifact reduction (MAR+) technique in CT-guided MWA for lung cancer. MATERIAL AND METHODS This retrospective study enrolled 30 lung cancer patients who received CT-guided MWA treatment from December 2017 to April 2018. Images after microwave antenna insertion into the tumor were reconstructed by the filter back projection (group A) and MAR+ reconstruction (group B). The CT values and standard deviations of the regions of interest (ROIs) on the chosen image were recorded, including the most significantly hypodense artifact (ROI₁), hyperdense artifacts (ROI₂), and chest muscles of the same layer (ROI₃). The metal artifact indexes based on ROI₁ and ROI₂ (AI₁, AI₂) and the overall metal artifact index (AI) were calculated. Subjective image quality was graded on a five-point scale (1=worst, 5=excellent). RESULTS The AI₁ (74.14±76.32), AI₂ (13.75±19.02) and AI (54.12±54.82) of group B were lower than those of group A [(153.33±89.04), (30.63±26.42), (112.00±63.10), respectively] (P<0.001 for all). Both radiologists reported that the subjective image value of group B was significantly higher than that of group A (P<0.001). The subjective image quality scores evaluated by 2 observers showed excellent consistency (ICC=0.829). CONCLUSIONS The MAR+ imaging reconstruction significantly reduced metal artifacts, which helps radiologists to clearly observe the relationship between the ablation antenna and the lesion.</AbstractText
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This was a pilot study to explore the diagnostic accuracy and safety of subtraction CTA combined with a single-energy metal artifact reduction algorithm (SEMAR) compared to DSA for the evaluation of intracranial aneurysm occlusion after flow diverter treatment.</AbstractText We included patients treated with a flow diverter for an unruptured intracranial aneurysm between November 2015 and November 2016. The patient cohort comprised 2 groups: those who underwent follow-up imaging 1 month after flow-diverter treatment and those with a known residual intracranial aneurysm after flow diverter treatment who underwent imaging at regular follow-ups. Full-brain subtraction CTA was performed on a 320-detector row CT system. A low-dose non-enhanced volume acquisition was followed by a contrast-enhanced volume CTA. Iterative and noise-reduction filters, SEMAR, and <sup Thirteen intracranial aneurysms were evaluated with subtraction CTA and DSA. Nine aneurysm remnants were demonstrated by both subtraction CTA and DSA. The sensitivity and specificity of subtraction CTA for the detection of aneurysm occlusion were 100% (95% CI, 82.41%-100%) and 100% (95% CI, 67.55%-100%), respectively. Agreement between readers was perfect (κ = 1.0). The smallest neck remnant detected on subtraction CTA was 1.2 mm. No complications occurred.</AbstractText Subtraction CTA with single-electron metal artifact reduction is effective in the reduction of metal artifacts of flow diverters and might therefore be a viable alternative in the assessment of intracranial aneurysm occlusion after flow diverter treatment.</AbstractText
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Oculomotor functions are established surrogate measures of visual attention shifting and rate of information processing, however, the temporal characteristics of saccades and fixations have seldom been compared in healthy educated samples of younger and older adults. Thus, the current study aimed to compare duration of eye movement components in younger (18-25 years) and older (50-81 years) adults during text reading and during object/alphanumeric Rapid Automatic Naming (RAN) tasks. The current study also aimed to examine the contribution of oculomotor functions to threshold time needed for accurate performance on visually-driven cognitive tasks (Inspection Time [IT] and Change Detection [CD]). Results showed that younger adults fixated on individual stimuli for significantly longer than the older participants, while older adults demonstrated significantly longer saccade durations than the younger group. Results also demonstrated that older adults required longer threshold durations (i.e., performed slower) on the visually-driven cognitive tasks, however, the age-group time difference on the CD task was eradicated when the effects of saccade duration were covaried. Thus, these results suggest that age-related cognitive decline is also related to increased duration of saccades and hence, highlights the need to dissociate the age-related motor constraints on the temporal aspects of oculomotor function from visuo-cognitive speed of processing.</AbstractText
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A Novel Metallic Artifact Reduction Technique When Using a Computed Tomography-Guided Percutaneous Metallic Antenna to Ablate Malignant Pulmonary Nodules: A Qualitative and Quantitative Assessment. BACKGROUND Metallic microwave ablation (MWA) antenna-related artifacts are usually created in conventional CT images, and these artifacts can influence the effect of ablation. The aim of this study was to evaluate a new type of metal artifact reduction (MAR+) technique in CT-guided MWA for lung cancer. MATERIAL AND METHODS This retrospective study enrolled 30 lung cancer patients who received CT-guided MWA treatment from December 2017 to April 2018. Images after microwave antenna insertion into the tumor were reconstructed by the filter back projection (group A) and MAR+ reconstruction (group B). The CT values and standard deviations of the regions of interest (ROIs) on the chosen image were recorded, including the most significantly hypodense artifact (ROI₁), hyperdense artifacts (ROI₂), and chest muscles of the same layer (ROI₃). The metal artifact indexes based on ROI₁ and ROI₂ (AI₁, AI₂) and the overall metal artifact index (AI) were calculated. Subjective image quality was graded on a five-point scale (1=worst, 5=excellent). RESULTS The AI₁ (74.14±76.32), AI₂ (13.75±19.02) and AI (54.12±54.82) of group B were lower than those of group A [(153.33±89.04), (30.63±26.42), (112.00±63.10), respectively] (P<0.001 for all). Both radiologists reported that the subjective image value of group B was significantly higher than that of group A (P<0.001). The subjective image quality scores evaluated by 2 observers showed excellent consistency (ICC=0.829). CONCLUSIONS The MAR+ imaging reconstruction significantly reduced metal artifacts, which helps radiologists to clearly observe the relationship between the ablation antenna and the lesion.</AbstractText
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Subtraction CTA: An Alternative Imaging Option for the Follow-Up of Flow-Diverter-Treated Aneurysms? This was a pilot study to explore the diagnostic accuracy and safety of subtraction CTA combined with a single-energy metal artifact reduction algorithm (SEMAR) compared to DSA for the evaluation of intracranial aneurysm occlusion after flow diverter treatment.</AbstractText We included patients treated with a flow diverter for an unruptured intracranial aneurysm between November 2015 and November 2016. The patient cohort comprised 2 groups: those who underwent follow-up imaging 1 month after flow-diverter treatment and those with a known residual intracranial aneurysm after flow diverter treatment who underwent imaging at regular follow-ups. Full-brain subtraction CTA was performed on a 320-detector row CT system. A low-dose non-enhanced volume acquisition was followed by a contrast-enhanced volume CTA. Iterative and noise-reduction filters, SEMAR, and <sup Thirteen intracranial aneurysms were evaluated with subtraction CTA and DSA. Nine aneurysm remnants were demonstrated by both subtraction CTA and DSA. The sensitivity and specificity of subtraction CTA for the detection of aneurysm occlusion were 100% (95% CI, 82.41%-100%) and 100% (95% CI, 67.55%-100%), respectively. Agreement between readers was perfect (κ = 1.0). The smallest neck remnant detected on subtraction CTA was 1.2 mm. No complications occurred.</AbstractText Subtraction CTA with single-electron metal artifact reduction is effective in the reduction of metal artifacts of flow diverters and might therefore be a viable alternative in the assessment of intracranial aneurysm occlusion after flow diverter treatment.</AbstractText
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The Contribution of Oculomotor Functions to Rates of Visual Information Processing in Younger and Older Adults. Oculomotor functions are established surrogate measures of visual attention shifting and rate of information processing, however, the temporal characteristics of saccades and fixations have seldom been compared in healthy educated samples of younger and older adults. Thus, the current study aimed to compare duration of eye movement components in younger (18-25 years) and older (50-81 years) adults during text reading and during object/alphanumeric Rapid Automatic Naming (RAN) tasks. The current study also aimed to examine the contribution of oculomotor functions to threshold time needed for accurate performance on visually-driven cognitive tasks (Inspection Time [IT] and Change Detection [CD]). Results showed that younger adults fixated on individual stimuli for significantly longer than the older participants, while older adults demonstrated significantly longer saccade durations than the younger group. Results also demonstrated that older adults required longer threshold durations (i.e., performed slower) on the visually-driven cognitive tasks, however, the age-group time difference on the CD task was eradicated when the effects of saccade duration were covaried. Thus, these results suggest that age-related cognitive decline is also related to increased duration of saccades and hence, highlights the need to dissociate the age-related motor constraints on the temporal aspects of oculomotor function from visuo-cognitive speed of processing.</AbstractText
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26257617
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22928717
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25689583
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Conditioned place preference successfully established in typically developing children.
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Annual Research Review: Resilient functioning in maltreated children--past, present, and future perspectives.
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Orally administrated Lactobacillus pentosus var. plantarum C29 ameliorates age-dependent colitis by inhibiting the nuclear factor-kappa B signaling pathway via the regulation of lipopolysaccharide production by gut microbiota.
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Affective processing, known to influence attention, motivation, and emotional regulation is poorly understood in young children, especially for those with neurodevelopmental disorders characterized by language impairments. Here we faithfully adapt a well-established animal paradigm used for affective processing, conditioned place preference (CPP) for use in typically developing children between the ages of 30-55 months. Children displayed a CPP, with an average 2.4 fold increase in time spent in the preferred room. Importantly, associative learning as assessed with CPP was not correlated with scores on the Mullen Scales of Early Learning (MSEL), indicating that CPP can be used with children with a wide range of cognitive skills.</AbstractText
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Through a process of probabilistic epigenesis, child maltreatment progressively contributes to compromised adaptation on a variety of developmental domains central to successful adjustment. These developmental failures pose significant risk for the emergence of psychopathology across the life course. In addition to the psychological consequences of maltreatment, a growing body of research has documented the deleterious effects of abuse and neglect on biological processes. Nonetheless, not all maltreated children develop maladaptively. Indeed, some percentage of maltreated children develops in a resilient fashion despite the significant adversity and stress they experience.</AbstractText The literature on the determinants of resilience in maltreated children is selectively reviewed and criteria for the inclusion of the studies are delineated.</AbstractText The majority of the research on the contributors to resilient functioning has focused on a single level of analysis and on psychosocial processes. Multilevel investigations have begun to appear, resulting in several studies on the processes to resilient functioning that integrate biological/genetic and psychological domains.</AbstractText Much additional research on the determinants of resilient functioning must be completed before we possess adequate knowledge based on a multiple levels of analysis approach that is commensurate with the complexity inherent in this dynamic developmental process. Suggestions for future research on the development of resilient functioning in maltreated children are proffered and intervention implications are discussed.</AbstractText
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To evaluate the anti-inflammaging effect of lactic acid bacteria (LAB) on age-dependent inflammation, we first screened and selected a tumor necrosis factor (TNF)-α and reactive oxygen species (ROS)-inhibitory LAB, Lactobacillus pentosus var. plantarum C29, among the LABs isolated from fermented vegetables using LPS-stimulated mouse peritoneal macrophages. Oral administration of C29 (2 × 109 CFU/rat) for 8 weeks in aged Fischer 344 rats (age, 16 months) inhibited the expression of the inflammatory markers myeloperoxidase, inducible nitric oxide (NO) synthase, cyclooxygenase-2, pro-inflammatory cytokines tumor necrosis factor (TNF)-α and IL-6 and the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), activator protein 1 (AP1), and mitogen-activated protein kinases (MAPKs). Treatment with C29 induced the expression of tight junction proteins ZO-1, occludin, and claudin-1, and reduced intestinal microbial LPS and plasmatic LPS levels and ROS, as well as the Firmicutes to Bacteroidetes ratio, which is significantly higher in aged rats than in young rats. C29 treatment also reduced plasmatic reactive oxygen species, malondialdehyde, C-reactive protein, and TNF-α, and suppressed expression of senescence markers p16 and p53 in the colon of the aged rats, but increased SIRT 1 expression. Based on these findings, we concluded that C29 treatment may suppress aging-dependent colitis by inhibiting NF-κB, AP1, and MAPK activation via the inhibition of gut microbiota LPS production and the induction of tight junction protein expression.</AbstractText
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Conditioned place preference successfully established in typically developing children. Affective processing, known to influence attention, motivation, and emotional regulation is poorly understood in young children, especially for those with neurodevelopmental disorders characterized by language impairments. Here we faithfully adapt a well-established animal paradigm used for affective processing, conditioned place preference (CPP) for use in typically developing children between the ages of 30-55 months. Children displayed a CPP, with an average 2.4 fold increase in time spent in the preferred room. Importantly, associative learning as assessed with CPP was not correlated with scores on the Mullen Scales of Early Learning (MSEL), indicating that CPP can be used with children with a wide range of cognitive skills.</AbstractText
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Annual Research Review: Resilient functioning in maltreated children--past, present, and future perspectives. Through a process of probabilistic epigenesis, child maltreatment progressively contributes to compromised adaptation on a variety of developmental domains central to successful adjustment. These developmental failures pose significant risk for the emergence of psychopathology across the life course. In addition to the psychological consequences of maltreatment, a growing body of research has documented the deleterious effects of abuse and neglect on biological processes. Nonetheless, not all maltreated children develop maladaptively. Indeed, some percentage of maltreated children develops in a resilient fashion despite the significant adversity and stress they experience.</AbstractText The literature on the determinants of resilience in maltreated children is selectively reviewed and criteria for the inclusion of the studies are delineated.</AbstractText The majority of the research on the contributors to resilient functioning has focused on a single level of analysis and on psychosocial processes. Multilevel investigations have begun to appear, resulting in several studies on the processes to resilient functioning that integrate biological/genetic and psychological domains.</AbstractText Much additional research on the determinants of resilient functioning must be completed before we possess adequate knowledge based on a multiple levels of analysis approach that is commensurate with the complexity inherent in this dynamic developmental process. Suggestions for future research on the development of resilient functioning in maltreated children are proffered and intervention implications are discussed.</AbstractText
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Orally administrated Lactobacillus pentosus var. plantarum C29 ameliorates age-dependent colitis by inhibiting the nuclear factor-kappa B signaling pathway via the regulation of lipopolysaccharide production by gut microbiota. To evaluate the anti-inflammaging effect of lactic acid bacteria (LAB) on age-dependent inflammation, we first screened and selected a tumor necrosis factor (TNF)-α and reactive oxygen species (ROS)-inhibitory LAB, Lactobacillus pentosus var. plantarum C29, among the LABs isolated from fermented vegetables using LPS-stimulated mouse peritoneal macrophages. Oral administration of C29 (2 × 109 CFU/rat) for 8 weeks in aged Fischer 344 rats (age, 16 months) inhibited the expression of the inflammatory markers myeloperoxidase, inducible nitric oxide (NO) synthase, cyclooxygenase-2, pro-inflammatory cytokines tumor necrosis factor (TNF)-α and IL-6 and the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), activator protein 1 (AP1), and mitogen-activated protein kinases (MAPKs). Treatment with C29 induced the expression of tight junction proteins ZO-1, occludin, and claudin-1, and reduced intestinal microbial LPS and plasmatic LPS levels and ROS, as well as the Firmicutes to Bacteroidetes ratio, which is significantly higher in aged rats than in young rats. C29 treatment also reduced plasmatic reactive oxygen species, malondialdehyde, C-reactive protein, and TNF-α, and suppressed expression of senescence markers p16 and p53 in the colon of the aged rats, but increased SIRT 1 expression. Based on these findings, we concluded that C29 treatment may suppress aging-dependent colitis by inhibiting NF-κB, AP1, and MAPK activation via the inhibition of gut microbiota LPS production and the induction of tight junction protein expression.</AbstractText
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22373615
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37192344
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22356744
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Perspective: Upcoming paradigm shifts for psychiatry in clinical care, research, and education.
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Optogenetic stimulation of the superior colliculus suppresses genetic absence seizures.
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Growth, photosynthesis and antioxidant responses of endophyte infected and non-infected rice under lead stress conditions.
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Psychiatry is facing a crisis fueled by a fragmented and inefficient system of care delivery and a disconnection between the state of research and the state of psychiatry education and practice. Many factors contribute to the current state of psychiatric care. Psychiatry is a shortage specialty, and this will become worse in the near future. In addition, financial pressures have led to decreases in psychiatric inpatient and outpatient services and to shorter lengths of hospitalization for even the sickest patients. This has resulted in fragmented care and an overreliance on polypharmacy. To reach the large number of patients needing psychiatric services, health care systems must change and take advantage of collaborative and integrative care models and new technologies. Psychiatrists must learn to partner more effectively with primary care providers to extend their expertise to the greatest number of patients. Currently, psychiatric diagnosis is based on a criteria-based system that was developed in the 1970s. Advances in systems and molecular neuroscience are beginning to elucidate specific brain systems that are dysfunctional in psychiatric illness. This has the potential to revolutionize psychiatric diagnosis and treatment in the future. However, psychiatry has not yet been successful in incorporating the language of this research into clinically meaningful terminology. If neuroscientific progress is to be translated into clinical advances, this must change. Residency programs must better prepare their graduates to keep up with a psychiatry literature that will increasingly use the language of neural circuits to describe psychiatric symptomatology and treatments.</AbstractText
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While anti-seizure medications are effective for many patients, nearly one-third of individuals have seizures that are refractory to pharmacotherapy. Prior studies using evoked preclinical seizure models have shown that pharmacological activation or excitatory optogenetic stimulation of the deep and intermediate layers of the superior colliculus (DLSC) display multi-potent anti-seizure effects. Here we monitored and modulated DLSC activity to suppress spontaneous seizures in the WAG/Rij genetic model of absence epilepsy. Female and male WAG/Rij adult rats were employed as study subjects. For electrophysiology studies, we recorded single unit activity from microwire arrays placed within the DLSC. For optogenetic experiments, animals were injected with virus coding for channelrhodopsin-2 or a control vector, and we compared the efficacy of continuous neuromodulation to that of closed-loop neuromodulation paradigms. For each, we compared three stimulation frequencies on a within-subject basis (5, 20, 100 Hz). For closed-loop stimulation, we detected seizures in real time based on the EEG power within the characteristic frequency band of spike-and-wave discharges (SWDs). We quantified the number and duration of each SWD during each 2 h-observation period. Following completion of the experiment, virus expression and fibre-optic placement was confirmed. We found that single-unit activity within the DLSC decreased seconds prior to SWD onset and increased during and after seizures. Nearly 40% of neurons displayed suppression of firing in response to the start of SWDs. Continuous optogenetic stimulation of the DLSC (at each of the three frequencies) resulted in a significant reduction of SWDs in males and was without effect in females. In contrast, closed-loop neuromodulation was effective in both females and males at all three frequencies. These data demonstrate that activity within the DLSC is suppressed prior to SWD onset, increases at SWD onset, and that excitatory optogenetic stimulation of the DLSC exerts anti-seizure effects against absence seizures. The striking difference between open- and closed-loop neuromodulation approaches underscores the importance of the stimulation paradigm in determining therapeutic effects.</AbstractText
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An endophytic fungus was tested in rice (Oryza sativa L.) exposed to four levels of lead (Pb) stress (0, 50, 100 and 200 μM) to assess effects on plant growth, photosynthesis and antioxidant enzyme activity. Under Pb stress conditions, endophyte-infected seedlings had greater shoot length but lower root length compared to non-infected controls, and endophyte-infected seedlings had greater dry weight in the 50 and 100 μM Pb treatments. Under Pb stress conditions, chlorophyll and carotenoid levels were significantly higher in the endophyte-infected seedlings. Net photosynthetic rate, transpiration rate and water use efficiency were significantly higher in endophyte-infected seedlings in the 50 and 100 μM Pb treatments. In addition, chlorophyll fluorescence parameters Fv/Fm and Fv/Fo were higher in the infected seedlings compared to the non-infected seedlings under Pb stress. Malondialdehyde accumulation was induced by Pb stress, and it was present in higher concentration in non-infected seedlings under higher concentrations of Pb (100 and 200 μM). Antioxidant activity was either higher or unchanged in the infected seedlings due to responses to the different Pb concentrations. These results suggest that the endophytic fungus improved rice growth under moderate Pb levels by enhancing photosynthesis and antioxidant activity relative to non-infected rice.</AbstractText
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Perspective: Upcoming paradigm shifts for psychiatry in clinical care, research, and education. Psychiatry is facing a crisis fueled by a fragmented and inefficient system of care delivery and a disconnection between the state of research and the state of psychiatry education and practice. Many factors contribute to the current state of psychiatric care. Psychiatry is a shortage specialty, and this will become worse in the near future. In addition, financial pressures have led to decreases in psychiatric inpatient and outpatient services and to shorter lengths of hospitalization for even the sickest patients. This has resulted in fragmented care and an overreliance on polypharmacy. To reach the large number of patients needing psychiatric services, health care systems must change and take advantage of collaborative and integrative care models and new technologies. Psychiatrists must learn to partner more effectively with primary care providers to extend their expertise to the greatest number of patients. Currently, psychiatric diagnosis is based on a criteria-based system that was developed in the 1970s. Advances in systems and molecular neuroscience are beginning to elucidate specific brain systems that are dysfunctional in psychiatric illness. This has the potential to revolutionize psychiatric diagnosis and treatment in the future. However, psychiatry has not yet been successful in incorporating the language of this research into clinically meaningful terminology. If neuroscientific progress is to be translated into clinical advances, this must change. Residency programs must better prepare their graduates to keep up with a psychiatry literature that will increasingly use the language of neural circuits to describe psychiatric symptomatology and treatments.</AbstractText
|
Optogenetic stimulation of the superior colliculus suppresses genetic absence seizures. While anti-seizure medications are effective for many patients, nearly one-third of individuals have seizures that are refractory to pharmacotherapy. Prior studies using evoked preclinical seizure models have shown that pharmacological activation or excitatory optogenetic stimulation of the deep and intermediate layers of the superior colliculus (DLSC) display multi-potent anti-seizure effects. Here we monitored and modulated DLSC activity to suppress spontaneous seizures in the WAG/Rij genetic model of absence epilepsy. Female and male WAG/Rij adult rats were employed as study subjects. For electrophysiology studies, we recorded single unit activity from microwire arrays placed within the DLSC. For optogenetic experiments, animals were injected with virus coding for channelrhodopsin-2 or a control vector, and we compared the efficacy of continuous neuromodulation to that of closed-loop neuromodulation paradigms. For each, we compared three stimulation frequencies on a within-subject basis (5, 20, 100 Hz). For closed-loop stimulation, we detected seizures in real time based on the EEG power within the characteristic frequency band of spike-and-wave discharges (SWDs). We quantified the number and duration of each SWD during each 2 h-observation period. Following completion of the experiment, virus expression and fibre-optic placement was confirmed. We found that single-unit activity within the DLSC decreased seconds prior to SWD onset and increased during and after seizures. Nearly 40% of neurons displayed suppression of firing in response to the start of SWDs. Continuous optogenetic stimulation of the DLSC (at each of the three frequencies) resulted in a significant reduction of SWDs in males and was without effect in females. In contrast, closed-loop neuromodulation was effective in both females and males at all three frequencies. These data demonstrate that activity within the DLSC is suppressed prior to SWD onset, increases at SWD onset, and that excitatory optogenetic stimulation of the DLSC exerts anti-seizure effects against absence seizures. The striking difference between open- and closed-loop neuromodulation approaches underscores the importance of the stimulation paradigm in determining therapeutic effects.</AbstractText
|
Growth, photosynthesis and antioxidant responses of endophyte infected and non-infected rice under lead stress conditions. An endophytic fungus was tested in rice (Oryza sativa L.) exposed to four levels of lead (Pb) stress (0, 50, 100 and 200 μM) to assess effects on plant growth, photosynthesis and antioxidant enzyme activity. Under Pb stress conditions, endophyte-infected seedlings had greater shoot length but lower root length compared to non-infected controls, and endophyte-infected seedlings had greater dry weight in the 50 and 100 μM Pb treatments. Under Pb stress conditions, chlorophyll and carotenoid levels were significantly higher in the endophyte-infected seedlings. Net photosynthetic rate, transpiration rate and water use efficiency were significantly higher in endophyte-infected seedlings in the 50 and 100 μM Pb treatments. In addition, chlorophyll fluorescence parameters Fv/Fm and Fv/Fo were higher in the infected seedlings compared to the non-infected seedlings under Pb stress. Malondialdehyde accumulation was induced by Pb stress, and it was present in higher concentration in non-infected seedlings under higher concentrations of Pb (100 and 200 μM). Antioxidant activity was either higher or unchanged in the infected seedlings due to responses to the different Pb concentrations. These results suggest that the endophytic fungus improved rice growth under moderate Pb levels by enhancing photosynthesis and antioxidant activity relative to non-infected rice.</AbstractText
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31210734
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28119135
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31649200
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Dissecting Static and Dynamic Functional Connectivity: Example From the Autism Spectrum.
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Relative latency and temporal variability of hemodynamic responses at the human primary visual cortex.
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Broadly protective human antibodies that target the active site of influenza virus neuraminidase.
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The ability to measure the intrinsic functional architecture of the brain has grown exponentially over the last 2 decades. Measures of intrinsic connectivity within the brain, typically measured using resting-state functional magnetic resonance imaging (MRI), have evolved from primarily "static" approaches, to include dynamic measures of functional connectivity. Measures of dynamic functional connectivity expand the assumptions to allow brain regions to have temporally different patterns of communication between different regions. That is, connections within the brain can differentially fire between different regions at different times, and these differences can be quantified. Applying approaches that measure the dynamic characteristics of functional brain connectivity have been fruitful in identifying differences during brain development and psychopathology. We provide a brief overview of static and dynamic measures of functional connectivity and illustrate the synergy in applying these approaches to identify both age-related differences in children and differences between typically developing children and children with autistic symptoms.</AbstractText
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The blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) signal is a robust surrogate for local neuronal activity. However, it has been shown to vary substantially across subjects, brain regions, and repetitive measurements. This variability represents a limit to the precision of the BOLD response and the ability to reliably discriminate brain hemodynamic responses elicited by external stimuli or behavior that are nearby in time. While the temporal variability of the BOLD signal at human visual cortex has been found in the range of a few hundreds of milliseconds, the spatial distributions of the average and standard deviation of this temporal variability have not been quantitatively characterized. Here we use fMRI measurements with a high sampling rate (10Hz) to map the latency, intra- and inter-subject variability of the evoked BOLD signal in human primary (V1) visual cortices using an event-related fMRI paradigm. The latency relative to the average BOLD signal evoked by 30 stimuli was estimated to be 0.03±0.20s. Within V1, the absolute value of the relative BOLD latency was found correlated to intra- and inter-subject temporal variability. After comparing these measures to retinotopic maps, we found that locations with V1 areas sensitive to smaller eccentricity have later responses and smaller inter-subject variabilities. These correlations were found from data with either short inter-stimulus interval (ISI; average 4s) or long ISI (average 30s). Maps of the relative latency as well as inter-/intra-subject variability were found visually asymmetric between hemispheres. Our results suggest that the latency and variability of regional BOLD signal measured with high spatiotemporal resolution may be used to detect regional differences in hemodynamics to inform fMRI studies. However, the physiological origins of timing index distributions and their hemispheric asymmetry remain to be investigated.</AbstractText
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Better vaccines against influenza virus are urgently needed to provide broader protection against diverse strains, subtypes, and types. Such efforts are assisted by the identification of novel broadly neutralizing epitopes targeted by protective antibodies. Influenza vaccine development has largely focused on the hemagglutinin, but the other major surface antigen, the neuraminidase, has reemerged as a potential target for universal vaccines. We describe three human monoclonal antibodies isolated from an H3N2-infected donor that bind with exceptional breadth to multiple different influenza A and B virus neuraminidases. These antibodies neutralize the virus, mediate effector functions, are broadly protective in vivo, and inhibit neuraminidase activity by directly binding to the active site. Structural and functional characterization of these antibodies will inform the development of neuraminidase-based universal vaccines against influenza virus.</AbstractText
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Dissecting Static and Dynamic Functional Connectivity: Example From the Autism Spectrum. The ability to measure the intrinsic functional architecture of the brain has grown exponentially over the last 2 decades. Measures of intrinsic connectivity within the brain, typically measured using resting-state functional magnetic resonance imaging (MRI), have evolved from primarily "static" approaches, to include dynamic measures of functional connectivity. Measures of dynamic functional connectivity expand the assumptions to allow brain regions to have temporally different patterns of communication between different regions. That is, connections within the brain can differentially fire between different regions at different times, and these differences can be quantified. Applying approaches that measure the dynamic characteristics of functional brain connectivity have been fruitful in identifying differences during brain development and psychopathology. We provide a brief overview of static and dynamic measures of functional connectivity and illustrate the synergy in applying these approaches to identify both age-related differences in children and differences between typically developing children and children with autistic symptoms.</AbstractText
|
Relative latency and temporal variability of hemodynamic responses at the human primary visual cortex. The blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) signal is a robust surrogate for local neuronal activity. However, it has been shown to vary substantially across subjects, brain regions, and repetitive measurements. This variability represents a limit to the precision of the BOLD response and the ability to reliably discriminate brain hemodynamic responses elicited by external stimuli or behavior that are nearby in time. While the temporal variability of the BOLD signal at human visual cortex has been found in the range of a few hundreds of milliseconds, the spatial distributions of the average and standard deviation of this temporal variability have not been quantitatively characterized. Here we use fMRI measurements with a high sampling rate (10Hz) to map the latency, intra- and inter-subject variability of the evoked BOLD signal in human primary (V1) visual cortices using an event-related fMRI paradigm. The latency relative to the average BOLD signal evoked by 30 stimuli was estimated to be 0.03±0.20s. Within V1, the absolute value of the relative BOLD latency was found correlated to intra- and inter-subject temporal variability. After comparing these measures to retinotopic maps, we found that locations with V1 areas sensitive to smaller eccentricity have later responses and smaller inter-subject variabilities. These correlations were found from data with either short inter-stimulus interval (ISI; average 4s) or long ISI (average 30s). Maps of the relative latency as well as inter-/intra-subject variability were found visually asymmetric between hemispheres. Our results suggest that the latency and variability of regional BOLD signal measured with high spatiotemporal resolution may be used to detect regional differences in hemodynamics to inform fMRI studies. However, the physiological origins of timing index distributions and their hemispheric asymmetry remain to be investigated.</AbstractText
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Broadly protective human antibodies that target the active site of influenza virus neuraminidase. Better vaccines against influenza virus are urgently needed to provide broader protection against diverse strains, subtypes, and types. Such efforts are assisted by the identification of novel broadly neutralizing epitopes targeted by protective antibodies. Influenza vaccine development has largely focused on the hemagglutinin, but the other major surface antigen, the neuraminidase, has reemerged as a potential target for universal vaccines. We describe three human monoclonal antibodies isolated from an H3N2-infected donor that bind with exceptional breadth to multiple different influenza A and B virus neuraminidases. These antibodies neutralize the virus, mediate effector functions, are broadly protective in vivo, and inhibit neuraminidase activity by directly binding to the active site. Structural and functional characterization of these antibodies will inform the development of neuraminidase-based universal vaccines against influenza virus.</AbstractText
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37451091
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30365023
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36437188
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Higher education level as a protective factor against executive dysfunction in patients with epilepsy in Mataram, Indonesia.
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Loneliness and Risk of Dementia.
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The chicken and egg problem of grid cells and place cells.
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Since the concept of cognitive reserve is applicable in epilepsy-associated cognitive impairment, the role of cognitive reserve components as a protective factor against epilepsy-associated executive dysfunction needs further investigation. This study aimed at investigating the association between cognitive reserve components and the frequency of epilepsy-associated executive dysfunction in Mataram, Indonesia.</AbstractText This case-control study involved both epilepsy outpatient and healthy participants recruited consecutively in 5 hospitals in Mataram, between October 2021 and September 2022. Data on sociodemographic, cognitive reserve components, and executive function status were collected from both groups, while data on seizure were collected only from epilepsy participants. The association between cognitive reserve components and the frequency of epilepsy-associated executive dysfunction was tested using logistic regression.</AbstractText A total of 119 epilepsy patients and 93 healthy participants were recruited. The frequency of epilepsy-associated executive dysfunction was 50.4%. Multivariate logistic regression analysis showed that higher education level was the only cognitive reserve component protective against epilepsy-associated executive dysfunction (odds ratio [OR]: 3.36; 95% confidence interval [CI]: 1.33 - 8.50).</AbstractText A high frequency of epilepsy-associated executive dysfunction was observed in Mataram. Higher education level was a cognitive reserve component protective against executive dysfunction in these patients.</AbstractText
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The present study tests whether loneliness is associated with risk of dementia in the largest sample to date and further examines whether the association is independent of social isolation, a related but independent component of social integration, and whether it varies by demographic factors and genetic vulnerability.</AbstractText Participants from the Health and Retirement Study (N = 12,030) reported on their loneliness, social isolation, and had information on clinical, behavioral, and genetic risk factors. Cognitive status was assessed at baseline and every 2 years over a 10-year follow-up with the modified Telephone Interview for Cognitive Status (TICSm). A TICSm score of 6 or less was indicative of dementia.</AbstractText Cox proportional hazards regression indicated that loneliness was associated with a 40% increased risk of dementia. This association held controlling for social isolation, and clinical, behavioral, and genetic risk factors. The association was similar across gender, race, ethnicity, education, and genetic risk.</AbstractText Loneliness is associated with increased risk of dementia. It is one modifiable factor that can be intervened on to reduce dementia risk.</AbstractText
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Place cells and grid cells are major building blocks of the hippocampal cognitive map. The prominent forward model postulates that grid-cell modules are generated by a continuous attractor network; that a velocity signal evoked during locomotion moves entorhinal activity bumps; and that place-cell activity constitutes summation of entorhinal grid-cell modules. Experimental data support the first postulate, but not the latter two. Several families of solutions that depart from these postulates have been put forward. We suggest a modified model (spatial modulation continuous attractor network; SCAN), whereby place cells are generated from spatially selective nongrid cells. Locomotion causes these cells to move the hippocampal activity bump, leading to movement of the entorhinal manifolds. Such inversion accords with the shift of hippocampal thought from navigation to more abstract functions.</AbstractText
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Higher education level as a protective factor against executive dysfunction in patients with epilepsy in Mataram, Indonesia. Since the concept of cognitive reserve is applicable in epilepsy-associated cognitive impairment, the role of cognitive reserve components as a protective factor against epilepsy-associated executive dysfunction needs further investigation. This study aimed at investigating the association between cognitive reserve components and the frequency of epilepsy-associated executive dysfunction in Mataram, Indonesia.</AbstractText This case-control study involved both epilepsy outpatient and healthy participants recruited consecutively in 5 hospitals in Mataram, between October 2021 and September 2022. Data on sociodemographic, cognitive reserve components, and executive function status were collected from both groups, while data on seizure were collected only from epilepsy participants. The association between cognitive reserve components and the frequency of epilepsy-associated executive dysfunction was tested using logistic regression.</AbstractText A total of 119 epilepsy patients and 93 healthy participants were recruited. The frequency of epilepsy-associated executive dysfunction was 50.4%. Multivariate logistic regression analysis showed that higher education level was the only cognitive reserve component protective against epilepsy-associated executive dysfunction (odds ratio [OR]: 3.36; 95% confidence interval [CI]: 1.33 - 8.50).</AbstractText A high frequency of epilepsy-associated executive dysfunction was observed in Mataram. Higher education level was a cognitive reserve component protective against executive dysfunction in these patients.</AbstractText
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Loneliness and Risk of Dementia. The present study tests whether loneliness is associated with risk of dementia in the largest sample to date and further examines whether the association is independent of social isolation, a related but independent component of social integration, and whether it varies by demographic factors and genetic vulnerability.</AbstractText Participants from the Health and Retirement Study (N = 12,030) reported on their loneliness, social isolation, and had information on clinical, behavioral, and genetic risk factors. Cognitive status was assessed at baseline and every 2 years over a 10-year follow-up with the modified Telephone Interview for Cognitive Status (TICSm). A TICSm score of 6 or less was indicative of dementia.</AbstractText Cox proportional hazards regression indicated that loneliness was associated with a 40% increased risk of dementia. This association held controlling for social isolation, and clinical, behavioral, and genetic risk factors. The association was similar across gender, race, ethnicity, education, and genetic risk.</AbstractText Loneliness is associated with increased risk of dementia. It is one modifiable factor that can be intervened on to reduce dementia risk.</AbstractText
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The chicken and egg problem of grid cells and place cells. Place cells and grid cells are major building blocks of the hippocampal cognitive map. The prominent forward model postulates that grid-cell modules are generated by a continuous attractor network; that a velocity signal evoked during locomotion moves entorhinal activity bumps; and that place-cell activity constitutes summation of entorhinal grid-cell modules. Experimental data support the first postulate, but not the latter two. Several families of solutions that depart from these postulates have been put forward. We suggest a modified model (spatial modulation continuous attractor network; SCAN), whereby place cells are generated from spatially selective nongrid cells. Locomotion causes these cells to move the hippocampal activity bump, leading to movement of the entorhinal manifolds. Such inversion accords with the shift of hippocampal thought from navigation to more abstract functions.</AbstractText
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19529979
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16342275
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19416835
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Evaluation of utility of asymmetric index for count-based oxygen extraction fraction on dual-tracer autoradiographic method for chronic unilateral brain infarction.
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Highly constrained backprojection for time-resolved MRI.
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Transgenic multivitamin corn through biofortification of endosperm with three vitamins representing three distinct metabolic pathways.
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For diagnosing patients with ischemic cerebrovascular disease, non-invasive count-based method with (15)O(2) and H (2) (15) O positron-emission tomography (PET) data is widely used to measure asymmetric increases in oxygen extraction fraction (OEF). For shortening study time, we have proposed dual-tracer autoradiographic (DARG) protocol in which (15)O(2) gas and C(15)O(2) gas are sequentially administrated within short period. In this paper, we evaluated feasibility of the non-invasive count-based method with the DARG protocol.</AbstractText Twenty-three patients [67.8 +/- 9.9 (mean +/- SD) years] with chronic unilateral brain infarction were examined by the use of measurements of asymmetric OEF elevation. As DARG protocol, (15)O(2) and C(15)O(2) gases were inhaled with 5-min interval and dynamic PET data were acquired for 8 min. Quantitative OEF (qOEF) image was computed with PET data and arterial input function. Ratio image of (15)O(2) and C(15)O(2) phases of PET data was computed as count-based OEF (cbOEF) image. The asymmetric indices (AI) of qOEF (qOEF-AI) and cbOEF (cbOEF-AI) were obtained from regions of interest symmetric placed on left and right sides of cerebral hemisphere. To optimize the summation time of PET data for the cbOEF image, qOEF and cbOEF images with various summation times were compared.</AbstractText Image quality of cbOEF image was better than that of qOEF image. The best correlation coefficient of 0.94 was obtained when the cbOEF image was calculated from 0 to 180 s of (15)O(2) summed image and 340 to 440 s of C(15)O(2) summed image.</AbstractText Using the appropriate summation time, we obtained the cbOEF image with good correlation with qOEF image, which suggests non-invasive cbOEF image can be used for evaluating the degree of misery perfusion in patients with chronic unilateral brain infarction. The count-based method with DARG protocol has a potential to dramatically reduce the examination time of (15)O PET study.</AbstractText
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Recent work in k-t BLAST and undersampled projection angiography has emphasized the value of using training data sets obtained during the acquisition of a series of images. These techniques have used iterative algorithms guided by the training set information to reconstruct time frames sampled at well below the Nyquist limit. We present here a simple non-iterative unfiltered backprojection algorithm that incorporates the idea of a composite image consisting of portions or all of the acquired data to constrain the backprojection process. This significantly reduces streak artifacts and increases the overall SNR, permitting decreased numbers of projections to be used when acquiring each image in the image time series. For undersampled 2D projection imaging applications, such as cine phase contrast (PC) angiography, our results suggest that the angular undersampling factor, relative to Nyquist requirements, can be increased from the present factor of 4 to about 100 while increasing SNR per individual time frame. Results are presented for a contrast-enhanced PR HYPR TRICKS acquisition in a volunteer using an angular undersampling factor of 75 and a TRICKS temporal undersampling factor of 3 for an overall undersampling factor of 225.</AbstractText
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Vitamin deficiency affects up to 50% of the world's population, disproportionately impacting on developing countries where populations endure monotonous, cereal-rich diets. Transgenic plants offer an effective way to increase the vitamin content of staple crops, but thus far it has only been possible to enhance individual vitamins. We created elite inbred South African transgenic corn plants in which the levels of 3 vitamins were increased specifically in the endosperm through the simultaneous modification of 3 separate metabolic pathways. The transgenic kernels contained 169-fold the normal amount of beta-carotene, 6-fold the normal amount of ascorbate, and double the normal amount of folate. Levels of engineered vitamins remained stable at least through to the T3 homozygous generation. This achievement, which vastly exceeds any realized thus far by conventional breeding alone, opens the way for the development of nutritionally complete cereals to benefit the world's poorest people.</AbstractText
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Evaluation of utility of asymmetric index for count-based oxygen extraction fraction on dual-tracer autoradiographic method for chronic unilateral brain infarction. For diagnosing patients with ischemic cerebrovascular disease, non-invasive count-based method with (15)O(2) and H (2) (15) O positron-emission tomography (PET) data is widely used to measure asymmetric increases in oxygen extraction fraction (OEF). For shortening study time, we have proposed dual-tracer autoradiographic (DARG) protocol in which (15)O(2) gas and C(15)O(2) gas are sequentially administrated within short period. In this paper, we evaluated feasibility of the non-invasive count-based method with the DARG protocol.</AbstractText Twenty-three patients [67.8 +/- 9.9 (mean +/- SD) years] with chronic unilateral brain infarction were examined by the use of measurements of asymmetric OEF elevation. As DARG protocol, (15)O(2) and C(15)O(2) gases were inhaled with 5-min interval and dynamic PET data were acquired for 8 min. Quantitative OEF (qOEF) image was computed with PET data and arterial input function. Ratio image of (15)O(2) and C(15)O(2) phases of PET data was computed as count-based OEF (cbOEF) image. The asymmetric indices (AI) of qOEF (qOEF-AI) and cbOEF (cbOEF-AI) were obtained from regions of interest symmetric placed on left and right sides of cerebral hemisphere. To optimize the summation time of PET data for the cbOEF image, qOEF and cbOEF images with various summation times were compared.</AbstractText Image quality of cbOEF image was better than that of qOEF image. The best correlation coefficient of 0.94 was obtained when the cbOEF image was calculated from 0 to 180 s of (15)O(2) summed image and 340 to 440 s of C(15)O(2) summed image.</AbstractText Using the appropriate summation time, we obtained the cbOEF image with good correlation with qOEF image, which suggests non-invasive cbOEF image can be used for evaluating the degree of misery perfusion in patients with chronic unilateral brain infarction. The count-based method with DARG protocol has a potential to dramatically reduce the examination time of (15)O PET study.</AbstractText
|
Highly constrained backprojection for time-resolved MRI. Recent work in k-t BLAST and undersampled projection angiography has emphasized the value of using training data sets obtained during the acquisition of a series of images. These techniques have used iterative algorithms guided by the training set information to reconstruct time frames sampled at well below the Nyquist limit. We present here a simple non-iterative unfiltered backprojection algorithm that incorporates the idea of a composite image consisting of portions or all of the acquired data to constrain the backprojection process. This significantly reduces streak artifacts and increases the overall SNR, permitting decreased numbers of projections to be used when acquiring each image in the image time series. For undersampled 2D projection imaging applications, such as cine phase contrast (PC) angiography, our results suggest that the angular undersampling factor, relative to Nyquist requirements, can be increased from the present factor of 4 to about 100 while increasing SNR per individual time frame. Results are presented for a contrast-enhanced PR HYPR TRICKS acquisition in a volunteer using an angular undersampling factor of 75 and a TRICKS temporal undersampling factor of 3 for an overall undersampling factor of 225.</AbstractText
|
Transgenic multivitamin corn through biofortification of endosperm with three vitamins representing three distinct metabolic pathways. Vitamin deficiency affects up to 50% of the world's population, disproportionately impacting on developing countries where populations endure monotonous, cereal-rich diets. Transgenic plants offer an effective way to increase the vitamin content of staple crops, but thus far it has only been possible to enhance individual vitamins. We created elite inbred South African transgenic corn plants in which the levels of 3 vitamins were increased specifically in the endosperm through the simultaneous modification of 3 separate metabolic pathways. The transgenic kernels contained 169-fold the normal amount of beta-carotene, 6-fold the normal amount of ascorbate, and double the normal amount of folate. Levels of engineered vitamins remained stable at least through to the T3 homozygous generation. This achievement, which vastly exceeds any realized thus far by conventional breeding alone, opens the way for the development of nutritionally complete cereals to benefit the world's poorest people.</AbstractText
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40381124
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35682902
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40209050
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Limettin and PD98059 Mitigated Alzheimer's Disease Like Pathology Induced by Streptozotocin in Mouse Model: Role of p-ERK1/2/p-GSK-3β/p-CREB/BDNF Pathway.
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Physical Activity Rewires the Human Brain against Neurodegeneration.
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What do patients with traumatic brachial plexus injuries need for social and emotional support? A qualitative analysis.
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Sporadic Alzheimer's disease (SAD) represents one of the major memory deficits that is characterized by tau hyperphosphorylation and amyloid beta (Aβ) deposition in the brain. Both are considered AD hallmarks which are mediated through neuroinflammation, oxidative stress, and cholinergic circuit interruption. This study aimed to show how limettin and PD98059 exert a neuroprotective effect against SAD and the possible role of the extracellular regulated kinase (p-ERK1/2) and glycogen synthase kinase-3 beta (p-GSK-3β) (Ser9)/cAMP-response element binding protein (p-CREB) (Ser133)/brain derived neurotrophic factor (BDNF) pathway. Control animals (Group I) received the vehicles, group II received PD98059 (10 mg/kg/i.p), while group III was administered limettin (15 mg/kg/i.p). Additionally, the other three groups received a single dose of streptozotocin (STZ; 3 mg/kg/ICV), where group IV served as the SAD group, while groups V and VI received PD98059 and limettin daily for 3 weeks, respectively. The SAD animals receiving PD98059 and limettin increased the number of arm entries, % alternations in Y-maze, with reduction in mean escape latency, increase in time spent in target quadrant and platform crossing in Morris Water Maze, compared to the SAD group. Additionally, PD98059 and limettin administration to the STZ group downregulated persistent activation of p-ERK1/2 which in turn increased p-GSK-3β (Ser9), leading to enhanced p-CREB (Ser133) and BDNF expressions, as well as reducing inflammatory markers viz., nuclear factor-kappa B and interleukin-6, leading to decreased Aβ deposition. Both treatments reduced immunohistochemical p-tau expression, brain edema, and increased intact neuron cells remarkably. Thus, based on these findings, PD98059 and limettin may have promising effects in protecting against SAD. Using blockers/inhibitory molecules are recommended to confirm effect through the corresponding pathway.</AbstractText
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Physical activity may offset cognitive decline and dementia, but the molecular mechanisms by which it promotes neuroprotection remain elusive. In the absence of disease-modifying therapies, understanding the molecular effects of physical activity in the brain may be useful for identifying novel targets for disease management. Here we employed several bioinformatic methods to dissect the molecular underpinnings of physical activity in brain health. Network analysis identified 'switch genes' associated with drastic hippocampal transcriptional changes in aged cognitively intact individuals. Switch genes are key genes associated with dramatic transcriptional changes and thus may play a fundamental role in disease pathogenesis. Switch genes are associated with protein processing pathways and the metabolic control of glucose, lipids, and fatty acids. Correlation analysis showed that transcriptional patterns associated with physical activity significantly overlapped and negatively correlated with those of neurodegenerative diseases. Functional analysis revealed that physical activity might confer neuroprotection in Alzheimer's (AD), Parkinson's (PD), and Huntington's (HD) diseases via the upregulation of synaptic signaling pathways. In contrast, in frontotemporal dementia (FTD) its effects are mediated by restoring mitochondrial function and energy precursors. Additionally, physical activity is associated with the downregulation of genes involved in inflammation in AD, neurogenesis in FTD, regulation of growth and transcriptional repression in PD, and glial cell differentiation in HD. Collectively, these findings suggest that physical activity directs transcriptional changes in the brain through different pathways across the broad spectrum of neurodegenerative diseases. These results provide new evidence on the unique and shared mechanisms between physical activity and neurodegenerative diseases.</AbstractText
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Patients with adult traumatic brachial plexus injury (BPI) face numerous challenges, both directly and indirectly related to their physical disability, during their adjustment to life after injury. Our goal was to identify domains of care in which a patient navigator could improve delivery of care for BPI patients as they await recovery of upper extremity function.</AbstractText We conducted semi-structured interviews with 28 brachial plexus patients after reconstruction. The interview guide focused on interactions with members of their care team and other sources of support. Inductive thematic analysis was used to identify recurring topics across patient experiences.</AbstractText Our study revealed four primary themes: 1) Patient perception of family engagement and personal responsibilities influence the desire for additional support from the care team. 2) The navigator role would include family education, appointment coordination, and help with transportation and insurance. 3) Patient and family education should emphasize the understanding of neuropathic pain, timeline of healing, and expected new roles. 4) A long-term solution to patient isolation may involve shared experiences with current BPI patients.</AbstractText Patients with BPI agreed that a navigator dedicated to helping them through the medical and social aspects of their care would benefit both patients and families. Patients identified areas of education that a navigator could help with, specifically gaps in knowledge regarding pain, expectations, recovery timeline, and lifestyle modifications. Additionally, building an accessible community of BPI patients may reciprocally improve social well-being, as some patients expressed a desire to guide other patients through their journey.</AbstractText
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Limettin and PD98059 Mitigated Alzheimer's Disease Like Pathology Induced by Streptozotocin in Mouse Model: Role of p-ERK1/2/p-GSK-3β/p-CREB/BDNF Pathway. Sporadic Alzheimer's disease (SAD) represents one of the major memory deficits that is characterized by tau hyperphosphorylation and amyloid beta (Aβ) deposition in the brain. Both are considered AD hallmarks which are mediated through neuroinflammation, oxidative stress, and cholinergic circuit interruption. This study aimed to show how limettin and PD98059 exert a neuroprotective effect against SAD and the possible role of the extracellular regulated kinase (p-ERK1/2) and glycogen synthase kinase-3 beta (p-GSK-3β) (Ser9)/cAMP-response element binding protein (p-CREB) (Ser133)/brain derived neurotrophic factor (BDNF) pathway. Control animals (Group I) received the vehicles, group II received PD98059 (10 mg/kg/i.p), while group III was administered limettin (15 mg/kg/i.p). Additionally, the other three groups received a single dose of streptozotocin (STZ; 3 mg/kg/ICV), where group IV served as the SAD group, while groups V and VI received PD98059 and limettin daily for 3 weeks, respectively. The SAD animals receiving PD98059 and limettin increased the number of arm entries, % alternations in Y-maze, with reduction in mean escape latency, increase in time spent in target quadrant and platform crossing in Morris Water Maze, compared to the SAD group. Additionally, PD98059 and limettin administration to the STZ group downregulated persistent activation of p-ERK1/2 which in turn increased p-GSK-3β (Ser9), leading to enhanced p-CREB (Ser133) and BDNF expressions, as well as reducing inflammatory markers viz., nuclear factor-kappa B and interleukin-6, leading to decreased Aβ deposition. Both treatments reduced immunohistochemical p-tau expression, brain edema, and increased intact neuron cells remarkably. Thus, based on these findings, PD98059 and limettin may have promising effects in protecting against SAD. Using blockers/inhibitory molecules are recommended to confirm effect through the corresponding pathway.</AbstractText
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Physical Activity Rewires the Human Brain against Neurodegeneration. Physical activity may offset cognitive decline and dementia, but the molecular mechanisms by which it promotes neuroprotection remain elusive. In the absence of disease-modifying therapies, understanding the molecular effects of physical activity in the brain may be useful for identifying novel targets for disease management. Here we employed several bioinformatic methods to dissect the molecular underpinnings of physical activity in brain health. Network analysis identified 'switch genes' associated with drastic hippocampal transcriptional changes in aged cognitively intact individuals. Switch genes are key genes associated with dramatic transcriptional changes and thus may play a fundamental role in disease pathogenesis. Switch genes are associated with protein processing pathways and the metabolic control of glucose, lipids, and fatty acids. Correlation analysis showed that transcriptional patterns associated with physical activity significantly overlapped and negatively correlated with those of neurodegenerative diseases. Functional analysis revealed that physical activity might confer neuroprotection in Alzheimer's (AD), Parkinson's (PD), and Huntington's (HD) diseases via the upregulation of synaptic signaling pathways. In contrast, in frontotemporal dementia (FTD) its effects are mediated by restoring mitochondrial function and energy precursors. Additionally, physical activity is associated with the downregulation of genes involved in inflammation in AD, neurogenesis in FTD, regulation of growth and transcriptional repression in PD, and glial cell differentiation in HD. Collectively, these findings suggest that physical activity directs transcriptional changes in the brain through different pathways across the broad spectrum of neurodegenerative diseases. These results provide new evidence on the unique and shared mechanisms between physical activity and neurodegenerative diseases.</AbstractText
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What do patients with traumatic brachial plexus injuries need for social and emotional support? A qualitative analysis. Patients with adult traumatic brachial plexus injury (BPI) face numerous challenges, both directly and indirectly related to their physical disability, during their adjustment to life after injury. Our goal was to identify domains of care in which a patient navigator could improve delivery of care for BPI patients as they await recovery of upper extremity function.</AbstractText We conducted semi-structured interviews with 28 brachial plexus patients after reconstruction. The interview guide focused on interactions with members of their care team and other sources of support. Inductive thematic analysis was used to identify recurring topics across patient experiences.</AbstractText Our study revealed four primary themes: 1) Patient perception of family engagement and personal responsibilities influence the desire for additional support from the care team. 2) The navigator role would include family education, appointment coordination, and help with transportation and insurance. 3) Patient and family education should emphasize the understanding of neuropathic pain, timeline of healing, and expected new roles. 4) A long-term solution to patient isolation may involve shared experiences with current BPI patients.</AbstractText Patients with BPI agreed that a navigator dedicated to helping them through the medical and social aspects of their care would benefit both patients and families. Patients identified areas of education that a navigator could help with, specifically gaps in knowledge regarding pain, expectations, recovery timeline, and lifestyle modifications. Additionally, building an accessible community of BPI patients may reciprocally improve social well-being, as some patients expressed a desire to guide other patients through their journey.</AbstractText
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40289813
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36801466
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39755228
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Renal Epithelioid Angiomyolipoma: Prognostic Implications of Targeted Immunohistochemical and Molecular Markers in Conjunction with Clinicopathologic Features.
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Determinants of Progression and Mortality in Lymphangioleiomyomatosis.
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Explaining neuronal membrane potentials: The Goldman equation vs. Lee's TELC hypothesis.
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Epithelioid angiomyolipoma (eAML) is an uncommon subtype of angiomyolipoma, a subset of which can demonstrate malignant behavior. While some studies have proposed histopathologic features predictive of aggressive behavior in eAML, there is limited data on the use of immunohistochemistry (IHC) and/or next-generation sequencing (NGS) to identify biomarkers for poor clinical outcome. Moreover, there is limited data on the proposed genetic dichotomy (tuberous sclerosis complex [ TSC ] alteration versus TFE3 rearrangement) of eAML. Clinicopathologic features (including purported histologic features associated with adverse outcome) of 30 eAML were recorded with IHC performed on 1 whole-slide section per tumor for the following markers (interpretations): p16 (positive or negative), p53 (wild type or mutant), TRIM63 ISH (>10% as positive or ≤10% as negative), ATRX (retained or lost), and RB1 (retained or lost). NGS was performed on 23 tumors. The 30 eAML tumors were from 30 patients (23 female, 7 male) of an age range 22 to 77 years (mean=51.9 y). Clinical follow-up was available from 27 patients (mean=36 mo). The features significantly associated with metastatic disease included ≥70% atypical epithelial cells ( P =0.04), ≥2 mitotic figures per 10 high-power fields ( P =0.0013), atypical mitotic figures ( P =0.0003), and necrosis ( P =0.0213). Other features such as local invasion, vascular invasion, tumor size, and immunohistochemical profile (p16, TRIM63, p53, ATRX, and RB1) showed no significant association with the development of metastasis. Interestingly, among the 7 tumors with clinical follow-up showing TFE3 rearrangement, 5 developed metastases (OR=4.50), while 6 of 14 TSC/MTOR mutated tumors with clinical follow-up had metastatic disease (OR=0.222). Notably, TRIM63 ISH showed high sensitivity (100%) for eAML with TFE3 rearrangement but with poor specificity (38%). The genetic dichotomy of eAML comes in the form of TSC/MTOR alterations or TFE3 rearrangement elucidated by NGS, both of which may be associated with poor outcome, and therefore show potential therapeutic implications. As eAML may show overlap with TFE3 -rearranged/ TFEB -altered renal cell carcinoma, shared TRIM63 ISH positivity for these tumor types represents an important potential diagnostic pitfall.</AbstractText
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Lymphangioleiomyomatosis is a progressive diffuse cystic lung disease with approximately 85% survival at 10 years. The determinants of disease progression and mortality after the introduction of sirolimus therapy and vascular endothelial growth factor D (VEGF-D) as a biomarker have not been well defined.</AbstractText Which factors, including VEGF-D and sirolimus therapy, influence disease progression and survival prognosis in patients with lymphangioleiomyomatosis?</AbstractText The progression dataset and the survival dataset included 282 and 574 patients, respectively, from Peking Union Medical College Hospital, Beijing, China. A mixed-effects model was used to compute the rate of decline in FEV<sub VEGF-D levels and sirolimus treatment were associated with FEV<sub Serum VEGF-D levels, a biomarker of lymphangioleiomyomatosis, are associated with disease progression and survival. Sirolimus therapy is associated with slower disease progression and better survival in patients with lymphangioleiomyomatosis.</AbstractText ClinicalTrials.gov; No.: NCT03193892; URL: www.</AbstractText gov.</AbstractText
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In two recent papers (Curr Trends Neurol 17: 83-98, 2023; J Neurophysiol 124: 1029-1044, 2020), James Lee has argued that his Transmembrane Electrostatically-Localized Cations (TELC) hypothesis offers a model of neuron transmembrane potentials that is superior to Hodgkin-Huxley classic cable theory and the Goldman-Hodgkin-Katz (GHK) equation. Here we examine critically the arguments in these papers, finding key weaknesses and fallacies. We also examine closely the literature cited by Lee, and find (i) strong support for the GHK equation; (ii) published measurements that contradict TELC predictions; and (iii) no convincing support for the TELC hypothesis.</AbstractText
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Renal Epithelioid Angiomyolipoma: Prognostic Implications of Targeted Immunohistochemical and Molecular Markers in Conjunction with Clinicopathologic Features. Epithelioid angiomyolipoma (eAML) is an uncommon subtype of angiomyolipoma, a subset of which can demonstrate malignant behavior. While some studies have proposed histopathologic features predictive of aggressive behavior in eAML, there is limited data on the use of immunohistochemistry (IHC) and/or next-generation sequencing (NGS) to identify biomarkers for poor clinical outcome. Moreover, there is limited data on the proposed genetic dichotomy (tuberous sclerosis complex [ TSC ] alteration versus TFE3 rearrangement) of eAML. Clinicopathologic features (including purported histologic features associated with adverse outcome) of 30 eAML were recorded with IHC performed on 1 whole-slide section per tumor for the following markers (interpretations): p16 (positive or negative), p53 (wild type or mutant), TRIM63 ISH (>10% as positive or ≤10% as negative), ATRX (retained or lost), and RB1 (retained or lost). NGS was performed on 23 tumors. The 30 eAML tumors were from 30 patients (23 female, 7 male) of an age range 22 to 77 years (mean=51.9 y). Clinical follow-up was available from 27 patients (mean=36 mo). The features significantly associated with metastatic disease included ≥70% atypical epithelial cells ( P =0.04), ≥2 mitotic figures per 10 high-power fields ( P =0.0013), atypical mitotic figures ( P =0.0003), and necrosis ( P =0.0213). Other features such as local invasion, vascular invasion, tumor size, and immunohistochemical profile (p16, TRIM63, p53, ATRX, and RB1) showed no significant association with the development of metastasis. Interestingly, among the 7 tumors with clinical follow-up showing TFE3 rearrangement, 5 developed metastases (OR=4.50), while 6 of 14 TSC/MTOR mutated tumors with clinical follow-up had metastatic disease (OR=0.222). Notably, TRIM63 ISH showed high sensitivity (100%) for eAML with TFE3 rearrangement but with poor specificity (38%). The genetic dichotomy of eAML comes in the form of TSC/MTOR alterations or TFE3 rearrangement elucidated by NGS, both of which may be associated with poor outcome, and therefore show potential therapeutic implications. As eAML may show overlap with TFE3 -rearranged/ TFEB -altered renal cell carcinoma, shared TRIM63 ISH positivity for these tumor types represents an important potential diagnostic pitfall.</AbstractText
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Determinants of Progression and Mortality in Lymphangioleiomyomatosis. Lymphangioleiomyomatosis is a progressive diffuse cystic lung disease with approximately 85% survival at 10 years. The determinants of disease progression and mortality after the introduction of sirolimus therapy and vascular endothelial growth factor D (VEGF-D) as a biomarker have not been well defined.</AbstractText Which factors, including VEGF-D and sirolimus therapy, influence disease progression and survival prognosis in patients with lymphangioleiomyomatosis?</AbstractText The progression dataset and the survival dataset included 282 and 574 patients, respectively, from Peking Union Medical College Hospital, Beijing, China. A mixed-effects model was used to compute the rate of decline in FEV<sub VEGF-D levels and sirolimus treatment were associated with FEV<sub Serum VEGF-D levels, a biomarker of lymphangioleiomyomatosis, are associated with disease progression and survival. Sirolimus therapy is associated with slower disease progression and better survival in patients with lymphangioleiomyomatosis.</AbstractText ClinicalTrials.gov; No.: NCT03193892; URL: www.</AbstractText gov.</AbstractText
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Explaining neuronal membrane potentials: The Goldman equation vs. Lee's TELC hypothesis. In two recent papers (Curr Trends Neurol 17: 83-98, 2023; J Neurophysiol 124: 1029-1044, 2020), James Lee has argued that his Transmembrane Electrostatically-Localized Cations (TELC) hypothesis offers a model of neuron transmembrane potentials that is superior to Hodgkin-Huxley classic cable theory and the Goldman-Hodgkin-Katz (GHK) equation. Here we examine critically the arguments in these papers, finding key weaknesses and fallacies. We also examine closely the literature cited by Lee, and find (i) strong support for the GHK equation; (ii) published measurements that contradict TELC predictions; and (iii) no convincing support for the TELC hypothesis.</AbstractText
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39212585
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33837273
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39060234
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Pharmacological Treatment of Tourette Disorder in Children.
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Whole-exome sequencing identifies genes associated with Tourette's disorder in multiplex families.
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Functional architecture of intracellular oscillations in hippocampal dendrites.
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<i
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Tourette's Disorder (TD) is a neurodevelopmental disorder (NDD) that affects about 0.7% of the population and is one of the most heritable NDDs. Nevertheless, because of its polygenic nature and genetic heterogeneity, the genetic etiology of TD is not well understood. In this study, we combined the segregation information in 13 TD multiplex families with high-throughput sequencing and genotyping to identify genes associated with TD. Using whole-exome sequencing and genotyping array data, we identified both small and large genetic variants within the individuals. We then combined multiple types of evidence to prioritize candidate genes for TD, including variant segregation pattern, variant function prediction, candidate gene expression, protein-protein interaction network, candidate genes from previous studies, etc. From the 13 families, 71 strong candidate genes were identified, including both known genes for NDDs and novel genes, such as HtrA Serine Peptidase 3 (HTRA3), Cadherin-Related Family Member 1 (CDHR1), and Zinc Finger DHHC-Type Palmitoyltransferase 17 (ZDHHC17). The candidate genes are enriched in several Gene Ontology categories, such as dynein complex and synaptic membrane. Candidate genes and pathways identified in this study provide biological insight into TD etiology and potential targets for future studies.</AbstractText
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Fast electrical signaling in dendrites is central to neural computations that support adaptive behaviors. Conventional techniques lack temporal and spatial resolution and the ability to track underlying membrane potential dynamics present across the complex three-dimensional dendritic arbor in vivo. Here, we perform fast two-photon imaging of dendritic and somatic membrane potential dynamics in single pyramidal cells in the CA1 region of the mouse hippocampus during awake behavior. We study the dynamics of subthreshold membrane potential and suprathreshold dendritic events throughout the dendritic arbor in vivo by combining voltage imaging with simultaneous local field potential recording, post hoc morphological reconstruction, and a spatial navigation task. We systematically quantify the modulation of local event rates by locomotion in distinct dendritic regions, report an advancing gradient of dendritic theta phase along the basal-tuft axis, and describe a predominant hyperpolarization of the dendritic arbor during sharp-wave ripples. Finally, we find that spatial tuning of dendritic representations dynamically reorganizes following place field formation. Our data reveal how the organization of electrical signaling in dendrites maps onto the anatomy of the dendritic tree across behavior, oscillatory network, and functional cell states.</AbstractText
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Pharmacological Treatment of Tourette Disorder in Children. <i
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Whole-exome sequencing identifies genes associated with Tourette's disorder in multiplex families. Tourette's Disorder (TD) is a neurodevelopmental disorder (NDD) that affects about 0.7% of the population and is one of the most heritable NDDs. Nevertheless, because of its polygenic nature and genetic heterogeneity, the genetic etiology of TD is not well understood. In this study, we combined the segregation information in 13 TD multiplex families with high-throughput sequencing and genotyping to identify genes associated with TD. Using whole-exome sequencing and genotyping array data, we identified both small and large genetic variants within the individuals. We then combined multiple types of evidence to prioritize candidate genes for TD, including variant segregation pattern, variant function prediction, candidate gene expression, protein-protein interaction network, candidate genes from previous studies, etc. From the 13 families, 71 strong candidate genes were identified, including both known genes for NDDs and novel genes, such as HtrA Serine Peptidase 3 (HTRA3), Cadherin-Related Family Member 1 (CDHR1), and Zinc Finger DHHC-Type Palmitoyltransferase 17 (ZDHHC17). The candidate genes are enriched in several Gene Ontology categories, such as dynein complex and synaptic membrane. Candidate genes and pathways identified in this study provide biological insight into TD etiology and potential targets for future studies.</AbstractText
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Functional architecture of intracellular oscillations in hippocampal dendrites. Fast electrical signaling in dendrites is central to neural computations that support adaptive behaviors. Conventional techniques lack temporal and spatial resolution and the ability to track underlying membrane potential dynamics present across the complex three-dimensional dendritic arbor in vivo. Here, we perform fast two-photon imaging of dendritic and somatic membrane potential dynamics in single pyramidal cells in the CA1 region of the mouse hippocampus during awake behavior. We study the dynamics of subthreshold membrane potential and suprathreshold dendritic events throughout the dendritic arbor in vivo by combining voltage imaging with simultaneous local field potential recording, post hoc morphological reconstruction, and a spatial navigation task. We systematically quantify the modulation of local event rates by locomotion in distinct dendritic regions, report an advancing gradient of dendritic theta phase along the basal-tuft axis, and describe a predominant hyperpolarization of the dendritic arbor during sharp-wave ripples. Finally, we find that spatial tuning of dendritic representations dynamically reorganizes following place field formation. Our data reveal how the organization of electrical signaling in dendrites maps onto the anatomy of the dendritic tree across behavior, oscillatory network, and functional cell states.</AbstractText
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40662180
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11699120
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40394205
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The emotional and motivational costs of poorly delivered academic feedback.
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The emotional dog and its rational tail: a social intuitionist approach to moral judgment.
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Attention-enhanced StrongSORT for robust vehicle tracking in complex environments.
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This study uses psychological reactance theory and self-determination theory to explore whether disrespectful or disorganized feedback affects student motivation and classroom engagement.</AbstractText A sample of 148 undergraduates read one of four vignettes describing professor feedback that varied by tone (respectful or disrespectful) and clarity (low or high hassle). After reading the email, students completed measures assessing their emotional reactions, perceptions of the professor, and willingness to participate in class.</AbstractText Students who received disrespectful messages reported stronger negative emotions, lower trust in the professor, and reduced willingness to participate. High-hassle feedback also lowered engagement, particularly when combined with a respectful tone. Interaction effects indicated that hassle weakened the positive impact of respectful communication.</AbstractText Students interpret tone and structure in feedback as signals of respect and fairness. When communication feels disrespectful or unnecessarily complicated, students may disengage or comply for the sake of appearances while withdrawing emotionally. These findings suggest that instructors can protect student motivation by using clear and respectful language, especially in digital formats where intent can be harder to interpret.</AbstractText
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Research on moral judgment has been dominated by rationalist models, in which moral judgment is thought to be caused by moral reasoning. The author gives 4 reasons for considering the hypothesis that moral reasoning does not cause moral judgment; rather, moral reasoning is usually a post hoc construction, generated after a judgment has been reached. The social intuitionist model is presented as an alternative to rationalist models. The model is a social model in that it deemphasizes the private reasoning done by individuals and emphasizes instead the importance of social and cultural influences. The model is an intuitionist model in that it states that moral judgment is generally the result of quick, automatic evaluations (intuitions). The model is more consistent that rationalist models with recent findings in social, cultural, evolutionary, and biological psychology, as well as in anthropology and primatology.</AbstractText
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While multi-object tracking is critical for autonomous driving systems, traditional algorithms exhibit three fundamental limitations in complex scenarios: (1) blurred feature representation under occlusion and re-identification scenarios causing identity switches, (2) insufficient sensitivity to scale-variant targets due to fixed geometric constraints in conventional IoU-based loss functions, and (3) gradient degradation in deep convolutional layers hindering discriminative feature learning. To address these challenges, we propose AE-StrongSORT (Attention-Enhanced StrongSORT), an attention-enhanced tracking framework featuring three systematic innovations: first, the GAM-YOLO (global attention mechanism-YOLO)hybrid architecture integrates multi-scale feature fusion with a global attention mechanism (GC2f structure). This design enhances cross-dimensional feature interaction through localized channel-spatial attention gates, significantly improving occlusion-resistant feature representation (IDF1 ↑ 9.99%, IDsw ↓ 9.85%). Second, the F-EIoU loss function introduces dynamic size-dependent penalty terms and difficulty-adaptive weighting factors, effectively balancing learning priorities between small targets and normal instances. Third, the optimized CBH-Conv module employs Hardswish activation and depthwise separable convolution to mitigate gradient vanishing while maintaining real-time efficiency (achieving a 17% MOTA improvement at 213 FPS).Evaluated on the MOT-16 dataset, AE-StrongSORT demonstrates substantial improvements over the baseline StrongSORT, with 17%, 2.78%, and 9.99% gains in MOTA, HOTA, and IDF1 metrics respectively, alongside significant reductions in false/missed detections. These advances establish a novel technical pathway for robust vehicle tracking in real-world traffic scenarios characterized by coexisting challenges of scale variation, motion blur, and dense occlusion.</AbstractText
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The emotional and motivational costs of poorly delivered academic feedback. This study uses psychological reactance theory and self-determination theory to explore whether disrespectful or disorganized feedback affects student motivation and classroom engagement.</AbstractText A sample of 148 undergraduates read one of four vignettes describing professor feedback that varied by tone (respectful or disrespectful) and clarity (low or high hassle). After reading the email, students completed measures assessing their emotional reactions, perceptions of the professor, and willingness to participate in class.</AbstractText Students who received disrespectful messages reported stronger negative emotions, lower trust in the professor, and reduced willingness to participate. High-hassle feedback also lowered engagement, particularly when combined with a respectful tone. Interaction effects indicated that hassle weakened the positive impact of respectful communication.</AbstractText Students interpret tone and structure in feedback as signals of respect and fairness. When communication feels disrespectful or unnecessarily complicated, students may disengage or comply for the sake of appearances while withdrawing emotionally. These findings suggest that instructors can protect student motivation by using clear and respectful language, especially in digital formats where intent can be harder to interpret.</AbstractText
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The emotional dog and its rational tail: a social intuitionist approach to moral judgment. Research on moral judgment has been dominated by rationalist models, in which moral judgment is thought to be caused by moral reasoning. The author gives 4 reasons for considering the hypothesis that moral reasoning does not cause moral judgment; rather, moral reasoning is usually a post hoc construction, generated after a judgment has been reached. The social intuitionist model is presented as an alternative to rationalist models. The model is a social model in that it deemphasizes the private reasoning done by individuals and emphasizes instead the importance of social and cultural influences. The model is an intuitionist model in that it states that moral judgment is generally the result of quick, automatic evaluations (intuitions). The model is more consistent that rationalist models with recent findings in social, cultural, evolutionary, and biological psychology, as well as in anthropology and primatology.</AbstractText
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Attention-enhanced StrongSORT for robust vehicle tracking in complex environments. While multi-object tracking is critical for autonomous driving systems, traditional algorithms exhibit three fundamental limitations in complex scenarios: (1) blurred feature representation under occlusion and re-identification scenarios causing identity switches, (2) insufficient sensitivity to scale-variant targets due to fixed geometric constraints in conventional IoU-based loss functions, and (3) gradient degradation in deep convolutional layers hindering discriminative feature learning. To address these challenges, we propose AE-StrongSORT (Attention-Enhanced StrongSORT), an attention-enhanced tracking framework featuring three systematic innovations: first, the GAM-YOLO (global attention mechanism-YOLO)hybrid architecture integrates multi-scale feature fusion with a global attention mechanism (GC2f structure). This design enhances cross-dimensional feature interaction through localized channel-spatial attention gates, significantly improving occlusion-resistant feature representation (IDF1 ↑ 9.99%, IDsw ↓ 9.85%). Second, the F-EIoU loss function introduces dynamic size-dependent penalty terms and difficulty-adaptive weighting factors, effectively balancing learning priorities between small targets and normal instances. Third, the optimized CBH-Conv module employs Hardswish activation and depthwise separable convolution to mitigate gradient vanishing while maintaining real-time efficiency (achieving a 17% MOTA improvement at 213 FPS).Evaluated on the MOT-16 dataset, AE-StrongSORT demonstrates substantial improvements over the baseline StrongSORT, with 17%, 2.78%, and 9.99% gains in MOTA, HOTA, and IDF1 metrics respectively, alongside significant reductions in false/missed detections. These advances establish a novel technical pathway for robust vehicle tracking in real-world traffic scenarios characterized by coexisting challenges of scale variation, motion blur, and dense occlusion.</AbstractText
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40614156
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36267854
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40725956
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Mutualistic Multi-Network Noisy Label Learning (MMNNLL) Method and Its Application to Transdiagnostic Classification of Bipolar Disorder and Schizophrenia.
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Effects of exercise on mortality rates of individuals with severe mental illness.
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The clinical effective of Baduanjin rehabilitation training on limb motor function, daily life, and quality of life in elderly patients with hemiplegia after stroke.
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The subjective nature of diagnosing mental disorders complicates achieving accurate diagnoses. The complex relationship among disorders further exacerbates this issue, particularly in clinical practice where conditions like bipolar disorder (BP) and schizophrenia (SZ) can present similar clinical symptoms and cognitive impairments. To address these challenges, this paper proposes a mutualistic multi-network noisy label learning (MMNNLL) method, which aims to enhance diagnostic accuracy by leveraging neuroimaging data under the presence of potential clinical diagnosis bias or errors. MMNNLL effectively utilizes multiple deep neural networks (DNNs) for learning from data with noisy labels by maximizing the consistency among DNNs in identifying and utilizing samples with clean and noisy labels. Experimental results on public CIFAR-10 and PathMNIST datasets demonstrate the effectiveness of our method in classifying independent test data across various types and levels of label noise. Additionally, our MMNNLL method significantly outperforms state-of-the-art noisy label learning methods. When applied to brain functional connectivity data from BP and SZ patients, our method identifies two biotypes that show more pronounced group differences, and improved classification accuracy compared to the original clinical categories, using both traditional machine learning and advanced deep learning techniques. In summary, our method effectively addresses the possible inaccuracy in nosology of mental disorders and achieves transdiagnostic classification through robust noisy label learning via multi-network collaboration and competition.</AbstractText
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Persons with severe mental illness have a 10-to-20-year shorter life span than the general public. Excess morbidity and mortality in this patient population has been described as a major public health challenge worldwide. Despite robust extant literature on the role of exercise in reducing morbidity and mortality, especially from cardiovascular disease and diabetes (highly prevalent in this patient population), Very few clinical programs or clinical research projects currently exist to implement and study the effects of exercise on decreasing morbidity and mortality in this highly vulnerable patient population. Given the global lack of trained mental health providers, the need to integrate healthcare providers from different disciplines, such as nurses, physical therapists, occupational therapists, physician assistants, cannot be overstated. This mini-review will provide an historic perspective and current data supporting the need to establish exercise, and other Lifestyle Psychiatry interventions, as a key component of treatment for all patients with serious mental illness.</AbstractText
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This study explores the clinical effects of Baduanjin rehabilitation training on limb motor function, daily living ability, and quality of life in elderly patients with hemiplegia after stroke. Clinical data of 185 elderly patients with hemiplegia after stroke in our hospital from January 2020 to December 2023 were retrospectively analyzed. According to intervention strategy, patients were divided into observation group (n = 75, Baduanjin rehabilitation training in addition to the conventional training therapy) and control group (n = 110, conventional rehabilitation training therapy). The intervention lasted for 8 weeks. The clinical therapeutic effects, such as National Institutes of Health Stroke Scale scores, modified Rankin Scale score, Barthel Index scores, Fugl-Meyer Assessment scores, 6-minute walking distance, Postural Assessment Scale for Stroke, and Short Form 36 Health Survey scores were compared between the 2 groups. There was no significant difference in baseline data between the 2 groups. The total effective rate of the observation group was significantly higher than that of the control group. After 8 weeks of intervention, the modified Rankin Scale and National Institutes of Health Stroke Scale score of the observation group was lower than that of the control group, while the Barthel Index score was higher, with statistically significant differences. The Fugl-Meyer Assessment scores of the upper and lower limbs of the observation group were significantly higher than those of the control group after 8 weeks of intervention. The 6-minute walking distance and Postural Assessment Scale for Stroke scores of the observation group were significantly higher than those of the control group after 8 weeks of intervention. The mental health, vitality, physical role, and physical function scores of the observation group were significantly higher than those of the control group after 8 weeks of intervention. Baduanjin rehabilitation training has a more favorable clinical therapeutic effective on elderly patients with hemiplegia after stroke, significantly improving their limb motor function, daily living ability, and quality of life.</AbstractText
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Mutualistic Multi-Network Noisy Label Learning (MMNNLL) Method and Its Application to Transdiagnostic Classification of Bipolar Disorder and Schizophrenia. The subjective nature of diagnosing mental disorders complicates achieving accurate diagnoses. The complex relationship among disorders further exacerbates this issue, particularly in clinical practice where conditions like bipolar disorder (BP) and schizophrenia (SZ) can present similar clinical symptoms and cognitive impairments. To address these challenges, this paper proposes a mutualistic multi-network noisy label learning (MMNNLL) method, which aims to enhance diagnostic accuracy by leveraging neuroimaging data under the presence of potential clinical diagnosis bias or errors. MMNNLL effectively utilizes multiple deep neural networks (DNNs) for learning from data with noisy labels by maximizing the consistency among DNNs in identifying and utilizing samples with clean and noisy labels. Experimental results on public CIFAR-10 and PathMNIST datasets demonstrate the effectiveness of our method in classifying independent test data across various types and levels of label noise. Additionally, our MMNNLL method significantly outperforms state-of-the-art noisy label learning methods. When applied to brain functional connectivity data from BP and SZ patients, our method identifies two biotypes that show more pronounced group differences, and improved classification accuracy compared to the original clinical categories, using both traditional machine learning and advanced deep learning techniques. In summary, our method effectively addresses the possible inaccuracy in nosology of mental disorders and achieves transdiagnostic classification through robust noisy label learning via multi-network collaboration and competition.</AbstractText
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Effects of exercise on mortality rates of individuals with severe mental illness. Persons with severe mental illness have a 10-to-20-year shorter life span than the general public. Excess morbidity and mortality in this patient population has been described as a major public health challenge worldwide. Despite robust extant literature on the role of exercise in reducing morbidity and mortality, especially from cardiovascular disease and diabetes (highly prevalent in this patient population), Very few clinical programs or clinical research projects currently exist to implement and study the effects of exercise on decreasing morbidity and mortality in this highly vulnerable patient population. Given the global lack of trained mental health providers, the need to integrate healthcare providers from different disciplines, such as nurses, physical therapists, occupational therapists, physician assistants, cannot be overstated. This mini-review will provide an historic perspective and current data supporting the need to establish exercise, and other Lifestyle Psychiatry interventions, as a key component of treatment for all patients with serious mental illness.</AbstractText
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The clinical effective of Baduanjin rehabilitation training on limb motor function, daily life, and quality of life in elderly patients with hemiplegia after stroke. This study explores the clinical effects of Baduanjin rehabilitation training on limb motor function, daily living ability, and quality of life in elderly patients with hemiplegia after stroke. Clinical data of 185 elderly patients with hemiplegia after stroke in our hospital from January 2020 to December 2023 were retrospectively analyzed. According to intervention strategy, patients were divided into observation group (n = 75, Baduanjin rehabilitation training in addition to the conventional training therapy) and control group (n = 110, conventional rehabilitation training therapy). The intervention lasted for 8 weeks. The clinical therapeutic effects, such as National Institutes of Health Stroke Scale scores, modified Rankin Scale score, Barthel Index scores, Fugl-Meyer Assessment scores, 6-minute walking distance, Postural Assessment Scale for Stroke, and Short Form 36 Health Survey scores were compared between the 2 groups. There was no significant difference in baseline data between the 2 groups. The total effective rate of the observation group was significantly higher than that of the control group. After 8 weeks of intervention, the modified Rankin Scale and National Institutes of Health Stroke Scale score of the observation group was lower than that of the control group, while the Barthel Index score was higher, with statistically significant differences. The Fugl-Meyer Assessment scores of the upper and lower limbs of the observation group were significantly higher than those of the control group after 8 weeks of intervention. The 6-minute walking distance and Postural Assessment Scale for Stroke scores of the observation group were significantly higher than those of the control group after 8 weeks of intervention. The mental health, vitality, physical role, and physical function scores of the observation group were significantly higher than those of the control group after 8 weeks of intervention. Baduanjin rehabilitation training has a more favorable clinical therapeutic effective on elderly patients with hemiplegia after stroke, significantly improving their limb motor function, daily living ability, and quality of life.</AbstractText
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37150568
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27918798
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38004481
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Piloting Peer Support to Decrease Secondary Traumatic Stress, Compassion Fatigue, and Burnout Among Air Medical Crewmembers.
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Controlled Interventions to Reduce Burnout in Physicians: A Systematic Review and Meta-analysis.
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Study of lncRNAs in Pediatric Neurological Diseases: Methods, Analysis of the State-of-Art and Possible Therapeutic Implications.
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The current research was performed to assess professional quality of life; identify factors associated with secondary traumatic stress, burnout, and compassion satisfaction; and evaluate the effectiveness of a peer support pilot intervention among air medical crewmembers.</AbstractText Quantitative research methods were used to assess secondary traumatic stress, compassion satisfaction, and burnout among flight nurses and paramedics. Demographic variables and secondary traumatic stress, burnout, and compassion satisfaction scores using the Professional Quality of Life Scale were assessed. A comparison of survey scores obtained before and 16 months after the implementation of a piloted peer support program was performed.</AbstractText Crewmembers with less experience within an air medical program and those without a support system are at the highest risk of developing secondary traumatic stress, burnout, and impaired compassion satisfaction. Observed scores for secondary traumatic stress, burnout, and compassion satisfaction suggest that peer support may be an effective intervention among air medical crewmembers. No statistically significant differences in secondary traumatic stress, burnout, or compassion satisfaction were observed by clinical role, marital status, or years in their profession.</AbstractText Peer support after emotionally challenging or stressful transports may combat secondary traumatic stress, compassion fatigue, and burnout. This intervention would be most beneficial for crewmembers who are newer to the transport organization and lack social or familial support.</AbstractText
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Burnout is prevalent in physicians and can have a negative influence on performance, career continuation, and patient care. Existing evidence does not allow clear recommendations for the management of burnout in physicians.</AbstractText To evaluate the effectiveness of interventions to reduce burnout in physicians and whether different types of interventions (physician-directed or organization-directed interventions), physician characteristics (length of experience), and health care setting characteristics (primary or secondary care) were associated with improved effects.</AbstractText MEDLINE, Embase, PsycINFO, CINAHL, and Cochrane Register of Controlled Trials were searched from inception to May 31, 2016. The reference lists of eligible studies and other relevant systematic reviews were hand searched.</AbstractText Randomized clinical trials and controlled before-after studies of interventions targeting burnout in physicians.</AbstractText Two independent reviewers extracted data and assessed the risk of bias. The main meta-analysis was followed by a number of prespecified subgroup and sensitivity analyses. All analyses were performed using random-effects models and heterogeneity was quantified.</AbstractText The core outcome was burnout scores focused on emotional exhaustion, reported as standardized mean differences and their 95% confidence intervals.</AbstractText Twenty independent comparisons from 19 studies were included in the meta-analysis (n = 1550 physicians; mean [SD] age, 40.3 [9.5] years; 49% male). Interventions were associated with small significant reductions in burnout (standardized mean difference [SMD] = -0.29; 95% CI, -0.42 to -0.16; equal to a drop of 3 points on the emotional exhaustion domain of the Maslach Burnout Inventory above change in the controls). Subgroup analyses suggested significantly improved effects for organization-directed interventions (SMD = -0.45; 95% CI, -0.62 to -0.28) compared with physician-directed interventions (SMD = -0.18; 95% CI, -0.32 to -0.03). Interventions delivered in experienced physicians and in primary care were associated with higher effects compared with interventions delivered in inexperienced physicians and in secondary care, but these differences were not significant. The results were not influenced by the risk of bias ratings.</AbstractText Evidence from this meta-analysis suggests that recent intervention programs for burnout in physicians were associated with small benefits that may be boosted by adoption of organization-directed approaches. This finding provides support for the view that burnout is a problem of the whole health care organization, rather than individuals.</AbstractText
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Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in various cellular processes, and their roles in pediatric neurological diseases are increasingly being explored. This review provides an overview of lncRNA implications in the central nervous system, both in its physiological state and when a pathological condition is present. We describe the role of lncRNAs in neural development, highlighting their significance in processes such as neural stem cell proliferation, differentiation, and synaptogenesis. Dysregulation of specific lncRNAs is associated with multiple pediatric neurological diseases, such as neurodevelopmental or neurodegenerative disorders and brain tumors. The collected evidence indicates that there is a need for further research to uncover the full spectrum of lncRNA involvement in pediatric neurological diseases and brain tumors. While challenges exist, ongoing advancements in technology and our understanding of lncRNA biology offer hope for future breakthroughs in the field of pediatric neurology, leveraging lncRNAs as potential therapeutic targets and biomarkers.</AbstractText
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Piloting Peer Support to Decrease Secondary Traumatic Stress, Compassion Fatigue, and Burnout Among Air Medical Crewmembers. The current research was performed to assess professional quality of life; identify factors associated with secondary traumatic stress, burnout, and compassion satisfaction; and evaluate the effectiveness of a peer support pilot intervention among air medical crewmembers.</AbstractText Quantitative research methods were used to assess secondary traumatic stress, compassion satisfaction, and burnout among flight nurses and paramedics. Demographic variables and secondary traumatic stress, burnout, and compassion satisfaction scores using the Professional Quality of Life Scale were assessed. A comparison of survey scores obtained before and 16 months after the implementation of a piloted peer support program was performed.</AbstractText Crewmembers with less experience within an air medical program and those without a support system are at the highest risk of developing secondary traumatic stress, burnout, and impaired compassion satisfaction. Observed scores for secondary traumatic stress, burnout, and compassion satisfaction suggest that peer support may be an effective intervention among air medical crewmembers. No statistically significant differences in secondary traumatic stress, burnout, or compassion satisfaction were observed by clinical role, marital status, or years in their profession.</AbstractText Peer support after emotionally challenging or stressful transports may combat secondary traumatic stress, compassion fatigue, and burnout. This intervention would be most beneficial for crewmembers who are newer to the transport organization and lack social or familial support.</AbstractText
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Controlled Interventions to Reduce Burnout in Physicians: A Systematic Review and Meta-analysis. Burnout is prevalent in physicians and can have a negative influence on performance, career continuation, and patient care. Existing evidence does not allow clear recommendations for the management of burnout in physicians.</AbstractText To evaluate the effectiveness of interventions to reduce burnout in physicians and whether different types of interventions (physician-directed or organization-directed interventions), physician characteristics (length of experience), and health care setting characteristics (primary or secondary care) were associated with improved effects.</AbstractText MEDLINE, Embase, PsycINFO, CINAHL, and Cochrane Register of Controlled Trials were searched from inception to May 31, 2016. The reference lists of eligible studies and other relevant systematic reviews were hand searched.</AbstractText Randomized clinical trials and controlled before-after studies of interventions targeting burnout in physicians.</AbstractText Two independent reviewers extracted data and assessed the risk of bias. The main meta-analysis was followed by a number of prespecified subgroup and sensitivity analyses. All analyses were performed using random-effects models and heterogeneity was quantified.</AbstractText The core outcome was burnout scores focused on emotional exhaustion, reported as standardized mean differences and their 95% confidence intervals.</AbstractText Twenty independent comparisons from 19 studies were included in the meta-analysis (n = 1550 physicians; mean [SD] age, 40.3 [9.5] years; 49% male). Interventions were associated with small significant reductions in burnout (standardized mean difference [SMD] = -0.29; 95% CI, -0.42 to -0.16; equal to a drop of 3 points on the emotional exhaustion domain of the Maslach Burnout Inventory above change in the controls). Subgroup analyses suggested significantly improved effects for organization-directed interventions (SMD = -0.45; 95% CI, -0.62 to -0.28) compared with physician-directed interventions (SMD = -0.18; 95% CI, -0.32 to -0.03). Interventions delivered in experienced physicians and in primary care were associated with higher effects compared with interventions delivered in inexperienced physicians and in secondary care, but these differences were not significant. The results were not influenced by the risk of bias ratings.</AbstractText Evidence from this meta-analysis suggests that recent intervention programs for burnout in physicians were associated with small benefits that may be boosted by adoption of organization-directed approaches. This finding provides support for the view that burnout is a problem of the whole health care organization, rather than individuals.</AbstractText
|
Study of lncRNAs in Pediatric Neurological Diseases: Methods, Analysis of the State-of-Art and Possible Therapeutic Implications. Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in various cellular processes, and their roles in pediatric neurological diseases are increasingly being explored. This review provides an overview of lncRNA implications in the central nervous system, both in its physiological state and when a pathological condition is present. We describe the role of lncRNAs in neural development, highlighting their significance in processes such as neural stem cell proliferation, differentiation, and synaptogenesis. Dysregulation of specific lncRNAs is associated with multiple pediatric neurological diseases, such as neurodevelopmental or neurodegenerative disorders and brain tumors. The collected evidence indicates that there is a need for further research to uncover the full spectrum of lncRNA involvement in pediatric neurological diseases and brain tumors. While challenges exist, ongoing advancements in technology and our understanding of lncRNA biology offer hope for future breakthroughs in the field of pediatric neurology, leveraging lncRNAs as potential therapeutic targets and biomarkers.</AbstractText
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35413649
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21514250
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35870168
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Diffusion tensor tractography of the fornix in cerebral amyloid angiopathy, mild cognitive impairment and Alzheimer's disease.
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The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease.
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Interaction of KCNA5, CX43, and CX40 proteins in the atrial muscle of patients with atrial fibrillation.
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Cerebral amyloid angiopathy (CAA) is a common neuropathological finding and clinical entity that occurs independently and with co-existent Alzheimer's disease (AD) and small vessel disease. We compared diffusion tensor imaging (DTI) metrics of the fornix, the primary efferent tract of the hippocampus between CAA, AD and Mild Cognitive Impairment (MCI) and healthy controls.</AbstractText Sixty-eight healthy controls, 32 CAA, 21 AD, and 26 MCI patients were recruited at two centers. Diffusion tensor images were acquired at 3 T with high spatial resolution and fluid-attenuated inversion recovery (FLAIR) to suppress cerebrospinal fluid (CSF) and minimize partial volume effects on the fornix. The fornix was delineated with deterministic tractography to yield mean diffusivity (MD), axial diffusivity (AXD), radial diffusivity (RD), fractional anisotropy (FA) and tract volume. Volumetric measurements of the hippocampus, thalamus, and lateral ventricles were obtained using T1-weighted MRI.</AbstractText Diffusivity (MD, AXD, and RD) of the fornix was highest in AD followed by CAA compared to controls; the MCI group was not significantly different from controls. FA was similar between groups. Fornix tract volume was ∼ 30% lower for all three patient groups compared to controls, but not significantly different between the patient groups. Thalamic and hippocampal volumes were preserved in CAA, but lower in AD and MCI compared to controls. Lateral ventricular volumes were increased in CAA, AD and MCI. Global cognition, memory, and executive function all correlated negatively with fornix diffusivity across the combined clinical group.</AbstractText There were significant diffusion changes of the fornix in CAA, AD and MCI compared to controls, despite relatively intact thalamic and hippocampal volumes in CAA, suggesting the mechanisms for fornix diffusion abnormalities may differ in CAA compared to AD and MCI.</AbstractText
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The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia.</AbstractText
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The objective of the study was to investigate the expression levels of potassium voltage-gated channel subfamily A member 5 (KCNA5), connexin 43 (Cx43), and connexin 40 (Cx40) in the left atrial appendage of patients with atrial fibrillation (AF) and the interactions between them. We gathered tissue samples from patients with persistent AF and sinus rhythm and used fluorescence quantitative polymerase chain reaction to evaluate messenger RNA (mRNA) changes of KCNA5, Cx43, and Cx40. Then, we studied the protein levels of KCNA5, Cx43, and Cx40 by immunofluorescence and western blot analysis and the interactions between these proteins were identified by immunoprecipitation and immunofluorescence colocation, respectively. Compared with the control group, the mRNA and protein levels of KCNA5, Cx43, and Cx40 in the AF group were decreased and the positive expression of KCNA5, Cx43, and Cx40 protein was also decreased by immunofluorescence staining in the AF group. In addition, immunoprecipitation and immunofluorescence colocation revealed that KCNA5 was coexpressed with Cx43 and Cx40 proteins. The expressions of KCNA5, Cx43, and Cx40 were substantially downregulated in the myocardium of patients with AF and KCNA5 interacted with Cx43 and Cx40 proteins, respectively.</AbstractText
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Diffusion tensor tractography of the fornix in cerebral amyloid angiopathy, mild cognitive impairment and Alzheimer's disease. Cerebral amyloid angiopathy (CAA) is a common neuropathological finding and clinical entity that occurs independently and with co-existent Alzheimer's disease (AD) and small vessel disease. We compared diffusion tensor imaging (DTI) metrics of the fornix, the primary efferent tract of the hippocampus between CAA, AD and Mild Cognitive Impairment (MCI) and healthy controls.</AbstractText Sixty-eight healthy controls, 32 CAA, 21 AD, and 26 MCI patients were recruited at two centers. Diffusion tensor images were acquired at 3 T with high spatial resolution and fluid-attenuated inversion recovery (FLAIR) to suppress cerebrospinal fluid (CSF) and minimize partial volume effects on the fornix. The fornix was delineated with deterministic tractography to yield mean diffusivity (MD), axial diffusivity (AXD), radial diffusivity (RD), fractional anisotropy (FA) and tract volume. Volumetric measurements of the hippocampus, thalamus, and lateral ventricles were obtained using T1-weighted MRI.</AbstractText Diffusivity (MD, AXD, and RD) of the fornix was highest in AD followed by CAA compared to controls; the MCI group was not significantly different from controls. FA was similar between groups. Fornix tract volume was ∼ 30% lower for all three patient groups compared to controls, but not significantly different between the patient groups. Thalamic and hippocampal volumes were preserved in CAA, but lower in AD and MCI compared to controls. Lateral ventricular volumes were increased in CAA, AD and MCI. Global cognition, memory, and executive function all correlated negatively with fornix diffusivity across the combined clinical group.</AbstractText There were significant diffusion changes of the fornix in CAA, AD and MCI compared to controls, despite relatively intact thalamic and hippocampal volumes in CAA, suggesting the mechanisms for fornix diffusion abnormalities may differ in CAA compared to AD and MCI.</AbstractText
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The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia.</AbstractText
|
Interaction of KCNA5, CX43, and CX40 proteins in the atrial muscle of patients with atrial fibrillation. The objective of the study was to investigate the expression levels of potassium voltage-gated channel subfamily A member 5 (KCNA5), connexin 43 (Cx43), and connexin 40 (Cx40) in the left atrial appendage of patients with atrial fibrillation (AF) and the interactions between them. We gathered tissue samples from patients with persistent AF and sinus rhythm and used fluorescence quantitative polymerase chain reaction to evaluate messenger RNA (mRNA) changes of KCNA5, Cx43, and Cx40. Then, we studied the protein levels of KCNA5, Cx43, and Cx40 by immunofluorescence and western blot analysis and the interactions between these proteins were identified by immunoprecipitation and immunofluorescence colocation, respectively. Compared with the control group, the mRNA and protein levels of KCNA5, Cx43, and Cx40 in the AF group were decreased and the positive expression of KCNA5, Cx43, and Cx40 protein was also decreased by immunofluorescence staining in the AF group. In addition, immunoprecipitation and immunofluorescence colocation revealed that KCNA5 was coexpressed with Cx43 and Cx40 proteins. The expressions of KCNA5, Cx43, and Cx40 were substantially downregulated in the myocardium of patients with AF and KCNA5 interacted with Cx43 and Cx40 proteins, respectively.</AbstractText
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37798693
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36875238
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36520154
|
Machine learning applied to fMRI patterns of brain activation in response to mutilation pictures predicts PTSD symptoms.
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Perspective taking in the human brain: complementary evidence from neuroimaging studies with media-based naturalistic stimuli and artificial controlled paradigms.
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Lack of bombesin receptor-activated protein homologous protein impairs hippocampal synaptic plasticity and promotes chronic unpredictable mild stress induced behavioral changes in mice.
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The present study aimed to apply multivariate pattern recognition methods to predict posttraumatic stress symptoms from whole-brain activation patterns during two contexts where the aversiveness of unpleasant pictures was manipulated by the presence or absence of safety cues.</AbstractText Trauma-exposed participants were presented with neutral and mutilation pictures during functional magnetic resonance imaging (fMRI) collection. Before the presentation of pictures, a text informed the subjects that the pictures were fictitious ("safe context") or real-life scenes ("real context"). We trained machine learning regression models (Gaussian process regression (GPR)) to predict PTSD symptoms in real and safe contexts.</AbstractText The GPR model could predict PTSD symptoms from brain responses to mutilation pictures in the real context but not in the safe context. The brain regions with the highest contribution to the model were the occipito-parietal regions, including the superior parietal gyrus, inferior parietal gyrus, and supramarginal gyrus. Additional analysis showed that GPR regression models accurately predicted clusters of PTSD symptoms, nominal intrusion, avoidance, and alterations in cognition. As expected, we obtained very similar results as those obtained in a model predicting PTSD total symptoms.</AbstractText This study is the first to show that machine learning applied to fMRI data collected in an aversive context can predict not only PTSD total symptoms but also clusters of PTSD symptoms in a more aversive context. Furthermore, this approach was able to identify potential biomarkers for PTSD, especially in occipitoparietal regions.</AbstractText
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Perception and interpretation of various types of events and information in life crucially depend on one's perspective. A specific perspective can be explicitly adopted, for example, <i
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Bombesin receptor-activated protein (BRAP) and its homologous protein in mice, which is encoded by <i
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Machine learning applied to fMRI patterns of brain activation in response to mutilation pictures predicts PTSD symptoms. The present study aimed to apply multivariate pattern recognition methods to predict posttraumatic stress symptoms from whole-brain activation patterns during two contexts where the aversiveness of unpleasant pictures was manipulated by the presence or absence of safety cues.</AbstractText Trauma-exposed participants were presented with neutral and mutilation pictures during functional magnetic resonance imaging (fMRI) collection. Before the presentation of pictures, a text informed the subjects that the pictures were fictitious ("safe context") or real-life scenes ("real context"). We trained machine learning regression models (Gaussian process regression (GPR)) to predict PTSD symptoms in real and safe contexts.</AbstractText The GPR model could predict PTSD symptoms from brain responses to mutilation pictures in the real context but not in the safe context. The brain regions with the highest contribution to the model were the occipito-parietal regions, including the superior parietal gyrus, inferior parietal gyrus, and supramarginal gyrus. Additional analysis showed that GPR regression models accurately predicted clusters of PTSD symptoms, nominal intrusion, avoidance, and alterations in cognition. As expected, we obtained very similar results as those obtained in a model predicting PTSD total symptoms.</AbstractText This study is the first to show that machine learning applied to fMRI data collected in an aversive context can predict not only PTSD total symptoms but also clusters of PTSD symptoms in a more aversive context. Furthermore, this approach was able to identify potential biomarkers for PTSD, especially in occipitoparietal regions.</AbstractText
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Perspective taking in the human brain: complementary evidence from neuroimaging studies with media-based naturalistic stimuli and artificial controlled paradigms. Perception and interpretation of various types of events and information in life crucially depend on one's perspective. A specific perspective can be explicitly adopted, for example, <i
|
Lack of bombesin receptor-activated protein homologous protein impairs hippocampal synaptic plasticity and promotes chronic unpredictable mild stress induced behavioral changes in mice. Bombesin receptor-activated protein (BRAP) and its homologous protein in mice, which is encoded by <i
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35560820
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31272740
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36384583
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Cardiac involvement in patients recovering from Delta Variant of COVID-19: a prospective multi-parametric MRI study.
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Early effects of kidney transplantation on the heart - A cardiac magnetic resonance multi-parametric study.
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Access to oral health care for children with fetal alcohol spectrum disorder: a cross-sectional study.
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The cardiac injury and sequelae of Delta Variant of coronavirus disease 2019 (COVID-19) remain unknown. This study aimed to evaluate the presence of cardiac involvement in patients recovering from Delta Variant of COVID-19 based on multi-parametric cardiac magnetic resonance imaging (MRI).</AbstractText We prospectively assessed patients recovering from Delta Variant of COVID-19 using multi-parametric cardiac magnetic resonance imaging (MRI) between June 2021 and July 2021. Comparison was made with 25 healthy controls. Forty-four patients (median age 51 years, 28 women) recovering from Delta Variant were recruited and had a median time of 35 days between diagnosis and cardiac MRI. There were no patients with chest pain (0/44, 0%) and high sensitivity cardiac troponin T troponin elevation (median levels 2.20 pg/mL, IQR levels 0.85-4.40 pg/mL). Regarding the cardiac imaging findings, a total of 14 (32%) patients presented cardiac tissue feature abnormalities, and a total of 9 (20%) patients had a myocarditis-like injury based on cardiac MRI 2018 Lake Louise criteria. When we further assessed the T1 and T2 mapping values for of patients' individual, abnormal raised global native T1, T2, and extracellular volume were seen in 6 (14%), 6 (14%), and 4 (9%) patients, respectively. Comparing with controls, the patients had lower LV global longitudinal strain and (-22.2 ± 2.8% vs. -24.6 ± 2.0%, P < 0.001) and global circumferential strain (-20.7 ± 6.8% vs. -24.3 ± 2.9%, P = 0.014), but higher global native T1 (1318.8 ± 55.5 ms vs. 1282.9 ± 38.1 ms, P = 0.006). Four (9%) patients presented myocardial late gadolinium enhancement with subepicardial pattern mostly common seen, and two (5%) patients presented pericardial enhancement.</AbstractText The cardiac MRI could detect subclinical functional and myocardial tissue characteristic abnormalities in individuals who were recovering from Delta Variant without cardiac-related clinical findings. The native T1 mapping and strain imaging may be a sensitive tool for the noninvasive detection of a subset of patients who are at risk for cardiac sequelae and more prone to myocardial damage in survivors with Delta Variant.</AbstractText
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Increased native myocardial T1 times in chronic kidney disease (CKD) may be due to diffuse interstitial myocardial fibrosis (DIF) or due to interstitial edema/inflammation. Concerns relating to nephrogenic systemic fibrosis with gadolinium-based contrast agents (GBCA) limit their use in end-stage kidney disease (ESKD) to measure extracellular volume (ECV) and characterise myocardial fibrosis. This study aimed to examine stability of myocardial T1 and T2 times before, and within 2 months after kidney transplantation; a time frame when volume status normalises but myocardial remodelling is unlikely to have occurred, and to compare these with ECV using GBCA after transplantation. Twenty-four patients with ESKD underwent serial cardiovascular magnetic resonance imaging, including T1 and T2 mapping. GBCA was administered on follow-up provided eGFR was >30 ml/min/1.73 m<sup
|
Individuals with developmental disabilities, including Fetal Alcohol Spectrum Disorder (FASD), often suffer from poorer oral health than the general population as they experience challenges with accessing care. However, few studies have investigated access to oral health care specific to children diagnosed with FASD. Thus, the objective of this cross-sectional study is to examine the use of oral health care services by children diagnosed with FASD in Saskatchewan, Canada, and to identify perceived barriers that affect their access to oral health care.</AbstractText Parents or caregivers for children with FASD under the age of 16 were recruited through community organizations. Between July 2020 and January 2021, 189 participants completed a 64-item questionnaire that assessed sociodemographic characteristics, oral health care utilization, and perceived barriers to care.</AbstractText Most children (85%) had visited the dentist within the last 24 months. 55% of children had required sedation for some treatment. 43% of caregivers experienced frustration trying to access care for their child. Common barriers were cost (63%), location (55%), the child's behaviour (78%) and caregiver anxiety (60%). 35% of caregivers believed their dentist lacked adequate knowledge of FASD. Univariate analysis reveals that income, caregiver education, residence location, and insurance status were significantly associated with reporting barriers. Multivariate logistic regression analysis reveals that caregivers who reported a high school education (OR=1.23; 95% CI 1.03 - 1.38); or public insurance (OR=1.33; 95% CI 1.24 - 1.42) or out-of-pocket payments (OR=1.37, 95% CI 1.20 - 1.46); or rural (OR=1.19, 95% CI 1.07 - 1.26) or remote (OR=1.23; 95% CI=1.12 - 1.31) residences were more likely to report difficulties accessing oral health care.</AbstractText Our findings indicate that children with FASD experience various barriers to accessing oral health care. Social determinants of health were significant variables that increased likelihood of barriers. Like other vulnerable populations, cost and clinic location are notable barriers. Oral health care providers' assessment and management of children with FASD are noteworthy for future research.</AbstractText
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Cardiac involvement in patients recovering from Delta Variant of COVID-19: a prospective multi-parametric MRI study. The cardiac injury and sequelae of Delta Variant of coronavirus disease 2019 (COVID-19) remain unknown. This study aimed to evaluate the presence of cardiac involvement in patients recovering from Delta Variant of COVID-19 based on multi-parametric cardiac magnetic resonance imaging (MRI).</AbstractText We prospectively assessed patients recovering from Delta Variant of COVID-19 using multi-parametric cardiac magnetic resonance imaging (MRI) between June 2021 and July 2021. Comparison was made with 25 healthy controls. Forty-four patients (median age 51 years, 28 women) recovering from Delta Variant were recruited and had a median time of 35 days between diagnosis and cardiac MRI. There were no patients with chest pain (0/44, 0%) and high sensitivity cardiac troponin T troponin elevation (median levels 2.20 pg/mL, IQR levels 0.85-4.40 pg/mL). Regarding the cardiac imaging findings, a total of 14 (32%) patients presented cardiac tissue feature abnormalities, and a total of 9 (20%) patients had a myocarditis-like injury based on cardiac MRI 2018 Lake Louise criteria. When we further assessed the T1 and T2 mapping values for of patients' individual, abnormal raised global native T1, T2, and extracellular volume were seen in 6 (14%), 6 (14%), and 4 (9%) patients, respectively. Comparing with controls, the patients had lower LV global longitudinal strain and (-22.2 ± 2.8% vs. -24.6 ± 2.0%, P < 0.001) and global circumferential strain (-20.7 ± 6.8% vs. -24.3 ± 2.9%, P = 0.014), but higher global native T1 (1318.8 ± 55.5 ms vs. 1282.9 ± 38.1 ms, P = 0.006). Four (9%) patients presented myocardial late gadolinium enhancement with subepicardial pattern mostly common seen, and two (5%) patients presented pericardial enhancement.</AbstractText The cardiac MRI could detect subclinical functional and myocardial tissue characteristic abnormalities in individuals who were recovering from Delta Variant without cardiac-related clinical findings. The native T1 mapping and strain imaging may be a sensitive tool for the noninvasive detection of a subset of patients who are at risk for cardiac sequelae and more prone to myocardial damage in survivors with Delta Variant.</AbstractText
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Early effects of kidney transplantation on the heart - A cardiac magnetic resonance multi-parametric study. Increased native myocardial T1 times in chronic kidney disease (CKD) may be due to diffuse interstitial myocardial fibrosis (DIF) or due to interstitial edema/inflammation. Concerns relating to nephrogenic systemic fibrosis with gadolinium-based contrast agents (GBCA) limit their use in end-stage kidney disease (ESKD) to measure extracellular volume (ECV) and characterise myocardial fibrosis. This study aimed to examine stability of myocardial T1 and T2 times before, and within 2 months after kidney transplantation; a time frame when volume status normalises but myocardial remodelling is unlikely to have occurred, and to compare these with ECV using GBCA after transplantation. Twenty-four patients with ESKD underwent serial cardiovascular magnetic resonance imaging, including T1 and T2 mapping. GBCA was administered on follow-up provided eGFR was >30 ml/min/1.73 m<sup
|
Access to oral health care for children with fetal alcohol spectrum disorder: a cross-sectional study. Individuals with developmental disabilities, including Fetal Alcohol Spectrum Disorder (FASD), often suffer from poorer oral health than the general population as they experience challenges with accessing care. However, few studies have investigated access to oral health care specific to children diagnosed with FASD. Thus, the objective of this cross-sectional study is to examine the use of oral health care services by children diagnosed with FASD in Saskatchewan, Canada, and to identify perceived barriers that affect their access to oral health care.</AbstractText Parents or caregivers for children with FASD under the age of 16 were recruited through community organizations. Between July 2020 and January 2021, 189 participants completed a 64-item questionnaire that assessed sociodemographic characteristics, oral health care utilization, and perceived barriers to care.</AbstractText Most children (85%) had visited the dentist within the last 24 months. 55% of children had required sedation for some treatment. 43% of caregivers experienced frustration trying to access care for their child. Common barriers were cost (63%), location (55%), the child's behaviour (78%) and caregiver anxiety (60%). 35% of caregivers believed their dentist lacked adequate knowledge of FASD. Univariate analysis reveals that income, caregiver education, residence location, and insurance status were significantly associated with reporting barriers. Multivariate logistic regression analysis reveals that caregivers who reported a high school education (OR=1.23; 95% CI 1.03 - 1.38); or public insurance (OR=1.33; 95% CI 1.24 - 1.42) or out-of-pocket payments (OR=1.37, 95% CI 1.20 - 1.46); or rural (OR=1.19, 95% CI 1.07 - 1.26) or remote (OR=1.23; 95% CI=1.12 - 1.31) residences were more likely to report difficulties accessing oral health care.</AbstractText Our findings indicate that children with FASD experience various barriers to accessing oral health care. Social determinants of health were significant variables that increased likelihood of barriers. Like other vulnerable populations, cost and clinic location are notable barriers. Oral health care providers' assessment and management of children with FASD are noteworthy for future research.</AbstractText
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32979458
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6493608
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32006555
|
Responses evoked by electrical stimulation of the brainstem reticular formation in the jaw-opening and hypoglossal motor nerves of an arterially perfused rat preparation.
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Peculiarities of cerebellar excitation of facial nucleus motoneurons.
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HDAC6 inhibitors: Translating genetic and molecular insights into a therapy for axonal CMT.
|
The interneuronal system in the brainstem reticular formation plays an important role in elaborate muscle coordination during various orofacial motor behaviors. In this study, we examined the distribution in the brainstem reticular formation of the sites that induce monosynaptic motor activity in the mylohyoid (jaw-opening) and hypoglossal nerves using an arterially perfused rat preparation. Electrical stimulation applied to 286 and 247 of the 309 sites in the brainstem evoked neural activity in the mylohyoid and hypoglossal nerves, respectively. The mean latency of the first component in the mylohyoid nerve response was significantly shorter than that in the hypoglossal nerve response. Moreover, the latency histogram of the first component in the hypoglossal nerve responses was bimodal, which was separated by 4.0 ms. The sites that induced short-latency (<4.0 ms) motor activity in the mylohyoid nerve and the hypoglossal nerve were frequently distributed in the rostral portion and the caudal portion of the brainstem reticular formation, respectively. Such difference in distributions of short-latency sites for mylohyoid and hypoglossal nerve responses likely corresponds to the distribution of excitatory premotor neurons targeting mylohyoid and hypoglossal motoneurons.</AbstractText
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Excitatory postsynaptic potentials (EPSPs) of facial nucleus motoneurons evoked by stimulation of the cerebellar nuclei, were studied in anesthetized cats. It is shown that the stimulation of nucleus interpositus and dentatus evoked mono-, oligo- and polysynaptic EPSPs in facial motoneurons. From the experiments with lesions in the red nucleus it is suggested that this structure is implicated in the mechanisms and pathways through which the cerebellar control over facial nucleus motoneurons is realized.</AbstractText
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Histone deacetylase 6 (HDAC6) plays a central role in various processes that are key for neuronal survival. In this review, we summarize the current evidence related to disease pathways in the axonal form of Charcot-Marie-Tooth disease (CMT) and highlight the role of HDAC6 in these pathways. We hypothesize that HDAC6 might in fact actively contribute to the pathogenesis of certain forms of axonal CMT. HDAC6 plays a deacetylase activity-dependent, negative role in axonal transport and axonal regeneration, which are both processes implicated in axonal CMT. On the other hand, HDAC6 coordinates a protective response during elimination of toxic misfolded proteins, but this is mostly mediated independent of its deacetylase activity. The current mechanistic insights on these functions of HDAC6 in axonal CMT, along with the selective druggability against its deacetylase activity, make the targeting of HDAC6 particularly attractive. We elaborate on the preclinical studies that demonstrated beneficial effects of HDAC6 inhibitors in axonal CMT models and outline possible modes of action. Overall, this overview ultimately provides a rationale for the use of small-molecule HDAC6 inhibitors as a therapeutic strategy for this devastating disease.</AbstractText
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Responses evoked by electrical stimulation of the brainstem reticular formation in the jaw-opening and hypoglossal motor nerves of an arterially perfused rat preparation. The interneuronal system in the brainstem reticular formation plays an important role in elaborate muscle coordination during various orofacial motor behaviors. In this study, we examined the distribution in the brainstem reticular formation of the sites that induce monosynaptic motor activity in the mylohyoid (jaw-opening) and hypoglossal nerves using an arterially perfused rat preparation. Electrical stimulation applied to 286 and 247 of the 309 sites in the brainstem evoked neural activity in the mylohyoid and hypoglossal nerves, respectively. The mean latency of the first component in the mylohyoid nerve response was significantly shorter than that in the hypoglossal nerve response. Moreover, the latency histogram of the first component in the hypoglossal nerve responses was bimodal, which was separated by 4.0 ms. The sites that induced short-latency (<4.0 ms) motor activity in the mylohyoid nerve and the hypoglossal nerve were frequently distributed in the rostral portion and the caudal portion of the brainstem reticular formation, respectively. Such difference in distributions of short-latency sites for mylohyoid and hypoglossal nerve responses likely corresponds to the distribution of excitatory premotor neurons targeting mylohyoid and hypoglossal motoneurons.</AbstractText
|
Peculiarities of cerebellar excitation of facial nucleus motoneurons. Excitatory postsynaptic potentials (EPSPs) of facial nucleus motoneurons evoked by stimulation of the cerebellar nuclei, were studied in anesthetized cats. It is shown that the stimulation of nucleus interpositus and dentatus evoked mono-, oligo- and polysynaptic EPSPs in facial motoneurons. From the experiments with lesions in the red nucleus it is suggested that this structure is implicated in the mechanisms and pathways through which the cerebellar control over facial nucleus motoneurons is realized.</AbstractText
|
HDAC6 inhibitors: Translating genetic and molecular insights into a therapy for axonal CMT. Histone deacetylase 6 (HDAC6) plays a central role in various processes that are key for neuronal survival. In this review, we summarize the current evidence related to disease pathways in the axonal form of Charcot-Marie-Tooth disease (CMT) and highlight the role of HDAC6 in these pathways. We hypothesize that HDAC6 might in fact actively contribute to the pathogenesis of certain forms of axonal CMT. HDAC6 plays a deacetylase activity-dependent, negative role in axonal transport and axonal regeneration, which are both processes implicated in axonal CMT. On the other hand, HDAC6 coordinates a protective response during elimination of toxic misfolded proteins, but this is mostly mediated independent of its deacetylase activity. The current mechanistic insights on these functions of HDAC6 in axonal CMT, along with the selective druggability against its deacetylase activity, make the targeting of HDAC6 particularly attractive. We elaborate on the preclinical studies that demonstrated beneficial effects of HDAC6 inhibitors in axonal CMT models and outline possible modes of action. Overall, this overview ultimately provides a rationale for the use of small-molecule HDAC6 inhibitors as a therapeutic strategy for this devastating disease.</AbstractText
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21422523
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17884583
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21304242
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Disconnection of frontal and parietal areas contributes to impaired attention in very early Alzheimer's disease.
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Comparing hemodynamic models with DCM.
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Hypoxemia during moderate sedation for gastrointestinal endoscopy: causes and associations.
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In Alzheimer's disease (AD), the loss of cerebral connectivity has been evidenced by numerous studies. There is growing evidence of attention related failures already in prodromal stages of AD; however, connectivity changes within attention networks have been rarely reported. Here we focused on effective connectivity of top-down attention control in patients with prodromal Alzheimer's disease (pAD). We scanned 15 pAD patients and 16 healthy elderly using the Attentional Network Task and determined effective connectivity within a cingulo-fronto-parietal network using Dynamic Causal Modeling. We related connectivity parameters to structural and behavioral parameters (gray matter volume as well as reaction time) to examine the relation between affected domains. Our analyses revealed that effective connectivity from the right middle frontal gyrus to the left superior parietal cortex as well as from the right to the left superior parietal gyrus was reduced in pAD patients. Furthermore, we found that, effective connectivity varied as a function of GM volume in the patient group: right middle frontal gray matter volume significantly correlated with connectivity from the right parietal cortex to the right middle frontal gyrus as well as from the middle frontal gyrus to the anterior cingulate cortex. In addition, inter-parietal connectivity was correlated to right and left parietal gray matter volume. We conclude that, at very early stages of AD, the reduction of effective connectivity in fronto-parietal circuits is related to regional gray matter volume and contributes to impairments in top-down attentional control.</AbstractText
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The classical model of blood oxygen level-dependent (BOLD) responses by Buxton et al. [Buxton, R.B., Wong, E.C., Frank, L.R., 1998. Dynamics of blood flow and oxygenation changes during brain activation: the Balloon model. Magn. Reson. Med. 39, 855-864] has been very important in providing a biophysically plausible framework for explaining different aspects of hemodynamic responses. It also plays an important role in the hemodynamic forward model for dynamic causal modeling (DCM) of fMRI data. A recent study by Obata et al. [Obata, T., Liu, T.T., Miller, K.L., Luh, W.M., Wong, E.C., Frank, L.R., Buxton, R.B., 2004. Discrepancies between BOLD and flow dynamics in primary and supplementary motor areas: application of the Balloon model to the interpretation of BOLD transients. NeuroImage 21, 144-153] linearized the BOLD signal equation and suggested a revised form for the model coefficients. In this paper, we show that the classical and revised models are special cases of a generalized model. The BOLD signal equation of this generalized model can be reduced to that of the classical Buxton model by simplifying the coefficients or can be linearized to give the Obata model. Given the importance of hemodynamic models for investigating BOLD responses and analyses of effective connectivity with DCM, the question arises which formulation is the best model for empirically measured BOLD responses. In this article, we address this question by embedding different variants of the BOLD signal equation in a well-established DCM of functional interactions among visual areas. This allows us to compare the ensuing models using Bayesian model selection. Our model comparison approach had a factorial structure, comparing eight different hemodynamic models based on (i) classical vs. revised forms for the coefficients, (ii) linear vs. non-linear output equations, and (iii) fixed vs. free parameters, epsilon, for region-specific ratios of intra- and extravascular signals. Using fMRI data from a group of twelve subjects, we demonstrate that the best model is a non-linear model with a revised form for the coefficients, in which epsilon is treated as a free parameter.</AbstractText
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Although prolonged hypoxemia (henceforth referred to as hypoxemia) is not uncommon during moderate sedation for endoscopy, there are only sparse data regarding its relationship with medications, endoscopic intubations and ventilation patterns. We aimed to study these relationships.</AbstractText 123 patients enrolled in the control arm of a randomized trial of ventilation monitoring during endoscopy were analyzed. Hypoxemia was defined as oxygen saturation of <90% for ≥15 s, and apnea as lack of respiratory activity for ≥15 s.</AbstractText There were 132 hypoxemic events; 46 (35%) and 112 (85%) events occurred within 1 and 5 min of medication administration/endoscopic intubations, and conversely, 46/638 (7%) and 112/638 (18%) of all medication administration/endoscopic intubations led to hypoxemia in 1 and 5 min, respectively. Apnea, abnormal ventilation and normal ventilation were associated with 36, 30 and 34% of all hypoxemia events, respectively. However, only 101/268 (38%) apnea/abnormal ventilation events led to hypoxemia. Significant predictors of apnea were total dose of meperidine/fentanyl 1.3 (1.02-1.6) and total dose of midazolam 0.84 (0.71-0.99).</AbstractText Hypoxemia occurs typically within 5 min of medication administration or endoscope intubation and only one third of all apnea/abnormal ventilation events eventually lead to hypoxemia.</AbstractText
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Disconnection of frontal and parietal areas contributes to impaired attention in very early Alzheimer's disease. In Alzheimer's disease (AD), the loss of cerebral connectivity has been evidenced by numerous studies. There is growing evidence of attention related failures already in prodromal stages of AD; however, connectivity changes within attention networks have been rarely reported. Here we focused on effective connectivity of top-down attention control in patients with prodromal Alzheimer's disease (pAD). We scanned 15 pAD patients and 16 healthy elderly using the Attentional Network Task and determined effective connectivity within a cingulo-fronto-parietal network using Dynamic Causal Modeling. We related connectivity parameters to structural and behavioral parameters (gray matter volume as well as reaction time) to examine the relation between affected domains. Our analyses revealed that effective connectivity from the right middle frontal gyrus to the left superior parietal cortex as well as from the right to the left superior parietal gyrus was reduced in pAD patients. Furthermore, we found that, effective connectivity varied as a function of GM volume in the patient group: right middle frontal gray matter volume significantly correlated with connectivity from the right parietal cortex to the right middle frontal gyrus as well as from the middle frontal gyrus to the anterior cingulate cortex. In addition, inter-parietal connectivity was correlated to right and left parietal gray matter volume. We conclude that, at very early stages of AD, the reduction of effective connectivity in fronto-parietal circuits is related to regional gray matter volume and contributes to impairments in top-down attentional control.</AbstractText
|
Comparing hemodynamic models with DCM. The classical model of blood oxygen level-dependent (BOLD) responses by Buxton et al. [Buxton, R.B., Wong, E.C., Frank, L.R., 1998. Dynamics of blood flow and oxygenation changes during brain activation: the Balloon model. Magn. Reson. Med. 39, 855-864] has been very important in providing a biophysically plausible framework for explaining different aspects of hemodynamic responses. It also plays an important role in the hemodynamic forward model for dynamic causal modeling (DCM) of fMRI data. A recent study by Obata et al. [Obata, T., Liu, T.T., Miller, K.L., Luh, W.M., Wong, E.C., Frank, L.R., Buxton, R.B., 2004. Discrepancies between BOLD and flow dynamics in primary and supplementary motor areas: application of the Balloon model to the interpretation of BOLD transients. NeuroImage 21, 144-153] linearized the BOLD signal equation and suggested a revised form for the model coefficients. In this paper, we show that the classical and revised models are special cases of a generalized model. The BOLD signal equation of this generalized model can be reduced to that of the classical Buxton model by simplifying the coefficients or can be linearized to give the Obata model. Given the importance of hemodynamic models for investigating BOLD responses and analyses of effective connectivity with DCM, the question arises which formulation is the best model for empirically measured BOLD responses. In this article, we address this question by embedding different variants of the BOLD signal equation in a well-established DCM of functional interactions among visual areas. This allows us to compare the ensuing models using Bayesian model selection. Our model comparison approach had a factorial structure, comparing eight different hemodynamic models based on (i) classical vs. revised forms for the coefficients, (ii) linear vs. non-linear output equations, and (iii) fixed vs. free parameters, epsilon, for region-specific ratios of intra- and extravascular signals. Using fMRI data from a group of twelve subjects, we demonstrate that the best model is a non-linear model with a revised form for the coefficients, in which epsilon is treated as a free parameter.</AbstractText
|
Hypoxemia during moderate sedation for gastrointestinal endoscopy: causes and associations. Although prolonged hypoxemia (henceforth referred to as hypoxemia) is not uncommon during moderate sedation for endoscopy, there are only sparse data regarding its relationship with medications, endoscopic intubations and ventilation patterns. We aimed to study these relationships.</AbstractText 123 patients enrolled in the control arm of a randomized trial of ventilation monitoring during endoscopy were analyzed. Hypoxemia was defined as oxygen saturation of <90% for ≥15 s, and apnea as lack of respiratory activity for ≥15 s.</AbstractText There were 132 hypoxemic events; 46 (35%) and 112 (85%) events occurred within 1 and 5 min of medication administration/endoscopic intubations, and conversely, 46/638 (7%) and 112/638 (18%) of all medication administration/endoscopic intubations led to hypoxemia in 1 and 5 min, respectively. Apnea, abnormal ventilation and normal ventilation were associated with 36, 30 and 34% of all hypoxemia events, respectively. However, only 101/268 (38%) apnea/abnormal ventilation events led to hypoxemia. Significant predictors of apnea were total dose of meperidine/fentanyl 1.3 (1.02-1.6) and total dose of midazolam 0.84 (0.71-0.99).</AbstractText Hypoxemia occurs typically within 5 min of medication administration or endoscope intubation and only one third of all apnea/abnormal ventilation events eventually lead to hypoxemia.</AbstractText
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40637595
|
36893722
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40754650
|
Real-world retention of newer ASMs, including lacosamide and brivaracetam as first or second therapies in adult-onset epilepsy.
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Real-world, long-term evaluation of the tolerability and therapy retention of Epidiolex® (cannabidiol) in patients with refractory epilepsy.
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Evaluating Musculoskeletal Physiotherapist's Self-Perceived Knowledge and Understanding of the Assessment, Diagnosis and Management of Degenerative Cervical Myelopathy: A Cross-Sectional Survey.
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Newer antiseizure medications (ASMs), such as lacosamide and brivaracetam, have promising retention in clinical trials but real-world data on their effectiveness when used as first or second treatments is missing. Because newer ASMs are often reserved for severe cases, such knowledge accumulates slowly. We utilized nationwide "big data" and aimed to evaluate real-world retention of these ASMs when used early in the disease course.</AbstractText We used longitudinal national register data to identify all adults with incident ASM-treated epilepsy in Sweden from 2007-2021. ASMs were tracked up to 2023, with recurring dispensations indicating continued treatment. Retention rates were calculated using Kaplan-Meier for each ASM as the first, second, or subsequent use (third ASM or later) with stratification for age and sex. Adjusted Cox regression was used to verify the risk of lacosamide discontinuation in comparison to levetiracetam.</AbstractText We followed 49 489 adults for a median of 5 years (Q1-Q3, 3-10). The 5-year retention rates (95% confidence interval [CI]) of lacosamide were 42% (32%-55%) as first ASM and 61% (55%-67%) as second ASM among individuals 18-49 year of age, and 61% (53%-71%) and 69% (64%-74%) among 50 years or older, respectively. Lacosamide retention was comparable to lamotrigine and levetiracetam, but higher as a second ASM in younger adults and in men. The 3-year retention rate of brivaracetam as the second ASM among adults ≥50 years was 77% (95% CI 68%-88%). First or second treatment with cenobamate, eslicarbazepine, or perampanel was rare. The likelihood of discontinuing lacosamide as first ASM did not differ significantly from levetiracetam in univariable or adjusted Cox modeling.</AbstractText Lacosamide and brivaracetam have at least similar real-world retention as lamotrigine or levetiracetam when used early in adult-onset epilepsy. This widens the therapeutic arsenal and the possibility of tailored ASM selection.</AbstractText
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Epidiolex® (CBD) is FDA-approved for seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and tuberous sclerosis complex (TSC). Phase III studies suggest that certain adverse effects (AEs), possibly linked to pharmacokinetic/pharmacodynamic (PK/PD) interactions may be therapy-limiting. We sought to identify these factors that contribute to treatment success and retention of therapy.</AbstractText A single-center, retrospective review of patients with refractory epilepsy taking Epidiolex® was performed. Kaplan-Meier analysis was performed to describe Epidiolex® retention, as a measure of overall effectiveness.</AbstractText One hundred and twelve patients were screened; 4 were excluded due to loss to follow-up or never starting Epidiolex®. Of 108 patients, mean age was 20.3 years (13.1, range 2 to 63), and 52.8% were female. Mean initial and maintenance doses were 5.3 mg/kg/day (1.3) and 15.3 mg/kg/day (5.8), respectively. At the final evaluation, 75% of patients remained on Epidiolex®. The 25th percentile for discontinuation was 19 months. 46.3% of patients experienced at least one treatment-emergent adverse effect (TEAE) with 14.5% d/c Epidiolex® due to treatment emerging adverse effects (TEAE). The most common reasons for discontinuation were lack of efficacy (37%), increased seizure activity (22%), worsened behavior (22%), and sedation (22%). One out of 27 discontinuations was due to liver function test (LFT) elevations (3.7%). At initiation, 47.2% were concurrently taking clobazam, and 39.2% of those patients had an initial clobazam dose decrease. 53% of patients were able to either discontinue or lower the dose of at least one other antiseizure medication.</AbstractText Epidiolex® is generally well-tolerated and the majority continued long-term treatment. Patterns of adverse effects were similar to clinical trials, however gastrointestinal complaints, and significant LFT elevations were less common. Our data suggest most patients discontinue within the first several months of treatment and suggest that further studies designed to evaluate early identification and potential mitigation of adverse effects and including drug interactions are warranted.</AbstractText
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Degenerative cervical myelopathy (DCM) is often inadequately managed, leading to serious long-term consequences for patients. Limited awareness of DCM among healthcare professionals may contribute to this problem.</AbstractText This study aimed to assess UK-based musculoskeletal (MSK) physiotherapists' knowledge and confidence in the assessment, diagnosis, and management of DCM.</AbstractText An online cross-sectional survey was conducted to gather data on MSK physiotherapists' understanding of DCM. It also explored perceived barriers to care and the value of additional training. The survey was distributed via the Chartered Society of Physiotherapy's (iCSP) website, professional networks, and social media. Responses were collected in March 2024.</AbstractText A total of 108 physiotherapists participated, most with over 10 years of experience. Many reported that they had not received DCM-specific training in their undergraduate programs. While most were fairly or very confident in their knowledge of DCM, subjective questioning relating to DCM, and management, nearly half expressed concern about missing a DCM diagnosis. Most participants felt they would benefit from further training.</AbstractText MSK physiotherapists are generally confident in their assessment and management of DCM but seek more comprehensive training, especially in symptomology and non-surgical management. The findings of this survey also suggest a gap in DCM education at the undergraduate level, highlighting an opportunity to improve training for early-career physiotherapists.</AbstractText
|
Real-world retention of newer ASMs, including lacosamide and brivaracetam as first or second therapies in adult-onset epilepsy. Newer antiseizure medications (ASMs), such as lacosamide and brivaracetam, have promising retention in clinical trials but real-world data on their effectiveness when used as first or second treatments is missing. Because newer ASMs are often reserved for severe cases, such knowledge accumulates slowly. We utilized nationwide "big data" and aimed to evaluate real-world retention of these ASMs when used early in the disease course.</AbstractText We used longitudinal national register data to identify all adults with incident ASM-treated epilepsy in Sweden from 2007-2021. ASMs were tracked up to 2023, with recurring dispensations indicating continued treatment. Retention rates were calculated using Kaplan-Meier for each ASM as the first, second, or subsequent use (third ASM or later) with stratification for age and sex. Adjusted Cox regression was used to verify the risk of lacosamide discontinuation in comparison to levetiracetam.</AbstractText We followed 49 489 adults for a median of 5 years (Q1-Q3, 3-10). The 5-year retention rates (95% confidence interval [CI]) of lacosamide were 42% (32%-55%) as first ASM and 61% (55%-67%) as second ASM among individuals 18-49 year of age, and 61% (53%-71%) and 69% (64%-74%) among 50 years or older, respectively. Lacosamide retention was comparable to lamotrigine and levetiracetam, but higher as a second ASM in younger adults and in men. The 3-year retention rate of brivaracetam as the second ASM among adults ≥50 years was 77% (95% CI 68%-88%). First or second treatment with cenobamate, eslicarbazepine, or perampanel was rare. The likelihood of discontinuing lacosamide as first ASM did not differ significantly from levetiracetam in univariable or adjusted Cox modeling.</AbstractText Lacosamide and brivaracetam have at least similar real-world retention as lamotrigine or levetiracetam when used early in adult-onset epilepsy. This widens the therapeutic arsenal and the possibility of tailored ASM selection.</AbstractText
|
Real-world, long-term evaluation of the tolerability and therapy retention of Epidiolex® (cannabidiol) in patients with refractory epilepsy. Epidiolex® (CBD) is FDA-approved for seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and tuberous sclerosis complex (TSC). Phase III studies suggest that certain adverse effects (AEs), possibly linked to pharmacokinetic/pharmacodynamic (PK/PD) interactions may be therapy-limiting. We sought to identify these factors that contribute to treatment success and retention of therapy.</AbstractText A single-center, retrospective review of patients with refractory epilepsy taking Epidiolex® was performed. Kaplan-Meier analysis was performed to describe Epidiolex® retention, as a measure of overall effectiveness.</AbstractText One hundred and twelve patients were screened; 4 were excluded due to loss to follow-up or never starting Epidiolex®. Of 108 patients, mean age was 20.3 years (13.1, range 2 to 63), and 52.8% were female. Mean initial and maintenance doses were 5.3 mg/kg/day (1.3) and 15.3 mg/kg/day (5.8), respectively. At the final evaluation, 75% of patients remained on Epidiolex®. The 25th percentile for discontinuation was 19 months. 46.3% of patients experienced at least one treatment-emergent adverse effect (TEAE) with 14.5% d/c Epidiolex® due to treatment emerging adverse effects (TEAE). The most common reasons for discontinuation were lack of efficacy (37%), increased seizure activity (22%), worsened behavior (22%), and sedation (22%). One out of 27 discontinuations was due to liver function test (LFT) elevations (3.7%). At initiation, 47.2% were concurrently taking clobazam, and 39.2% of those patients had an initial clobazam dose decrease. 53% of patients were able to either discontinue or lower the dose of at least one other antiseizure medication.</AbstractText Epidiolex® is generally well-tolerated and the majority continued long-term treatment. Patterns of adverse effects were similar to clinical trials, however gastrointestinal complaints, and significant LFT elevations were less common. Our data suggest most patients discontinue within the first several months of treatment and suggest that further studies designed to evaluate early identification and potential mitigation of adverse effects and including drug interactions are warranted.</AbstractText
|
Evaluating Musculoskeletal Physiotherapist's Self-Perceived Knowledge and Understanding of the Assessment, Diagnosis and Management of Degenerative Cervical Myelopathy: A Cross-Sectional Survey. Degenerative cervical myelopathy (DCM) is often inadequately managed, leading to serious long-term consequences for patients. Limited awareness of DCM among healthcare professionals may contribute to this problem.</AbstractText This study aimed to assess UK-based musculoskeletal (MSK) physiotherapists' knowledge and confidence in the assessment, diagnosis, and management of DCM.</AbstractText An online cross-sectional survey was conducted to gather data on MSK physiotherapists' understanding of DCM. It also explored perceived barriers to care and the value of additional training. The survey was distributed via the Chartered Society of Physiotherapy's (iCSP) website, professional networks, and social media. Responses were collected in March 2024.</AbstractText A total of 108 physiotherapists participated, most with over 10 years of experience. Many reported that they had not received DCM-specific training in their undergraduate programs. While most were fairly or very confident in their knowledge of DCM, subjective questioning relating to DCM, and management, nearly half expressed concern about missing a DCM diagnosis. Most participants felt they would benefit from further training.</AbstractText MSK physiotherapists are generally confident in their assessment and management of DCM but seek more comprehensive training, especially in symptomology and non-surgical management. The findings of this survey also suggest a gap in DCM education at the undergraduate level, highlighting an opportunity to improve training for early-career physiotherapists.</AbstractText
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23248590
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20456660
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22448217
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Perception-action in children with ASD.
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The involvement of emotion recognition in affective theory of mind.
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Dynamic 5-HT2C receptor editing in a mouse model of obesity.
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How do disturbances to perception and action relate to the deficiencies expressed by children with autism? The ability to predict what is going to happen next is crucial for the construction of all actions and children develop these predictive abilities early in development. Children with autism, however, are deficient in the ability to foresee future events and to plan movements and movement sequences. They are also deficient in the understanding of other people's actions. This includes communicative actions as they are ultimately based on movements. Today there are two promising neurobiological interpretation of Autism Spectrum Disorder (ASD). First, there is strong evidence that the Mirror Neuron System (MNS) is impaired. As stated by this hypothesis, action production and action understanding are intimately related. Both these functions rely on predictive models of the sensory consequences of actions and depend on connectivity between the parietal and premotor areas. Secondly, action prediction is accomplished through a system that includes a loop from the posterior parietal cortex (PPC) through the cerebellum and back to the premotor and motor areas of the brain. Impairment of this loop is probably also part of the explanation of the prediction problems in children with ASD. Both the cortico-cerebellar loop and the MNS rely on distant neural connections. There are multiple evidence that such connections are weak in children with autism.</AbstractText
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This study was conducted to explore the relationship between emotion recognition and affective Theory of Mind (ToM). Forty subjects performed a facial emotion recognition and an emotional intention recognition task (affective ToM) in an event-related fMRI study. Conjunction analysis revealed overlapping activation during both tasks. Activation in some of these conjunctly activated regions was even stronger during affective ToM than during emotion recognition, namely in the inferior frontal gyrus, the superior temporal sulcus, the temporal pole, and the amygdala. In contrast to previous studies investigating ToM, we found no activation in the anterior cingulate, commonly assumed as the key region for ToM. The results point to a close relationship of emotion recognition and affective ToM and can be interpreted as evidence for the assumption that at least basal forms of ToM occur by an embodied, non-cognitive process.</AbstractText
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The central serotonergic signalling system has been shown to play an important role in appetite control and the regulation of food intake. Serotonin exerts its anorectic effects mainly through the 5-HT(1B), 5-HT(2C) and 5-HT(6) receptors and these are therefore receiving increasing attention as principal pharmacotherapeutic targets for the treatment of obesity. The 5-HT(2C) receptor has the distinctive ability to be modified by posttranscriptional RNA editing on 5 nucleotide positions (A, B, C, D, E), having an overall decreased receptor function. Recently, it has been shown that feeding behaviour and fat mass are altered when the 5-HT(2C) receptor RNA is fully edited, suggesting a potential role for 5-HT(2C) editing in obesity. The present studies investigate the expression of serotonin receptors involved in central regulation of food intake, appetite and energy expenditure, with particular focus on the level of 5-HT(2C) receptor editing. Using a leptin-deficient mouse model of obesity (ob/ob), we show increased hypothalamic 5-HT(1A) receptor expression as well as increased hippocampal 5-HT(1A), 5-HT(1B), and 5-HT(6) receptor mRNA expression in obese mice compared to lean control mice. An increase in full-length 5-HT(2C) expression, depending on time of day, as well as differences in 5-HT(2C) receptor editing were found, independent of changes in total 5-HT(2C) receptor mRNA expression. This suggests that a dynamic regulation exists of the appetite-suppressing effects of the 5-HT(2C) receptor in both the hypothalamus and the hippocampus in the ob/ob mice model of obesity. The differential 5-HT(1A), 5-HT(1B) and 5-HT(6) receptor expression and altered 5-HT(2C) receptor editing profile reported here is poised to have important consequences for the development of novel anti-obesity therapies.</AbstractText
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Perception-action in children with ASD. How do disturbances to perception and action relate to the deficiencies expressed by children with autism? The ability to predict what is going to happen next is crucial for the construction of all actions and children develop these predictive abilities early in development. Children with autism, however, are deficient in the ability to foresee future events and to plan movements and movement sequences. They are also deficient in the understanding of other people's actions. This includes communicative actions as they are ultimately based on movements. Today there are two promising neurobiological interpretation of Autism Spectrum Disorder (ASD). First, there is strong evidence that the Mirror Neuron System (MNS) is impaired. As stated by this hypothesis, action production and action understanding are intimately related. Both these functions rely on predictive models of the sensory consequences of actions and depend on connectivity between the parietal and premotor areas. Secondly, action prediction is accomplished through a system that includes a loop from the posterior parietal cortex (PPC) through the cerebellum and back to the premotor and motor areas of the brain. Impairment of this loop is probably also part of the explanation of the prediction problems in children with ASD. Both the cortico-cerebellar loop and the MNS rely on distant neural connections. There are multiple evidence that such connections are weak in children with autism.</AbstractText
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The involvement of emotion recognition in affective theory of mind. This study was conducted to explore the relationship between emotion recognition and affective Theory of Mind (ToM). Forty subjects performed a facial emotion recognition and an emotional intention recognition task (affective ToM) in an event-related fMRI study. Conjunction analysis revealed overlapping activation during both tasks. Activation in some of these conjunctly activated regions was even stronger during affective ToM than during emotion recognition, namely in the inferior frontal gyrus, the superior temporal sulcus, the temporal pole, and the amygdala. In contrast to previous studies investigating ToM, we found no activation in the anterior cingulate, commonly assumed as the key region for ToM. The results point to a close relationship of emotion recognition and affective ToM and can be interpreted as evidence for the assumption that at least basal forms of ToM occur by an embodied, non-cognitive process.</AbstractText
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Dynamic 5-HT2C receptor editing in a mouse model of obesity. The central serotonergic signalling system has been shown to play an important role in appetite control and the regulation of food intake. Serotonin exerts its anorectic effects mainly through the 5-HT(1B), 5-HT(2C) and 5-HT(6) receptors and these are therefore receiving increasing attention as principal pharmacotherapeutic targets for the treatment of obesity. The 5-HT(2C) receptor has the distinctive ability to be modified by posttranscriptional RNA editing on 5 nucleotide positions (A, B, C, D, E), having an overall decreased receptor function. Recently, it has been shown that feeding behaviour and fat mass are altered when the 5-HT(2C) receptor RNA is fully edited, suggesting a potential role for 5-HT(2C) editing in obesity. The present studies investigate the expression of serotonin receptors involved in central regulation of food intake, appetite and energy expenditure, with particular focus on the level of 5-HT(2C) receptor editing. Using a leptin-deficient mouse model of obesity (ob/ob), we show increased hypothalamic 5-HT(1A) receptor expression as well as increased hippocampal 5-HT(1A), 5-HT(1B), and 5-HT(6) receptor mRNA expression in obese mice compared to lean control mice. An increase in full-length 5-HT(2C) expression, depending on time of day, as well as differences in 5-HT(2C) receptor editing were found, independent of changes in total 5-HT(2C) receptor mRNA expression. This suggests that a dynamic regulation exists of the appetite-suppressing effects of the 5-HT(2C) receptor in both the hypothalamus and the hippocampus in the ob/ob mice model of obesity. The differential 5-HT(1A), 5-HT(1B) and 5-HT(6) receptor expression and altered 5-HT(2C) receptor editing profile reported here is poised to have important consequences for the development of novel anti-obesity therapies.</AbstractText
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37422763
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30291974
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37473791
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Distinct ventral stream and prefrontal cortex representational dynamics during sustained conscious visual perception.
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Mapping the human brain's cortical-subcortical functional network organization.
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Effects of inhaled corticosteroids on brain volumetry, depression and anxiety-like behaviors in a rat model of asthma.
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Instances of sustained stationary sensory input are ubiquitous. However, previous work focused almost exclusively on transient onset responses. This presents a critical challenge for neural theories of consciousness, which should account for the full temporal extent of experience. To address this question, we use intracranial recordings from ten human patients with epilepsy to view diverse images of multiple durations. We reveal that, in sensory regions, despite dramatic changes in activation magnitude, the distributed representation of categories and exemplars remains sustained and stable. In contrast, in frontoparietal regions, we find transient content representation at stimulus onset. Our results highlight the connection between the anatomical and temporal correlates of experience. To the extent perception is sustained, it may rely on sensory representations and to the extent perception is discrete, centered on perceptual updating, it may rely on frontoparietal representations.</AbstractText
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Understanding complex systems such as the human brain requires characterization of the system's architecture across multiple levels of organization - from neurons, to local circuits, to brain regions, and ultimately large-scale brain networks. Here we focus on characterizing the human brain's large-scale network organization, as it provides an overall framework for the organization of all other levels. We developed a highly principled approach to identify cortical network communities at the level of functional systems, calibrating our community detection algorithm using extremely well-established sensory and motor systems as guides. Building on previous network partitions, we replicated and expanded upon well-known and recently-identified networks, including several higher-order cognitive networks such as a left-lateralized language network. We expanded these cortical networks to subcortex, revealing 358 highly-organized subcortical parcels that take part in forming whole-brain functional networks. Notably, the identified subcortical parcels are similar in number to a recent estimate of the number of cortical parcels (360). This whole-brain network atlas - released as an open resource for the neuroscience community - places all brain structures across both cortex and subcortex into a single large-scale functional framework, with the potential to facilitate a variety of studies investigating large-scale functional networks in health and disease.</AbstractText
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Brain functional deficits have been reported in asthma patients which can result in behavioral disorders like depression and anxiety. These deficits may be associated with factors like resistance to treatment, incorrect self-evaluation, and inadequate self-control. However, changes in the brain volume in allergic asthma and the effects of inhaled corticosteroids, the most common anti-inflammatory agents for asthma treatment, on these alterations remain largely unclear. Here, we evaluated depression and anxiety-like behavior as well as volume changes in different brain area, using magnetic resonance imaging in an animal model of allergic asthma with pretreatment of inhaled fluticasone propionate. Asthma-induced behavioral changes were partially, but not completely, prevented by pretreatment with inhaled fluticasone propionate. Volumetry findings showed that the allergen decreased volumes of the corpus callosum and subcortical white matter, as well as the septal region and hippocampus (especially CA1 and fimbria). However, volumes of neocortex, insular, and anterior cingulate cortex increased in asthmatic rats compared to controls. Namely, pretreatment with inhaled fluticasone propionate partially prevented asthma-induced brain volume changes, but not completely. These findings suggest that asthma is associated with structural alterations in the brain, which may contribute to the induction of psychological disorders. Thus, considering brain changes in the clinical assessments could have important implications for asthma treatment.</AbstractText
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Distinct ventral stream and prefrontal cortex representational dynamics during sustained conscious visual perception. Instances of sustained stationary sensory input are ubiquitous. However, previous work focused almost exclusively on transient onset responses. This presents a critical challenge for neural theories of consciousness, which should account for the full temporal extent of experience. To address this question, we use intracranial recordings from ten human patients with epilepsy to view diverse images of multiple durations. We reveal that, in sensory regions, despite dramatic changes in activation magnitude, the distributed representation of categories and exemplars remains sustained and stable. In contrast, in frontoparietal regions, we find transient content representation at stimulus onset. Our results highlight the connection between the anatomical and temporal correlates of experience. To the extent perception is sustained, it may rely on sensory representations and to the extent perception is discrete, centered on perceptual updating, it may rely on frontoparietal representations.</AbstractText
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Mapping the human brain's cortical-subcortical functional network organization. Understanding complex systems such as the human brain requires characterization of the system's architecture across multiple levels of organization - from neurons, to local circuits, to brain regions, and ultimately large-scale brain networks. Here we focus on characterizing the human brain's large-scale network organization, as it provides an overall framework for the organization of all other levels. We developed a highly principled approach to identify cortical network communities at the level of functional systems, calibrating our community detection algorithm using extremely well-established sensory and motor systems as guides. Building on previous network partitions, we replicated and expanded upon well-known and recently-identified networks, including several higher-order cognitive networks such as a left-lateralized language network. We expanded these cortical networks to subcortex, revealing 358 highly-organized subcortical parcels that take part in forming whole-brain functional networks. Notably, the identified subcortical parcels are similar in number to a recent estimate of the number of cortical parcels (360). This whole-brain network atlas - released as an open resource for the neuroscience community - places all brain structures across both cortex and subcortex into a single large-scale functional framework, with the potential to facilitate a variety of studies investigating large-scale functional networks in health and disease.</AbstractText
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Effects of inhaled corticosteroids on brain volumetry, depression and anxiety-like behaviors in a rat model of asthma. Brain functional deficits have been reported in asthma patients which can result in behavioral disorders like depression and anxiety. These deficits may be associated with factors like resistance to treatment, incorrect self-evaluation, and inadequate self-control. However, changes in the brain volume in allergic asthma and the effects of inhaled corticosteroids, the most common anti-inflammatory agents for asthma treatment, on these alterations remain largely unclear. Here, we evaluated depression and anxiety-like behavior as well as volume changes in different brain area, using magnetic resonance imaging in an animal model of allergic asthma with pretreatment of inhaled fluticasone propionate. Asthma-induced behavioral changes were partially, but not completely, prevented by pretreatment with inhaled fluticasone propionate. Volumetry findings showed that the allergen decreased volumes of the corpus callosum and subcortical white matter, as well as the septal region and hippocampus (especially CA1 and fimbria). However, volumes of neocortex, insular, and anterior cingulate cortex increased in asthmatic rats compared to controls. Namely, pretreatment with inhaled fluticasone propionate partially prevented asthma-induced brain volume changes, but not completely. These findings suggest that asthma is associated with structural alterations in the brain, which may contribute to the induction of psychological disorders. Thus, considering brain changes in the clinical assessments could have important implications for asthma treatment.</AbstractText
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39483919
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38155477
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39145525
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More similarity than difference: comparison of within- and between-sex variance in early adolescent brain structure.
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Association between structural brain MRI abnormalities and epilepsy in older adults.
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Astrocytic centrin-2 expression in entorhinal cortex correlates with Alzheimer's disease severity.
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Adolescent neuroimaging studies of sex differences in the human brain predominantly examine mean differences between males and females. This focus on between-groups differences without probing relative distributions and similarities may contribute to both conflation and overestimation of sex differences and sexual dimorphism in the developing human brain.</AbstractText We aimed to characterize the variance in brain macro- and micro-structure in early adolescence as it pertains to sex at birth using a large sample of 9-11 year-olds from the Adolescent Brain Cognitive Development (ABCD) Study (N=7,723). Specifically, for global and regional estimates of gray and white matter volume, cortical thickness, and white matter microstructure (i.e., fractional anisotropy and mean diffusivity), we examined: within- and between-sex variance, overlap between male and female distributions, inhomogeneity of variance via the Fligner-Killeen test, and an analysis of similarities (ANOSIM). For completeness, we examined these sex differences using both uncorrected (raw) brain estimates and residualized brain estimates after using mixed-effects modeling to account for age, pubertal development, socioeconomic status, race, ethnicity, MRI scanner manufacturer, and total brain volume, where applicable.</AbstractText The overlap between male and female distributions was universally greater than the difference (overlap coefficient range: 0.585 - 0.985) and the ratio of within-sex and between-sex differences was similar (ANOSIM R range: -0.001 - 0.117). All cortical and subcortical volumes showed significant inhomogeneity of variance, whereas a minority of brain regions showed significant sex differences in variance for cortical thickness, white matter volume, fractional anisotropy, and mean diffusivity. Inhomogeneity of variance was reduced after accounting for other sources of variance. Overlap coefficients were larger and ANOSIM R values were smaller for residualized outcomes, indicating greater within- and smaller between-sex differences once accounting for other covariates.</AbstractText Reported sex differences in early adolescent human brain structure may be driven by disparities in variance, rather than binary, sex-based phenotypes. Contrary to the popular view of the brain as sexually dimorphic, we found more similarity than difference between sexes in all global and regional measurements of brain structure examined. This study builds upon previous findings illustrating the importance of considering variance when examining sex differences in brain structure.</AbstractText
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To determine the association between brain MRI abnormalities and incident epilepsy in older adults.</AbstractText Men and women (ages 45-64 years) from the Atherosclerosis Risk in Communities study were followed up from 1987 to 2018 with brain MRI performed between 2011 and 2013. We identified cases of incident late-onset epilepsy (LOE) with onset of seizures occurring after the acquisition of brain MRI. We evaluated the relative pattern of cortical thickness, subcortical volume, and white matter integrity among participants with incident LOE after MRI in comparison with participants without seizures. We examined the association between MRI abnormalities and incident LOE using Cox proportional hazards regression. Models were adjusted for demographics, hypertension, diabetes, smoking, stroke, and dementia status.</AbstractText Among 1251 participants with brain MRI data, 27 (2.2%) developed LOE after MRI over a median of 6.4 years (25-75 percentile 5.8-6.9) of follow-up. Participants with incident LOE after MRI had higher levels of cortical thinning and white matter microstructural abnormalities before seizure onset compared to those without seizures. In longitudinal analyses, greater number of abnormalities was associated with incident LOE after controlling for demographic factors, risk factors for cardiovascular disease, stroke, and dementia (gray matter: hazard ratio [HR]: 2.3, 95% confidence interval [CI]: 1.0-4.9; white matter diffusivity: HR: 3.0, 95% CI: 1.2-7.3).</AbstractText This study demonstrates considerable gray and white matter pathology among individuals with LOE, which is present prior to the onset of seizures and provides important insights into the role of neurodegeneration, both of gray and white matter, and the risk of LOE.</AbstractText
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Astrogliosis is a condition shared by acute and chronic neurological diseases and includes morphological, proteomic, and functional rearrangements of astroglia. In Alzheimer's disease (AD), reactive astrocytes frame amyloid deposits and exhibit structural changes associated with the overexpression of specific proteins, mostly belonging to intermediate filaments. At a functional level, amyloid beta triggers dysfunctional calcium signaling in astrocytes, which contributes to the maintenance of chronic neuroinflammation. Therefore, the identification of intracellular players that participate in astrocyte calcium signaling can help unveil the mechanisms underlying astrocyte reactivity and loss of function in AD. We have recently identified the calcium-binding protein centrin-2 (CETN2) as a novel astrocyte marker in the human brain and, in order to determine whether astrocytic CETN2 expression and distribution could be affected by neurodegenerative conditions, we examined its pattern in control and sporadic AD patients. By immunoblot, immunohistochemistry, and targeted-mass spectrometry, we report a positive correlation between entorhinal CETN2 immunoreactivity and neurocognitive impairment, along with the abundance of amyloid depositions and neurofibrillary tangles, thus highlighting a linear relationship between CETN2 expression and AD progression. CETN2-positive astrocytes were dispersed in the entorhinal cortex with a clustered pattern and colocalized with reactive glia markers STAT3, NFATc3, and YKL-40, indicating a human-specific role in AD-induced astrogliosis. Collectively, our data provide the first evidence that CETN2 is part of the astrocytic calcium toolkit undergoing rearrangements in AD and adds CETN2 to the list of proteins that could play a role in disease evolution.</AbstractText
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More similarity than difference: comparison of within- and between-sex variance in early adolescent brain structure. Adolescent neuroimaging studies of sex differences in the human brain predominantly examine mean differences between males and females. This focus on between-groups differences without probing relative distributions and similarities may contribute to both conflation and overestimation of sex differences and sexual dimorphism in the developing human brain.</AbstractText We aimed to characterize the variance in brain macro- and micro-structure in early adolescence as it pertains to sex at birth using a large sample of 9-11 year-olds from the Adolescent Brain Cognitive Development (ABCD) Study (N=7,723). Specifically, for global and regional estimates of gray and white matter volume, cortical thickness, and white matter microstructure (i.e., fractional anisotropy and mean diffusivity), we examined: within- and between-sex variance, overlap between male and female distributions, inhomogeneity of variance via the Fligner-Killeen test, and an analysis of similarities (ANOSIM). For completeness, we examined these sex differences using both uncorrected (raw) brain estimates and residualized brain estimates after using mixed-effects modeling to account for age, pubertal development, socioeconomic status, race, ethnicity, MRI scanner manufacturer, and total brain volume, where applicable.</AbstractText The overlap between male and female distributions was universally greater than the difference (overlap coefficient range: 0.585 - 0.985) and the ratio of within-sex and between-sex differences was similar (ANOSIM R range: -0.001 - 0.117). All cortical and subcortical volumes showed significant inhomogeneity of variance, whereas a minority of brain regions showed significant sex differences in variance for cortical thickness, white matter volume, fractional anisotropy, and mean diffusivity. Inhomogeneity of variance was reduced after accounting for other sources of variance. Overlap coefficients were larger and ANOSIM R values were smaller for residualized outcomes, indicating greater within- and smaller between-sex differences once accounting for other covariates.</AbstractText Reported sex differences in early adolescent human brain structure may be driven by disparities in variance, rather than binary, sex-based phenotypes. Contrary to the popular view of the brain as sexually dimorphic, we found more similarity than difference between sexes in all global and regional measurements of brain structure examined. This study builds upon previous findings illustrating the importance of considering variance when examining sex differences in brain structure.</AbstractText
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Association between structural brain MRI abnormalities and epilepsy in older adults. To determine the association between brain MRI abnormalities and incident epilepsy in older adults.</AbstractText Men and women (ages 45-64 years) from the Atherosclerosis Risk in Communities study were followed up from 1987 to 2018 with brain MRI performed between 2011 and 2013. We identified cases of incident late-onset epilepsy (LOE) with onset of seizures occurring after the acquisition of brain MRI. We evaluated the relative pattern of cortical thickness, subcortical volume, and white matter integrity among participants with incident LOE after MRI in comparison with participants without seizures. We examined the association between MRI abnormalities and incident LOE using Cox proportional hazards regression. Models were adjusted for demographics, hypertension, diabetes, smoking, stroke, and dementia status.</AbstractText Among 1251 participants with brain MRI data, 27 (2.2%) developed LOE after MRI over a median of 6.4 years (25-75 percentile 5.8-6.9) of follow-up. Participants with incident LOE after MRI had higher levels of cortical thinning and white matter microstructural abnormalities before seizure onset compared to those without seizures. In longitudinal analyses, greater number of abnormalities was associated with incident LOE after controlling for demographic factors, risk factors for cardiovascular disease, stroke, and dementia (gray matter: hazard ratio [HR]: 2.3, 95% confidence interval [CI]: 1.0-4.9; white matter diffusivity: HR: 3.0, 95% CI: 1.2-7.3).</AbstractText This study demonstrates considerable gray and white matter pathology among individuals with LOE, which is present prior to the onset of seizures and provides important insights into the role of neurodegeneration, both of gray and white matter, and the risk of LOE.</AbstractText
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Astrocytic centrin-2 expression in entorhinal cortex correlates with Alzheimer's disease severity. Astrogliosis is a condition shared by acute and chronic neurological diseases and includes morphological, proteomic, and functional rearrangements of astroglia. In Alzheimer's disease (AD), reactive astrocytes frame amyloid deposits and exhibit structural changes associated with the overexpression of specific proteins, mostly belonging to intermediate filaments. At a functional level, amyloid beta triggers dysfunctional calcium signaling in astrocytes, which contributes to the maintenance of chronic neuroinflammation. Therefore, the identification of intracellular players that participate in astrocyte calcium signaling can help unveil the mechanisms underlying astrocyte reactivity and loss of function in AD. We have recently identified the calcium-binding protein centrin-2 (CETN2) as a novel astrocyte marker in the human brain and, in order to determine whether astrocytic CETN2 expression and distribution could be affected by neurodegenerative conditions, we examined its pattern in control and sporadic AD patients. By immunoblot, immunohistochemistry, and targeted-mass spectrometry, we report a positive correlation between entorhinal CETN2 immunoreactivity and neurocognitive impairment, along with the abundance of amyloid depositions and neurofibrillary tangles, thus highlighting a linear relationship between CETN2 expression and AD progression. CETN2-positive astrocytes were dispersed in the entorhinal cortex with a clustered pattern and colocalized with reactive glia markers STAT3, NFATc3, and YKL-40, indicating a human-specific role in AD-induced astrogliosis. Collectively, our data provide the first evidence that CETN2 is part of the astrocytic calcium toolkit undergoing rearrangements in AD and adds CETN2 to the list of proteins that could play a role in disease evolution.</AbstractText
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40657200
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28426964
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40304470
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Anti-Inflammatory Treatment of Subarachnoid Hemorrhage by Self-Assembled Silymarin Nanoparticles.
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iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases.
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The impact of temperature and insect-specific viruses on the transmission of alphaviruses by Aedes japonicus japonicus.
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Subarachnoid hemorrhage (SAH) is a common hemorrhagic cerebrovascular disease with high disability rate and high mortality. Early brain injury (EBI) is the main cause of high mortality and delayed neurological dysfunction in patients with SAH. Neuroinflammation is the important pathological processes of EBI.We prepared Silymarin nanoparticles (SIM NPs) through the solvent precipitation method and investigated their role in combating EBI following SAH in mice. We found that SIM NPs with a diameter of 150 nm have the strongest ability to cross the blood-brain barrier. SIM nanoparticles are spherical and contain irregular particles inside, which may be composed mainly of silibinin and assembled through hydrogen bonding. Further in vivo experiments showed that SIM NPs improved short-term neurological dysfunction in SAH mice, reduced cortical neural damage, and reduced EBI inflammation through the Nrf2/STING pathway. Finally, water maze experiments showed that SIM NPs can improve long-term memory and learning ability in SAH mice. Based on the above results, we conclude that silymarin nanoparticles can reduce EBI after SAH by inhibiting the Nrf2/STING pathway, inhibiting neuroinflammation and M1 polarization of microglia.</AbstractText
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Microglia play critical roles in brain development, homeostasis, and neurological disorders. Here, we report that human microglial-like cells (iMGLs) can be differentiated from iPSCs to study their function in neurological diseases, like Alzheimer's disease (AD). We find that iMGLs develop in vitro similarly to microglia in vivo, and whole-transcriptome analysis demonstrates that they are highly similar to cultured adult and fetal human microglia. Functional assessment of iMGLs reveals that they secrete cytokines in response to inflammatory stimuli, migrate and undergo calcium transients, and robustly phagocytose CNS substrates. iMGLs were used to examine the effects of Aβ fibrils and brain-derived tau oligomers on AD-related gene expression and to interrogate mechanisms involved in synaptic pruning. Furthermore, iMGLs transplanted into transgenic mice and human brain organoids resemble microglia in vivo. Together, these findings demonstrate that iMGLs can be used to study microglial function, providing important new insight into human neurological disease.</AbstractText
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Arthropod-borne virus (arbovirus) infections are increasing globally, and invasive mosquito species are spreading. Since the end of the last century, <i The spread of invasive mosquito species like <i
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Anti-Inflammatory Treatment of Subarachnoid Hemorrhage by Self-Assembled Silymarin Nanoparticles. Subarachnoid hemorrhage (SAH) is a common hemorrhagic cerebrovascular disease with high disability rate and high mortality. Early brain injury (EBI) is the main cause of high mortality and delayed neurological dysfunction in patients with SAH. Neuroinflammation is the important pathological processes of EBI.We prepared Silymarin nanoparticles (SIM NPs) through the solvent precipitation method and investigated their role in combating EBI following SAH in mice. We found that SIM NPs with a diameter of 150 nm have the strongest ability to cross the blood-brain barrier. SIM nanoparticles are spherical and contain irregular particles inside, which may be composed mainly of silibinin and assembled through hydrogen bonding. Further in vivo experiments showed that SIM NPs improved short-term neurological dysfunction in SAH mice, reduced cortical neural damage, and reduced EBI inflammation through the Nrf2/STING pathway. Finally, water maze experiments showed that SIM NPs can improve long-term memory and learning ability in SAH mice. Based on the above results, we conclude that silymarin nanoparticles can reduce EBI after SAH by inhibiting the Nrf2/STING pathway, inhibiting neuroinflammation and M1 polarization of microglia.</AbstractText
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iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases. Microglia play critical roles in brain development, homeostasis, and neurological disorders. Here, we report that human microglial-like cells (iMGLs) can be differentiated from iPSCs to study their function in neurological diseases, like Alzheimer's disease (AD). We find that iMGLs develop in vitro similarly to microglia in vivo, and whole-transcriptome analysis demonstrates that they are highly similar to cultured adult and fetal human microglia. Functional assessment of iMGLs reveals that they secrete cytokines in response to inflammatory stimuli, migrate and undergo calcium transients, and robustly phagocytose CNS substrates. iMGLs were used to examine the effects of Aβ fibrils and brain-derived tau oligomers on AD-related gene expression and to interrogate mechanisms involved in synaptic pruning. Furthermore, iMGLs transplanted into transgenic mice and human brain organoids resemble microglia in vivo. Together, these findings demonstrate that iMGLs can be used to study microglial function, providing important new insight into human neurological disease.</AbstractText
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The impact of temperature and insect-specific viruses on the transmission of alphaviruses by Aedes japonicus japonicus. Arthropod-borne virus (arbovirus) infections are increasing globally, and invasive mosquito species are spreading. Since the end of the last century, <i The spread of invasive mosquito species like <i
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39855672
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27636179
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40469522
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Efficacy and safety of mechanical thrombectomy in patients with acute ischemic stroke and left ventricular assist device: review of the literature and meta-analysis.
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Image-guided endoscopic surgery for spontaneous supratentorial intracerebral hematoma.
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ggClusterNet 2: An R package for microbial co-occurrence networks and associated indicator correlation patterns.
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Left ventricular assist devices (LVADs) are used as definitive therapy or as a bridge to heart transplant in patients with advanced heart failure. Thromboembolic complications such as acute ischemic stroke (AIS) are common among patients with LVAD support. This study aims to evaluate the current evidence on the efficacy and safety of mechanical thrombectomy (MT) in patients with AIS due to large vessel occlusions (LVO) and LVAD-support.</AbstractText A comprehensive systematic review was conducted in PubMed, Embase, and Scopus to find observational studies with reports of ≥5 MTs in adult patients with LVAD support (PROSPERO registration code CRD42024597541). Rates of successful and complete reperfusion, favorable functional outcomes at 90 days (modified Rankin Scale (mRS) 0-2 or equal to pre-stroke mRS), mortality at 90 days, any intracerebral hemorrhage (ICH) and symptomatic ICH (sICH) were pooled using generalized linear mixed models.</AbstractText Eight studies were included with data from 51 patients and 62 MTs. The rate of successful reperfusion was 87.4% (95% CI 62.5% to 96.6%) and complete reperfusion rate was 57.3% (95% CI 35.1% to 76.9%). Rate of favorable functional recovery was 62.5% (95% CI 42.2% to 79.2%). Rate of sICH was 6.4% (95% CI 0.9% to 34.0%). Mortality rate was 16.7% (95% CI 7.1% to 34.7%). Between 25-40% of patients who were waiting for a heart transplant before their stroke received a heart transplant after MT.</AbstractText MT for the emergent treatment of AIS in the setting of LVAD is relatively safe and efficacious for achieving successful reperfusion and good functional recovery.</AbstractText
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OBJECTIVE Endoscopic removal of intracerebral hematomas is becoming increasingly common, but there is no standard technique. The authors explored the use of a simple image-guided endoscopic method for removal of spontaneous supratentorial hematomas. METHODS Virtual reality technology based on a hospital picture archiving and communications systems (PACS) was used in 3D hematoma visualization and surgical planning. Augmented reality based on an Android smartphone app, Sina neurosurgical assist, allowed a projection of the hematoma to be seen on the patient's scalp to facilitate selection of the best trajectory to the center of the hematoma. A obturator and transparent sheath were used to establish a working channel, and an endoscope and a metal suction apparatus were used to remove the hematoma. RESULTS A total of 25 patients were included in the study, including 18 with putamen hemorrhages and 7 with lobar cerebral hemorrhages. Virtual reality combined with augmented reality helped in achieving the desired position with the obturator and sheath. The median time from the initial surgical incision to completion of closure was 50 minutes (range 40-70 minutes). The actual endoscopic operating time was 30 (range 15-50) minutes. The median blood loss was 80 (range 40-150) ml. No patient experienced postoperative rebleeding. The average hematoma evacuation rate was 97%. The mean (± SD) preoperative Glasgow Coma Scale (GCS) score was 6.7 ± 3.2; 1 week after hematoma evacuation the mean GCS score had improved to 11.9 ± 3.1 (p < 0.01). CONCLUSIONS Virtual reality using hospital PACS and augmented reality with a smartphone app helped precisely localize hematomas and plan the appropriate endoscopic approach. A transparent sheath helped establish a surgical channel, and an endoscope enabled observation of the hematoma's location to achieve satisfactory hematoma removal.</AbstractText
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Since its initial release in 2022, <i
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Efficacy and safety of mechanical thrombectomy in patients with acute ischemic stroke and left ventricular assist device: review of the literature and meta-analysis. Left ventricular assist devices (LVADs) are used as definitive therapy or as a bridge to heart transplant in patients with advanced heart failure. Thromboembolic complications such as acute ischemic stroke (AIS) are common among patients with LVAD support. This study aims to evaluate the current evidence on the efficacy and safety of mechanical thrombectomy (MT) in patients with AIS due to large vessel occlusions (LVO) and LVAD-support.</AbstractText A comprehensive systematic review was conducted in PubMed, Embase, and Scopus to find observational studies with reports of ≥5 MTs in adult patients with LVAD support (PROSPERO registration code CRD42024597541). Rates of successful and complete reperfusion, favorable functional outcomes at 90 days (modified Rankin Scale (mRS) 0-2 or equal to pre-stroke mRS), mortality at 90 days, any intracerebral hemorrhage (ICH) and symptomatic ICH (sICH) were pooled using generalized linear mixed models.</AbstractText Eight studies were included with data from 51 patients and 62 MTs. The rate of successful reperfusion was 87.4% (95% CI 62.5% to 96.6%) and complete reperfusion rate was 57.3% (95% CI 35.1% to 76.9%). Rate of favorable functional recovery was 62.5% (95% CI 42.2% to 79.2%). Rate of sICH was 6.4% (95% CI 0.9% to 34.0%). Mortality rate was 16.7% (95% CI 7.1% to 34.7%). Between 25-40% of patients who were waiting for a heart transplant before their stroke received a heart transplant after MT.</AbstractText MT for the emergent treatment of AIS in the setting of LVAD is relatively safe and efficacious for achieving successful reperfusion and good functional recovery.</AbstractText
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Image-guided endoscopic surgery for spontaneous supratentorial intracerebral hematoma. OBJECTIVE Endoscopic removal of intracerebral hematomas is becoming increasingly common, but there is no standard technique. The authors explored the use of a simple image-guided endoscopic method for removal of spontaneous supratentorial hematomas. METHODS Virtual reality technology based on a hospital picture archiving and communications systems (PACS) was used in 3D hematoma visualization and surgical planning. Augmented reality based on an Android smartphone app, Sina neurosurgical assist, allowed a projection of the hematoma to be seen on the patient's scalp to facilitate selection of the best trajectory to the center of the hematoma. A obturator and transparent sheath were used to establish a working channel, and an endoscope and a metal suction apparatus were used to remove the hematoma. RESULTS A total of 25 patients were included in the study, including 18 with putamen hemorrhages and 7 with lobar cerebral hemorrhages. Virtual reality combined with augmented reality helped in achieving the desired position with the obturator and sheath. The median time from the initial surgical incision to completion of closure was 50 minutes (range 40-70 minutes). The actual endoscopic operating time was 30 (range 15-50) minutes. The median blood loss was 80 (range 40-150) ml. No patient experienced postoperative rebleeding. The average hematoma evacuation rate was 97%. The mean (± SD) preoperative Glasgow Coma Scale (GCS) score was 6.7 ± 3.2; 1 week after hematoma evacuation the mean GCS score had improved to 11.9 ± 3.1 (p < 0.01). CONCLUSIONS Virtual reality using hospital PACS and augmented reality with a smartphone app helped precisely localize hematomas and plan the appropriate endoscopic approach. A transparent sheath helped establish a surgical channel, and an endoscope enabled observation of the hematoma's location to achieve satisfactory hematoma removal.</AbstractText
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ggClusterNet 2: An R package for microbial co-occurrence networks and associated indicator correlation patterns. Since its initial release in 2022, <i
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38007285
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28501096
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38537123
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Clinical Interpretation of Intravoxel Incoherent Motion Perfusion Imaging in the Brain.
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Combined diffusion-weighted imaging and dynamic contrast-enhanced MRI for differentiating radiologically indeterminate malignant from benign orbital masses.
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Excitatory cerebellar transcranial direct current stimulation boosts the leverage of prior knowledge for predicting actions.
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Intravoxel incoherent motion (IVIM) perfusion imaging extracts information on blood motion in biological tissue from diffusion-weighted MR images. The method is attractive from a clinical stand point, because it measures in essence local quantitative perfusion, without intravenous contrast injection. Currently, the clinical interpretation of IVIM perfusion maps focuses on the IVIM perfusion fraction maps, but improvements in image quality of the IVIM pseudo-diffusion maps, using advanced postprocessing tools involving artificial intelligence, could lead to an increased interest in this parameters, as it could provide additional local perfusion information in the clinical setting, not otherwise available with other perfusion techniques.</AbstractText
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To evaluate the performance of the combination of diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for differentiating radiologically indeterminate malignant from benign orbital masses.</AbstractText Sixty-five patients with orbital masses (36 benign and 29 malignant) underwent DW and DCE MRI examinations for pre-treatment evaluation. The apparent diffusion coefficient (ADC) was derived from DW imaging data using the mono-exponential model. The volume transfer constant (K<sup The malignant group demonstrated significantly lower ADC (0.711±0.260 versus 1.187±0.389, p<0.001) and higher K<sub K<sub
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The cerebellum causally supports social processing by generating internal models of social events based on statistical learning of behavioral regularities. However, whether the cerebellum is only involved in forming or also in using internal models for the prediction of forthcoming actions is still unclear. We used cerebellar transcranial Direct Current Stimulation (ctDCS) to modulate the performance of healthy adults in using previously learned expectations in an action prediction task. In a first learning phase of this task, participants were exposed to different levels of associations between specific actions and contextual elements, to induce the formation of either strongly or moderately informative expectations. In a following testing phase, which assessed the use of these expectations for predicting ambiguous (i.e. temporally occluded) actions, we delivered ctDCS. Results showed that anodic, compared to sham, ctDCS boosted the prediction of actions embedded in moderately, but not strongly, informative contexts. Since ctDCS was delivered during the testing phase, that is after expectations were established, our findings suggest that the cerebellum is causally involved in using internal models (and not just in generating them). This encourages the exploration of the clinical effects of ctDCS to compensate poor use of predictive internal models for social perception.</AbstractText
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Clinical Interpretation of Intravoxel Incoherent Motion Perfusion Imaging in the Brain. Intravoxel incoherent motion (IVIM) perfusion imaging extracts information on blood motion in biological tissue from diffusion-weighted MR images. The method is attractive from a clinical stand point, because it measures in essence local quantitative perfusion, without intravenous contrast injection. Currently, the clinical interpretation of IVIM perfusion maps focuses on the IVIM perfusion fraction maps, but improvements in image quality of the IVIM pseudo-diffusion maps, using advanced postprocessing tools involving artificial intelligence, could lead to an increased interest in this parameters, as it could provide additional local perfusion information in the clinical setting, not otherwise available with other perfusion techniques.</AbstractText
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Combined diffusion-weighted imaging and dynamic contrast-enhanced MRI for differentiating radiologically indeterminate malignant from benign orbital masses. To evaluate the performance of the combination of diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for differentiating radiologically indeterminate malignant from benign orbital masses.</AbstractText Sixty-five patients with orbital masses (36 benign and 29 malignant) underwent DW and DCE MRI examinations for pre-treatment evaluation. The apparent diffusion coefficient (ADC) was derived from DW imaging data using the mono-exponential model. The volume transfer constant (K<sup The malignant group demonstrated significantly lower ADC (0.711±0.260 versus 1.187±0.389, p<0.001) and higher K<sub K<sub
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Excitatory cerebellar transcranial direct current stimulation boosts the leverage of prior knowledge for predicting actions. The cerebellum causally supports social processing by generating internal models of social events based on statistical learning of behavioral regularities. However, whether the cerebellum is only involved in forming or also in using internal models for the prediction of forthcoming actions is still unclear. We used cerebellar transcranial Direct Current Stimulation (ctDCS) to modulate the performance of healthy adults in using previously learned expectations in an action prediction task. In a first learning phase of this task, participants were exposed to different levels of associations between specific actions and contextual elements, to induce the formation of either strongly or moderately informative expectations. In a following testing phase, which assessed the use of these expectations for predicting ambiguous (i.e. temporally occluded) actions, we delivered ctDCS. Results showed that anodic, compared to sham, ctDCS boosted the prediction of actions embedded in moderately, but not strongly, informative contexts. Since ctDCS was delivered during the testing phase, that is after expectations were established, our findings suggest that the cerebellum is causally involved in using internal models (and not just in generating them). This encourages the exploration of the clinical effects of ctDCS to compensate poor use of predictive internal models for social perception.</AbstractText
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38165369
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21890158
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39128571
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Characteristics and Prognosis of Tumor-Related Epilepsy During Tumor Evolution in Patients With IDH Wild-Type Glioblastoma.
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Brain tumor epilepsy: a reappraisal and six remaining issues to be debated.
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Alpha-synuclein fine-tunes neuronal response to pro-inflammatory cytokines.
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Tumor-related epilepsy is a well-known symptom of glioblastoma. However, the particular characteristics of epileptic seizures related to glioblastoma, <i We performed an observational, retrospective single-center study at one tertiary referral neuro-oncology surgical center (2000-2020). We included adult patients treated for a newly diagnosed supratentorial glioblastoma, <i One thousand six patients were enrolled. The cumulative incidence of tumor-related epilepsy increased during tumor evolution (33.1% at diagnosis, 44.7% after oncologic treatment, 52.4% at progression, and 51.8% at the end-of-life phase) and is related to tumor features (cortex involvement, no necrosis, and small volume). Uncontrolled epileptic seizures increased during tumor evolution (20.1% at diagnosis, 32.0% after oncologic treatment, 46.7% at progression, and 41.1% at the end-of-life phase). Epileptic seizure control after oncologic treatment was related to seizure features (uncontrolled before oncologic treatment and focal-to-bilateral tonic-clonic seizures) and to the extent of resection. Epileptic seizure control at tumor progression was related to seizure features (presence at diagnosis and uncontrolled after oncologic treatment) and to the time to progression. Tumor-related epilepsy at diagnosis was a predictor of a longer overall survival (adjusted hazard ratio, 0.78; 95% CI 0.67-0.90; <i The progression of tumor-related epilepsy with the evolution of glioblastoma, <i
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Epilepsy associated with brain tumors presents with specific features deserving medical attention. Although commonly reported in patients with brain tumor, either as revealing mode or as a remote complication, limited knowledge is available regarding their epidemiology, clinical evolution, surgical outcome, physiopathology and treatment, providing only clues for clinical management. Seizures appear even more threatening for patients and caregivers, providing seizures could mean tumor progression and recurrence. This factor adds to the negative impact of epilepsy carried on quality of life measures. Pharmacotherapy is complicated by the use of chemotherapy and interaction between antiepileptic drugs and antineoplastic agents are frequent and potentially harmful. The high incidence of epilepsy enlights the question of prophylaxy with antiepileptic drugs, in patients without seizures, or during the perioperative period, and after surgery, when gross total resection has been achieved. This article attempts to provide the reader with an overview of brain tumor epilepsy in its specific aspects and to comment on some remaining issues.</AbstractText
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Pro-inflammatory cytokines are emerging as neuroinflammatory mediators in Parkinson's disease (PD) due to their ability to act through neuronal cytokine receptors. Critical questions persist regarding the role of cytokines in neuronal dysfunction and their contribution to PD pathology. Specifically, the potential synergy of the hallmark PD protein alpha-synuclein (α-syn) with cytokines is of interest. We therefore investigated the direct impact of pro-inflammatory cytokines on neurons and hypothesized that α-syn pathology exacerbates cytokine-induced neuronal deficits in PD. iPSC-derived cortical neurons (CNs) from healthy controls and patients with α-syn gene locus duplication (SNCA dupl) were stimulated with IL-17A, TNF-α, IFN-γ, or a combination thereof. For rescue experiments, CNs were pre-treated with α-syn anti-oligomerisation compound NPT100-18A prior to IL-17A stimulation. Cytokine receptor expression, microtubule cytoskeleton, axonal transport and neuronal activity were assessed. SNCA dupl CNs displayed an increased IL-17A receptor expression and impaired IL-17A-mediated cytokine receptor regulation. Cytokines exacerbated the altered distribution of tubulin post-translational modifications in SNCA dupl neurites, with SNCA dupl-specific IL-17A effects. Tau pathology in SNCA dupl CNs was also aggravated by IL-17A and cytokine mix. Cytokines slowed down mitochondrial axonal transport, with IL-17A-mediated retrograde slowing in SNCA dupl only. The pre-treatment of SNCA dupl CNs with NPT100-18A prevented the IL-17A-induced functional impairments in axonal transport and neural activity. Our work elucidates the detrimental effects of pro-inflammatory cytokines, particularly IL-17A, on human neuronal structure and function in the context of α-syn pathology, suggesting that cytokine-mediated inflammation represents a second hit to neurons in PD which is amenable to disease modifying therapies that are currently in clinical trials.</AbstractText
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Characteristics and Prognosis of Tumor-Related Epilepsy During Tumor Evolution in Patients With IDH Wild-Type Glioblastoma. Tumor-related epilepsy is a well-known symptom of glioblastoma. However, the particular characteristics of epileptic seizures related to glioblastoma, <i We performed an observational, retrospective single-center study at one tertiary referral neuro-oncology surgical center (2000-2020). We included adult patients treated for a newly diagnosed supratentorial glioblastoma, <i One thousand six patients were enrolled. The cumulative incidence of tumor-related epilepsy increased during tumor evolution (33.1% at diagnosis, 44.7% after oncologic treatment, 52.4% at progression, and 51.8% at the end-of-life phase) and is related to tumor features (cortex involvement, no necrosis, and small volume). Uncontrolled epileptic seizures increased during tumor evolution (20.1% at diagnosis, 32.0% after oncologic treatment, 46.7% at progression, and 41.1% at the end-of-life phase). Epileptic seizure control after oncologic treatment was related to seizure features (uncontrolled before oncologic treatment and focal-to-bilateral tonic-clonic seizures) and to the extent of resection. Epileptic seizure control at tumor progression was related to seizure features (presence at diagnosis and uncontrolled after oncologic treatment) and to the time to progression. Tumor-related epilepsy at diagnosis was a predictor of a longer overall survival (adjusted hazard ratio, 0.78; 95% CI 0.67-0.90; <i The progression of tumor-related epilepsy with the evolution of glioblastoma, <i
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Brain tumor epilepsy: a reappraisal and six remaining issues to be debated. Epilepsy associated with brain tumors presents with specific features deserving medical attention. Although commonly reported in patients with brain tumor, either as revealing mode or as a remote complication, limited knowledge is available regarding their epidemiology, clinical evolution, surgical outcome, physiopathology and treatment, providing only clues for clinical management. Seizures appear even more threatening for patients and caregivers, providing seizures could mean tumor progression and recurrence. This factor adds to the negative impact of epilepsy carried on quality of life measures. Pharmacotherapy is complicated by the use of chemotherapy and interaction between antiepileptic drugs and antineoplastic agents are frequent and potentially harmful. The high incidence of epilepsy enlights the question of prophylaxy with antiepileptic drugs, in patients without seizures, or during the perioperative period, and after surgery, when gross total resection has been achieved. This article attempts to provide the reader with an overview of brain tumor epilepsy in its specific aspects and to comment on some remaining issues.</AbstractText
|
Alpha-synuclein fine-tunes neuronal response to pro-inflammatory cytokines. Pro-inflammatory cytokines are emerging as neuroinflammatory mediators in Parkinson's disease (PD) due to their ability to act through neuronal cytokine receptors. Critical questions persist regarding the role of cytokines in neuronal dysfunction and their contribution to PD pathology. Specifically, the potential synergy of the hallmark PD protein alpha-synuclein (α-syn) with cytokines is of interest. We therefore investigated the direct impact of pro-inflammatory cytokines on neurons and hypothesized that α-syn pathology exacerbates cytokine-induced neuronal deficits in PD. iPSC-derived cortical neurons (CNs) from healthy controls and patients with α-syn gene locus duplication (SNCA dupl) were stimulated with IL-17A, TNF-α, IFN-γ, or a combination thereof. For rescue experiments, CNs were pre-treated with α-syn anti-oligomerisation compound NPT100-18A prior to IL-17A stimulation. Cytokine receptor expression, microtubule cytoskeleton, axonal transport and neuronal activity were assessed. SNCA dupl CNs displayed an increased IL-17A receptor expression and impaired IL-17A-mediated cytokine receptor regulation. Cytokines exacerbated the altered distribution of tubulin post-translational modifications in SNCA dupl neurites, with SNCA dupl-specific IL-17A effects. Tau pathology in SNCA dupl CNs was also aggravated by IL-17A and cytokine mix. Cytokines slowed down mitochondrial axonal transport, with IL-17A-mediated retrograde slowing in SNCA dupl only. The pre-treatment of SNCA dupl CNs with NPT100-18A prevented the IL-17A-induced functional impairments in axonal transport and neural activity. Our work elucidates the detrimental effects of pro-inflammatory cytokines, particularly IL-17A, on human neuronal structure and function in the context of α-syn pathology, suggesting that cytokine-mediated inflammation represents a second hit to neurons in PD which is amenable to disease modifying therapies that are currently in clinical trials.</AbstractText
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40546462
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38112964
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40263772
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Gut Microbiota as a Key Modulator of Chronic Disease: Implications for Diabetes, Autoimmunity, and Cancer.
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Neuroprotective effect of curcumin against experimental autoimmune encephalomyelitis-induced cognitive and physical impairments in mice: an insight into the role of the AMPK/SIRT1 pathway.
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Reduced Cacna1c Expression Produces Anhedonic Reactions to Palatable Sucrose in Rats: No Interactions With Juvenile or Adult Stress.
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The gut microbiota (GM) represents an intricate, dynamic, and complex ecosystem. It plays a key role in health and disease. The GM interacts with the host and modulates various physiological functions, including metabolism, immune regulation, and neurological function. This narrative review comprehensively analyses the role of the GM in the development and progression of three major chronic conditions, namely diabetes, autoimmune disorders, and cancer. Using a structured literature search strategy across databases such as Google Scholar, PubMed, Scopus, and Web of Science, relevant studies published between 2000 and 2025 were identified and analysed. This review highlights that dysbiosis contributes significantly to the pathogenesis of these chronic conditions. In type 2 diabetes mellitus (T2DM), alterations in the GM are associated with systemic inflammation, insulin resistance, and decreased microbial diversity. Similarly, in autoimmune disorders such as rheumatoid arthritis (RA), multiple sclerosis (MS), and inflammatory bowel disease (IBD), dysbiosis disrupts immune homeostasis, which in turn causes sustained inflammation and aberrant immune responses. Lastly, dysbiosis has been linked to the onset and progression of various gastrointestinal cancers through mechanisms including chronic inflammation and the production of carcinogenic metabolites. Fecal microbiota transplantation (FMT), probiotics, prebiotics, and dietary modifications are being explored for their potential to restore microbial balance and improve clinical outcomes. In conclusion, this review highlights the GM's pivotal role in the pathogenesis of chronic diseases and its potential as a therapeutic target.</AbstractText
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Multiple sclerosis (MS) is an incurable chronic neurodegenerative disease where autoimmunity, oxidative stress, and neuroinflammation collaboration predispose myelin sheath destruction. Interestingly, curcumin, a natural polyphenol, showed a neuroprotective effect in numerous neurodegenerative diseases, including MS. Nevertheless, the influence of curcumin against MS-induced cognitive impairment is still vague. Hence, we induced experimental autoimmune encephalomyelitis (EAE) in mice using spinal cord homogenate (SCH) and complete Freund's adjuvant, which eventually mimic MS. This study aimed not only to evaluate curcumin efficacy against EAE-induced cognitive and motor dysfunction, but also to explore a novel mechanism of action, by which curcumin exerts its beneficial effects in MS. Curcumin (200 mg/kg/day) efficacy was evaluated by behavioral tests, histopathological examination, and biochemical tests. Concisely, curcumin amended EAE-induced cognitive and motor impairments, as demonstrated by the behavioral tests and histopathological examination of the hippocampus. Interestingly, curcumin activated the adenosine monophosphate (AMP)-activated protein kinase/silent mating type information regulation 2 homolog 1 (AMPK/SIRT1) axis, which triggered cyclic AMP response element-binding protein/brain-derived neurotrophic factor/myelin basic protein (CREB/BDNF/MBP) pathway, hindering demyelination of the corpus callosum. Furthermore, AMPK/SIRT1 activation augmented nuclear factor erythroid 2-related factor 2 (Nrf2), a powerful antioxidant, amending EAE-induced oxidative stress. Additionally, curcumin abolished EAE-induced neuroinflammation by inhibiting Janus kinase 2 /signal transducers and activators of transcription 3 (JAK2/STAT3) axis, by various pathways, including AMPK/SIRT1 activation. JAK2/STAT3 inhibition halts inflammatory cytokines synthesis. In conclusion, curcumin's neuroprotective effect in EAE is controlled, at least in part, by AMPK/SIRT1 activation, which ultimately minimizes EAE-induced neuronal demyelination, oxidative stress, and neuroinflammation.</AbstractText
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Genetic variation in CACNA1C, which encodes the alpha-1 subunit of Ca<sub
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Gut Microbiota as a Key Modulator of Chronic Disease: Implications for Diabetes, Autoimmunity, and Cancer. The gut microbiota (GM) represents an intricate, dynamic, and complex ecosystem. It plays a key role in health and disease. The GM interacts with the host and modulates various physiological functions, including metabolism, immune regulation, and neurological function. This narrative review comprehensively analyses the role of the GM in the development and progression of three major chronic conditions, namely diabetes, autoimmune disorders, and cancer. Using a structured literature search strategy across databases such as Google Scholar, PubMed, Scopus, and Web of Science, relevant studies published between 2000 and 2025 were identified and analysed. This review highlights that dysbiosis contributes significantly to the pathogenesis of these chronic conditions. In type 2 diabetes mellitus (T2DM), alterations in the GM are associated with systemic inflammation, insulin resistance, and decreased microbial diversity. Similarly, in autoimmune disorders such as rheumatoid arthritis (RA), multiple sclerosis (MS), and inflammatory bowel disease (IBD), dysbiosis disrupts immune homeostasis, which in turn causes sustained inflammation and aberrant immune responses. Lastly, dysbiosis has been linked to the onset and progression of various gastrointestinal cancers through mechanisms including chronic inflammation and the production of carcinogenic metabolites. Fecal microbiota transplantation (FMT), probiotics, prebiotics, and dietary modifications are being explored for their potential to restore microbial balance and improve clinical outcomes. In conclusion, this review highlights the GM's pivotal role in the pathogenesis of chronic diseases and its potential as a therapeutic target.</AbstractText
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Neuroprotective effect of curcumin against experimental autoimmune encephalomyelitis-induced cognitive and physical impairments in mice: an insight into the role of the AMPK/SIRT1 pathway. Multiple sclerosis (MS) is an incurable chronic neurodegenerative disease where autoimmunity, oxidative stress, and neuroinflammation collaboration predispose myelin sheath destruction. Interestingly, curcumin, a natural polyphenol, showed a neuroprotective effect in numerous neurodegenerative diseases, including MS. Nevertheless, the influence of curcumin against MS-induced cognitive impairment is still vague. Hence, we induced experimental autoimmune encephalomyelitis (EAE) in mice using spinal cord homogenate (SCH) and complete Freund's adjuvant, which eventually mimic MS. This study aimed not only to evaluate curcumin efficacy against EAE-induced cognitive and motor dysfunction, but also to explore a novel mechanism of action, by which curcumin exerts its beneficial effects in MS. Curcumin (200 mg/kg/day) efficacy was evaluated by behavioral tests, histopathological examination, and biochemical tests. Concisely, curcumin amended EAE-induced cognitive and motor impairments, as demonstrated by the behavioral tests and histopathological examination of the hippocampus. Interestingly, curcumin activated the adenosine monophosphate (AMP)-activated protein kinase/silent mating type information regulation 2 homolog 1 (AMPK/SIRT1) axis, which triggered cyclic AMP response element-binding protein/brain-derived neurotrophic factor/myelin basic protein (CREB/BDNF/MBP) pathway, hindering demyelination of the corpus callosum. Furthermore, AMPK/SIRT1 activation augmented nuclear factor erythroid 2-related factor 2 (Nrf2), a powerful antioxidant, amending EAE-induced oxidative stress. Additionally, curcumin abolished EAE-induced neuroinflammation by inhibiting Janus kinase 2 /signal transducers and activators of transcription 3 (JAK2/STAT3) axis, by various pathways, including AMPK/SIRT1 activation. JAK2/STAT3 inhibition halts inflammatory cytokines synthesis. In conclusion, curcumin's neuroprotective effect in EAE is controlled, at least in part, by AMPK/SIRT1 activation, which ultimately minimizes EAE-induced neuronal demyelination, oxidative stress, and neuroinflammation.</AbstractText
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Reduced Cacna1c Expression Produces Anhedonic Reactions to Palatable Sucrose in Rats: No Interactions With Juvenile or Adult Stress. Genetic variation in CACNA1C, which encodes the alpha-1 subunit of Ca<sub
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35821766
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33613274
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33502474
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Impairments in the Default Mode and Executive Networks in Methamphetamine Users During Short-Term Abstinence.
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Alterations in Dynamic Functional Connectivity in Individuals With Subjective Cognitive Decline.
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Humanized Transgenic Mice Are Resistant to Chronic Wasting Disease Prions From Norwegian Reindeer and Moose.
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Methamphetamine use may cause severe neurotoxicity and cognitive impairment, leading to addiction, overdose, and high rates of relapse. However, few studies have systematically focused on functional impairments detected by neuroimaging in methamphetamine abstainers (MAs) during short-term abstinence. This study aimed to investigate effective connectivity, resting-state networks, and internetwork functional connectivity in MA brains to improve clinical treatment.</AbstractText Twenty MAs and 27 age- and education-matched healthy controls underwent resting-state functional magnetic resonance imaging. The amplitude of low-frequency fluctuations and Granger causality were analyzed to investigate disrupted brain regions and effective connectivity, respectively. Independent component analysis and functional network connectivity were used to identify resting-state networks and internetwork functional connectivity, respectively.</AbstractText Compared with healthy controls, MAs demonstrated abnormal amplitudes of low-frequency fluctuations in the bilateral precuneus, left posterior cingulate cortex (PCC), left middle frontal gyrus (MFG), left superior parietal lobule, left supplementary motor area (SMA), and left inferior parietal lobule (IPL). Moreover, MAs showed decreased effective connectivity from the left PCC to the left precuneus, increased effective connectivity from the left precuneus to the left MFG and from the right precuneus to the left SMA, and altered functional connectivity within the default mode network (DMN), frontoparietal network, sensorimotor network, ventral attention network, cerebellar network, and visual network. Importantly, hyperconnectivity between the DMN and ventral attention network and hypoconnectivity between the DMN and cerebellar network as well as the DMN and frontoparietal network were demonstrated in MAs.</AbstractText Our study implies that in short-term methamphetamine abstinence, disruptions to the DMN and executive network may a play key role, providing new insights for early rehabilitation.</AbstractText
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<b
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Chronic wasting disease (CWD) is the transmissible spongiform encephalopathy or prion disease affecting cervids. In 2016, the first cases of CWD were reported in Europe in Norwegian wild reindeer and moose. The origin and zoonotic potential of these new prion isolates remain unknown. In this study to investigate zoonotic potential we inoculated brain tissue from CWD-infected Norwegian reindeer and moose into transgenic mice overexpressing human prion protein. After prolonged postinoculation survival periods no evidence for prion transmission was seen, suggesting that the zoonotic potential of these isolates is low.</AbstractText
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Impairments in the Default Mode and Executive Networks in Methamphetamine Users During Short-Term Abstinence. Methamphetamine use may cause severe neurotoxicity and cognitive impairment, leading to addiction, overdose, and high rates of relapse. However, few studies have systematically focused on functional impairments detected by neuroimaging in methamphetamine abstainers (MAs) during short-term abstinence. This study aimed to investigate effective connectivity, resting-state networks, and internetwork functional connectivity in MA brains to improve clinical treatment.</AbstractText Twenty MAs and 27 age- and education-matched healthy controls underwent resting-state functional magnetic resonance imaging. The amplitude of low-frequency fluctuations and Granger causality were analyzed to investigate disrupted brain regions and effective connectivity, respectively. Independent component analysis and functional network connectivity were used to identify resting-state networks and internetwork functional connectivity, respectively.</AbstractText Compared with healthy controls, MAs demonstrated abnormal amplitudes of low-frequency fluctuations in the bilateral precuneus, left posterior cingulate cortex (PCC), left middle frontal gyrus (MFG), left superior parietal lobule, left supplementary motor area (SMA), and left inferior parietal lobule (IPL). Moreover, MAs showed decreased effective connectivity from the left PCC to the left precuneus, increased effective connectivity from the left precuneus to the left MFG and from the right precuneus to the left SMA, and altered functional connectivity within the default mode network (DMN), frontoparietal network, sensorimotor network, ventral attention network, cerebellar network, and visual network. Importantly, hyperconnectivity between the DMN and ventral attention network and hypoconnectivity between the DMN and cerebellar network as well as the DMN and frontoparietal network were demonstrated in MAs.</AbstractText Our study implies that in short-term methamphetamine abstinence, disruptions to the DMN and executive network may a play key role, providing new insights for early rehabilitation.</AbstractText
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Alterations in Dynamic Functional Connectivity in Individuals With Subjective Cognitive Decline. <b
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Humanized Transgenic Mice Are Resistant to Chronic Wasting Disease Prions From Norwegian Reindeer and Moose. Chronic wasting disease (CWD) is the transmissible spongiform encephalopathy or prion disease affecting cervids. In 2016, the first cases of CWD were reported in Europe in Norwegian wild reindeer and moose. The origin and zoonotic potential of these new prion isolates remain unknown. In this study to investigate zoonotic potential we inoculated brain tissue from CWD-infected Norwegian reindeer and moose into transgenic mice overexpressing human prion protein. After prolonged postinoculation survival periods no evidence for prion transmission was seen, suggesting that the zoonotic potential of these isolates is low.</AbstractText
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39926461
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37237103
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40341990
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Immunoexcitoxicity as the possible major pathophysiology behind multiple sclerosis and other autoimmune disorders.
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The impact of the human thalamus on brain-wide information processing.
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Navigating the risks and rewards of scavenging in multipredator, human-impacted landscapes.
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Autoimmune disorders are destructive processes considered to be an attack on "self " antigens by the immune system CD-+4 T-cells that are directed toward antigens, in the case of multiple sclerosis (MS), particularly myelin antigens. Yet, there is growing evidence that the major destructive events in MS, as well as other non-central nervous system (CNS) autoimmune disorders, are much more than an immune attack on the CNS initiated by a misdirected immune system that attacks a "self " antigen or antigens by a process called molecular mimicry. Extensive evidence suggests that inflammation, in turn, initiates excitotoxicity, which is responsible for the majority of pathological findings in all stages of the disease, especially a loss of oligodendroglia (source of myelin) and axon injury in MS. Excitotoxicity also is a better explanation for progressive MS, in which the immune attack has either slowed or is halted; yet, the destructive pathology continues to progress. It also explains the destructive lesions seen in gray matter, which is essentially devoid of inflammation. It has recently been shown that most of the damage to the oligodendrocytes, as well as axonal injury, is secondary to excitotoxicity. While there is a growing appreciation that excitotoxicity plays a major role, there has been little effort to link the immune changes to the excitotoxic process, recently named immunoexcitotoxicity, even though the role of excitotoxicity has been shown to occur in the inflammatory stage in the beginning and throughout the process of the disease, particularly the chronic progressive stage. It is also known that peripheral glutamate receptors exist throughout the body, thus making the process of immunoexcitotoxicity a possible integral part of all or most autoimmune disorders in which the immune system is intimately linked to enhancing the excitotoxic process. This is of special concern now that peripheral glutamate receptors have been isolated in many peripheral tissues and are known to be fully functional.</AbstractText
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The thalamus is a small, bilateral structure in the diencephalon that integrates signals from many areas of the CNS. This critical anatomical position allows the thalamus to influence whole-brain activity and adaptive behaviour. However, traditional research paradigms have struggled to attribute specific functions to the thalamus, and it has remained understudied in the human neuroimaging literature. Recent advances in analytical techniques and increased accessibility to large, high-quality data sets have brought forth a series of studies and findings that (re-)establish the thalamus as a core region of interest in human cognitive neuroscience, a field that otherwise remains cortico-centric. In this Perspective, we argue that using whole-brain neuroimaging approaches to investigate the thalamus and its interaction with the rest of the brain is key for understanding systems-level control of information processing. To this end, we highlight the role of the thalamus in shaping a range of functional signatures, including evoked activity, interregional connectivity, network topology and neuronal variability, both at rest and during the performance of cognitive tasks.</AbstractText
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Large carnivores can influence smaller scavengers through both positive and negative interactions (e.g., carrion provisioning and intraguild killing) and ultimately shape scavenging efficiency. However, we know little about this trade-off in anthropogenic landscapes where humans kill carnivores and provide carrion subsidies. In the context of wolf (Canis lupus) recolonization of human-impacted landscapes in Washington, USA, we investigated how sources of ungulate mortality (wolves, cougars [Puma concolor], and vehicles) shape scavenging efficiency, community-wide carcass visitations, and the strategies used by scavengers to navigate risk-reward trade-offs. Cougar and wolf kills mostly occurred in areas with low-to-moderate human influence, whereas roadkill typically occurred in areas with high human impact. Wolves consumed their kills most rapidly (median <4.7 days), providing fewer scavenging opportunities than cougar- and vehicle-killed ungulates, which persisted longer (median = 8.9 and 12 days, respectively). Roadkill primarily attracted avian scavengers, whereas mammalian scavengers used roadkill to a lesser degree and did so by shifting to more nocturnal foraging. The absence in winter of turkey vultures (Cathartes aura) and black bears (Ursus americanus), which are obligate and apex scavengers, respectively, coincided with a seasonal increase in scavenging by most other species. The two mammalian mesocarnivores exhibited divergent strategies: Coyotes (Canis latrans) frequently scavenged but usually for short durations and with heightened vigilance at predator kills, whereas bobcats (Lynx rufus) visited carcasses less frequently but fed for longer durations and displayed low vigilance while scavenging. These results suggest a hierarchical decision-making process whereby scavengers first choose whether to forage at a carcass before fine-tuning foraging duration, using temporal refugia, or increasing vigilance. Predator recovery in human-dominated landscapes therefore adds complexity to the spatiotemporal landscape of risks and rewards, and outcomes for scavengers will likely depend on their propensity to scavenge and vulnerability to humans and large predators.</AbstractText
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Immunoexcitoxicity as the possible major pathophysiology behind multiple sclerosis and other autoimmune disorders. Autoimmune disorders are destructive processes considered to be an attack on "self " antigens by the immune system CD-+4 T-cells that are directed toward antigens, in the case of multiple sclerosis (MS), particularly myelin antigens. Yet, there is growing evidence that the major destructive events in MS, as well as other non-central nervous system (CNS) autoimmune disorders, are much more than an immune attack on the CNS initiated by a misdirected immune system that attacks a "self " antigen or antigens by a process called molecular mimicry. Extensive evidence suggests that inflammation, in turn, initiates excitotoxicity, which is responsible for the majority of pathological findings in all stages of the disease, especially a loss of oligodendroglia (source of myelin) and axon injury in MS. Excitotoxicity also is a better explanation for progressive MS, in which the immune attack has either slowed or is halted; yet, the destructive pathology continues to progress. It also explains the destructive lesions seen in gray matter, which is essentially devoid of inflammation. It has recently been shown that most of the damage to the oligodendrocytes, as well as axonal injury, is secondary to excitotoxicity. While there is a growing appreciation that excitotoxicity plays a major role, there has been little effort to link the immune changes to the excitotoxic process, recently named immunoexcitotoxicity, even though the role of excitotoxicity has been shown to occur in the inflammatory stage in the beginning and throughout the process of the disease, particularly the chronic progressive stage. It is also known that peripheral glutamate receptors exist throughout the body, thus making the process of immunoexcitotoxicity a possible integral part of all or most autoimmune disorders in which the immune system is intimately linked to enhancing the excitotoxic process. This is of special concern now that peripheral glutamate receptors have been isolated in many peripheral tissues and are known to be fully functional.</AbstractText
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The impact of the human thalamus on brain-wide information processing. The thalamus is a small, bilateral structure in the diencephalon that integrates signals from many areas of the CNS. This critical anatomical position allows the thalamus to influence whole-brain activity and adaptive behaviour. However, traditional research paradigms have struggled to attribute specific functions to the thalamus, and it has remained understudied in the human neuroimaging literature. Recent advances in analytical techniques and increased accessibility to large, high-quality data sets have brought forth a series of studies and findings that (re-)establish the thalamus as a core region of interest in human cognitive neuroscience, a field that otherwise remains cortico-centric. In this Perspective, we argue that using whole-brain neuroimaging approaches to investigate the thalamus and its interaction with the rest of the brain is key for understanding systems-level control of information processing. To this end, we highlight the role of the thalamus in shaping a range of functional signatures, including evoked activity, interregional connectivity, network topology and neuronal variability, both at rest and during the performance of cognitive tasks.</AbstractText
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Navigating the risks and rewards of scavenging in multipredator, human-impacted landscapes. Large carnivores can influence smaller scavengers through both positive and negative interactions (e.g., carrion provisioning and intraguild killing) and ultimately shape scavenging efficiency. However, we know little about this trade-off in anthropogenic landscapes where humans kill carnivores and provide carrion subsidies. In the context of wolf (Canis lupus) recolonization of human-impacted landscapes in Washington, USA, we investigated how sources of ungulate mortality (wolves, cougars [Puma concolor], and vehicles) shape scavenging efficiency, community-wide carcass visitations, and the strategies used by scavengers to navigate risk-reward trade-offs. Cougar and wolf kills mostly occurred in areas with low-to-moderate human influence, whereas roadkill typically occurred in areas with high human impact. Wolves consumed their kills most rapidly (median <4.7 days), providing fewer scavenging opportunities than cougar- and vehicle-killed ungulates, which persisted longer (median = 8.9 and 12 days, respectively). Roadkill primarily attracted avian scavengers, whereas mammalian scavengers used roadkill to a lesser degree and did so by shifting to more nocturnal foraging. The absence in winter of turkey vultures (Cathartes aura) and black bears (Ursus americanus), which are obligate and apex scavengers, respectively, coincided with a seasonal increase in scavenging by most other species. The two mammalian mesocarnivores exhibited divergent strategies: Coyotes (Canis latrans) frequently scavenged but usually for short durations and with heightened vigilance at predator kills, whereas bobcats (Lynx rufus) visited carcasses less frequently but fed for longer durations and displayed low vigilance while scavenging. These results suggest a hierarchical decision-making process whereby scavengers first choose whether to forage at a carcass before fine-tuning foraging duration, using temporal refugia, or increasing vigilance. Predator recovery in human-dominated landscapes therefore adds complexity to the spatiotemporal landscape of risks and rewards, and outcomes for scavengers will likely depend on their propensity to scavenge and vulnerability to humans and large predators.</AbstractText
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37933745
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28642283
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38473363
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Progressive Brain Atrophy in Multiple System Atrophy: A Longitudinal, Multicenter, Magnetic Resonance Imaging Study.
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Selective Inhibition of Trigeminovascular Neurons by Fremanezumab: A Humanized Monoclonal Anti-CGRP Antibody.
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Pixelwise Gradient Model with GAN for Virtual Contrast Enhancement in MRI Imaging.
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To determine the rates of brain atrophy progression in vivo in patients with multiple system atrophy (MSA).</AbstractText Surrogate biomarkers of disease progression are a major unmet need in MSA. Small-scale longitudinal studies in patients with MSA using magnetic resonance imaging (MRI) to assess progression of brain atrophy have produced inconsistent results. In recent years, novel MRI post-processing methods have been developed enabling reliable quantification of brain atrophy in an automated fashion.</AbstractText Serial 3D-T1-weighted MRI assessments (baseline and after 1 year of follow-up) of 43 patients with MSA were analyzed and compared to a cohort of early-stage Parkinson's disease (PD) patients and healthy controls (HC). FreeSurfer's longitudinal analysis stream was used to determine the brain atrophy rates in an observer-independent fashion.</AbstractText Mean ages at baseline were 64.4 ± 8.3, 60.0 ± 7.5, and 59.8 ± 9.2 years in MSA, PD patients and HC, respectively. A mean disease duration at baseline of 4.1 ± 2.5 years in MSA patients and 2.3 ± 1.4 years in PD patients was observed. Brain regions chiefly affected by MSA pathology showed progressive atrophy with annual rates of atrophy for the cerebellar cortex, cerebellar white matter, pons, and putamen of -4.24 ± 6.8%, -8.22 ± 8.8%, -4.67 ± 4.9%, and - 4.25 ± 4.9%, respectively. Similar to HC, atrophy rates in PD patients were minimal with values of -0.41% ± 1.8%, -1.47% ± 4.1%, -0.04% ± 1.8%, and -1.54% ± 2.2% for cerebellar cortex, cerebellar white matter, pons, and putamen, respectively.</AbstractText Patients with MSA show significant brain volume loss over 12 months, and cerebellar, pontine, and putaminal volumes were the most sensitive to change in mid-stage disease. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</AbstractText
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A large body of evidence supports an important role for calcitonin gene-related peptide (CGRP) in migraine pathophysiology. This evidence gave rise to a global effort to develop a new generation of therapeutics that inhibit the interaction of CGRP with its receptor in migraineurs. Recently, a new class of such drugs, humanized anti-CGRP monoclonal antibodies (CGRP-mAbs), were found to be effective in reducing the frequency of migraine. The purpose of this study was to better understand how the CGRP-mAb fremanezumab (TEV-48125) modulates meningeal sensory pathways. To answer this question, we used single-unit recording to determine the effects of fremanezumab (30 mg/kg, IV) and its isotype control Ab on spontaneous and evoked activity in naive and cortical spreading depression (CSD)-sensitized trigeminovascular neurons in the spinal trigeminal nucleus of anesthetized male and female rats. The study demonstrates that, in both sexes, fremanezumab inhibited naive high-threshold (HT) neurons, but not wide-dynamic range trigeminovascular neurons, and that the inhibitory effects on the neurons were limited to their activation from the intracranial dura but not facial skin or cornea. In addition, when given sufficient time, fremanezumab prevents the activation and sensitization of HT neurons by CSD. Mechanistically, these findings suggest that HT neurons play a critical role in the initiation of the perception of headache and the development of cutaneous allodynia and central sensitization. Clinically, the findings may help to explain the therapeutic benefit of CGRP-mAb in reducing headaches of intracranial origin such as migraine with aura and why this therapeutic approach may not be effective for every migraine patient.<b
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<b
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Progressive Brain Atrophy in Multiple System Atrophy: A Longitudinal, Multicenter, Magnetic Resonance Imaging Study. To determine the rates of brain atrophy progression in vivo in patients with multiple system atrophy (MSA).</AbstractText Surrogate biomarkers of disease progression are a major unmet need in MSA. Small-scale longitudinal studies in patients with MSA using magnetic resonance imaging (MRI) to assess progression of brain atrophy have produced inconsistent results. In recent years, novel MRI post-processing methods have been developed enabling reliable quantification of brain atrophy in an automated fashion.</AbstractText Serial 3D-T1-weighted MRI assessments (baseline and after 1 year of follow-up) of 43 patients with MSA were analyzed and compared to a cohort of early-stage Parkinson's disease (PD) patients and healthy controls (HC). FreeSurfer's longitudinal analysis stream was used to determine the brain atrophy rates in an observer-independent fashion.</AbstractText Mean ages at baseline were 64.4 ± 8.3, 60.0 ± 7.5, and 59.8 ± 9.2 years in MSA, PD patients and HC, respectively. A mean disease duration at baseline of 4.1 ± 2.5 years in MSA patients and 2.3 ± 1.4 years in PD patients was observed. Brain regions chiefly affected by MSA pathology showed progressive atrophy with annual rates of atrophy for the cerebellar cortex, cerebellar white matter, pons, and putamen of -4.24 ± 6.8%, -8.22 ± 8.8%, -4.67 ± 4.9%, and - 4.25 ± 4.9%, respectively. Similar to HC, atrophy rates in PD patients were minimal with values of -0.41% ± 1.8%, -1.47% ± 4.1%, -0.04% ± 1.8%, and -1.54% ± 2.2% for cerebellar cortex, cerebellar white matter, pons, and putamen, respectively.</AbstractText Patients with MSA show significant brain volume loss over 12 months, and cerebellar, pontine, and putaminal volumes were the most sensitive to change in mid-stage disease. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</AbstractText
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Selective Inhibition of Trigeminovascular Neurons by Fremanezumab: A Humanized Monoclonal Anti-CGRP Antibody. A large body of evidence supports an important role for calcitonin gene-related peptide (CGRP) in migraine pathophysiology. This evidence gave rise to a global effort to develop a new generation of therapeutics that inhibit the interaction of CGRP with its receptor in migraineurs. Recently, a new class of such drugs, humanized anti-CGRP monoclonal antibodies (CGRP-mAbs), were found to be effective in reducing the frequency of migraine. The purpose of this study was to better understand how the CGRP-mAb fremanezumab (TEV-48125) modulates meningeal sensory pathways. To answer this question, we used single-unit recording to determine the effects of fremanezumab (30 mg/kg, IV) and its isotype control Ab on spontaneous and evoked activity in naive and cortical spreading depression (CSD)-sensitized trigeminovascular neurons in the spinal trigeminal nucleus of anesthetized male and female rats. The study demonstrates that, in both sexes, fremanezumab inhibited naive high-threshold (HT) neurons, but not wide-dynamic range trigeminovascular neurons, and that the inhibitory effects on the neurons were limited to their activation from the intracranial dura but not facial skin or cornea. In addition, when given sufficient time, fremanezumab prevents the activation and sensitization of HT neurons by CSD. Mechanistically, these findings suggest that HT neurons play a critical role in the initiation of the perception of headache and the development of cutaneous allodynia and central sensitization. Clinically, the findings may help to explain the therapeutic benefit of CGRP-mAb in reducing headaches of intracranial origin such as migraine with aura and why this therapeutic approach may not be effective for every migraine patient.<b
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Pixelwise Gradient Model with GAN for Virtual Contrast Enhancement in MRI Imaging. <b
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21820518
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16306418
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22822175
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Network modulation during complex syntactic processing.
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Separate face and body selectivity on the fusiform gyrus.
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Transdiagnostic treatment of bipolar disorder and comorbid anxiety with the unified protocol: a clinical replication series.
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Complex sentence processing is supported by a left-lateralized neural network including inferior frontal cortex and posterior superior temporal cortex. This study investigates the pattern of connectivity and information flow within this network. We used fMRI BOLD data derived from 12 healthy participants reported in an earlier study (Thompson, C. K., Den Ouden, D. B., Bonakdarpour, B., Garibaldi, K., & Parrish, T. B. (2010b). Neural plasticity and treatment-induced recovery of sentence processing in agrammatism. Neuropsychologia, 48(11), 3211-3227) to identify activation peaks associated with object-cleft over syntactically less complex subject-cleft processing. Directed Partial Correlation Analysis was conducted on time series extracted from participant-specific activation peaks and showed evidence of functional connectivity between four regions, linearly between premotor cortex, inferior frontal gyrus, posterior superior temporal sulcus and anterior middle temporal gyrus. This pattern served as the basis for Dynamic Causal Modeling of networks with a driving input to posterior superior temporal cortex, which likely supports thematic role assignment, and networks with a driving input to inferior frontal cortex, a core region associated with syntactic computation. The optimal model was determined through both frequentist and Bayesian Model Selection and turned out to reflect a network with a primary drive from inferior frontal cortex and modulation of the connection between inferior frontal cortex and posterior superior temporal cortex by complex sentence processing. The winning model also showed a substantive role for a feedback mechanism from posterior superior temporal cortex back to inferior frontal cortex. We suggest that complex syntactic processing is driven by word-order analysis, supported by inferior frontal cortex, in an interactive relation with posterior superior temporal cortex, which supports verb argument structure processing.</AbstractText
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Recent reports of a high response to bodies in the fusiform face area (FFA) challenge the idea that the FFA is exclusively selective for face stimuli. We examined this claim by conducting a functional magnetic resonance imaging experiment at both standard (3.125 x 3.125 x 4.0 mm) and high resolution (1.4 x 1.4 x 2.0 mm). In both experiments, regions of interest (ROIs) were defined using data from blocked localizer runs. Within each ROI, we measured the mean peak response to a variety of stimulus types in independent data from a subsequent event-related experiment. Our localizer scans identified a fusiform body area (FBA), a body-selective region reported recently by Peelen and Downing (2005) that is anatomically distinct from the extrastriate body area. The FBA overlapped with and was adjacent to the FFA in all but two participants. Selectivity of the FFA to faces and FBA to bodies was stronger for the high-resolution scans, as expected from the reduction in partial volume effects. When new ROIs were constructed for the high-resolution experiment by omitting the voxels showing overlapping selectivity for both bodies and faces in the localizer scans, the resulting FFA* ROI showed no response above control objects for body stimuli, and the FBA* ROI showed no response above control objects for face stimuli. These results demonstrate strong selectivities in distinct but adjacent regions in the fusiform gyrus for only faces in one region (the FFA*) and only bodies in the other (the FBA*).</AbstractText
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Bipolar disorder (BD) is a chronic, debilitating disorder with recurrent manic and depressive episodes. More than 75% of bipolar patients have a current or lifetime diagnosis of a comorbid anxiety disorder. Comorbid anxiety in BD is associated with greater illness severity, greater functional impairment, and poorer illness-related outcomes. Effectively treating comorbid anxiety in individuals with BD has been recognized as one of the biggest unmet needs in the field of BD. Recently, the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) was developed to be applicable to the full range of anxiety and mood disorders, based on converging evidence from genetics, cognitive and affective neuroscience, and behavioral research suggesting common, core emotion-related pathology. Here, the authors present a preliminary evaluation of the efficacy of the UP for the treatment of BD with comorbid anxiety, in a clinical replication series consisting of three cases.</AbstractText
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Network modulation during complex syntactic processing. Complex sentence processing is supported by a left-lateralized neural network including inferior frontal cortex and posterior superior temporal cortex. This study investigates the pattern of connectivity and information flow within this network. We used fMRI BOLD data derived from 12 healthy participants reported in an earlier study (Thompson, C. K., Den Ouden, D. B., Bonakdarpour, B., Garibaldi, K., & Parrish, T. B. (2010b). Neural plasticity and treatment-induced recovery of sentence processing in agrammatism. Neuropsychologia, 48(11), 3211-3227) to identify activation peaks associated with object-cleft over syntactically less complex subject-cleft processing. Directed Partial Correlation Analysis was conducted on time series extracted from participant-specific activation peaks and showed evidence of functional connectivity between four regions, linearly between premotor cortex, inferior frontal gyrus, posterior superior temporal sulcus and anterior middle temporal gyrus. This pattern served as the basis for Dynamic Causal Modeling of networks with a driving input to posterior superior temporal cortex, which likely supports thematic role assignment, and networks with a driving input to inferior frontal cortex, a core region associated with syntactic computation. The optimal model was determined through both frequentist and Bayesian Model Selection and turned out to reflect a network with a primary drive from inferior frontal cortex and modulation of the connection between inferior frontal cortex and posterior superior temporal cortex by complex sentence processing. The winning model also showed a substantive role for a feedback mechanism from posterior superior temporal cortex back to inferior frontal cortex. We suggest that complex syntactic processing is driven by word-order analysis, supported by inferior frontal cortex, in an interactive relation with posterior superior temporal cortex, which supports verb argument structure processing.</AbstractText
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Separate face and body selectivity on the fusiform gyrus. Recent reports of a high response to bodies in the fusiform face area (FFA) challenge the idea that the FFA is exclusively selective for face stimuli. We examined this claim by conducting a functional magnetic resonance imaging experiment at both standard (3.125 x 3.125 x 4.0 mm) and high resolution (1.4 x 1.4 x 2.0 mm). In both experiments, regions of interest (ROIs) were defined using data from blocked localizer runs. Within each ROI, we measured the mean peak response to a variety of stimulus types in independent data from a subsequent event-related experiment. Our localizer scans identified a fusiform body area (FBA), a body-selective region reported recently by Peelen and Downing (2005) that is anatomically distinct from the extrastriate body area. The FBA overlapped with and was adjacent to the FFA in all but two participants. Selectivity of the FFA to faces and FBA to bodies was stronger for the high-resolution scans, as expected from the reduction in partial volume effects. When new ROIs were constructed for the high-resolution experiment by omitting the voxels showing overlapping selectivity for both bodies and faces in the localizer scans, the resulting FFA* ROI showed no response above control objects for body stimuli, and the FBA* ROI showed no response above control objects for face stimuli. These results demonstrate strong selectivities in distinct but adjacent regions in the fusiform gyrus for only faces in one region (the FFA*) and only bodies in the other (the FBA*).</AbstractText
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Transdiagnostic treatment of bipolar disorder and comorbid anxiety with the unified protocol: a clinical replication series. Bipolar disorder (BD) is a chronic, debilitating disorder with recurrent manic and depressive episodes. More than 75% of bipolar patients have a current or lifetime diagnosis of a comorbid anxiety disorder. Comorbid anxiety in BD is associated with greater illness severity, greater functional impairment, and poorer illness-related outcomes. Effectively treating comorbid anxiety in individuals with BD has been recognized as one of the biggest unmet needs in the field of BD. Recently, the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) was developed to be applicable to the full range of anxiety and mood disorders, based on converging evidence from genetics, cognitive and affective neuroscience, and behavioral research suggesting common, core emotion-related pathology. Here, the authors present a preliminary evaluation of the efficacy of the UP for the treatment of BD with comorbid anxiety, in a clinical replication series consisting of three cases.</AbstractText
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39378968
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26500511
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40728555
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Maternal heart exhibits metabolic and redox adaptations post-uncomplicated pregnancy.
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Neurogenesis paradoxically decreases both pattern separation and memory interference.
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Molecular Characterization of Carbapenemase Genes in Carbapenem-Resistant Klebsiella pneumoniae Isolates.
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Pregnancy may be a challenging period for the maternal systems and has been regarded as a stress test, as imperceptible/mild dysfunctions eventually present may be exacerbated during this period. The cardiovascular system is no exception, and several morphological and functional adaptations accompanying pregnancy have been described. However, long-term pregnancy-induced cardiac molecular alterations remain highly unexplored. The postpartum is marked by reverse remodeling of the pregnancy-induced cardiovascular adaptations, representing a possible critical period for assessing future maternal cardiovascular health. The current study explored the molecular and metabolic alterations in the cardiac tissue eight weeks after a physiological uncomplicated pregnancy. Female Sprague-Dawley rats were fed a chow diet through pregnancy, lactation, and weaning and compared to their non-pregnant counterparts. Eight weeks postpartum, increased levels of the phosphorylated form of AMPKα (Thr172) and its ratio to total AMPKα indicated possible alterations in cardiac metabolic flexibility, accompanied by increased Pparα and Hif1α transcripts levels. Additionally, postpartum hearts exhibited higher mitochondrial ATP and NADH levels without major changes in mitochondrial respiratory function. Elevated Nrf2 levels in the cardiac tissue suggested potential implications for cardiac redox balance, further supported by increased levels or activity of proteins directly regulated by Nrf2. The findings herein reported suggest that at eight weeks postpartum, molecular alterations induced by pregnancy, especially regarding redox balance, are still observed in the mothers' heart. These alterations present at late postpartum may open new avenues to understand the different risk for cardiovascular complications development after normal pregnancies.</AbstractText
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The hippocampus has been the focus of memory research for decades. While the functional role of this structure is not fully understood, it is widely recognized as being vital for rapid yet accurate encoding and retrieval of associative memories. Since the discovery of adult hippocampal neurogenesis in the dentate gyrus by Altman and Das in the 1960's, many theories and models have been put forward to explain the functional role it plays in learning and memory. These models postulate different ways in which new neurons are introduced into the dentate gyrus and their functional importance for learning and memory. Few if any previous models have incorporated the unique properties of young adult-born dentate granule cells and the developmental trajectory. In this paper, we propose a novel computational model of the dentate gyrus that incorporates the developmental trajectory of the adult-born dentate granule cells, including changes in synaptic plasticity, connectivity, excitability and lateral inhibition, using a modified version of the Restricted Boltzmann machine. Our results show superior performance on memory reconstruction tasks for both recent and distally learned items, when the unique characteristics of young dentate granule cells are taken into account. Even though the hyperexcitability of the young neurons generates more overlapping neural codes, reducing pattern separation, the unique properties of the young neurons nonetheless contribute to reducing retroactive and proactive interference, at both short and long time scales. The sparse connectivity is particularly important for generating distinct memory traces for highly overlapping patterns that are learned within the same context.</AbstractText
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Carbapenemase genes play important role in the formation and dissemination of carbapenem-resistant Klebsiella pneumoniae (CRKP). The aim of this study was to investigate the distribution of carbapenemase genes in clinical CRKP isolates. Eighty-three clinical CRKPs were collected and antimicrobial susceptibility testing was conducted. Whole-genome sequencing was performed to analyze carbapenemase genes and genetic environments of bla<sub
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Maternal heart exhibits metabolic and redox adaptations post-uncomplicated pregnancy. Pregnancy may be a challenging period for the maternal systems and has been regarded as a stress test, as imperceptible/mild dysfunctions eventually present may be exacerbated during this period. The cardiovascular system is no exception, and several morphological and functional adaptations accompanying pregnancy have been described. However, long-term pregnancy-induced cardiac molecular alterations remain highly unexplored. The postpartum is marked by reverse remodeling of the pregnancy-induced cardiovascular adaptations, representing a possible critical period for assessing future maternal cardiovascular health. The current study explored the molecular and metabolic alterations in the cardiac tissue eight weeks after a physiological uncomplicated pregnancy. Female Sprague-Dawley rats were fed a chow diet through pregnancy, lactation, and weaning and compared to their non-pregnant counterparts. Eight weeks postpartum, increased levels of the phosphorylated form of AMPKα (Thr172) and its ratio to total AMPKα indicated possible alterations in cardiac metabolic flexibility, accompanied by increased Pparα and Hif1α transcripts levels. Additionally, postpartum hearts exhibited higher mitochondrial ATP and NADH levels without major changes in mitochondrial respiratory function. Elevated Nrf2 levels in the cardiac tissue suggested potential implications for cardiac redox balance, further supported by increased levels or activity of proteins directly regulated by Nrf2. The findings herein reported suggest that at eight weeks postpartum, molecular alterations induced by pregnancy, especially regarding redox balance, are still observed in the mothers' heart. These alterations present at late postpartum may open new avenues to understand the different risk for cardiovascular complications development after normal pregnancies.</AbstractText
|
Neurogenesis paradoxically decreases both pattern separation and memory interference. The hippocampus has been the focus of memory research for decades. While the functional role of this structure is not fully understood, it is widely recognized as being vital for rapid yet accurate encoding and retrieval of associative memories. Since the discovery of adult hippocampal neurogenesis in the dentate gyrus by Altman and Das in the 1960's, many theories and models have been put forward to explain the functional role it plays in learning and memory. These models postulate different ways in which new neurons are introduced into the dentate gyrus and their functional importance for learning and memory. Few if any previous models have incorporated the unique properties of young adult-born dentate granule cells and the developmental trajectory. In this paper, we propose a novel computational model of the dentate gyrus that incorporates the developmental trajectory of the adult-born dentate granule cells, including changes in synaptic plasticity, connectivity, excitability and lateral inhibition, using a modified version of the Restricted Boltzmann machine. Our results show superior performance on memory reconstruction tasks for both recent and distally learned items, when the unique characteristics of young dentate granule cells are taken into account. Even though the hyperexcitability of the young neurons generates more overlapping neural codes, reducing pattern separation, the unique properties of the young neurons nonetheless contribute to reducing retroactive and proactive interference, at both short and long time scales. The sparse connectivity is particularly important for generating distinct memory traces for highly overlapping patterns that are learned within the same context.</AbstractText
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Molecular Characterization of Carbapenemase Genes in Carbapenem-Resistant Klebsiella pneumoniae Isolates. Carbapenemase genes play important role in the formation and dissemination of carbapenem-resistant Klebsiella pneumoniae (CRKP). The aim of this study was to investigate the distribution of carbapenemase genes in clinical CRKP isolates. Eighty-three clinical CRKPs were collected and antimicrobial susceptibility testing was conducted. Whole-genome sequencing was performed to analyze carbapenemase genes and genetic environments of bla<sub
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40603121
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38967126
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40788849
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[Analysis of rapeutic effect of musculoskeletal ultrasound-guided acupuncture for the treatment of myofascial pain syndrome after rotator cuff suture under shoulder arthroscopy].
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The molecular biology of NF2/Merlin on tumorigenesis and development.
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The ghost of infections past: Accounting for heterogeneity in individual infection history improves accuracy in epidemic forecasting.
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To compare clinical efficacy of musculoskeletal ultrasound-guided acupuncture treatment and radiation extracorporeal shock wave therapy in myofascial pain syndrome after rotator cuff suture under shoulder arthroscopy.</AbstractText From June 2021 to April 2022, 75 patients with myofascial pain syndrome after rotator cuff suture under shoulder arthroscopy were admitted and divided into musculoskeletal ultrasound group and extracorporeal shock wave group according to different treatment methods. There were 39 patients in musculoskeletal ultrasound group, including 12 males and 27 females, aged from 43 to 77 years old with an average of (56.33±9.45) years old;11 patients on the left side and 28 patients on the right side;the course of disease with a median of 7.00(4.00, 12.00) weeks;acupuncture treatment was performed under the guidance of musculoskeletal ultrasound. There were 36 patients in extracorporeal shock wave group, including 16 males and 20 females, aged from 46 to 72 years old with a median of (58.94±8.94) years old;12 patients on the left side and 24 patients on the right side;the course of disease with an average of 5.50(4.00, 8.00) weeks;extracorporeal shock wave therapy with radiation were performed. Visual analogue scale (VAS) and American shoulder and elbow surgeons score (ASES) were compared between two groups to evaluate improvement of shoulder joint pain and function before treatment and 1, 3, 6, 12, and 24 months after treatment.</AbstractText Both of two groups were followed up for 24 to 27 months with an average of (24.68±0.89) months. No complications such as infection and vascular and nerve injury occurred during follow-up period. At 6 months after treatment, VAS of musculoskeletal ultrasound group (2.00±1.19) was lower than that of extracorporeal shock wave group (3.08±1.02), and the difference was statistically significant (<i Musculoskeletal ultrasound-guided acupuncture treatment has advantages of faster pain relief and more rapid improvement of shoulder joint function for myofascial pain syndrome after rotator cuff suture under shoulder arthroscopy compared with radioactive extracorporeal shock wave therapy.</AbstractText
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The neurofibromatosis type 2 (NF2) gene, known for encoding the tumor suppressor protein Merlin, is central to the study of tumorigenesis and associated cellular processes. This review comprehensively examines the multifaceted role of NF2/Merlin, detailing its structural characteristics, functional diversity, and involvement in various signaling pathways such as Wnt/β-catenin, Hippo, TGF-β, RTKs, mTOR, Notch, and Hedgehog. These pathways are crucial for cellular growth, proliferation, and differentiation. NF2 mutations are specifically linked to the development of schwannomas, meningiomas, and ependymomas, although the precise mechanisms of tumor formation in these specific cell types remain unclear. Additionally, the review explores Merlin's role in embryogenesis, highlighting the severe developmental defects and embryonic lethality caused by NF2 deficiency. The potential therapeutic strategies targeting these genetic aberrations are also discussed, emphasizing inhibitors of mTOR, HDAC, and VEGF as promising avenues for treatment. This synthesis of current knowledge underscores the necessity for ongoing research to elucidate the detailed mechanisms of NF2/Merlin and develop effective therapeutic strategies, ultimately aiming to improve the prognosis and quality of life for individuals with NF2 mutations.</AbstractText
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Variation in infection history is an important but often underappreciated driver of individual variability in responses to infections. Such individual heterogeneity in immune responses, stemming from variable previous exposure to pathogens, subsequently influences epidemiological outcomes. By comparing research on innate immune priming in invertebrates, which lack adaptive immune memory but demonstrate enhanced responses to re-infections, to patterns seen in vertebrates, this Essay reveals broad implications for disease dynamics. Insights from mathematical modelling and experimental data highlight the critical need to integrate evolutionary disease ecology into public health initiatives to better predict and manage infectious diseases.</AbstractText
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[Analysis of rapeutic effect of musculoskeletal ultrasound-guided acupuncture for the treatment of myofascial pain syndrome after rotator cuff suture under shoulder arthroscopy]. To compare clinical efficacy of musculoskeletal ultrasound-guided acupuncture treatment and radiation extracorporeal shock wave therapy in myofascial pain syndrome after rotator cuff suture under shoulder arthroscopy.</AbstractText From June 2021 to April 2022, 75 patients with myofascial pain syndrome after rotator cuff suture under shoulder arthroscopy were admitted and divided into musculoskeletal ultrasound group and extracorporeal shock wave group according to different treatment methods. There were 39 patients in musculoskeletal ultrasound group, including 12 males and 27 females, aged from 43 to 77 years old with an average of (56.33±9.45) years old;11 patients on the left side and 28 patients on the right side;the course of disease with a median of 7.00(4.00, 12.00) weeks;acupuncture treatment was performed under the guidance of musculoskeletal ultrasound. There were 36 patients in extracorporeal shock wave group, including 16 males and 20 females, aged from 46 to 72 years old with a median of (58.94±8.94) years old;12 patients on the left side and 24 patients on the right side;the course of disease with an average of 5.50(4.00, 8.00) weeks;extracorporeal shock wave therapy with radiation were performed. Visual analogue scale (VAS) and American shoulder and elbow surgeons score (ASES) were compared between two groups to evaluate improvement of shoulder joint pain and function before treatment and 1, 3, 6, 12, and 24 months after treatment.</AbstractText Both of two groups were followed up for 24 to 27 months with an average of (24.68±0.89) months. No complications such as infection and vascular and nerve injury occurred during follow-up period. At 6 months after treatment, VAS of musculoskeletal ultrasound group (2.00±1.19) was lower than that of extracorporeal shock wave group (3.08±1.02), and the difference was statistically significant (<i Musculoskeletal ultrasound-guided acupuncture treatment has advantages of faster pain relief and more rapid improvement of shoulder joint function for myofascial pain syndrome after rotator cuff suture under shoulder arthroscopy compared with radioactive extracorporeal shock wave therapy.</AbstractText
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The molecular biology of NF2/Merlin on tumorigenesis and development. The neurofibromatosis type 2 (NF2) gene, known for encoding the tumor suppressor protein Merlin, is central to the study of tumorigenesis and associated cellular processes. This review comprehensively examines the multifaceted role of NF2/Merlin, detailing its structural characteristics, functional diversity, and involvement in various signaling pathways such as Wnt/β-catenin, Hippo, TGF-β, RTKs, mTOR, Notch, and Hedgehog. These pathways are crucial for cellular growth, proliferation, and differentiation. NF2 mutations are specifically linked to the development of schwannomas, meningiomas, and ependymomas, although the precise mechanisms of tumor formation in these specific cell types remain unclear. Additionally, the review explores Merlin's role in embryogenesis, highlighting the severe developmental defects and embryonic lethality caused by NF2 deficiency. The potential therapeutic strategies targeting these genetic aberrations are also discussed, emphasizing inhibitors of mTOR, HDAC, and VEGF as promising avenues for treatment. This synthesis of current knowledge underscores the necessity for ongoing research to elucidate the detailed mechanisms of NF2/Merlin and develop effective therapeutic strategies, ultimately aiming to improve the prognosis and quality of life for individuals with NF2 mutations.</AbstractText
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The ghost of infections past: Accounting for heterogeneity in individual infection history improves accuracy in epidemic forecasting. Variation in infection history is an important but often underappreciated driver of individual variability in responses to infections. Such individual heterogeneity in immune responses, stemming from variable previous exposure to pathogens, subsequently influences epidemiological outcomes. By comparing research on innate immune priming in invertebrates, which lack adaptive immune memory but demonstrate enhanced responses to re-infections, to patterns seen in vertebrates, this Essay reveals broad implications for disease dynamics. Insights from mathematical modelling and experimental data highlight the critical need to integrate evolutionary disease ecology into public health initiatives to better predict and manage infectious diseases.</AbstractText
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37334197
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16389308
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36454259
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C. elegans ATG-5 mutants associated with ataxia.
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The use of the R6 transgenic mouse models of Huntington's disease in attempts to develop novel therapeutic strategies.
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Diagnostic accuracy of ultrasound-based multimodal radiomics modeling for fibrosis detection in chronic kidney disease.
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Intercellular cleaning via autophagy is crucial for maintaining cellular homeostasis, and impaired autophagy has been associated with the accumulation of protein aggregates that can contribute to neurological diseases. Specifically, the loss-of-function mutation in the human autophagy-related gene 5 (ATG5) at E122D has been linked to the pathogenesis of spinocerebellar ataxia in humans. In this study, we generated two homozygous <i
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Huntington's disease (HD) is a genetic neurodegenerative disorder. Since identification of the disease-causing gene in 1993, a number of genetically modified animal models of HD have been generated. The first transgenic mouse models, R6/1 and R6/2 lines, were established 8 years ago. The R6/2 mice have been the best characterized and the most widely used model to study pathogenesis of HD and therapeutic interventions. In the present review, we especially focus on the characteristics of R6 transgenic mouse models and, in greater detail, describe the different therapeutic strategies that have been tested in these mice. We also, at the end, critically assess the relevance of the HD mouse models compared with the human disease and discuss how they can be best used in the future.</AbstractText
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To predict kidney fibrosis in patients with chronic kidney disease using radiomics of two-dimensional ultrasound (B-mode) and Sound Touch Elastography (STE) images in combination with clinical features.</AbstractText The Mindray Resona 7 ultrasonic diagnostic apparatus with SC5-1U convex array probe (bandwidth frequency of 1-5 MHz) was used to perform two-dimensional ultrasound and STE software. The severity of cortical tubulointerstitial fibrosis was divided into three grades: mild interstitial fibrosis and tubular atrophy (IFTA), fibrotic area < 25%; moderate IFTA, fibrotic area 26-50%; and severe IFTA, fibrotic area > 50%. After extracting radiomics from B-mode and STE images in these patients, we analyzed two classification schemes: mild versus moderate-to-severe IFTA, and mild-to-moderate versus severe IFTA. A nomogram was constructed based on multiple logistic regression analyses, combining clinical and radiomics. The performance of the nomogram for differentiation was evaluated using receiver operating characteristic (ROC), calibration, and decision curves.</AbstractText A total of 150 patients undergoing kidney biopsy were enrolled (mild IFTA: n = 74; moderate IFTA: n = 33; severe IFTA: n = 43) and randomized into training (n = 105) and validation cohorts (n = 45). To differentiate between mild and moderate-to-severe IFTA, a nomogram incorporating STE radiomics, albumin, and estimated glomerular filtration (eGFR) rate achieved an area under the ROC curve (AUC) of 0.91 (95% confidence interval [CI]: 0.85-0.97) and 0.85 (95% CI: 0.77-0.98) in the training and validation cohorts, respectively. Between mild-to-moderate and severe IFTA, the nomogram incorporating B-mode and STE radiomics features, age, and eGFR achieved an AUC of 0.93 (95% CI: 0.89-0.98) and 0.83 (95% CI: 0.70-0.95) in the training and validation cohorts, respectively. Finally, we performed a decision curve analysis and found that the nomogram using both radiomics and clinical features exhibited better predictability than any other model (DeLong test, p < 0.05 for the training and validation cohorts).</AbstractText A nomogram based on two-dimensional ultrasound and STE radiomics and clinical features served as a non-invasive tool capable of differentiating kidney fibrosis of different severities.</AbstractText • Radiomics calculated based on the ultrasound imaging may be used to predict the severities of kidney fibrosis. • Radiomics may be used to identify clinical features associated with the progression of tubulointerstitial fibrosis in patients with CKD. • Non-invasive ultrasound imaging-based radiomics method with accuracy aids in detecting renal fibrosis with different IFTA severities.</AbstractText
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C. elegans ATG-5 mutants associated with ataxia. Intercellular cleaning via autophagy is crucial for maintaining cellular homeostasis, and impaired autophagy has been associated with the accumulation of protein aggregates that can contribute to neurological diseases. Specifically, the loss-of-function mutation in the human autophagy-related gene 5 (ATG5) at E122D has been linked to the pathogenesis of spinocerebellar ataxia in humans. In this study, we generated two homozygous <i
|
The use of the R6 transgenic mouse models of Huntington's disease in attempts to develop novel therapeutic strategies. Huntington's disease (HD) is a genetic neurodegenerative disorder. Since identification of the disease-causing gene in 1993, a number of genetically modified animal models of HD have been generated. The first transgenic mouse models, R6/1 and R6/2 lines, were established 8 years ago. The R6/2 mice have been the best characterized and the most widely used model to study pathogenesis of HD and therapeutic interventions. In the present review, we especially focus on the characteristics of R6 transgenic mouse models and, in greater detail, describe the different therapeutic strategies that have been tested in these mice. We also, at the end, critically assess the relevance of the HD mouse models compared with the human disease and discuss how they can be best used in the future.</AbstractText
|
Diagnostic accuracy of ultrasound-based multimodal radiomics modeling for fibrosis detection in chronic kidney disease. To predict kidney fibrosis in patients with chronic kidney disease using radiomics of two-dimensional ultrasound (B-mode) and Sound Touch Elastography (STE) images in combination with clinical features.</AbstractText The Mindray Resona 7 ultrasonic diagnostic apparatus with SC5-1U convex array probe (bandwidth frequency of 1-5 MHz) was used to perform two-dimensional ultrasound and STE software. The severity of cortical tubulointerstitial fibrosis was divided into three grades: mild interstitial fibrosis and tubular atrophy (IFTA), fibrotic area < 25%; moderate IFTA, fibrotic area 26-50%; and severe IFTA, fibrotic area > 50%. After extracting radiomics from B-mode and STE images in these patients, we analyzed two classification schemes: mild versus moderate-to-severe IFTA, and mild-to-moderate versus severe IFTA. A nomogram was constructed based on multiple logistic regression analyses, combining clinical and radiomics. The performance of the nomogram for differentiation was evaluated using receiver operating characteristic (ROC), calibration, and decision curves.</AbstractText A total of 150 patients undergoing kidney biopsy were enrolled (mild IFTA: n = 74; moderate IFTA: n = 33; severe IFTA: n = 43) and randomized into training (n = 105) and validation cohorts (n = 45). To differentiate between mild and moderate-to-severe IFTA, a nomogram incorporating STE radiomics, albumin, and estimated glomerular filtration (eGFR) rate achieved an area under the ROC curve (AUC) of 0.91 (95% confidence interval [CI]: 0.85-0.97) and 0.85 (95% CI: 0.77-0.98) in the training and validation cohorts, respectively. Between mild-to-moderate and severe IFTA, the nomogram incorporating B-mode and STE radiomics features, age, and eGFR achieved an AUC of 0.93 (95% CI: 0.89-0.98) and 0.83 (95% CI: 0.70-0.95) in the training and validation cohorts, respectively. Finally, we performed a decision curve analysis and found that the nomogram using both radiomics and clinical features exhibited better predictability than any other model (DeLong test, p < 0.05 for the training and validation cohorts).</AbstractText A nomogram based on two-dimensional ultrasound and STE radiomics and clinical features served as a non-invasive tool capable of differentiating kidney fibrosis of different severities.</AbstractText • Radiomics calculated based on the ultrasound imaging may be used to predict the severities of kidney fibrosis. • Radiomics may be used to identify clinical features associated with the progression of tubulointerstitial fibrosis in patients with CKD. • Non-invasive ultrasound imaging-based radiomics method with accuracy aids in detecting renal fibrosis with different IFTA severities.</AbstractText
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38781152
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30104762
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37812733
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Brain health index as a predictor of possible vascular dementia in the Mexican health and aging study 2012-2015.
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Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations.
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Computed tomography dose index determination in dose modulation prospectively involving the third-generation iterative reconstruction and noise index.
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To determine the burden of disease among subjects at risk of developing stroke or dementia, brain health indexes (BHI) tend to rely on anatomical features. Recent definitions emphasize the need of a broader perspective that encompasses cardiovascular risk factors (CVRFS) and lifestyle components which can be considered partial contributors to optimal brain health. In this study, we aimed to establish the association and risk detected by a Brain Health Index and the risk of possible vascular dementia (PVD) using data from the Mexican Health and Aging Study (MHAS) 2012-2015. The MHAS is a longitudinal study of adults aged ≥ 50 years. We analyzed the data obtained between 2012 and 2015. CVRFS included in the index were diabetes mellitus, hypertension, myocardial infarction, depression, obesity, physical inactivity, and smoking history. A PVD diagnosis was established when scores in the Cross-Cultural Cognitive Examination were below reference norms and limitations in ≥1 instrumental activities of daily living and a history of stroke were present. A multinomial regression model was developed to determine the association between BHI scores and PVD. In 2015, 75 PVD cases were identified. Mean age was 67.1 ±13.2 years, 35.8% were female, and the mean educational level was 5.8 ±5.5 years. In cases with a higher score in the BHI, the model revealed a hazards ratio of 1.63 (95% CI: 1.63-1.64, p< 0.001) for PVD. In this longitudinal study, with the use of a feasible multifactorial BHI in the Mexican population, a greater score was associated with a 1.63-fold risk of developing PVD during the 3-year follow-up, while the risk for stroke was 1.75. This index could potentially be used to predict the risk of PVD in adults with modifiable CVRFS.</AbstractText
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A key public health need is to identify individuals at high risk for a given disease to enable enhanced screening or preventive therapies. Because most common diseases have a genetic component, one important approach is to stratify individuals based on inherited DNA variation<sup
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Optimizing CT protocols is challenging in the presence of automatic dose modulation because the CT dose index (CTDI<sub Dose modulation data were collected on a GE Revolution 256-slice scanner utilizing a Mercury phantom and selections of the noise index (NI) from 8 to 17, the third generation iterative reconstruction (ASIR-V) from 0% to 80%, and phantom diameters from 16 to 36 cm. The fixed parameters were 120 kVp, a pitch of .984, and a collimation of 40 mm with a primary slice width of 2.5 mm. The CTDI<sub The ASIR-V fit parameters versus diameter followed a Lorentz function while the NI exponent versus diameter followed an exponential growth function. The CTDI<sub The fitted relationship for CTDI<sub
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Brain health index as a predictor of possible vascular dementia in the Mexican health and aging study 2012-2015. To determine the burden of disease among subjects at risk of developing stroke or dementia, brain health indexes (BHI) tend to rely on anatomical features. Recent definitions emphasize the need of a broader perspective that encompasses cardiovascular risk factors (CVRFS) and lifestyle components which can be considered partial contributors to optimal brain health. In this study, we aimed to establish the association and risk detected by a Brain Health Index and the risk of possible vascular dementia (PVD) using data from the Mexican Health and Aging Study (MHAS) 2012-2015. The MHAS is a longitudinal study of adults aged ≥ 50 years. We analyzed the data obtained between 2012 and 2015. CVRFS included in the index were diabetes mellitus, hypertension, myocardial infarction, depression, obesity, physical inactivity, and smoking history. A PVD diagnosis was established when scores in the Cross-Cultural Cognitive Examination were below reference norms and limitations in ≥1 instrumental activities of daily living and a history of stroke were present. A multinomial regression model was developed to determine the association between BHI scores and PVD. In 2015, 75 PVD cases were identified. Mean age was 67.1 ±13.2 years, 35.8% were female, and the mean educational level was 5.8 ±5.5 years. In cases with a higher score in the BHI, the model revealed a hazards ratio of 1.63 (95% CI: 1.63-1.64, p< 0.001) for PVD. In this longitudinal study, with the use of a feasible multifactorial BHI in the Mexican population, a greater score was associated with a 1.63-fold risk of developing PVD during the 3-year follow-up, while the risk for stroke was 1.75. This index could potentially be used to predict the risk of PVD in adults with modifiable CVRFS.</AbstractText
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Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. A key public health need is to identify individuals at high risk for a given disease to enable enhanced screening or preventive therapies. Because most common diseases have a genetic component, one important approach is to stratify individuals based on inherited DNA variation<sup
|
Computed tomography dose index determination in dose modulation prospectively involving the third-generation iterative reconstruction and noise index. Optimizing CT protocols is challenging in the presence of automatic dose modulation because the CT dose index (CTDI<sub Dose modulation data were collected on a GE Revolution 256-slice scanner utilizing a Mercury phantom and selections of the noise index (NI) from 8 to 17, the third generation iterative reconstruction (ASIR-V) from 0% to 80%, and phantom diameters from 16 to 36 cm. The fixed parameters were 120 kVp, a pitch of .984, and a collimation of 40 mm with a primary slice width of 2.5 mm. The CTDI<sub The ASIR-V fit parameters versus diameter followed a Lorentz function while the NI exponent versus diameter followed an exponential growth function. The CTDI<sub The fitted relationship for CTDI<sub
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39276720
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30620687
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37647984
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Prominent loss of striatal dopamine transporter binding in frontotemporal lobar degeneration with the MAPT N279K mutation present as early as at prodromal stage without parkinsonism.
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Spinal cord involvement in Lewy body-related α-synucleinopathies.
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Insights into plant salt stress signaling and tolerance.
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Our research found out, from <sup
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<b
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Soil salinization is an essential environmental stressor, threatening agricultural yield and ecological security worldwide. Saline soils accumulate excessive soluble salts which are detrimental to most plants by limiting plant growth and productivity. It is of great necessity for plants to efficiently deal with the adverse effects caused by salt stress for survival and successful reproduction. Multiple determinants of salt tolerance have been identified in plants, and the cellular and physiological mechanisms of plant salt response and adaption have been intensely characterized. Plants respond to salt stress signals and rapidly initiate signaling pathways to re-establish cellular homeostasis with adjusted growth and cellular metabolism. This review summarizes the advances in salt stress perception, signaling, and response in plants. A better understanding of plant salt resistance will contribute to improving crop performance under saline conditions using multiple engineering approaches. The rhizosphere microbiome-mediated plant salt tolerance as well as chemical priming for enhanced plant salt resistance are also discussed in this review.</AbstractText
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Prominent loss of striatal dopamine transporter binding in frontotemporal lobar degeneration with the MAPT N279K mutation present as early as at prodromal stage without parkinsonism. Our research found out, from <sup
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Spinal cord involvement in Lewy body-related α-synucleinopathies. <b
|
Insights into plant salt stress signaling and tolerance. Soil salinization is an essential environmental stressor, threatening agricultural yield and ecological security worldwide. Saline soils accumulate excessive soluble salts which are detrimental to most plants by limiting plant growth and productivity. It is of great necessity for plants to efficiently deal with the adverse effects caused by salt stress for survival and successful reproduction. Multiple determinants of salt tolerance have been identified in plants, and the cellular and physiological mechanisms of plant salt response and adaption have been intensely characterized. Plants respond to salt stress signals and rapidly initiate signaling pathways to re-establish cellular homeostasis with adjusted growth and cellular metabolism. This review summarizes the advances in salt stress perception, signaling, and response in plants. A better understanding of plant salt resistance will contribute to improving crop performance under saline conditions using multiple engineering approaches. The rhizosphere microbiome-mediated plant salt tolerance as well as chemical priming for enhanced plant salt resistance are also discussed in this review.</AbstractText
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40411939
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39371035
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40693647
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Epidemiology of adult brain tumors in the Philippine General Hospital from 2018 to 2022: Initial steps to a national brain tumor registry in a lower-middle income country.
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CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2017-2021.
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Efficacy of Low-Dose BoNT-A Acupoint Injections in Managing Headache, Vertigo, and Allodynia in Vestibular Migraine.
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In the Philippines, there is a lack of epidemiological data on brain tumors due to the absence of a national registry. To bridge this gap, our team has set out to review histopathologically-confirmed brain tumor cases from 2018 to 2022 at the largest neurosurgical center in the country. 766 brain tumor cases were identified: 115 in 2018, 173 in 2019, 143 in 2020, 148 in 2021, and 187 in 2022. The crude incidences per year were 0.39, 0.58, 0.48, 0.50 and 0.66 per 100,000 from 2018 to 2022, respectively. The 5-year crude incidence rate was 2.58 per 100,000 persons. The five-year prevalence was 115.00, 266.00, 367.48, 456.39, and 566.30. Among patients, the mean age was 49 years old, with a male:female ratio of 2:3. Most cases were among the 51-60 age group (23.6 %). The most common types were meningioma (46 %) and gliomas, glioneuronal tumors, and neuronal tumors (23 %). Metastasis to the brain accounted for 6.5 % of all brain tumors. In our study, prevalence estimates were lower than globally-reported ones, likely due to its single-center nature. Tumor types approximated international reports, except for brain metastasis frequency. This initial work is a stepping stone for a future national brain tumor registry for the Philippines.</AbstractText
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The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention and the National Cancer Institute, is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors available and supersedes all previous reports in terms of completeness and accuracy. All rates are age-adjusted using the 2000 US standard population and presented per 100,000 population. Between 2017 and 2021, the average annual age-adjusted incidence rate (AAAIR) of all primary malignant and non-malignant brain and other CNS tumors was 25.34 per 100,000 population (malignant AAAIR=6.89 and non-malignant AAAIR=18.46). This overall rate was higher in females compared to males (28.77 versus 21.78 per 100,000) and non-Hispanic Black persons compared to persons who were non-Hispanic White (26.60 versus 25.72 per 100,000), non-Hispanic American Indian/Alaska Native (23.48 per 100,000), non-Hispanic Asian or Pacific Islander (19.86 per 100,000), and Hispanic persons of all races (22.37 per 100,000). Gliomas accounted for 22.9% of all tumors. The most commonly occurring malignant brain and other CNS histopathology was glioblastoma (13.9% of all tumors and 51.5% of all malignant tumors), and the most common predominantly non-malignant histopathology was meningioma (41.7% of all tumors and 56.8% of all non-malignant tumors). Glioblastomas were more common in males, and meningiomas were more common in females. In children and adolescents (ages 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.02 per 100,000 population. There were 87,053 deaths attributed to malignant brain and other CNS tumors between 2017 and 2021. This represents an average annual mortality rate of 4.41 per 100,000 population and an average of 17,411 deaths per year. The five-year relative survival rate following diagnosis of a malignant brain or other CNS tumor was 35.7%. For a non-malignant brain or other CNS tumor the five-year relative survival rate was 92.0%.</AbstractText
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BACKGROUND: This study examines low-dose botulinum toxin at acupuncture points for its effects on vestibular symptoms, headaches, depression, anxiety, and stress in vestibular migraine patients. METHODS: This prospective study included patients with vestibular migraine per Barany Society criteria. Fifty units of Onabotulinum toxin were injected using a 31-gauge needle at 5 units/0.1 mL, diluted from 100 units with 2 mL of 0.9% sodium chloride. The injections were given at predetermined acupuncture points: Yintang (EX-HN3), Taiyang (EX-HN5), Baihui (GV20), Shuaigu (GB8), Fengchi (GB20), and Tianzhu (BL10). Six-month follow-up assessments included assessments using the Migraine Disability Assessment Scale (MIDAS), Dizziness Handicap Inventory-Screening Form (DHI-S), Vertigo Symptom Scale-Short Form (VSS-SF), Depression Anxiety Stress Scale (DASS-21), and Allodynia Symptom Checklist (ASC-12). RESULTS: Statistically significant improvements were observed in MIDAS, VSS-SF, DHI-S, and DASS-21 scores at both 3 and 6 months (P < .05). CONCLUSION: Application of Onabotulinum toxin A (BoNT-A) to acupuncture points alleviated headache, vestibular symptoms, and anxiety, with benefits persisting for up to 6 months.</AbstractText
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Epidemiology of adult brain tumors in the Philippine General Hospital from 2018 to 2022: Initial steps to a national brain tumor registry in a lower-middle income country. In the Philippines, there is a lack of epidemiological data on brain tumors due to the absence of a national registry. To bridge this gap, our team has set out to review histopathologically-confirmed brain tumor cases from 2018 to 2022 at the largest neurosurgical center in the country. 766 brain tumor cases were identified: 115 in 2018, 173 in 2019, 143 in 2020, 148 in 2021, and 187 in 2022. The crude incidences per year were 0.39, 0.58, 0.48, 0.50 and 0.66 per 100,000 from 2018 to 2022, respectively. The 5-year crude incidence rate was 2.58 per 100,000 persons. The five-year prevalence was 115.00, 266.00, 367.48, 456.39, and 566.30. Among patients, the mean age was 49 years old, with a male:female ratio of 2:3. Most cases were among the 51-60 age group (23.6 %). The most common types were meningioma (46 %) and gliomas, glioneuronal tumors, and neuronal tumors (23 %). Metastasis to the brain accounted for 6.5 % of all brain tumors. In our study, prevalence estimates were lower than globally-reported ones, likely due to its single-center nature. Tumor types approximated international reports, except for brain metastasis frequency. This initial work is a stepping stone for a future national brain tumor registry for the Philippines.</AbstractText
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CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2017-2021. The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention and the National Cancer Institute, is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors available and supersedes all previous reports in terms of completeness and accuracy. All rates are age-adjusted using the 2000 US standard population and presented per 100,000 population. Between 2017 and 2021, the average annual age-adjusted incidence rate (AAAIR) of all primary malignant and non-malignant brain and other CNS tumors was 25.34 per 100,000 population (malignant AAAIR=6.89 and non-malignant AAAIR=18.46). This overall rate was higher in females compared to males (28.77 versus 21.78 per 100,000) and non-Hispanic Black persons compared to persons who were non-Hispanic White (26.60 versus 25.72 per 100,000), non-Hispanic American Indian/Alaska Native (23.48 per 100,000), non-Hispanic Asian or Pacific Islander (19.86 per 100,000), and Hispanic persons of all races (22.37 per 100,000). Gliomas accounted for 22.9% of all tumors. The most commonly occurring malignant brain and other CNS histopathology was glioblastoma (13.9% of all tumors and 51.5% of all malignant tumors), and the most common predominantly non-malignant histopathology was meningioma (41.7% of all tumors and 56.8% of all non-malignant tumors). Glioblastomas were more common in males, and meningiomas were more common in females. In children and adolescents (ages 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.02 per 100,000 population. There were 87,053 deaths attributed to malignant brain and other CNS tumors between 2017 and 2021. This represents an average annual mortality rate of 4.41 per 100,000 population and an average of 17,411 deaths per year. The five-year relative survival rate following diagnosis of a malignant brain or other CNS tumor was 35.7%. For a non-malignant brain or other CNS tumor the five-year relative survival rate was 92.0%.</AbstractText
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Efficacy of Low-Dose BoNT-A Acupoint Injections in Managing Headache, Vertigo, and Allodynia in Vestibular Migraine. BACKGROUND: This study examines low-dose botulinum toxin at acupuncture points for its effects on vestibular symptoms, headaches, depression, anxiety, and stress in vestibular migraine patients. METHODS: This prospective study included patients with vestibular migraine per Barany Society criteria. Fifty units of Onabotulinum toxin were injected using a 31-gauge needle at 5 units/0.1 mL, diluted from 100 units with 2 mL of 0.9% sodium chloride. The injections were given at predetermined acupuncture points: Yintang (EX-HN3), Taiyang (EX-HN5), Baihui (GV20), Shuaigu (GB8), Fengchi (GB20), and Tianzhu (BL10). Six-month follow-up assessments included assessments using the Migraine Disability Assessment Scale (MIDAS), Dizziness Handicap Inventory-Screening Form (DHI-S), Vertigo Symptom Scale-Short Form (VSS-SF), Depression Anxiety Stress Scale (DASS-21), and Allodynia Symptom Checklist (ASC-12). RESULTS: Statistically significant improvements were observed in MIDAS, VSS-SF, DHI-S, and DASS-21 scores at both 3 and 6 months (P < .05). CONCLUSION: Application of Onabotulinum toxin A (BoNT-A) to acupuncture points alleviated headache, vestibular symptoms, and anxiety, with benefits persisting for up to 6 months.</AbstractText
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36924807
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30394561
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37718484
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Characterization of motion dependent magnetic field inhomogeneity for DWI in the kidneys.
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Evaluating corrections for Eddy-currents and other EPI distortions in diffusion MRI: methodology and a dataset for benchmarking.
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Treatment resistance in schizophrenia: a meta-analysis of prevalence and correlates.
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Diffusion-weighted imaging (DWI) of the abdomen has increased dramatically for both research and clinical purposes. Motion and static field inhomogeneity related challenges limit image quality of abdominopelvic imaging with the most conventional echo-planar imaging (EPI) pulse sequence. While reversed phase encoded imaging is increasingly used to facilitate distortion correction, it typically assumes one motion independent magnetic field distribution. In this study, we describe a more generalized workflow for the case of kidney DWI in which the field inhomogeneity at multiple respiratory phases is mapped and used to correct all images in a multi-contrast DWI series.</AbstractText In this HIPAA-compliant and IRB-approved prospective study, 8 volunteers (6 M, ages 28-51) had abdominal imaging performed in a 3 T MRI system (MAGNETOM Prisma; Siemens Healthcare, Erlangen, Germany) with ECG gating. Coronal oblique T2-weighted HASTE images were collected for anatomical reference. Sagittal phase-contrast (PC) MRI images through the left renal artery were collected to determine systolic and diastolic phases. Cardiac triggered oblique coronal DWI were collected at 10 b-values between 0 and 800 s/mm2 and 12 directions. DWI series were distortion corrected using field maps generated by forward and reversed phase encoded b = 0 images collected over the full respiratory cycle and matched by respiratory phase. Morphologic accuracy, intraseries spatial variability, and diffusion tensor imaging (DTI) metrics mean diffusivity (MD) and fractional anisotropy (FA) were compared for results generated with no distortion correction, correction with only one respiratory bin, and correction with multiple respiratory bins across the breathing cycle.</AbstractText Computed field maps showed significant variation in static field with kidney laterality, region, and respiratory phase. Distortion corrected images showed significantly better registration to morphologic images than uncorrected images; for the left kidney, the multiple bin correction outperformed one bin correction. Line profile analysis showed significantly reduced spatial variation with multiple bins than one bin correction. DTI metrics were mostly similar between correction methods, with some differences observed in MD between uncorrected and corrected datasets.</AbstractText Our results indicate improved morphology of kidney DWI and derived parametric maps as well as reduced variability over the full image series using the motion-resolved distortion correction. This work highlights some morphologic and quantitative metric improvements can be obtained for kidney DWI when distortion correction is performed in a respiratory-resolved manner.</AbstractText
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To propose a methodology for assessment of algorithms that correct distortions due to motion, eddy-currents, and echo planar imaging in diffusion weighted images (DWIs).</AbstractText The proposed method evaluates correction performance by measuring variability across datasets of the same object acquired with images having distortions in different directions, thereby overcoming the unavailability of ground-truth, undistorted DWIs. A comprehensive diffusion MRI dataset, collected using a suitable experimental design, is made available to the scientific community, consisting of three DWI shells (Bmax = 5000 s/mm<sup The median variability of the original distorted data was 123% higher for DWIs, 100-168% higher for tensor-derived metrics and 28-111% higher for MAPMRI metrics, than in the corrected versions. EPI distortions induced substantial variability, nearly comparable to the contribution of eddy-current distortions.</AbstractText The dataset and the evaluation strategy proposed herein enable quantitative comparison of different methods for correction of distortions due to motion, eddy-currents, and other EPI distortions, and can be useful in benchmarking newly developed algorithms.</AbstractText
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To determine the prevalence and correlates of treatment-resistant schizophrenia (TRS) through a systematic review and meta-analysis.</AbstractText Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, an electronic search was performed in PubMed and Embase through May 17, 2022. All study designs that assessed a minimum of 20 schizophrenia-spectrum patients and provided data on TRS prevalence or allowed its calculation were included. Estimates were produced using a random-effects model meta-analysis.</AbstractText The TRS prevalence across 50 studies (n = 29,390) was 36.7% (95%CI 33.1-40.5, p < 0.0001). The prevalence ranged from 22% (95%CI 18.4-25.8) in first-episode to 39.5% (95%CI 32.2-47.0) in multiple-episode samples (Q = 18.27, p < 0.0001). Primary treatment resistance, defined as no response from the first episode, was 23.6% (95%CI 20.5-26.8) vs. 9.3% (95%CI 6.8-12.2) for later-onset/secondary (≥ 6 months after initial treatment response). Longer illness duration and recruitment from long-term hospitals or clozapine clinics were associated with higher prevalence estimates. In meta-regression analyses, older age and poor functioning predicted greater TRS. When including only studies with lower bias risk, the TRS prevalence was 28.4%.</AbstractText Different study designs and recruitment strategies accounted for most of the observed heterogeneity in TRS prevalence rates. The results point to early-onset and later-onset TRS as two separate disease pathways requiring clinical attention.</AbstractText
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Characterization of motion dependent magnetic field inhomogeneity for DWI in the kidneys. Diffusion-weighted imaging (DWI) of the abdomen has increased dramatically for both research and clinical purposes. Motion and static field inhomogeneity related challenges limit image quality of abdominopelvic imaging with the most conventional echo-planar imaging (EPI) pulse sequence. While reversed phase encoded imaging is increasingly used to facilitate distortion correction, it typically assumes one motion independent magnetic field distribution. In this study, we describe a more generalized workflow for the case of kidney DWI in which the field inhomogeneity at multiple respiratory phases is mapped and used to correct all images in a multi-contrast DWI series.</AbstractText In this HIPAA-compliant and IRB-approved prospective study, 8 volunteers (6 M, ages 28-51) had abdominal imaging performed in a 3 T MRI system (MAGNETOM Prisma; Siemens Healthcare, Erlangen, Germany) with ECG gating. Coronal oblique T2-weighted HASTE images were collected for anatomical reference. Sagittal phase-contrast (PC) MRI images through the left renal artery were collected to determine systolic and diastolic phases. Cardiac triggered oblique coronal DWI were collected at 10 b-values between 0 and 800 s/mm2 and 12 directions. DWI series were distortion corrected using field maps generated by forward and reversed phase encoded b = 0 images collected over the full respiratory cycle and matched by respiratory phase. Morphologic accuracy, intraseries spatial variability, and diffusion tensor imaging (DTI) metrics mean diffusivity (MD) and fractional anisotropy (FA) were compared for results generated with no distortion correction, correction with only one respiratory bin, and correction with multiple respiratory bins across the breathing cycle.</AbstractText Computed field maps showed significant variation in static field with kidney laterality, region, and respiratory phase. Distortion corrected images showed significantly better registration to morphologic images than uncorrected images; for the left kidney, the multiple bin correction outperformed one bin correction. Line profile analysis showed significantly reduced spatial variation with multiple bins than one bin correction. DTI metrics were mostly similar between correction methods, with some differences observed in MD between uncorrected and corrected datasets.</AbstractText Our results indicate improved morphology of kidney DWI and derived parametric maps as well as reduced variability over the full image series using the motion-resolved distortion correction. This work highlights some morphologic and quantitative metric improvements can be obtained for kidney DWI when distortion correction is performed in a respiratory-resolved manner.</AbstractText
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Evaluating corrections for Eddy-currents and other EPI distortions in diffusion MRI: methodology and a dataset for benchmarking. To propose a methodology for assessment of algorithms that correct distortions due to motion, eddy-currents, and echo planar imaging in diffusion weighted images (DWIs).</AbstractText The proposed method evaluates correction performance by measuring variability across datasets of the same object acquired with images having distortions in different directions, thereby overcoming the unavailability of ground-truth, undistorted DWIs. A comprehensive diffusion MRI dataset, collected using a suitable experimental design, is made available to the scientific community, consisting of three DWI shells (Bmax = 5000 s/mm<sup The median variability of the original distorted data was 123% higher for DWIs, 100-168% higher for tensor-derived metrics and 28-111% higher for MAPMRI metrics, than in the corrected versions. EPI distortions induced substantial variability, nearly comparable to the contribution of eddy-current distortions.</AbstractText The dataset and the evaluation strategy proposed herein enable quantitative comparison of different methods for correction of distortions due to motion, eddy-currents, and other EPI distortions, and can be useful in benchmarking newly developed algorithms.</AbstractText
|
Treatment resistance in schizophrenia: a meta-analysis of prevalence and correlates. To determine the prevalence and correlates of treatment-resistant schizophrenia (TRS) through a systematic review and meta-analysis.</AbstractText Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, an electronic search was performed in PubMed and Embase through May 17, 2022. All study designs that assessed a minimum of 20 schizophrenia-spectrum patients and provided data on TRS prevalence or allowed its calculation were included. Estimates were produced using a random-effects model meta-analysis.</AbstractText The TRS prevalence across 50 studies (n = 29,390) was 36.7% (95%CI 33.1-40.5, p < 0.0001). The prevalence ranged from 22% (95%CI 18.4-25.8) in first-episode to 39.5% (95%CI 32.2-47.0) in multiple-episode samples (Q = 18.27, p < 0.0001). Primary treatment resistance, defined as no response from the first episode, was 23.6% (95%CI 20.5-26.8) vs. 9.3% (95%CI 6.8-12.2) for later-onset/secondary (≥ 6 months after initial treatment response). Longer illness duration and recruitment from long-term hospitals or clozapine clinics were associated with higher prevalence estimates. In meta-regression analyses, older age and poor functioning predicted greater TRS. When including only studies with lower bias risk, the TRS prevalence was 28.4%.</AbstractText Different study designs and recruitment strategies accounted for most of the observed heterogeneity in TRS prevalence rates. The results point to early-onset and later-onset TRS as two separate disease pathways requiring clinical attention.</AbstractText
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24319599
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19395674
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24075840
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Making memories: the development of long-term visual knowledge in children with visual agnosia.
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The ITP syndrome: pathogenic and clinical diversity.
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Solid-state NMR investigations of peptide-lipid interactions of the transmembrane domain of a plant-derived protein, Hcf106.
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There are few reports about the effects of perinatal acquired brain lesions on the development of visual perception. These studies demonstrate nonseverely impaired visual-spatial abilities and preserved visual memory. Longitudinal data analyzing the effects of compromised perceptions on long-term visual knowledge in agnosics are limited to lesions having occurred in adulthood. The study of children with focal lesions of the visual pathways provides a unique opportunity to assess the development of visual memory when perceptual input is degraded. We assessed visual recognition and visual memory in three children with lesions to the visual cortex having occurred in early infancy. We then explored the time course of visual memory impairment in two of them at 2  years and 3.7  years from the initial assessment. All children exhibited apperceptive visual agnosia and visual memory impairment. We observed a longitudinal improvement of visual memory modulated by the structural properties of objects. Our findings indicate that processing of degraded perceptions from birth results in impoverished memories. The dynamic interaction between perception and memory during development might modulate the long-term construction of visual representations, resulting in less severe impairment.</AbstractText
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Immune thrombocytopenia (ITP) is mediated by platelet autoantibodies that accelerate platelet destruction and inhibit their production. Most cases are considered idiopathic, whereas others are secondary to coexisting conditions. Insights from secondary forms suggest that the proclivity to develop platelet-reactive antibodies arises through diverse mechanisms. Variability in natural history and response to therapy suggests that primary ITP is also heterogeneous. Certain cases may be secondary to persistent, sometimes inapparent, infections, accompanied by coexisting antibodies that influence outcome. Alternatively, underlying immune deficiencies may emerge. In addition, environmental and genetic factors may impact platelet turnover, propensity to bleed, and response to ITP-directed therapy. We review the pathophysiology of several common secondary forms of ITP. We suggest that primary ITP is also best thought of as an autoimmune syndrome. Better understanding of pathogenesis and tolerance checkpoint defects leading to autoantibody formation may facilitate patient-specific approaches to diagnosis and management.</AbstractText
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The chloroplast twin arginine translocation system transports highly folded precursor proteins across the thylakoid using the protonmotive force as its only energy source. Hcf106 and another thylakoid protein, cpTatC compose the precursor receptor complex. Hcf106 is predicted to contain a single amino terminal transmembrane domain (TMD) followed by a Pro-Gly hinge, an amphipathic α-helix, and a loosely structured carboxyl terminus. Hcf106 has been shown biochemically to insert spontaneously into thylakoid membranes; however, how this occurs is not understood. To investigate how Hcf106 inserts itself into the membrane unassisted, solid-state NMR spectroscopy was used to investigate the membrane activity of the TMD. A synthetic peptide of the Hcf106 TMD was incorporated into multilamellar vesicles made of 100% 1-palmitoyl-2-oleoyl-sn-glycero-phosphocholine (POPC) or 85%:15% ratio with monogalactosyl diacylglycerol (POPC/MGDG) to probe peptide-lipid interaction. Solid-state (31)P NMR and (2)H NMR spectroscopic techniques were used to reveal peptide perturbations of the phospholipid membranes. Changes in spectral lineshape, chemical shift anisotropy width, (31)P T1 relaxation time and SCD order parameters demonstrated that the Hcf106 TMD peptide interacted with the phospholipids. Furthermore, the comparison between POPC and POPC/MGDG multilamellar vesicles indicated that lipid bilayer composition affected the peptide-lipid interaction with the peptide interacting preferentially with vesicles that more closely mimic the thylakoid.</AbstractText
|
Making memories: the development of long-term visual knowledge in children with visual agnosia. There are few reports about the effects of perinatal acquired brain lesions on the development of visual perception. These studies demonstrate nonseverely impaired visual-spatial abilities and preserved visual memory. Longitudinal data analyzing the effects of compromised perceptions on long-term visual knowledge in agnosics are limited to lesions having occurred in adulthood. The study of children with focal lesions of the visual pathways provides a unique opportunity to assess the development of visual memory when perceptual input is degraded. We assessed visual recognition and visual memory in three children with lesions to the visual cortex having occurred in early infancy. We then explored the time course of visual memory impairment in two of them at 2  years and 3.7  years from the initial assessment. All children exhibited apperceptive visual agnosia and visual memory impairment. We observed a longitudinal improvement of visual memory modulated by the structural properties of objects. Our findings indicate that processing of degraded perceptions from birth results in impoverished memories. The dynamic interaction between perception and memory during development might modulate the long-term construction of visual representations, resulting in less severe impairment.</AbstractText
|
The ITP syndrome: pathogenic and clinical diversity. Immune thrombocytopenia (ITP) is mediated by platelet autoantibodies that accelerate platelet destruction and inhibit their production. Most cases are considered idiopathic, whereas others are secondary to coexisting conditions. Insights from secondary forms suggest that the proclivity to develop platelet-reactive antibodies arises through diverse mechanisms. Variability in natural history and response to therapy suggests that primary ITP is also heterogeneous. Certain cases may be secondary to persistent, sometimes inapparent, infections, accompanied by coexisting antibodies that influence outcome. Alternatively, underlying immune deficiencies may emerge. In addition, environmental and genetic factors may impact platelet turnover, propensity to bleed, and response to ITP-directed therapy. We review the pathophysiology of several common secondary forms of ITP. We suggest that primary ITP is also best thought of as an autoimmune syndrome. Better understanding of pathogenesis and tolerance checkpoint defects leading to autoantibody formation may facilitate patient-specific approaches to diagnosis and management.</AbstractText
|
Solid-state NMR investigations of peptide-lipid interactions of the transmembrane domain of a plant-derived protein, Hcf106. The chloroplast twin arginine translocation system transports highly folded precursor proteins across the thylakoid using the protonmotive force as its only energy source. Hcf106 and another thylakoid protein, cpTatC compose the precursor receptor complex. Hcf106 is predicted to contain a single amino terminal transmembrane domain (TMD) followed by a Pro-Gly hinge, an amphipathic α-helix, and a loosely structured carboxyl terminus. Hcf106 has been shown biochemically to insert spontaneously into thylakoid membranes; however, how this occurs is not understood. To investigate how Hcf106 inserts itself into the membrane unassisted, solid-state NMR spectroscopy was used to investigate the membrane activity of the TMD. A synthetic peptide of the Hcf106 TMD was incorporated into multilamellar vesicles made of 100% 1-palmitoyl-2-oleoyl-sn-glycero-phosphocholine (POPC) or 85%:15% ratio with monogalactosyl diacylglycerol (POPC/MGDG) to probe peptide-lipid interaction. Solid-state (31)P NMR and (2)H NMR spectroscopic techniques were used to reveal peptide perturbations of the phospholipid membranes. Changes in spectral lineshape, chemical shift anisotropy width, (31)P T1 relaxation time and SCD order parameters demonstrated that the Hcf106 TMD peptide interacted with the phospholipids. Furthermore, the comparison between POPC and POPC/MGDG multilamellar vesicles indicated that lipid bilayer composition affected the peptide-lipid interaction with the peptide interacting preferentially with vesicles that more closely mimic the thylakoid.</AbstractText
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16834334
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11234013
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16360124
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Andersen's syndrome mutation effects on the structure and assembly of the cytoplasmic domains of Kir2.1.
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A sodium-channel mutation causes isolated cardiac conduction disease.
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Desensitization of 5-HT2A receptor function by chronic administration of selective serotonin reuptake inhibitors.
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Kir2.1 channels play a key role in maintaining the correct resting potential in eukaryotic cells. Recently, specific amino acid mutations in the Kir2.1 inwardly rectifying potassium channel have been found to cause Andersen's Syndrome in humans. Here, we have characterized individual Andersen's Syndrome mutants R218Q, G300V, E303K, and delta314-315 and have found multiple effects on the ability of the cytoplasmic domains in Kir2.1 channels to form proper tetrameric assemblies. For the R218Q mutation, we identified a second site mutation (T309K) that restored tetrameric assembly but not function. We successfully crystallized and solved the structure (at 2.0 A) of the N- and C-terminal cytoplasmic domains of Kir2.1-R218Q/T309K(S). This new structure revealed multiple conformations of the G-loop and CD loop, providing an explanation for channels that assemble but do not conduct ions. Interestingly, Glu303 forms both intra- and intersubunit salt bridges, depending on the conformation of the G-loop, suggesting that the E303K mutant stabilizes both closed and open G-loop conformations. In the Kir2.1-R218Q/T309K(S) structure, we discovered that the DE loop forms a hydrophobic pocket that binds 2-methyl-2,4-pentanediol, which is located near the putative G(betagamma)-activation site of Kir3 channels. Finally, we observed a potassium ion bound to the cytoplasmic domain for this class of K+ channels.</AbstractText
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Cardiac conduction disorders slow the heart rhythm and cause disability in millions of people worldwide. Inherited mutations in SCN5A, the gene encoding the human cardiac sodium (Na+) channel, have been associated with rapid heart rhythms that occur suddenly and are life-threatening; however, a chief function of the Na+ channel is to initiate cardiac impulse conduction. Here we provide the first functional characterization of an SCN5A mutation that causes a sustained, isolated conduction defect with pathological slowing of the cardiac rhythm. By analysing the SCN5A coding region, we have identified a single mutation in five affected family members; this mutation results in the substitution of cysteine 514 for glycine (G514C) in the channel protein. Biophysical characterization of the mutant channel shows that there are abnormalities in voltage-dependent 'gating' behaviour that can be partially corrected by dexamethasone, consistent with the salutary effects of glucocorticoids on the clinical phenotype. Computational analysis predicts that the gating defects of G514C selectively slow myocardial conduction, but do not provoke the rapid cardiac arrhythmias associated previously with SCN5A mutations.</AbstractText
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We have previously shown that chronic treatment with selective serotonin reuptake inhibitors (SSRIs), fluvoxamine and paroxetine, attenuated m-chlorophenylpiperazine (mCPP)-induced hypolocomotion in rats. The effect of these SSRIs on the response to mCPP is thought to be caused by the desensitization of 5-HT2C receptor function. In the present study, we investigated whether chronic administration of SSRI could reduce another pharmacological response to mCPP in rats, i.e., the induction of the secretion of corticosterone. The mCPP-induced increase in the serum concentration of corticosterone was not blocked by the 5-HT2C antagonist SB242084, but was blocked by the 5-HT2A antagonist ketanserin. Chronic treatment with fluvoxamine and paroxetine attenuated the response to mCPP, while these SSRIs had no effects in control rats. These results suggest that the desensitization of 5-HT2A receptor function occurs in the same way as that of 5-HT2C receptor function through chronic treatment with either fluvoxamine or paroxetine as a consequence of prolonged exposure to elevated levels of serotonin. The hypersensitivity of 5-HT2A receptors is observed in depressed patients, and chronic treatment with many antidepressants such as tricyclic antidepressants have been reported to reduce 5-HT2A receptor density and/or efficacy. The desensitization of 5-HT2A receptor function might contribute to the therapeutic mechanism of action of these SSRIs, as seen with other classes of antidepressants.</AbstractText
|
Andersen's syndrome mutation effects on the structure and assembly of the cytoplasmic domains of Kir2.1. Kir2.1 channels play a key role in maintaining the correct resting potential in eukaryotic cells. Recently, specific amino acid mutations in the Kir2.1 inwardly rectifying potassium channel have been found to cause Andersen's Syndrome in humans. Here, we have characterized individual Andersen's Syndrome mutants R218Q, G300V, E303K, and delta314-315 and have found multiple effects on the ability of the cytoplasmic domains in Kir2.1 channels to form proper tetrameric assemblies. For the R218Q mutation, we identified a second site mutation (T309K) that restored tetrameric assembly but not function. We successfully crystallized and solved the structure (at 2.0 A) of the N- and C-terminal cytoplasmic domains of Kir2.1-R218Q/T309K(S). This new structure revealed multiple conformations of the G-loop and CD loop, providing an explanation for channels that assemble but do not conduct ions. Interestingly, Glu303 forms both intra- and intersubunit salt bridges, depending on the conformation of the G-loop, suggesting that the E303K mutant stabilizes both closed and open G-loop conformations. In the Kir2.1-R218Q/T309K(S) structure, we discovered that the DE loop forms a hydrophobic pocket that binds 2-methyl-2,4-pentanediol, which is located near the putative G(betagamma)-activation site of Kir3 channels. Finally, we observed a potassium ion bound to the cytoplasmic domain for this class of K+ channels.</AbstractText
|
A sodium-channel mutation causes isolated cardiac conduction disease. Cardiac conduction disorders slow the heart rhythm and cause disability in millions of people worldwide. Inherited mutations in SCN5A, the gene encoding the human cardiac sodium (Na+) channel, have been associated with rapid heart rhythms that occur suddenly and are life-threatening; however, a chief function of the Na+ channel is to initiate cardiac impulse conduction. Here we provide the first functional characterization of an SCN5A mutation that causes a sustained, isolated conduction defect with pathological slowing of the cardiac rhythm. By analysing the SCN5A coding region, we have identified a single mutation in five affected family members; this mutation results in the substitution of cysteine 514 for glycine (G514C) in the channel protein. Biophysical characterization of the mutant channel shows that there are abnormalities in voltage-dependent 'gating' behaviour that can be partially corrected by dexamethasone, consistent with the salutary effects of glucocorticoids on the clinical phenotype. Computational analysis predicts that the gating defects of G514C selectively slow myocardial conduction, but do not provoke the rapid cardiac arrhythmias associated previously with SCN5A mutations.</AbstractText
|
Desensitization of 5-HT2A receptor function by chronic administration of selective serotonin reuptake inhibitors. We have previously shown that chronic treatment with selective serotonin reuptake inhibitors (SSRIs), fluvoxamine and paroxetine, attenuated m-chlorophenylpiperazine (mCPP)-induced hypolocomotion in rats. The effect of these SSRIs on the response to mCPP is thought to be caused by the desensitization of 5-HT2C receptor function. In the present study, we investigated whether chronic administration of SSRI could reduce another pharmacological response to mCPP in rats, i.e., the induction of the secretion of corticosterone. The mCPP-induced increase in the serum concentration of corticosterone was not blocked by the 5-HT2C antagonist SB242084, but was blocked by the 5-HT2A antagonist ketanserin. Chronic treatment with fluvoxamine and paroxetine attenuated the response to mCPP, while these SSRIs had no effects in control rats. These results suggest that the desensitization of 5-HT2A receptor function occurs in the same way as that of 5-HT2C receptor function through chronic treatment with either fluvoxamine or paroxetine as a consequence of prolonged exposure to elevated levels of serotonin. The hypersensitivity of 5-HT2A receptors is observed in depressed patients, and chronic treatment with many antidepressants such as tricyclic antidepressants have been reported to reduce 5-HT2A receptor density and/or efficacy. The desensitization of 5-HT2A receptor function might contribute to the therapeutic mechanism of action of these SSRIs, as seen with other classes of antidepressants.</AbstractText
|
25345488
|
25934706
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26471732
|
Prolactin and natural killer cells: evaluating the neuroendocrine-immune axis in women with primary infertility and recurrent spontaneous abortion.
|
60 YEARS OF NEUROENDOCRINOLOGY: Redefining neuroendocrinology: stress, sex and cognitive and emotional regulation.
|
Mg(2+) shifts ligand-mediated folding of a riboswitch from induced-fit to conformational selection.
|
An association between serum prolactin (PRL) and peripheral blood natural killer (NK) cells has been described in healthy women. We explored for the first time the PRL response to the thyrotrophin-releasing hormone (TRH) test and the association between PRL and NK cells in women with reproductive failure.</AbstractText A total of 130 women [31 primary infertility, 69 recurrent spontaneous abortion (RSA), and 30 fertile women] were evaluated by a TRH test to analyze the following: basal PRL (bPRL), peak-time PRL, PRL absolute and relative increase, decline-time PRL. Hyperprolactinaemia (HPRL) was defined as bPRL ≥15 ng/mL. NK cells were characterized by immunophenotyping.</AbstractText Significantly higher bPRL levels were found in the infertile women than in controls. Both the infertile and the RSA women showed significantly elevated NK levels. bPRL levels correlated with NK cells in HPRL-infertile women.</AbstractText In patients with HPRL, an association between NK cell and bPRL results. The dynamic test in the infertile women would help in the management of the pregnancy impairment.</AbstractText
|
The discovery of steroid hormone receptors in brain regions that mediate every aspect of brain function has broadened the definition of 'neuroendocrinology' to include the reciprocal communication between the brain and the body via hormonal and neural pathways. The brain is the central organ of stress and adaptation to stress because it perceives and determines what is threatening, as well as the behavioral and physiological responses to the stressor. The adult and developing brain possess remarkable structural and functional plasticity in response to stress, including neuronal replacement, dendritic remodeling, and synapse turnover. Stress causes an imbalance of neural circuitry subserving cognition, decision-making, anxiety and mood that can alter expression of those behaviors and behavioral states. This imbalance, in turn, affects systemic physiology via neuroendocrine, autonomic, immune and metabolic mediators. In the short term, as for increased fearful vigilance and anxiety in a threatening environment, these changes may be adaptive. But, if the danger passes and the behavioral state persists along with the changes in neural circuitry, such maladaptation may need intervention with a combination of pharmacological and behavioral therapies, as is the case for chronic anxiety and depression. There are important sex differences in the brain responses to stressors that are in urgent need of further exploration. Moreover, adverse early-life experience, interacting with alleles of certain genes, produce lasting effects on brain and body over the life-course via epigenetic mechanisms. While prevention is most important, the plasticity of the brain gives hope for therapies that take into consideration brain-body interactions.</AbstractText
|
Bacterial riboswitches couple small-molecule ligand binding to RNA conformational changes that widely regulate gene expression, rendering them potential targets for antibiotic intervention. Despite structural insights, the ligand-mediated folding mechanisms of riboswitches are still poorly understood. Using single-molecule fluorescence resonance energy transfer (smFRET), we have investigated the folding mechanism of an H-type pseudoknotted preQ1 riboswitch in dependence of Mg(2+) and three ligands of distinct affinities. We show that, in the absence of Mg(2+), both weakly and strongly bound ligands promote pseudoknot docking through an induced-fit mechanism. By contrast, addition of as low as 10 μM Mg(2+) generally shifts docking toward conformational selection by stabilizing a folded-like conformation prior to ligand binding. Supporting evidence from transition-state analysis further highlights the particular importance of stacking interactions during induced-fit and of specific hydrogen bonds during conformational selection. Our mechanistic dissection provides unprecedented insights into the intricate synergy between ligand- and Mg(2+)-mediated RNA folding.</AbstractText
|
Prolactin and natural killer cells: evaluating the neuroendocrine-immune axis in women with primary infertility and recurrent spontaneous abortion. An association between serum prolactin (PRL) and peripheral blood natural killer (NK) cells has been described in healthy women. We explored for the first time the PRL response to the thyrotrophin-releasing hormone (TRH) test and the association between PRL and NK cells in women with reproductive failure.</AbstractText A total of 130 women [31 primary infertility, 69 recurrent spontaneous abortion (RSA), and 30 fertile women] were evaluated by a TRH test to analyze the following: basal PRL (bPRL), peak-time PRL, PRL absolute and relative increase, decline-time PRL. Hyperprolactinaemia (HPRL) was defined as bPRL ≥15 ng/mL. NK cells were characterized by immunophenotyping.</AbstractText Significantly higher bPRL levels were found in the infertile women than in controls. Both the infertile and the RSA women showed significantly elevated NK levels. bPRL levels correlated with NK cells in HPRL-infertile women.</AbstractText In patients with HPRL, an association between NK cell and bPRL results. The dynamic test in the infertile women would help in the management of the pregnancy impairment.</AbstractText
|
60 YEARS OF NEUROENDOCRINOLOGY: Redefining neuroendocrinology: stress, sex and cognitive and emotional regulation. The discovery of steroid hormone receptors in brain regions that mediate every aspect of brain function has broadened the definition of 'neuroendocrinology' to include the reciprocal communication between the brain and the body via hormonal and neural pathways. The brain is the central organ of stress and adaptation to stress because it perceives and determines what is threatening, as well as the behavioral and physiological responses to the stressor. The adult and developing brain possess remarkable structural and functional plasticity in response to stress, including neuronal replacement, dendritic remodeling, and synapse turnover. Stress causes an imbalance of neural circuitry subserving cognition, decision-making, anxiety and mood that can alter expression of those behaviors and behavioral states. This imbalance, in turn, affects systemic physiology via neuroendocrine, autonomic, immune and metabolic mediators. In the short term, as for increased fearful vigilance and anxiety in a threatening environment, these changes may be adaptive. But, if the danger passes and the behavioral state persists along with the changes in neural circuitry, such maladaptation may need intervention with a combination of pharmacological and behavioral therapies, as is the case for chronic anxiety and depression. There are important sex differences in the brain responses to stressors that are in urgent need of further exploration. Moreover, adverse early-life experience, interacting with alleles of certain genes, produce lasting effects on brain and body over the life-course via epigenetic mechanisms. While prevention is most important, the plasticity of the brain gives hope for therapies that take into consideration brain-body interactions.</AbstractText
|
Mg(2+) shifts ligand-mediated folding of a riboswitch from induced-fit to conformational selection. Bacterial riboswitches couple small-molecule ligand binding to RNA conformational changes that widely regulate gene expression, rendering them potential targets for antibiotic intervention. Despite structural insights, the ligand-mediated folding mechanisms of riboswitches are still poorly understood. Using single-molecule fluorescence resonance energy transfer (smFRET), we have investigated the folding mechanism of an H-type pseudoknotted preQ1 riboswitch in dependence of Mg(2+) and three ligands of distinct affinities. We show that, in the absence of Mg(2+), both weakly and strongly bound ligands promote pseudoknot docking through an induced-fit mechanism. By contrast, addition of as low as 10 μM Mg(2+) generally shifts docking toward conformational selection by stabilizing a folded-like conformation prior to ligand binding. Supporting evidence from transition-state analysis further highlights the particular importance of stacking interactions during induced-fit and of specific hydrogen bonds during conformational selection. Our mechanistic dissection provides unprecedented insights into the intricate synergy between ligand- and Mg(2+)-mediated RNA folding.</AbstractText
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38952000
|
33547610
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39771868
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Syndromic Surveillance Tracks COVID-19 Cases in University and County Settings: Retrospective Observational Study.
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Meteorological factors, COVID-19 cases, and deaths in top 10 most affected countries: an econometric investigation.
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Dynamic Emotion Recognition and Expression Imitation in Neurotypical Adults and Their Associations with Autistic Traits.
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Syndromic surveillance represents a potentially inexpensive supplement to test-based COVID-19 surveillance. By strengthening surveillance of COVID-19-like illness (CLI), targeted and rapid interventions can be facilitated that prevent COVID-19 outbreaks without primary reliance on testing.</AbstractText This study aims to assess the temporal relationship between confirmed SARS-CoV-2 infections and self-reported and health care provider-reported CLI in university and county settings, respectively.</AbstractText We collected aggregated COVID-19 testing and symptom reporting surveillance data from Cornell University (2020-2021) and Tompkins County Health Department (2020-2022). We used negative binomial and linear regression models to correlate confirmed COVID-19 case counts and positive test rates with CLI rate time series, lagged COVID-19 cases or rates, and day of the week as independent variables. Optimal lag periods were identified using Granger causality and likelihood ratio tests.</AbstractText In modeling undergraduate student cases, the CLI rate (P=.003) and rate of exposure to CLI (P<.001) were significantly correlated with the COVID-19 test positivity rate with no lag in the linear models. At the county level, the health care provider-reported CLI rate was significantly correlated with SARS-CoV-2 test positivity with a 3-day lag in both the linear (P<.001) and negative binomial model (P=.005).</AbstractText The real-time correlation between syndromic surveillance and COVID-19 cases on a university campus suggests symptom reporting is a viable alternative or supplement to COVID-19 surveillance testing. At the county level, syndromic surveillance is also a leading indicator of COVID-19 cases, enabling quick action to reduce transmission. Further research should investigate COVID-19 risk using syndromic surveillance in other settings, such as low-resource settings like low- and middle-income countries.</AbstractText
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This paper examines the nexus between the Covid-19 confirmed cases, deaths, meteorological factors, including an air pollutant among the world's top 10 infected countries, from 1 February 2020 through 30 June 2020, using advanced econometric techniques to address heterogeneity across the nations. The findings of the study suggest that there exists a strong cross-sectional dependence between Covid-19 cases, deaths, and all the meteorological factors for the countries under study. The findings also reveal that a long-term relationship exists between all the meteorological factors. There exists a bi-directional causality running between the Covid-19 cases and all the meteorological factors. With Covid-19 death cases as the dependent variable, there exists bi-directional causality running between the Covid-19 death cases and Covid-19 confirmed cases, air pressure, humidity, and temperature. Temperature and air pressure exhibit a statistically significant and negative impact on the Covid-19 confirmed cases. Air pollutant PM2.5 also exhibits a significant but positive impact on the Covid-19 confirmed cases. Temperature indicates a statistically significant and negative impact on the Covid-19 death cases. At the same time, Covid-19 confirmed cases and air pollutant PM2.5 exhibit a statistically significant and positive impact on the Covid-19 death cases across the ten countries under study. Hence, it is possible to postulate that cool and dry weather conditions with lower temperatures may promote indoor activities and human gatherings (assembling), leading to virus transmission. This study contributes both practically and theoretically to the concerned field of pandemic management. Our results assist in taking appropriate measures in implementing intersectoral policies and actions as necessary in a timely and efficient manner. Causal relations of Meteorological factors and Covid-19 (2 models used in the study).</AbstractText
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Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction and communication. While many studies suggest that individuals with ASD struggle with emotion processing, the association between emotion processing and autistic traits in non-clinical populations is still unclear. We examine whether neurotypical adults' facial emotion recognition and expression imitation are associated with autistic traits. We recruited 32 neurotypical adults; each received two computerized tasks, the Dynamic Emotion Recognition and Expression Imitation, and two standardized measures: the Chinese version AQ and the Twenty-Item Prosopagnosia Index (PI-20). Results for the dynamic emotion recognition showed that happiness has the highest mean accuracy, followed by surprise, sadness, anger, fear, and disgust. For expression imitation, it was easiest to imitate surprise and happiness, followed by disgust, while the accuracy of imitating sadness, anger, and fear was much lower. Importantly, individual AQ scores negatively correlated with emotion recognition accuracy and positively correlated with PI-20. The AQ imagination, communication sub-scores, and PI-20 positively correlated with the expression imitation of surprise. In summary, we found a significant link between recognizing emotional expressions and the level of autistic traits in non-clinical populations, supporting the concept of broader autism phenotype.</AbstractText
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Syndromic Surveillance Tracks COVID-19 Cases in University and County Settings: Retrospective Observational Study. Syndromic surveillance represents a potentially inexpensive supplement to test-based COVID-19 surveillance. By strengthening surveillance of COVID-19-like illness (CLI), targeted and rapid interventions can be facilitated that prevent COVID-19 outbreaks without primary reliance on testing.</AbstractText This study aims to assess the temporal relationship between confirmed SARS-CoV-2 infections and self-reported and health care provider-reported CLI in university and county settings, respectively.</AbstractText We collected aggregated COVID-19 testing and symptom reporting surveillance data from Cornell University (2020-2021) and Tompkins County Health Department (2020-2022). We used negative binomial and linear regression models to correlate confirmed COVID-19 case counts and positive test rates with CLI rate time series, lagged COVID-19 cases or rates, and day of the week as independent variables. Optimal lag periods were identified using Granger causality and likelihood ratio tests.</AbstractText In modeling undergraduate student cases, the CLI rate (P=.003) and rate of exposure to CLI (P<.001) were significantly correlated with the COVID-19 test positivity rate with no lag in the linear models. At the county level, the health care provider-reported CLI rate was significantly correlated with SARS-CoV-2 test positivity with a 3-day lag in both the linear (P<.001) and negative binomial model (P=.005).</AbstractText The real-time correlation between syndromic surveillance and COVID-19 cases on a university campus suggests symptom reporting is a viable alternative or supplement to COVID-19 surveillance testing. At the county level, syndromic surveillance is also a leading indicator of COVID-19 cases, enabling quick action to reduce transmission. Further research should investigate COVID-19 risk using syndromic surveillance in other settings, such as low-resource settings like low- and middle-income countries.</AbstractText
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Meteorological factors, COVID-19 cases, and deaths in top 10 most affected countries: an econometric investigation. This paper examines the nexus between the Covid-19 confirmed cases, deaths, meteorological factors, including an air pollutant among the world's top 10 infected countries, from 1 February 2020 through 30 June 2020, using advanced econometric techniques to address heterogeneity across the nations. The findings of the study suggest that there exists a strong cross-sectional dependence between Covid-19 cases, deaths, and all the meteorological factors for the countries under study. The findings also reveal that a long-term relationship exists between all the meteorological factors. There exists a bi-directional causality running between the Covid-19 cases and all the meteorological factors. With Covid-19 death cases as the dependent variable, there exists bi-directional causality running between the Covid-19 death cases and Covid-19 confirmed cases, air pressure, humidity, and temperature. Temperature and air pressure exhibit a statistically significant and negative impact on the Covid-19 confirmed cases. Air pollutant PM2.5 also exhibits a significant but positive impact on the Covid-19 confirmed cases. Temperature indicates a statistically significant and negative impact on the Covid-19 death cases. At the same time, Covid-19 confirmed cases and air pollutant PM2.5 exhibit a statistically significant and positive impact on the Covid-19 death cases across the ten countries under study. Hence, it is possible to postulate that cool and dry weather conditions with lower temperatures may promote indoor activities and human gatherings (assembling), leading to virus transmission. This study contributes both practically and theoretically to the concerned field of pandemic management. Our results assist in taking appropriate measures in implementing intersectoral policies and actions as necessary in a timely and efficient manner. Causal relations of Meteorological factors and Covid-19 (2 models used in the study).</AbstractText
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Dynamic Emotion Recognition and Expression Imitation in Neurotypical Adults and Their Associations with Autistic Traits. Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction and communication. While many studies suggest that individuals with ASD struggle with emotion processing, the association between emotion processing and autistic traits in non-clinical populations is still unclear. We examine whether neurotypical adults' facial emotion recognition and expression imitation are associated with autistic traits. We recruited 32 neurotypical adults; each received two computerized tasks, the Dynamic Emotion Recognition and Expression Imitation, and two standardized measures: the Chinese version AQ and the Twenty-Item Prosopagnosia Index (PI-20). Results for the dynamic emotion recognition showed that happiness has the highest mean accuracy, followed by surprise, sadness, anger, fear, and disgust. For expression imitation, it was easiest to imitate surprise and happiness, followed by disgust, while the accuracy of imitating sadness, anger, and fear was much lower. Importantly, individual AQ scores negatively correlated with emotion recognition accuracy and positively correlated with PI-20. The AQ imagination, communication sub-scores, and PI-20 positively correlated with the expression imitation of surprise. In summary, we found a significant link between recognizing emotional expressions and the level of autistic traits in non-clinical populations, supporting the concept of broader autism phenotype.</AbstractText
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37182185
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37995674
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36732369
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Case Report: A novel heterozygous nonsense mutation in KRIT1 cause hereditary cerebral cavernous malformation.
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Hemorrhagic Outcome of Brainstem Cavernous Malformations following Radiosurgery: Dose-Response Relationship.
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Lead exposure in childhood and historical land use: a geostatistical analysis of soil lead concentrations in South Philadelphia parks.
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Cerebral cavernous malformation (CCM) is a vascular malformation of the central nervous system and mainly characterized by enlarged capillary cavities without intervening brain parenchyma. Genetic studies have identified three disease-causing genes (<i
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This study aimed to assess the impact of gamma knife radiosurgery on brainstem cavernous malformations (CMs).</AbstractText A total of 85 patients (35 females; median age 41.0 years) who underwent gamma knife radiosurgery for brainstem CMs at our institute between 2006 and 2015 were enrolled in a prospective clinical observation trial. Risk factors for hemorrhagic outcomes were evaluated, and outcomes were compared across different margin doses.</AbstractText The pre-radiosurgery annual hemorrhage rate (AHR) was 32.3% (44 hemorrhages during 136.2 patient-years). The median planning target volume was 1.292 cc. The median margin and maximum doses were 15.0 and 29.2 Gy, respectively, with a median isodose line of 50.0%. The post-radiosurgery AHR was 2.7% (21 hemorrhages during 769.9 patient-years), with a rate of 5.5% within the first 2 years and 2.0% thereafter. The post-radiosurgery AHR for patients with margin doses of ≤13.0 Gy (n = 15), 14.0-15.0 Gy (n = 50), and ≥16.0 Gy (n = 20) was 5.4, 2.7, and 0.6%, respectively. Correspondingly, transient adverse radiation effects were observed in 6.7 (1/15), 10.0 (5/50), and 30.0% (6/20) of cases, respectively. An increased margin dose per 1 Gy (hazard ratio: 0.530, 95% CI: 0.341-0.826, p = 0.005) was identified as an independent protective factor against post-radiosurgery hemorrhage. Margin doses of ≥16.0 Gy were associated with improved hemorrhagic outcomes (hazard ratio: 0.343, 95% confidence interval [CI]: 0.157-0.749, p = 0.007), but an increased risk of adverse radiation effects (odds ratio: 3.006, 95% CI: 1.041-8.677, p = 0.042).</AbstractText The AHR of brainstem CMs decreased following radiosurgery, and our study revealed a significant dose-response relationship. Margin doses of 14-15 Gy were recommended. Further studies are required to validate our findings.</AbstractText
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Elevated soil lead (Pb) concentrations in public parks and outdoor spaces continue to have a significant impact on the public health of urban communities. This study evaluated the geospatial and statistical relationships between soil Pb concentrations, the urban environment, and child blood lead levels (BLLs) in the neighborhood of South Philadelphia, PA. Soil samples (n = 240) were collected from forty (40) public parks and analyzed for Pb using a field portable X-ray fluorescence (XRF) analyzer. Geospatial mapping was used to investigate historical land use of each park, vehicular traffic on adjacent roadways, and density of residential/commercial development. Predicted child BLLs and BLL "high-risk areas" were identified using interpolation and biokinetic modeling. Childhood BLL data for South Philadelphia (n = 10,379) was provided by the Philadelphia Department of Public Health (2013-2015). Of the two hundred forty (240) soil samples collected, Pb levels for 10.8% of samples were ≥ 400 ppm. Two hundred sixty-nine of 10,379 children screened were identified with BLLs ≥ 5 µg/dL. Historical land use of each park was shown to be significantly correlated (p = 0.01) with soil Pb concentrations and child BLLs ≥ 5 µg/dL. Approximately 13.3% of the variance in child BLLs ≥ 5 µg/dL was attributed to historical site land use. Overall, undeveloped/greenspace historical land use exhibited the highest soil Pb concentrations in the study. Geospatial relationships were identified between census tracts with higher percentages of children with BLLs ≥ 5 µg/dL and interpolated BLL "high-risk" areas (≥ 3.5 µg/dL). The results of this study suggest soil accumulation time and historical land use may influence soil Pb concentrations and child BLLs in urban communities. Measured soil Pb concentrations were determined to effectively model community-wide contamination and childhood Pb exposure.</AbstractText
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Case Report: A novel heterozygous nonsense mutation in KRIT1 cause hereditary cerebral cavernous malformation. Cerebral cavernous malformation (CCM) is a vascular malformation of the central nervous system and mainly characterized by enlarged capillary cavities without intervening brain parenchyma. Genetic studies have identified three disease-causing genes (<i
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Hemorrhagic Outcome of Brainstem Cavernous Malformations following Radiosurgery: Dose-Response Relationship. This study aimed to assess the impact of gamma knife radiosurgery on brainstem cavernous malformations (CMs).</AbstractText A total of 85 patients (35 females; median age 41.0 years) who underwent gamma knife radiosurgery for brainstem CMs at our institute between 2006 and 2015 were enrolled in a prospective clinical observation trial. Risk factors for hemorrhagic outcomes were evaluated, and outcomes were compared across different margin doses.</AbstractText The pre-radiosurgery annual hemorrhage rate (AHR) was 32.3% (44 hemorrhages during 136.2 patient-years). The median planning target volume was 1.292 cc. The median margin and maximum doses were 15.0 and 29.2 Gy, respectively, with a median isodose line of 50.0%. The post-radiosurgery AHR was 2.7% (21 hemorrhages during 769.9 patient-years), with a rate of 5.5% within the first 2 years and 2.0% thereafter. The post-radiosurgery AHR for patients with margin doses of ≤13.0 Gy (n = 15), 14.0-15.0 Gy (n = 50), and ≥16.0 Gy (n = 20) was 5.4, 2.7, and 0.6%, respectively. Correspondingly, transient adverse radiation effects were observed in 6.7 (1/15), 10.0 (5/50), and 30.0% (6/20) of cases, respectively. An increased margin dose per 1 Gy (hazard ratio: 0.530, 95% CI: 0.341-0.826, p = 0.005) was identified as an independent protective factor against post-radiosurgery hemorrhage. Margin doses of ≥16.0 Gy were associated with improved hemorrhagic outcomes (hazard ratio: 0.343, 95% confidence interval [CI]: 0.157-0.749, p = 0.007), but an increased risk of adverse radiation effects (odds ratio: 3.006, 95% CI: 1.041-8.677, p = 0.042).</AbstractText The AHR of brainstem CMs decreased following radiosurgery, and our study revealed a significant dose-response relationship. Margin doses of 14-15 Gy were recommended. Further studies are required to validate our findings.</AbstractText
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Lead exposure in childhood and historical land use: a geostatistical analysis of soil lead concentrations in South Philadelphia parks. Elevated soil lead (Pb) concentrations in public parks and outdoor spaces continue to have a significant impact on the public health of urban communities. This study evaluated the geospatial and statistical relationships between soil Pb concentrations, the urban environment, and child blood lead levels (BLLs) in the neighborhood of South Philadelphia, PA. Soil samples (n = 240) were collected from forty (40) public parks and analyzed for Pb using a field portable X-ray fluorescence (XRF) analyzer. Geospatial mapping was used to investigate historical land use of each park, vehicular traffic on adjacent roadways, and density of residential/commercial development. Predicted child BLLs and BLL "high-risk areas" were identified using interpolation and biokinetic modeling. Childhood BLL data for South Philadelphia (n = 10,379) was provided by the Philadelphia Department of Public Health (2013-2015). Of the two hundred forty (240) soil samples collected, Pb levels for 10.8% of samples were ≥ 400 ppm. Two hundred sixty-nine of 10,379 children screened were identified with BLLs ≥ 5 µg/dL. Historical land use of each park was shown to be significantly correlated (p = 0.01) with soil Pb concentrations and child BLLs ≥ 5 µg/dL. Approximately 13.3% of the variance in child BLLs ≥ 5 µg/dL was attributed to historical site land use. Overall, undeveloped/greenspace historical land use exhibited the highest soil Pb concentrations in the study. Geospatial relationships were identified between census tracts with higher percentages of children with BLLs ≥ 5 µg/dL and interpolated BLL "high-risk" areas (≥ 3.5 µg/dL). The results of this study suggest soil accumulation time and historical land use may influence soil Pb concentrations and child BLLs in urban communities. Measured soil Pb concentrations were determined to effectively model community-wide contamination and childhood Pb exposure.</AbstractText
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33314281
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31332874
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34494108
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Diffusion-PEPTIDE: Distortion- and blurring-free diffusion imaging with self-navigated motion-correction and relaxometry capabilities.
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Data Quality and Optimal Background Correction Order of Respiratory-Gated k-Space Segmented Spoiled Gradient Echo (SGRE) and Echo Planar Imaging (EPI)-Based 4D Flow MRI.
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Higher Ultra-Processed Food Consumption Is Associated with Increased Risk of Incident Coronary Artery Disease in the Atherosclerosis Risk in Communities Study.
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To implement the time-resolved relaxometry PEPTIDE technique into a diffusion acquisition to provide self-navigated, distortion- and blurring-free diffusion imaging that is robust to motion, while simultaneously providing T<sub The PEPTIDE readout was implemented into a spin-echo diffusion acquisition, enabling reconstruction of a time-series of T<sub Diffusion-PEPTIDE showed the capability to provide high quality diffusion images and T<sub Diffusion-PEPTIDE provides highly robust diffusion and relaxometry data and offers potential for future applications in diffusion-relaxometry multi-compartment modeling.</AbstractText
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A reduction in scan time of 4D Flow MRI would facilitate clinical application. A recent study indicates that echo-planar imaging (EPI) 4D Flow MRI allows for a reduction in scan time and better data quality than the recommended k-space segmented spoiled gradient echo (SGRE) sequence. It was argued that the poor data quality of SGRE was related to the nonrecommended absence of respiratory motion compensation. However, data quality can also be affected by the background offset compensation.</AbstractText To compare the data quality of respiratory motion-compensated SGRE and EPI 4D Flow MRI and their dependence on background correction (BC) order.</AbstractText Retrospective.</AbstractText Eighteen healthy subjects (eight female, mean age 32 ± 5 years).</AbstractText 1.5 T. [Correction added on July 26, 2019, after first online publication: The preceding field strength was corrected.] SGRE and EPI-based 4D Flow MRI.</AbstractText Data quality was investigated visually and by comparing flows through the cardiac valves and aorta. Measurements were obtained from transvalvular flow and pathline analysis.</AbstractText Linear regression and Bland-Altman analysis were used. Wilcoxon test was used for comparison of visual scoring. Student's t-test was used for comparison of flow volumes.</AbstractText No significant difference was found by visual inspection (P = 0.08). Left ventricular (LV) flows were strongly and very strongly associated with SGRE and EPI, respectively (R<sup Both sequences yielded good internal data consistency when an adequate background correction was applied. Second and first BC order were considered sufficient for transvalvular flow analysis in SGRE and EPI, respectively. Higher BC orders were preferred for particle tracing. Level of Evidence 4 Technical Efficacy Stage 1 J. Magn. Reson. Imaging 2020;51:885-896.</AbstractText
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Higher ultra-processed food intake has been linked with several cardiometabolic and cardiovascular diseases. However, prospective evidence from US populations remains scarce.</AbstractText To test the hypothesis that higher intake of ultra-processed foods is associated with higher risk of coronary artery disease.</AbstractText A total of 13,548 adults aged 45-65 y from the Atherosclerosis Risk in Communities study were included in the analytic sample. Dietary intake data were collected through a 66-item FFQ. Ultra-processed foods were defined using the NOVA classification, and the level of intake (servings/d) was calculated for each participant and divided into quartiles. We used Cox proportional hazards models and restricted cubic splines to assess the association between quartiles of ultra-processed food intake and incident coronary artery disease.</AbstractText There were 2006 incident coronary artery disease cases documented over a median follow-up of 27 y. Incidence rates were higher in the highest quartile of ultra-processed food intake (70.8 per 10,000 person-y; 95% CI: 65.1, 77.1) compared with the lowest quartile (59.3 per 10,000 person-y; 95% CI: 54.1, 65.0). Participants in the highest compared with lowest quartile of ultra-processed food intake had a 19% higher risk of coronary artery disease (HR: 1.19; 95% CI: 1.05, 1.35) after adjusting for sociodemographic factors and health behaviors. An approximately linear relation was observed between ultra-processed food intake and risk of coronary artery disease.</AbstractText Higher ultra-processed food intake was associated with a higher risk of coronary artery disease among middle-aged US adults. Further prospective studies are needed to confirm these findings and to investigate the mechanisms by which ultra-processed foods may affect health.</AbstractText
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Diffusion-PEPTIDE: Distortion- and blurring-free diffusion imaging with self-navigated motion-correction and relaxometry capabilities. To implement the time-resolved relaxometry PEPTIDE technique into a diffusion acquisition to provide self-navigated, distortion- and blurring-free diffusion imaging that is robust to motion, while simultaneously providing T<sub The PEPTIDE readout was implemented into a spin-echo diffusion acquisition, enabling reconstruction of a time-series of T<sub Diffusion-PEPTIDE showed the capability to provide high quality diffusion images and T<sub Diffusion-PEPTIDE provides highly robust diffusion and relaxometry data and offers potential for future applications in diffusion-relaxometry multi-compartment modeling.</AbstractText
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Data Quality and Optimal Background Correction Order of Respiratory-Gated k-Space Segmented Spoiled Gradient Echo (SGRE) and Echo Planar Imaging (EPI)-Based 4D Flow MRI. A reduction in scan time of 4D Flow MRI would facilitate clinical application. A recent study indicates that echo-planar imaging (EPI) 4D Flow MRI allows for a reduction in scan time and better data quality than the recommended k-space segmented spoiled gradient echo (SGRE) sequence. It was argued that the poor data quality of SGRE was related to the nonrecommended absence of respiratory motion compensation. However, data quality can also be affected by the background offset compensation.</AbstractText To compare the data quality of respiratory motion-compensated SGRE and EPI 4D Flow MRI and their dependence on background correction (BC) order.</AbstractText Retrospective.</AbstractText Eighteen healthy subjects (eight female, mean age 32 ± 5 years).</AbstractText 1.5 T. [Correction added on July 26, 2019, after first online publication: The preceding field strength was corrected.] SGRE and EPI-based 4D Flow MRI.</AbstractText Data quality was investigated visually and by comparing flows through the cardiac valves and aorta. Measurements were obtained from transvalvular flow and pathline analysis.</AbstractText Linear regression and Bland-Altman analysis were used. Wilcoxon test was used for comparison of visual scoring. Student's t-test was used for comparison of flow volumes.</AbstractText No significant difference was found by visual inspection (P = 0.08). Left ventricular (LV) flows were strongly and very strongly associated with SGRE and EPI, respectively (R<sup Both sequences yielded good internal data consistency when an adequate background correction was applied. Second and first BC order were considered sufficient for transvalvular flow analysis in SGRE and EPI, respectively. Higher BC orders were preferred for particle tracing. Level of Evidence 4 Technical Efficacy Stage 1 J. Magn. Reson. Imaging 2020;51:885-896.</AbstractText
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Higher Ultra-Processed Food Consumption Is Associated with Increased Risk of Incident Coronary Artery Disease in the Atherosclerosis Risk in Communities Study. Higher ultra-processed food intake has been linked with several cardiometabolic and cardiovascular diseases. However, prospective evidence from US populations remains scarce.</AbstractText To test the hypothesis that higher intake of ultra-processed foods is associated with higher risk of coronary artery disease.</AbstractText A total of 13,548 adults aged 45-65 y from the Atherosclerosis Risk in Communities study were included in the analytic sample. Dietary intake data were collected through a 66-item FFQ. Ultra-processed foods were defined using the NOVA classification, and the level of intake (servings/d) was calculated for each participant and divided into quartiles. We used Cox proportional hazards models and restricted cubic splines to assess the association between quartiles of ultra-processed food intake and incident coronary artery disease.</AbstractText There were 2006 incident coronary artery disease cases documented over a median follow-up of 27 y. Incidence rates were higher in the highest quartile of ultra-processed food intake (70.8 per 10,000 person-y; 95% CI: 65.1, 77.1) compared with the lowest quartile (59.3 per 10,000 person-y; 95% CI: 54.1, 65.0). Participants in the highest compared with lowest quartile of ultra-processed food intake had a 19% higher risk of coronary artery disease (HR: 1.19; 95% CI: 1.05, 1.35) after adjusting for sociodemographic factors and health behaviors. An approximately linear relation was observed between ultra-processed food intake and risk of coronary artery disease.</AbstractText Higher ultra-processed food intake was associated with a higher risk of coronary artery disease among middle-aged US adults. Further prospective studies are needed to confirm these findings and to investigate the mechanisms by which ultra-processed foods may affect health.</AbstractText
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30382380
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28981354
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31905629
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Impact of sodium (18)F-fluoride PET/CT, (18)F-fluorocholine PET/CT and whole-body diffusion-weighted MRI on the management of patients with prostate cancer suspicious for metastasis: a prospective multicentre study.
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Whole-Body MRI: Current Applications in Oncology.
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A Low-Power CMOS Wireless Acoustic Sensing Platform for Remote Surveillance Applications.
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To compare the impact of 18F-sodium-fluoride (NaF) PET/CT, 18F-fluorocholine (FCH) PET/CT and diffusion-weighted whole-body MRI (DW-MRI) on the management of patients with prostate cancer (PCa) suspicious for distant metastasis.</AbstractText Prostate cancer patients were prospectively included between December 2011 and August 2014 and benefited from these three whole-body imaging (WBI) modalities within 1 month in addition to the standard PCa workup. Management was prospectively decided by clinicians during two multidisciplinary meetings, before and after the whole-body imaging workup. Rates of induced changes of whole-body imaging modalities were compared by Cochran's Q test.</AbstractText One-hundred-one patients (27 at staging, 59 at first biochemical recurrence (BCR) and 15 at first episode of rising serum level of prostate-specific antigen during androgen-deprivation therapy) were included. The overall rate of management changes was 52%: 29% as a consequence of WBI, higher for FCH-PET/CT than for NaF-PET/CT or DW-MRI (p < 0.0001) and highest (41%) for FCH-PET/CT at BCR. Actual management was adequate in all patients but two.</AbstractText Whole-body imaging induced a change in management in approximately a third of PCa patients suspicious for metastasis. The impact rate was determined to be greatest at first BCR using FCH-PET/CT. NaF-PET/CT and DW-MRI seemed less useful in this context.</AbstractText
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The purpose of this article is to review current image acquisition and interpretation for whole-body MRI, clinical applications, and the emerging roles in oncologic imaging, especially in the assessment of bone marrow diseases.</AbstractText Whole-body MRI is an emerging technique used for early diagnosis, staging, and assessment of therapeutic response in oncology. The improved accessibility and advances in technology, including widely available sequences (Dixon and DWI), have accelerated its deployment and acceptance in clinical practice.</AbstractText
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A low-power wireless acoustic sensing platform for remote surveillance applications based on a 180 nm CMOS technology is proposed in this paper. The audio signal, which is acquired by a microphone, is first amplified and filtered. Then, the analog signal is converted to a digital signal by a 10-bit analog-to-digital converter (ADC). A digital automatic gain control module is integrated to obtain an optimal input of the ADC. The digital signal is modulated and transmitted at the 433 MHz ISM band after being repacked and encoded. To save power for portable applications, the chip switches to standby mode when no audio is detected. The wireless sensing platform occupies a chip area of 1.76 mm 2 . The supply voltage is 2.5 V for the power amplifier and 1.8 V for other circuits. The measured maximum output power is 5.7 dBm and the transmission distance is over 500 m for real application scenarios. The chip consumes 25.1 mW power in normal work mode and 0.058 mW in standby mode. Compared to existing wireless acoustic sensors, the proposed wireless acoustic sensing platform can achieve features such as compactness, power efficiency, and reliability.</AbstractText
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Impact of sodium (18)F-fluoride PET/CT, (18)F-fluorocholine PET/CT and whole-body diffusion-weighted MRI on the management of patients with prostate cancer suspicious for metastasis: a prospective multicentre study. To compare the impact of 18F-sodium-fluoride (NaF) PET/CT, 18F-fluorocholine (FCH) PET/CT and diffusion-weighted whole-body MRI (DW-MRI) on the management of patients with prostate cancer (PCa) suspicious for distant metastasis.</AbstractText Prostate cancer patients were prospectively included between December 2011 and August 2014 and benefited from these three whole-body imaging (WBI) modalities within 1 month in addition to the standard PCa workup. Management was prospectively decided by clinicians during two multidisciplinary meetings, before and after the whole-body imaging workup. Rates of induced changes of whole-body imaging modalities were compared by Cochran's Q test.</AbstractText One-hundred-one patients (27 at staging, 59 at first biochemical recurrence (BCR) and 15 at first episode of rising serum level of prostate-specific antigen during androgen-deprivation therapy) were included. The overall rate of management changes was 52%: 29% as a consequence of WBI, higher for FCH-PET/CT than for NaF-PET/CT or DW-MRI (p < 0.0001) and highest (41%) for FCH-PET/CT at BCR. Actual management was adequate in all patients but two.</AbstractText Whole-body imaging induced a change in management in approximately a third of PCa patients suspicious for metastasis. The impact rate was determined to be greatest at first BCR using FCH-PET/CT. NaF-PET/CT and DW-MRI seemed less useful in this context.</AbstractText
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Whole-Body MRI: Current Applications in Oncology. The purpose of this article is to review current image acquisition and interpretation for whole-body MRI, clinical applications, and the emerging roles in oncologic imaging, especially in the assessment of bone marrow diseases.</AbstractText Whole-body MRI is an emerging technique used for early diagnosis, staging, and assessment of therapeutic response in oncology. The improved accessibility and advances in technology, including widely available sequences (Dixon and DWI), have accelerated its deployment and acceptance in clinical practice.</AbstractText
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A Low-Power CMOS Wireless Acoustic Sensing Platform for Remote Surveillance Applications. A low-power wireless acoustic sensing platform for remote surveillance applications based on a 180 nm CMOS technology is proposed in this paper. The audio signal, which is acquired by a microphone, is first amplified and filtered. Then, the analog signal is converted to a digital signal by a 10-bit analog-to-digital converter (ADC). A digital automatic gain control module is integrated to obtain an optimal input of the ADC. The digital signal is modulated and transmitted at the 433 MHz ISM band after being repacked and encoded. To save power for portable applications, the chip switches to standby mode when no audio is detected. The wireless sensing platform occupies a chip area of 1.76 mm 2 . The supply voltage is 2.5 V for the power amplifier and 1.8 V for other circuits. The measured maximum output power is 5.7 dBm and the transmission distance is over 500 m for real application scenarios. The chip consumes 25.1 mW power in normal work mode and 0.058 mW in standby mode. Compared to existing wireless acoustic sensors, the proposed wireless acoustic sensing platform can achieve features such as compactness, power efficiency, and reliability.</AbstractText
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40422416
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33343039
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40476782
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A Semantic Generalization of Shannon's Information Theory and Applications.
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Active inference on discrete state-spaces: A synthesis.
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Dixon-Based Water T1 Mapping for Fat-Corrected Assessment of Hepatic Fibrosis in Chronic Liver Disease.
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Does semantic communication require a semantic information theory parallel to Shannon's information theory, or can Shannon's work be generalized for semantic communication? This paper advocates for the latter and introduces a semantic generalization of Shannon's information theory (G theory for short). The core idea is to replace the distortion constraint with the semantic constraint, achieved by utilizing a set of truth functions as a semantic channel. These truth functions enable the expressions of semantic distortion, semantic information measures, and semantic information loss. Notably, the maximum semantic information criterion is equivalent to the maximum likelihood criterion and similar to the Regularized Least Squares criterion. This paper shows G theory's applications to daily and electronic semantic communication, machine learning, constraint control, Bayesian confirmation, portfolio theory, and information value. The improvements in machine learning methods involve multi-label learning and classification, maximum mutual information classification, mixture models, and solving latent variables. Furthermore, insights from statistical physics are discussed: Shannon information is similar to free energy; semantic information to free energy in local equilibrium systems; and information efficiency to the efficiency of free energy in performing work. The paper also proposes refining Friston's minimum free energy principle into the maximum information efficiency principle. Lastly, it compares G theory with other semantic information theories and discusses its limitation in representing the semantics of complex data.</AbstractText
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Active inference is a normative principle underwriting perception, action, planning, decision-making and learning in biological or artificial agents. From its inception, its associated process theory has grown to incorporate complex generative models, enabling simulation of a wide range of complex behaviours. Due to successive developments in active inference, it is often difficult to see how its underlying principle relates to process theories and practical implementation. In this paper, we try to bridge this gap by providing a complete mathematical synthesis of active inference on discrete state-space models. This technical summary provides an overview of the theory, derives neuronal dynamics from first principles and relates this dynamics to biological processes. Furthermore, this paper provides a fundamental building block needed to understand active inference for mixed generative models; allowing continuous sensations to inform discrete representations. This paper may be used as follows: to guide research towards outstanding challenges, a practical guide on how to implement active inference to simulate experimental behaviour, or a pointer towards various in-silico neurophysiological responses that may be used to make empirical predictions.</AbstractText
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The diagnostic value of conventional T1 mapping for noninvasive assessment of liver fibrosis is limited in the presence of hepatic steatosis. To evaluate the diagnostic value of water T1 (wT1) with continuous inversion-recovery Look-Locker (CIR-LL) method, integrating spiral readout, Dixon, and dictionary-based processing, for the fat-corrected assessment of hepatic fibrosis in patients with chronic liver disease (CLD).</AbstractText In this prospective study, consecutive participants with CLD underwent liver magnetic resonance imaging (MRI), which included assessment of MR-elastography (MRE)-derived liver stiffness, proton density fat fraction (PDFF), T1 relaxation times using modified Look-Locker inversion recovery (T1-MOLLI) and extracellular volume fraction (ECV), and wT1 relaxation times. MRE served as the reference standard to evaluate the diagnostic performance of MRI-based mapping parameters. Significant fibrosis (≥F2) was defined as MRE-derived liver stiffness >3.66 kPa in patients with PDFF≤5%, or >3.14 kPa in patients with PDFF>5%. Statistical analysis included Student t test, receiver operating characteristic (ROC) analysis, and Spearman correlation coefficient.</AbstractText A total of 81 CLD patients (mean age, 50±14 y; 32 female; 40 patients with PDFF>5%) were included. All measured mapping values were significantly higher in patients with significant fibrosis compared with those without (eg, wT1: 628±82 vs. 546±41 ms, P<0.001). wT1 showed a strong correlation with MRE-derived liver stiffness, outperforming T1-MOLLI and ECV mapping [whole cohort: r=0.67 (wT1) vs. 0.53 (T1-MOLLI) vs. 0.48 (ECV); cohort with PDFF>5%: r=0.69 (wT1) vs. 0.44 (T1) vs. 0.49 (ECV); P<0.05 in each case, respectively]. wT1 had a superior diagnostic performance for the detection of significant fibrosis [whole cohort, area under the curve (AUC): 0.82 (wT1); 0.77 (T1-MOLLI); 0.73 (ECV), P<0.001 in each case; cohort with PDFF>5%, AUC: 0.84, P=0.002 (wT1), 0.70, P=0.04 (T1-MOLLI), 0.70, P=0.04 (ECV)].</AbstractText Compared with T1-MOLLI and ECV mapping, the proposed fat-corrected CIR-LL wT1 method proved to be a more robust marker of hepatic fibrosis in CLD, also in the presence of hepatic steatosis.</AbstractText
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A Semantic Generalization of Shannon's Information Theory and Applications. Does semantic communication require a semantic information theory parallel to Shannon's information theory, or can Shannon's work be generalized for semantic communication? This paper advocates for the latter and introduces a semantic generalization of Shannon's information theory (G theory for short). The core idea is to replace the distortion constraint with the semantic constraint, achieved by utilizing a set of truth functions as a semantic channel. These truth functions enable the expressions of semantic distortion, semantic information measures, and semantic information loss. Notably, the maximum semantic information criterion is equivalent to the maximum likelihood criterion and similar to the Regularized Least Squares criterion. This paper shows G theory's applications to daily and electronic semantic communication, machine learning, constraint control, Bayesian confirmation, portfolio theory, and information value. The improvements in machine learning methods involve multi-label learning and classification, maximum mutual information classification, mixture models, and solving latent variables. Furthermore, insights from statistical physics are discussed: Shannon information is similar to free energy; semantic information to free energy in local equilibrium systems; and information efficiency to the efficiency of free energy in performing work. The paper also proposes refining Friston's minimum free energy principle into the maximum information efficiency principle. Lastly, it compares G theory with other semantic information theories and discusses its limitation in representing the semantics of complex data.</AbstractText
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Active inference on discrete state-spaces: A synthesis. Active inference is a normative principle underwriting perception, action, planning, decision-making and learning in biological or artificial agents. From its inception, its associated process theory has grown to incorporate complex generative models, enabling simulation of a wide range of complex behaviours. Due to successive developments in active inference, it is often difficult to see how its underlying principle relates to process theories and practical implementation. In this paper, we try to bridge this gap by providing a complete mathematical synthesis of active inference on discrete state-space models. This technical summary provides an overview of the theory, derives neuronal dynamics from first principles and relates this dynamics to biological processes. Furthermore, this paper provides a fundamental building block needed to understand active inference for mixed generative models; allowing continuous sensations to inform discrete representations. This paper may be used as follows: to guide research towards outstanding challenges, a practical guide on how to implement active inference to simulate experimental behaviour, or a pointer towards various in-silico neurophysiological responses that may be used to make empirical predictions.</AbstractText
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Dixon-Based Water T1 Mapping for Fat-Corrected Assessment of Hepatic Fibrosis in Chronic Liver Disease. The diagnostic value of conventional T1 mapping for noninvasive assessment of liver fibrosis is limited in the presence of hepatic steatosis. To evaluate the diagnostic value of water T1 (wT1) with continuous inversion-recovery Look-Locker (CIR-LL) method, integrating spiral readout, Dixon, and dictionary-based processing, for the fat-corrected assessment of hepatic fibrosis in patients with chronic liver disease (CLD).</AbstractText In this prospective study, consecutive participants with CLD underwent liver magnetic resonance imaging (MRI), which included assessment of MR-elastography (MRE)-derived liver stiffness, proton density fat fraction (PDFF), T1 relaxation times using modified Look-Locker inversion recovery (T1-MOLLI) and extracellular volume fraction (ECV), and wT1 relaxation times. MRE served as the reference standard to evaluate the diagnostic performance of MRI-based mapping parameters. Significant fibrosis (≥F2) was defined as MRE-derived liver stiffness >3.66 kPa in patients with PDFF≤5%, or >3.14 kPa in patients with PDFF>5%. Statistical analysis included Student t test, receiver operating characteristic (ROC) analysis, and Spearman correlation coefficient.</AbstractText A total of 81 CLD patients (mean age, 50±14 y; 32 female; 40 patients with PDFF>5%) were included. All measured mapping values were significantly higher in patients with significant fibrosis compared with those without (eg, wT1: 628±82 vs. 546±41 ms, P<0.001). wT1 showed a strong correlation with MRE-derived liver stiffness, outperforming T1-MOLLI and ECV mapping [whole cohort: r=0.67 (wT1) vs. 0.53 (T1-MOLLI) vs. 0.48 (ECV); cohort with PDFF>5%: r=0.69 (wT1) vs. 0.44 (T1) vs. 0.49 (ECV); P<0.05 in each case, respectively]. wT1 had a superior diagnostic performance for the detection of significant fibrosis [whole cohort, area under the curve (AUC): 0.82 (wT1); 0.77 (T1-MOLLI); 0.73 (ECV), P<0.001 in each case; cohort with PDFF>5%, AUC: 0.84, P=0.002 (wT1), 0.70, P=0.04 (T1-MOLLI), 0.70, P=0.04 (ECV)].</AbstractText Compared with T1-MOLLI and ECV mapping, the proposed fat-corrected CIR-LL wT1 method proved to be a more robust marker of hepatic fibrosis in CLD, also in the presence of hepatic steatosis.</AbstractText
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39859050
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37968392
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40371542
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Differentiating Apical and Basal Left Ventricular Aneurysms Using Sphericity Index: A Clinical Study.
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CD201(+) fascia progenitors choreograph injury repair.
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Polyphenisms in the reproductive response of male quail to short days are driven by testosterone-independent uncoupling in the photoperiodic TSH-DIO2/DIO3 pathway.
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<i
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Optimal tissue recovery and organismal survival are achieved by spatiotemporal tuning of tissue inflammation, contraction and scar formation<sup
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The neuroendocrine control of seasonal breeding in vertebrates depends upon a TSH/DIO2-3 pathway located in the medio-basal hypothalamus. In male quail, early data demonstrated that this photoperiodic control is independent of testosterone. At least two strong predictions arise from this. First, testosterone is unlikely to exert any significant feedback upon the expression of Tshb/Dio2/Dio3. Second, in situations where photoperiod is invariable but reproductive output differs amongst individuals, differential expression of Tshb and/or Dio2/Dio3 may be expected. Here, we validate these two predictions. First, using castration/implantation in male quails maintained under a long photoperiod, we show that the expression of Tshb/Dio2/Dio3 is testosterone independent, while aggressiveness and cognitive behaviours are testosterone driven. Second, taking advantage of the large inter-individual variability in the response of the gonadal axis to short days (i.e. phenotypic morphs), we demonstrate that the magnitude of the decrease in testes mass, size of the cloacal gland and testosterone plasma level is positively associated with levels of induction of Dio3 and repression of Dio2. In contrast, a uniformly low expression of Tshb expression is found in all morphs. These data provide strong evidence that the TSH/DIO2-3 pathway governs the reproductive axis in male quail independently of testosterone. Furthermore, our findings are consistent with the notion that substantial uncoupling in the photoperiodic TSH/DIO2-3 pathway is responsible for the reproductive polyphenisms.</AbstractText
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Differentiating Apical and Basal Left Ventricular Aneurysms Using Sphericity Index: A Clinical Study. <i
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CD201(+) fascia progenitors choreograph injury repair. Optimal tissue recovery and organismal survival are achieved by spatiotemporal tuning of tissue inflammation, contraction and scar formation<sup
|
Polyphenisms in the reproductive response of male quail to short days are driven by testosterone-independent uncoupling in the photoperiodic TSH-DIO2/DIO3 pathway. The neuroendocrine control of seasonal breeding in vertebrates depends upon a TSH/DIO2-3 pathway located in the medio-basal hypothalamus. In male quail, early data demonstrated that this photoperiodic control is independent of testosterone. At least two strong predictions arise from this. First, testosterone is unlikely to exert any significant feedback upon the expression of Tshb/Dio2/Dio3. Second, in situations where photoperiod is invariable but reproductive output differs amongst individuals, differential expression of Tshb and/or Dio2/Dio3 may be expected. Here, we validate these two predictions. First, using castration/implantation in male quails maintained under a long photoperiod, we show that the expression of Tshb/Dio2/Dio3 is testosterone independent, while aggressiveness and cognitive behaviours are testosterone driven. Second, taking advantage of the large inter-individual variability in the response of the gonadal axis to short days (i.e. phenotypic morphs), we demonstrate that the magnitude of the decrease in testes mass, size of the cloacal gland and testosterone plasma level is positively associated with levels of induction of Dio3 and repression of Dio2. In contrast, a uniformly low expression of Tshb expression is found in all morphs. These data provide strong evidence that the TSH/DIO2-3 pathway governs the reproductive axis in male quail independently of testosterone. Furthermore, our findings are consistent with the notion that substantial uncoupling in the photoperiodic TSH/DIO2-3 pathway is responsible for the reproductive polyphenisms.</AbstractText
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34322861
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30242519
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33831597
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gammaCore for Cluster Headaches: A NICE Medical Technologies Guidance.
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Migraine and cluster headache - the common link.
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Proteomic analysis of Caenorhabditis elegans wound model reveals novel molecular players involved in repair.
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Cluster headaches are excruciating attacks of pain that can last between 15 min and 3 h. Cluster headaches can be episodic, where patients have long pain-free intervals between attacks, or chronic, where they do not. As part of the Medical Technologies Evaluation Programme, the UK National Institute for Health and Care Excellence (NICE) considered the clinical effectiveness and cost impact of gammaCore (electroCore), a handheld, patient-controlled device used to treat and prevent cluster headache. gammaCore is a non-invasive vagus nerve stimulator, the aim of which is to modify pain signals by stimulating the vagus nerve through the skin of the neck. Evidence suggests that gammaCore reduces the intensity and frequency of cluster headaches and that the addition of gammaCore to standard care is cost saving. Therefore, the guidance published by NICE in December 2019 recommends routine adoption of gammaCore into the UK national health service. However, the guidance noted that gammaCore does not work for everyone and recommended that treatment with gammaCore should stop after 3 months in patients whose symptoms do not improve.</AbstractText
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Although clinically distinguishable, migraine and cluster headache share prominent features such as unilateral pain, common pharmacological triggers such glyceryl trinitrate, histamine, calcitonin gene-related peptide (CGRP) and response to triptans and neuromodulation. Recent data also suggest efficacy of anti CGRP monoclonal antibodies in both migraine and cluster headache. While exact mechanisms behind both disorders remain to be fully understood, the trigeminovascular system represents one possible common pathophysiological pathway and network of both disorders. Here, we review past and current literature shedding light on similarities and differences in phenotype, heritability, pathophysiology, imaging findings and treatment options of migraine and cluster headache. A continued focus on their shared pathophysiological pathways may be important in paving future treatment avenues that could benefit both migraine and cluster headache patients.</AbstractText
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Wound repair is a multistep process which involves coordination of multiple molecular players from different cell types and pathways. Though the cellular processes that are taking place in order to repair damage is already known, molecular players involved in crucial pathways are still scarce. In this regard, the present study intends to uncover crucial players that are involved in the central repair events through proteomics approach which included 2-D GE and LC-MS/MS using Caenorhabditis elegans wound model. Initial gel-based 2-D GE and following protein-protein interaction (PPI) network analyses revealed active role of calcium signaling, acetylcholine transport and serotonergic neurotransmitter pathways. Further, gel-free LC-MS/MS and following PPI network analyses revealed the incidence of actin nucleation at the initial hours immediately after injury. Further by visualizing the PPI network and the interacting players, pink-1, a mitochondrial Serine/threonine-protein kinase which is known to regulate mitochondrial dynamics, was found to be the central player in facilitating the mitochondrial fission and its role was further verified using qPCR analysis and pink-1 transgenic worms. Overall, the study delivers new insights from crucial regulatory pathways and central players involved in wound repair using high throughput proteomic approaches and the mass spectrometry Data (PXD024629/PXD024744) are available via ProteomeXchange. SIGNIFICANCE.</AbstractText
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gammaCore for Cluster Headaches: A NICE Medical Technologies Guidance. Cluster headaches are excruciating attacks of pain that can last between 15 min and 3 h. Cluster headaches can be episodic, where patients have long pain-free intervals between attacks, or chronic, where they do not. As part of the Medical Technologies Evaluation Programme, the UK National Institute for Health and Care Excellence (NICE) considered the clinical effectiveness and cost impact of gammaCore (electroCore), a handheld, patient-controlled device used to treat and prevent cluster headache. gammaCore is a non-invasive vagus nerve stimulator, the aim of which is to modify pain signals by stimulating the vagus nerve through the skin of the neck. Evidence suggests that gammaCore reduces the intensity and frequency of cluster headaches and that the addition of gammaCore to standard care is cost saving. Therefore, the guidance published by NICE in December 2019 recommends routine adoption of gammaCore into the UK national health service. However, the guidance noted that gammaCore does not work for everyone and recommended that treatment with gammaCore should stop after 3 months in patients whose symptoms do not improve.</AbstractText
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Migraine and cluster headache - the common link. Although clinically distinguishable, migraine and cluster headache share prominent features such as unilateral pain, common pharmacological triggers such glyceryl trinitrate, histamine, calcitonin gene-related peptide (CGRP) and response to triptans and neuromodulation. Recent data also suggest efficacy of anti CGRP monoclonal antibodies in both migraine and cluster headache. While exact mechanisms behind both disorders remain to be fully understood, the trigeminovascular system represents one possible common pathophysiological pathway and network of both disorders. Here, we review past and current literature shedding light on similarities and differences in phenotype, heritability, pathophysiology, imaging findings and treatment options of migraine and cluster headache. A continued focus on their shared pathophysiological pathways may be important in paving future treatment avenues that could benefit both migraine and cluster headache patients.</AbstractText
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Proteomic analysis of Caenorhabditis elegans wound model reveals novel molecular players involved in repair. Wound repair is a multistep process which involves coordination of multiple molecular players from different cell types and pathways. Though the cellular processes that are taking place in order to repair damage is already known, molecular players involved in crucial pathways are still scarce. In this regard, the present study intends to uncover crucial players that are involved in the central repair events through proteomics approach which included 2-D GE and LC-MS/MS using Caenorhabditis elegans wound model. Initial gel-based 2-D GE and following protein-protein interaction (PPI) network analyses revealed active role of calcium signaling, acetylcholine transport and serotonergic neurotransmitter pathways. Further, gel-free LC-MS/MS and following PPI network analyses revealed the incidence of actin nucleation at the initial hours immediately after injury. Further by visualizing the PPI network and the interacting players, pink-1, a mitochondrial Serine/threonine-protein kinase which is known to regulate mitochondrial dynamics, was found to be the central player in facilitating the mitochondrial fission and its role was further verified using qPCR analysis and pink-1 transgenic worms. Overall, the study delivers new insights from crucial regulatory pathways and central players involved in wound repair using high throughput proteomic approaches and the mass spectrometry Data (PXD024629/PXD024744) are available via ProteomeXchange. SIGNIFICANCE.</AbstractText
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15120171
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15122676
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15300207
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Cardiac phosphorus-31 two-dimensional chemical shift imaging in patients with hereditary hemochromatosis.
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Quantitative description of proton exchange processes between water and endogenous and exogenous agents for WEX, CEST, and APT experiments.
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Murine hindlimb reperfusion injury can be initiated by a self-reactive monoclonal IgM.
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Hemochromatosis is a hereditary iron overload syndrome characterized by increased iron storage, followed by liver cirrhosis and is often associated with restrictive cardiomyopathy. The purpose of this study was to detect alterations of cardiac high-energy phosphate metabolism in patients with hereditary hemochromatosis (HHC) prior to the development of structural heart diseases. Therefore cardiac phosphorus-31 two-dimensional chemical shift imaging ((31)P 2D CSI) was employed. Twenty-four male patients (mean age 47.2 +/- 12 years) homozygous for the C282Y mutation in the hemochromatosis associated HFE gene and twenty-four male healthy volunteers (mean age 47 +/- 11 years) as age-matched controls were included in this study. Using a 1.5-Tesla whole-body magnetic resonance scanner, electrocardiograph-triggered transversal 31P 2D CSI was performed. Left ventricle mean phosphocreatine (PCr) to beta-adenosine triphosphate (beta-ATP) ratios of patients with HHC (1.60 +/- 0.41) were significantly decreased in comparison to healthy volunteers (1.93 +/- 0.36; p = 0.004). Furthermore, we detected moderate, negative correlations between left ventricular PCr to beta-ATP ratios and transferrin saturation, cholesterol, low-density lipoprotein as well as triglyceride. This study shows that 31P 2D CSI permits the detection of alterations of cardiac high-energy phosphate metabolism in patients with HHC, but without any evidence for heart disease. The decreased PCr to beta-ATP ratios in HHC might be caused by mitochondrial impairment due to cardiac iron overload.</AbstractText
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The proton exchange processes between water and solutes containing exchangeable protons have recently become of interest for monitoring pH effects, detecting cellular mobile proteins and peptides, and enhancing the detection sensitivity of various low-concentration endogenous and exogenous species. In this work, the analytic expressions for water exchange (WEX) filter spectroscopy, chemical exchange-dependent saturation transfer (CEST), and amide proton transfer (APT) experiments are derived by the use of Bloch equations with exchange terms. The effects of the initial states for the system, the difference between a steady state and a saturation state, and the relative contributions of the forward and backward exchange processes are discussed. The theory, in combination with numerical calculations, provides a useful tool for designing experimental schemes and assessing magnetization transfer (MT) processes between water protons and solvent-exchangeable protons. As an example, the case of endogenous amide proton exchange in the rat brain at 4.7 T is analyzed in detail.</AbstractText
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Murine hindlimb reperfusion injury (I/R), is initiated by activation of the classical pathway of complement. Complement receptor-2 knockout mice (Cr2-/-) are protected from I/R injury due to defective B-1 cells with a resulting deficient natural immunoglobulin M (IgM) repertoire. Cr2-/- and wild type (WT) mice were studied to isolate the antibody or antibodies responsible for initiation of I/R.</AbstractText IgM-secreting B-1 cell clones were produced with hybridoma technology from WT cells. Of 21 clones tested in murine I/R models, only 1 clone, CM22, was found to restore injury in protected mice. Cr2-/- mice reconstituted with IgM from individual clones, WT serum, or saline were subjected to 2 hours hindlimb ischemia and 3 hours reperfusion and compared with WT.</AbstractText Muscle injury in Cr2-/- mice reconstituted with CM22 was similar to injury in WT mice reconstituted with saline and Cr2-/- mice reconstituted with WT serum. This injury was 137% greater (P < .05) than in both Cr2-/- mice reconstituted with saline and those reconstituted with a different IgM clone, CM31. IgM and C3 deposition was found only on injured muscle of WT mice or Cr2-/- mice reconstituted with CM22 or WT serum.</AbstractText A single clone of self-reactive IgM, CM22, can initiate complement-dependent I/R injury.</AbstractText
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Cardiac phosphorus-31 two-dimensional chemical shift imaging in patients with hereditary hemochromatosis. Hemochromatosis is a hereditary iron overload syndrome characterized by increased iron storage, followed by liver cirrhosis and is often associated with restrictive cardiomyopathy. The purpose of this study was to detect alterations of cardiac high-energy phosphate metabolism in patients with hereditary hemochromatosis (HHC) prior to the development of structural heart diseases. Therefore cardiac phosphorus-31 two-dimensional chemical shift imaging ((31)P 2D CSI) was employed. Twenty-four male patients (mean age 47.2 +/- 12 years) homozygous for the C282Y mutation in the hemochromatosis associated HFE gene and twenty-four male healthy volunteers (mean age 47 +/- 11 years) as age-matched controls were included in this study. Using a 1.5-Tesla whole-body magnetic resonance scanner, electrocardiograph-triggered transversal 31P 2D CSI was performed. Left ventricle mean phosphocreatine (PCr) to beta-adenosine triphosphate (beta-ATP) ratios of patients with HHC (1.60 +/- 0.41) were significantly decreased in comparison to healthy volunteers (1.93 +/- 0.36; p = 0.004). Furthermore, we detected moderate, negative correlations between left ventricular PCr to beta-ATP ratios and transferrin saturation, cholesterol, low-density lipoprotein as well as triglyceride. This study shows that 31P 2D CSI permits the detection of alterations of cardiac high-energy phosphate metabolism in patients with HHC, but without any evidence for heart disease. The decreased PCr to beta-ATP ratios in HHC might be caused by mitochondrial impairment due to cardiac iron overload.</AbstractText
|
Quantitative description of proton exchange processes between water and endogenous and exogenous agents for WEX, CEST, and APT experiments. The proton exchange processes between water and solutes containing exchangeable protons have recently become of interest for monitoring pH effects, detecting cellular mobile proteins and peptides, and enhancing the detection sensitivity of various low-concentration endogenous and exogenous species. In this work, the analytic expressions for water exchange (WEX) filter spectroscopy, chemical exchange-dependent saturation transfer (CEST), and amide proton transfer (APT) experiments are derived by the use of Bloch equations with exchange terms. The effects of the initial states for the system, the difference between a steady state and a saturation state, and the relative contributions of the forward and backward exchange processes are discussed. The theory, in combination with numerical calculations, provides a useful tool for designing experimental schemes and assessing magnetization transfer (MT) processes between water protons and solvent-exchangeable protons. As an example, the case of endogenous amide proton exchange in the rat brain at 4.7 T is analyzed in detail.</AbstractText
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Murine hindlimb reperfusion injury can be initiated by a self-reactive monoclonal IgM. Murine hindlimb reperfusion injury (I/R), is initiated by activation of the classical pathway of complement. Complement receptor-2 knockout mice (Cr2-/-) are protected from I/R injury due to defective B-1 cells with a resulting deficient natural immunoglobulin M (IgM) repertoire. Cr2-/- and wild type (WT) mice were studied to isolate the antibody or antibodies responsible for initiation of I/R.</AbstractText IgM-secreting B-1 cell clones were produced with hybridoma technology from WT cells. Of 21 clones tested in murine I/R models, only 1 clone, CM22, was found to restore injury in protected mice. Cr2-/- mice reconstituted with IgM from individual clones, WT serum, or saline were subjected to 2 hours hindlimb ischemia and 3 hours reperfusion and compared with WT.</AbstractText Muscle injury in Cr2-/- mice reconstituted with CM22 was similar to injury in WT mice reconstituted with saline and Cr2-/- mice reconstituted with WT serum. This injury was 137% greater (P < .05) than in both Cr2-/- mice reconstituted with saline and those reconstituted with a different IgM clone, CM31. IgM and C3 deposition was found only on injured muscle of WT mice or Cr2-/- mice reconstituted with CM22 or WT serum.</AbstractText A single clone of self-reactive IgM, CM22, can initiate complement-dependent I/R injury.</AbstractText
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22182778
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19458219
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22809782
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Prolonged exposure to NMDAR antagonist induces cell-type specific changes of glutamatergic receptors in rat prefrontal cortex.
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Synaptic scaling requires the GluR2 subunit of the AMPA receptor.
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Validity of the American College of Rheumatology criteria for the diagnosis of giant cell arteritis.
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N-methyl-d-aspartic acid (NMDA) receptors are critical for both normal brain functions and the pathogenesis of schizophrenia. We investigated the functional changes of glutamatergic receptors in the pyramidal cells and fast-spiking (FS) interneurons in the adolescent rat prefrontal cortex in MK-801 model of schizophrenia. We found that although both pyramidal cells and FS interneurons were affected by in vivo subchronic blockade of NMDA receptors, MK-801 induced distinct changes in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA receptors in the FS interneurons compared with pyramidal cells. Specifically, the amplitude, but not the frequency, of AMPA-mediated miniature excitatory postsynaptic currents (mEPSCs) in FS interneurons was significantly decreased whereas both the frequency and amplitude in pyramidal neurons were increased. In addition, MK-801-induced new presynaptic NMDA receptors were detected in the glutamatergic terminals targeting pyramidal neurons but not FS interneurons. MK-801 also induced distinct alterations in FS interneurons but not in pyramidal neurons, including significantly decreased rectification index and increased calcium permeability. These data suggest a distinct cell-type specific and homeostatic synaptic scaling and redistribution of AMPA and NMDA receptors in response to the subchronic blockade of NMDA receptors and thus provide a direct mechanistic explanation for the NMDA hypofunction hypothesis that have long been proposed for the schizophrenia pathophysiology.</AbstractText
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Two functionally distinct forms of synaptic plasticity, Hebbian long-term potentiation (LTP) and homeostatic synaptic scaling, are thought to cooperate to promote information storage and circuit refinement. Both arise through changes in the synaptic accumulation of AMPA receptors (AMPARs), but whether they use similar or distinct receptor-trafficking pathways is unknown. Here, we show that TTX-induced synaptic scaling in cultured visual cortical neurons leads to the insertion of GluR2-containing AMPARs at synapses. Similarly, visual deprivation with monocular TTX injections results in synaptic accumulation of GluR2-containing AMPARs. Unlike chemical LTP, synaptic scaling is blocked by a GluR2 C-tail peptide but not by a GluR1 C-tail peptide. Knockdown of endogenous GluR2 with an short hairpin RNA (shRNA) also blocks synaptic scaling but not chemical LTP. Scaling can be rescued with expression of exogenous GluR2 resistant to the shRNA, but a chimeric GluR2 subunit with the C-terminal domain swapped with the GluR1 C-terminal domain (GluR2/CT1) does not rescue synaptic scaling, indicating that regulatory sequences on the GluR2 C-tail are required for the accumulation of synaptic AMPARs during scaling. Together, our results suggest that synaptic scaling and LTP use different trafficking pathways, making these two forms of plasticity both functionally and molecularly distinct.</AbstractText
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To assess the clinical utility of the American College of Rheumatology criteria for the diagnosis of giant cell arteritis (GCA) in patients with positive and negative temporal artery biopsies.</AbstractText Retrospective case series of all patients undergoing temporal artery biopsy.</AbstractText Retrospective chart review of all patients seen in the Neuro-ophthalmology Service of the Wills Eye Institute undergoing biopsy. One hundred twelve patients were identified between October 2001 and May 2006. Charts were reviewed for American College of Rheumatology criteria, biopsy results, and progression of visual loss after diagnosis.</AbstractText Nine of 35 patients (25.7%) with positive biopsies would not have been diagnosed with GCA using American College of Rheumatology criteria alone. An additional 16 patients (45.7%) met only 2 criteria and required the positive biopsy to establish the American College of Rheumatology diagnosis of GCA. Eleven of 39 patients (28.2%) with negative biopsies met the criteria and would have been diagnosed with GCA. Diagnostic agreement between the American College of Rheumatology criteria without biopsy results and biopsy results alone was 51.4%; with the addition of biopsy results to the criteria, this increased to 73.0%.</AbstractText The current American College of Rheumatology criteria should not be used to diagnose GCA and all patients suspected of having GCA should undergo a temporal artery biopsy.</AbstractText
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Prolonged exposure to NMDAR antagonist induces cell-type specific changes of glutamatergic receptors in rat prefrontal cortex. N-methyl-d-aspartic acid (NMDA) receptors are critical for both normal brain functions and the pathogenesis of schizophrenia. We investigated the functional changes of glutamatergic receptors in the pyramidal cells and fast-spiking (FS) interneurons in the adolescent rat prefrontal cortex in MK-801 model of schizophrenia. We found that although both pyramidal cells and FS interneurons were affected by in vivo subchronic blockade of NMDA receptors, MK-801 induced distinct changes in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA receptors in the FS interneurons compared with pyramidal cells. Specifically, the amplitude, but not the frequency, of AMPA-mediated miniature excitatory postsynaptic currents (mEPSCs) in FS interneurons was significantly decreased whereas both the frequency and amplitude in pyramidal neurons were increased. In addition, MK-801-induced new presynaptic NMDA receptors were detected in the glutamatergic terminals targeting pyramidal neurons but not FS interneurons. MK-801 also induced distinct alterations in FS interneurons but not in pyramidal neurons, including significantly decreased rectification index and increased calcium permeability. These data suggest a distinct cell-type specific and homeostatic synaptic scaling and redistribution of AMPA and NMDA receptors in response to the subchronic blockade of NMDA receptors and thus provide a direct mechanistic explanation for the NMDA hypofunction hypothesis that have long been proposed for the schizophrenia pathophysiology.</AbstractText
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Synaptic scaling requires the GluR2 subunit of the AMPA receptor. Two functionally distinct forms of synaptic plasticity, Hebbian long-term potentiation (LTP) and homeostatic synaptic scaling, are thought to cooperate to promote information storage and circuit refinement. Both arise through changes in the synaptic accumulation of AMPA receptors (AMPARs), but whether they use similar or distinct receptor-trafficking pathways is unknown. Here, we show that TTX-induced synaptic scaling in cultured visual cortical neurons leads to the insertion of GluR2-containing AMPARs at synapses. Similarly, visual deprivation with monocular TTX injections results in synaptic accumulation of GluR2-containing AMPARs. Unlike chemical LTP, synaptic scaling is blocked by a GluR2 C-tail peptide but not by a GluR1 C-tail peptide. Knockdown of endogenous GluR2 with an short hairpin RNA (shRNA) also blocks synaptic scaling but not chemical LTP. Scaling can be rescued with expression of exogenous GluR2 resistant to the shRNA, but a chimeric GluR2 subunit with the C-terminal domain swapped with the GluR1 C-terminal domain (GluR2/CT1) does not rescue synaptic scaling, indicating that regulatory sequences on the GluR2 C-tail are required for the accumulation of synaptic AMPARs during scaling. Together, our results suggest that synaptic scaling and LTP use different trafficking pathways, making these two forms of plasticity both functionally and molecularly distinct.</AbstractText
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Validity of the American College of Rheumatology criteria for the diagnosis of giant cell arteritis. To assess the clinical utility of the American College of Rheumatology criteria for the diagnosis of giant cell arteritis (GCA) in patients with positive and negative temporal artery biopsies.</AbstractText Retrospective case series of all patients undergoing temporal artery biopsy.</AbstractText Retrospective chart review of all patients seen in the Neuro-ophthalmology Service of the Wills Eye Institute undergoing biopsy. One hundred twelve patients were identified between October 2001 and May 2006. Charts were reviewed for American College of Rheumatology criteria, biopsy results, and progression of visual loss after diagnosis.</AbstractText Nine of 35 patients (25.7%) with positive biopsies would not have been diagnosed with GCA using American College of Rheumatology criteria alone. An additional 16 patients (45.7%) met only 2 criteria and required the positive biopsy to establish the American College of Rheumatology diagnosis of GCA. Eleven of 39 patients (28.2%) with negative biopsies met the criteria and would have been diagnosed with GCA. Diagnostic agreement between the American College of Rheumatology criteria without biopsy results and biopsy results alone was 51.4%; with the addition of biopsy results to the criteria, this increased to 73.0%.</AbstractText The current American College of Rheumatology criteria should not be used to diagnose GCA and all patients suspected of having GCA should undergo a temporal artery biopsy.</AbstractText
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39005951
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30648799
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38649908
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Evidence for Two Types of Task Conflict in a Color-Digit Stroop Task.
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Disentangling the Mechanisms of Symbolic Number Processing in Adults' Mathematics and Arithmetic Achievement.
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Interruptible demyelination in avian riboflavin deficient neuropathy.
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In the present study, we conducted a Stroop-like task in which the participants were required to decide whether the presented stimulus, which could be either a colored digit or a colored rectangle, consisted of more or less than five colors. Like other Stroop-like tasks, the stimuli could be congruent (the stimulus was a digit that was equal to the presented number of colors), incongruent (the stimulus was a digit that was different than the presented number of colors), or neutral (a colored rectangle). We utilized a two-to-one response setting so that in some incongruent trials the digit and the number of colors would elicit the same response (e.g., the digit 3 containing two colors; both are smaller than 5), while in some incongruent trials, the digit and the number of colors would elicit different responses (e.g., the digit 3 containing 6 colors). This enabled us to measure both conflicts arising from stimulus-stimulus and stimulus-response compatibilities. Our results indicated the existence of stimulus-stimulus compatibility (SSC), stimulus-response compatibility (SRC), and task conflict. Interestingly, these effects were in interaction with the number of colors, so that in small numbers, SSC and SRC were found, and in large numbers, SRC and task conflict were found. Moreover, the results suggest that our task includes two types of task conflict that are raised due to three different tasks: processing the meaning of the digit vs. estimating the number of colors and counting the number of colors vs. estimating the number of colors.</AbstractText
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A growing body of research has shown that symbolic number processing relates to individual differences in mathematics. However, it remains unclear which mechanisms of symbolic number processing are crucial-accessing underlying magnitude representation of symbols (i.e., symbol-magnitude associations), processing relative order of symbols (i.e., symbol-symbol associations), or processing of symbols per se. To address this question, in this study adult participants performed a dots-number word matching task-thought to be a measure of symbol-magnitude associations (numerical magnitude processing)-a numeral-ordering task that focuses on symbol-symbol associations (numerical order processing), and a digit-number word matching task targeting symbolic processing per se. Results showed that both numerical magnitude and order processing were uniquely related to arithmetic achievement, beyond the effects of domain-general factors (intellectual ability, working memory, inhibitory control, and non-numerical ordering). Importantly, results were different when a general measure of mathematics achievement was considered. Those mechanisms of symbolic number processing did not contribute to math achievement. Furthermore, a path analysis revealed that numerical magnitude and order processing might draw on a common mechanism. Each process explained a portion of the relation of the other with arithmetic (but not with a general measure of math achievement). These findings are consistent with the notion that adults' arithmetic skills build upon symbol-magnitude associations, and they highlight the effects that different math measures have in the study of numerical cognition.</AbstractText
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The evolution of demyelination in individual internodes remains unclear although it has been noticed the paranodal demyelination precedes internodal demyelination in neuropathies with diverse aetiologies. For therapeutic purpose, it is fundamental to know whether the demyelinating procedure in affected internodes can be interrupted. This study aimed to delineate the development of demyelination in individual internodes in avian riboflavin deficient neuropathy.</AbstractText Newborn broiler meat chickens were maintained either on a routine diet containing 5.0 mg/kg riboflavin, a riboflavin deficient diet containing 1.8 mg/kg riboflavin, or initially a riboflavin deficient diet for 11 days and then routine diet plus riboflavin repletion from day 12. Evolution of demyelination in individual internodes was analyzed by teased nerve fibre studies from day 11 to 21.</AbstractText In riboflavin deficient chickens, demyelination was the predominant feature: it was mainly confined to the paranodal region at day 11; extended into internodal region, but less than half of the internodal length in most affected internodes at day 16; involved more than half or whole internode at day 21. In the internode undergoing demyelination, myelin degeneration of varying degrees was noticed in the cytoplasm of the Schwann cell wrapping the internode. Two days after riboflavin repletion, co-existence of remyelination and active demyelination within individual internodes was noticed. Remyelination together with preserved short original internodes was the characteristic feature 4 and 9 days after riboflavin repletion.</AbstractText Riboflavin repletion interrupts the progression from paranodal to internodal demyelination in riboflavin deficient chickens and promotes remyelination before complete internodal demyelination.</AbstractText
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Evidence for Two Types of Task Conflict in a Color-Digit Stroop Task. In the present study, we conducted a Stroop-like task in which the participants were required to decide whether the presented stimulus, which could be either a colored digit or a colored rectangle, consisted of more or less than five colors. Like other Stroop-like tasks, the stimuli could be congruent (the stimulus was a digit that was equal to the presented number of colors), incongruent (the stimulus was a digit that was different than the presented number of colors), or neutral (a colored rectangle). We utilized a two-to-one response setting so that in some incongruent trials the digit and the number of colors would elicit the same response (e.g., the digit 3 containing two colors; both are smaller than 5), while in some incongruent trials, the digit and the number of colors would elicit different responses (e.g., the digit 3 containing 6 colors). This enabled us to measure both conflicts arising from stimulus-stimulus and stimulus-response compatibilities. Our results indicated the existence of stimulus-stimulus compatibility (SSC), stimulus-response compatibility (SRC), and task conflict. Interestingly, these effects were in interaction with the number of colors, so that in small numbers, SSC and SRC were found, and in large numbers, SRC and task conflict were found. Moreover, the results suggest that our task includes two types of task conflict that are raised due to three different tasks: processing the meaning of the digit vs. estimating the number of colors and counting the number of colors vs. estimating the number of colors.</AbstractText
|
Disentangling the Mechanisms of Symbolic Number Processing in Adults' Mathematics and Arithmetic Achievement. A growing body of research has shown that symbolic number processing relates to individual differences in mathematics. However, it remains unclear which mechanisms of symbolic number processing are crucial-accessing underlying magnitude representation of symbols (i.e., symbol-magnitude associations), processing relative order of symbols (i.e., symbol-symbol associations), or processing of symbols per se. To address this question, in this study adult participants performed a dots-number word matching task-thought to be a measure of symbol-magnitude associations (numerical magnitude processing)-a numeral-ordering task that focuses on symbol-symbol associations (numerical order processing), and a digit-number word matching task targeting symbolic processing per se. Results showed that both numerical magnitude and order processing were uniquely related to arithmetic achievement, beyond the effects of domain-general factors (intellectual ability, working memory, inhibitory control, and non-numerical ordering). Importantly, results were different when a general measure of mathematics achievement was considered. Those mechanisms of symbolic number processing did not contribute to math achievement. Furthermore, a path analysis revealed that numerical magnitude and order processing might draw on a common mechanism. Each process explained a portion of the relation of the other with arithmetic (but not with a general measure of math achievement). These findings are consistent with the notion that adults' arithmetic skills build upon symbol-magnitude associations, and they highlight the effects that different math measures have in the study of numerical cognition.</AbstractText
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Interruptible demyelination in avian riboflavin deficient neuropathy. The evolution of demyelination in individual internodes remains unclear although it has been noticed the paranodal demyelination precedes internodal demyelination in neuropathies with diverse aetiologies. For therapeutic purpose, it is fundamental to know whether the demyelinating procedure in affected internodes can be interrupted. This study aimed to delineate the development of demyelination in individual internodes in avian riboflavin deficient neuropathy.</AbstractText Newborn broiler meat chickens were maintained either on a routine diet containing 5.0 mg/kg riboflavin, a riboflavin deficient diet containing 1.8 mg/kg riboflavin, or initially a riboflavin deficient diet for 11 days and then routine diet plus riboflavin repletion from day 12. Evolution of demyelination in individual internodes was analyzed by teased nerve fibre studies from day 11 to 21.</AbstractText In riboflavin deficient chickens, demyelination was the predominant feature: it was mainly confined to the paranodal region at day 11; extended into internodal region, but less than half of the internodal length in most affected internodes at day 16; involved more than half or whole internode at day 21. In the internode undergoing demyelination, myelin degeneration of varying degrees was noticed in the cytoplasm of the Schwann cell wrapping the internode. Two days after riboflavin repletion, co-existence of remyelination and active demyelination within individual internodes was noticed. Remyelination together with preserved short original internodes was the characteristic feature 4 and 9 days after riboflavin repletion.</AbstractText Riboflavin repletion interrupts the progression from paranodal to internodal demyelination in riboflavin deficient chickens and promotes remyelination before complete internodal demyelination.</AbstractText
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40464173
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39568474
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38659785
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Computer-Aided Decision Support Systems of Alzheimer's Disease Diagnosis - A Systematic Review.
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FLEX-SMOTE: Synthetic over-sampling technique that flexibly adjusts to different minority class distributions.
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Imaging of brain electric field networks with spatially resolved EEG.
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The incidence of Alzheimer's disease is rising with the increasing elderly population worldwide. While no cure exists, early diagnosis can significantly slow disease progression. Computer-aided diagnostic systems are becoming critical tools for assisting in the early detection of Alzheimer's disease. In this systematic review, we aim to evaluate recent advancements in computer-aided decision support systems for Alzheimer's disease diagnosis, focusing on data modalities, machine learning methods, and performance metrics.</AbstractText We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies published between 2021 and 2024 were retrieved from PubMed, IEEEXplore and Web of Science, using search terms related to Alzheimer's disease classification, neuroimaging, machine learning, and diagnostic performance. A total of 39 studies met the inclusion criteria, focusing on the use of Magnetic Resonance Imaging, Positron Emission Tomography, and biomarkers for Alzheimer's disease classification using machine learning models.</AbstractText Multimodal approaches, combining Magnetic Resonance Imaging with Positron Emission Tomography and Cognitive assessments, outperformed single-modality studies in diagnostic accuracy reliability. Convolutional Neural Networks were the most commonly used machine learning models, followed by hybrid models and Random Forest. The highest accuracy reported for binary classification was 100%, while multi-class classification achieved up to 99.98%. Techniques like Synthetic Minority Over-sampling Technique and data augmentation were frequently employed to address data imbalance, improving model generalizability.</AbstractText Our review highlights the advantages of using multimodal data in computer-aided decision support systems for more accurate Alzheimer's disease diagnosis. However, we also identified several limitations, including data imbalance, small sample sizes, and the lack of external validation in most studies. Future research should utilize larger, more diverse datasets, incorporate longitudinal data, and validate models in real-world clinical trials. Additionally, there is a growing need for explainability in machine learning models to ensure they are interpretable and trusted in clinical settings.</AbstractText While computer-aided decision support systems show great promise in improving the early diagnosis of Alzheimer's disease, further work is needed to enhance their robustness, generalizability, and clinical applicability. By addressing these challenges, computer-aided decision support systems could play a pivotal role in the early detection and management of Alzheimer's disease, potentially improving patient outcomes and reducing healthcare costs.</AbstractText
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Class imbalance is a challenge that affects the prediction rate on a minority class. To remedy this problem, various SMOTEs (synthetic minority over-sampling techniques) have been designed to populate synthetic minority instances. Some SMOTEs operate on the border of a minority class, while others concentrate on the class core. Unfortunately, it is difficult to put the right SMOTE to the right dataset because distributions of classes are varied and might not be obvious. This paper proposes a new technique, called FLEX-SMOTE, that is flexible enough to be used with all sorts of datasets. The key idea is that an over-sampled region is selected based on the characteristics of minority classes. This approach is based on a density function that is used to describe the distributions of minority classes. Herein, we have included experimental results showing that FLEX-SMOTE can significantly improve the predictive performance of a minority class.</AbstractText
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We present a method for spatially resolving the electric field potential throughout the entire volume of the human brain from electroencephalography (EEG) data. The method is <i
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Computer-Aided Decision Support Systems of Alzheimer's Disease Diagnosis - A Systematic Review. The incidence of Alzheimer's disease is rising with the increasing elderly population worldwide. While no cure exists, early diagnosis can significantly slow disease progression. Computer-aided diagnostic systems are becoming critical tools for assisting in the early detection of Alzheimer's disease. In this systematic review, we aim to evaluate recent advancements in computer-aided decision support systems for Alzheimer's disease diagnosis, focusing on data modalities, machine learning methods, and performance metrics.</AbstractText We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies published between 2021 and 2024 were retrieved from PubMed, IEEEXplore and Web of Science, using search terms related to Alzheimer's disease classification, neuroimaging, machine learning, and diagnostic performance. A total of 39 studies met the inclusion criteria, focusing on the use of Magnetic Resonance Imaging, Positron Emission Tomography, and biomarkers for Alzheimer's disease classification using machine learning models.</AbstractText Multimodal approaches, combining Magnetic Resonance Imaging with Positron Emission Tomography and Cognitive assessments, outperformed single-modality studies in diagnostic accuracy reliability. Convolutional Neural Networks were the most commonly used machine learning models, followed by hybrid models and Random Forest. The highest accuracy reported for binary classification was 100%, while multi-class classification achieved up to 99.98%. Techniques like Synthetic Minority Over-sampling Technique and data augmentation were frequently employed to address data imbalance, improving model generalizability.</AbstractText Our review highlights the advantages of using multimodal data in computer-aided decision support systems for more accurate Alzheimer's disease diagnosis. However, we also identified several limitations, including data imbalance, small sample sizes, and the lack of external validation in most studies. Future research should utilize larger, more diverse datasets, incorporate longitudinal data, and validate models in real-world clinical trials. Additionally, there is a growing need for explainability in machine learning models to ensure they are interpretable and trusted in clinical settings.</AbstractText While computer-aided decision support systems show great promise in improving the early diagnosis of Alzheimer's disease, further work is needed to enhance their robustness, generalizability, and clinical applicability. By addressing these challenges, computer-aided decision support systems could play a pivotal role in the early detection and management of Alzheimer's disease, potentially improving patient outcomes and reducing healthcare costs.</AbstractText
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FLEX-SMOTE: Synthetic over-sampling technique that flexibly adjusts to different minority class distributions. Class imbalance is a challenge that affects the prediction rate on a minority class. To remedy this problem, various SMOTEs (synthetic minority over-sampling techniques) have been designed to populate synthetic minority instances. Some SMOTEs operate on the border of a minority class, while others concentrate on the class core. Unfortunately, it is difficult to put the right SMOTE to the right dataset because distributions of classes are varied and might not be obvious. This paper proposes a new technique, called FLEX-SMOTE, that is flexible enough to be used with all sorts of datasets. The key idea is that an over-sampled region is selected based on the characteristics of minority classes. This approach is based on a density function that is used to describe the distributions of minority classes. Herein, we have included experimental results showing that FLEX-SMOTE can significantly improve the predictive performance of a minority class.</AbstractText
|
Imaging of brain electric field networks with spatially resolved EEG. We present a method for spatially resolving the electric field potential throughout the entire volume of the human brain from electroencephalography (EEG) data. The method is <i
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38102180
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11990806
|
31068653
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Usefulness of thalamic beta activity for closed-loop therapy in essential tremor.
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Comparison of atlas- and magnetic resonance imaging-based stereotactic targeting of the globus pallidus internus in the performance of deep brain stimulation for treatment of dystonia.
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Further characterization of the zebrafish model of acrylamide acute neurotoxicity: gait abnormalities and oxidative stress.
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A partial loss of effectiveness of deep brain stimulation of the ventral intermediate nucleus of the thalamus (VIM) has been reported in some patients with essential tremor (ET), possibly due to habituation to permanent stimulation. This study focused on the evolution of VIM local-field potentials (LFPs) data over time to assess the long-term feasibility of closed-loop therapy based on thalamic activity. We performed recordings of thalamic LFPs in 10 patients with severe ET using the ACTIVA™ PC + S (Medtronic plc.) allowing both recordings and stimulation in the same region. Particular attention was paid to describing the evolution of LFPs over time from 3 to 24 months after surgery when the stimulation was Off. We demonstrated a significant decrease in high-beta LFPs amplitude during movements inducing tremor in comparison to the rest condition 3 months after surgery (1.91 ± 0.89 at rest vs. 1.27 ± 1.37 µV<sup
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To assess the validity of relying on atlases during stereotactic neurosurgery, the authors compared target coordinates in the globus pallidus internus (GPi) obtained using magnetic resonance (MR) imaging with those determined using an atlas. The targets were used in deep brain stimulation (DBS) for the treatment of generalized dystonia.</AbstractText Thirty-five patients, who were treated using bilateral DBS of the GPi, were included in this study. The target was selected on three-dimensional MR images by direct visual recognition of the GPi. The coordinates were automatically recorded using dedicated software. They were translated into the anterior commissure-posterior commissure (AC-PC) coordinate system by using a matrix transformation process. The same GPi target was defined, based on the locations of brain structures shown in the atlases of Schaltenbrand and Talairach. Magnetic resonance imaging-based GPi target coordinates were statistically compared with the corresponding atlas-based coordinates by applying the Student t-test. A significant difference (p < 0.001) was demonstrated in x, y, and z directions between MR imaging-based and Schaltenbrand atlas-derived target coordinates. The comparison with normalized Talairach atlas coordinates demonstrated a significant difference (p < 0.01) in the y and z directions, although not in the x direction (p = 0.12). No significant correlation existed between MR imaging-based target coordinates and patient age (p > 0.1). No significant correlation was observed between MR imaging-based target coordinates and patient sex in the y and z directions (p > 0.9), although it was significant in the x direction (p < 0.05). A significant variation in coordinates and the length of the AC-PC line was revealed only in the y direction (p < 0.005).</AbstractText A significant difference was found between target coordinates obtained by direct visual targeting on MR images (validated by postoperative clinical results) and those obtained by indirect targeting based on atlases.</AbstractText
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Occupational, accidental, or suicidal exposure to acrylamide (ACR) may result in a neurotoxic syndrome. Development of animal models of acrylamide neurotoxicity is necessary for increasing our mechanistic understanding of this syndrome and developing more effective therapies. A new model for acute ACR neurotoxicity has been recently developed in adult zebrafish. Whereas the results of the initial characterization were really promising, a further characterization is needed for testing the construct validity of the model. In this study, the presence of gait abnormalities has been investigated by using ZebraGait, software specifically designed to analyze the kinematics of fish swimming in a water tunnel. The results of the kinematic analyses demonstrated that the model exhibits mild-to-moderate gait abnormalities. Moreover, the model exhibited negative scototaxis, a result confirming a phenotype of anxiety comorbid with depression phenotype. Interestingly, depletion of the reduced glutathione levels was found in the brain without a concomitant increase in oxidative stress. Finally, hypolocomotion and positive geotaxis exhibited by this model were fully recovered 5 days after transferring the fish to clean fish-water. All this data support the validity of the ACR acute neurotoxicity model developed in adult zebrafish.</AbstractText
|
Usefulness of thalamic beta activity for closed-loop therapy in essential tremor. A partial loss of effectiveness of deep brain stimulation of the ventral intermediate nucleus of the thalamus (VIM) has been reported in some patients with essential tremor (ET), possibly due to habituation to permanent stimulation. This study focused on the evolution of VIM local-field potentials (LFPs) data over time to assess the long-term feasibility of closed-loop therapy based on thalamic activity. We performed recordings of thalamic LFPs in 10 patients with severe ET using the ACTIVA™ PC + S (Medtronic plc.) allowing both recordings and stimulation in the same region. Particular attention was paid to describing the evolution of LFPs over time from 3 to 24 months after surgery when the stimulation was Off. We demonstrated a significant decrease in high-beta LFPs amplitude during movements inducing tremor in comparison to the rest condition 3 months after surgery (1.91 ± 0.89 at rest vs. 1.27 ± 1.37 µV<sup
|
Comparison of atlas- and magnetic resonance imaging-based stereotactic targeting of the globus pallidus internus in the performance of deep brain stimulation for treatment of dystonia. To assess the validity of relying on atlases during stereotactic neurosurgery, the authors compared target coordinates in the globus pallidus internus (GPi) obtained using magnetic resonance (MR) imaging with those determined using an atlas. The targets were used in deep brain stimulation (DBS) for the treatment of generalized dystonia.</AbstractText Thirty-five patients, who were treated using bilateral DBS of the GPi, were included in this study. The target was selected on three-dimensional MR images by direct visual recognition of the GPi. The coordinates were automatically recorded using dedicated software. They were translated into the anterior commissure-posterior commissure (AC-PC) coordinate system by using a matrix transformation process. The same GPi target was defined, based on the locations of brain structures shown in the atlases of Schaltenbrand and Talairach. Magnetic resonance imaging-based GPi target coordinates were statistically compared with the corresponding atlas-based coordinates by applying the Student t-test. A significant difference (p < 0.001) was demonstrated in x, y, and z directions between MR imaging-based and Schaltenbrand atlas-derived target coordinates. The comparison with normalized Talairach atlas coordinates demonstrated a significant difference (p < 0.01) in the y and z directions, although not in the x direction (p = 0.12). No significant correlation existed between MR imaging-based target coordinates and patient age (p > 0.1). No significant correlation was observed between MR imaging-based target coordinates and patient sex in the y and z directions (p > 0.9), although it was significant in the x direction (p < 0.05). A significant variation in coordinates and the length of the AC-PC line was revealed only in the y direction (p < 0.005).</AbstractText A significant difference was found between target coordinates obtained by direct visual targeting on MR images (validated by postoperative clinical results) and those obtained by indirect targeting based on atlases.</AbstractText
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Further characterization of the zebrafish model of acrylamide acute neurotoxicity: gait abnormalities and oxidative stress. Occupational, accidental, or suicidal exposure to acrylamide (ACR) may result in a neurotoxic syndrome. Development of animal models of acrylamide neurotoxicity is necessary for increasing our mechanistic understanding of this syndrome and developing more effective therapies. A new model for acute ACR neurotoxicity has been recently developed in adult zebrafish. Whereas the results of the initial characterization were really promising, a further characterization is needed for testing the construct validity of the model. In this study, the presence of gait abnormalities has been investigated by using ZebraGait, software specifically designed to analyze the kinematics of fish swimming in a water tunnel. The results of the kinematic analyses demonstrated that the model exhibits mild-to-moderate gait abnormalities. Moreover, the model exhibited negative scototaxis, a result confirming a phenotype of anxiety comorbid with depression phenotype. Interestingly, depletion of the reduced glutathione levels was found in the brain without a concomitant increase in oxidative stress. Finally, hypolocomotion and positive geotaxis exhibited by this model were fully recovered 5 days after transferring the fish to clean fish-water. All this data support the validity of the ACR acute neurotoxicity model developed in adult zebrafish.</AbstractText
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37053195
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22450384
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37134278
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In vivo detection of substantia nigra and locus coeruleus volume loss in Parkinson's disease using neuromelanin-sensitive MRI: Replication in two cohorts.
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Effects of image distortion correction on voxel-based morphometry.
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STING/TBK1 Regulates Inflammation in Macrophages and Titanium Particles-Induced Osteolysis.
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Patients with Parkinson's disease undergo a loss of melanized neurons in substantia nigra pars compacta and locus coeruleus. Very few studies have assessed substantia nigra pars compacta and locus coeruleus pathology in Parkinson's disease simultaneously with magnetic resonance imaging (MRI). Neuromelanin-sensitive MRI measures of substantia nigra pars compacta and locus coeruleus volume based on explicit magnetization transfer contrast have been shown to have high scan-rescan reproducibility in controls, but no study has replicated detection of Parkinson's disease-associated volume loss in substantia nigra pars compacta and locus coeruleus in multiple cohorts with the same methodology. Two separate cohorts of Parkinson's disease patients and controls were recruited from the Emory Movement Disorders Clinic and scanned on two different MRI scanners. In cohort 1, imaging data from 19 controls and 22 Parkinson's disease patients were acquired with a Siemens Trio 3 Tesla scanner using a 2D gradient echo sequence with magnetization transfer preparation pulse. Cohort 2 consisted of 33 controls and 39 Parkinson's disease patients who were scanned on a Siemens Prisma 3 Tesla scanner with a similar imaging protocol. Locus coeruleus and substantia nigra pars compacta volumes were segmented in both cohorts. Substantia nigra pars compacta volume (Cohort 1: p = 0.0148; Cohort 2: p = 0.0011) and locus coeruleus volume (Cohort 1: p = 0.0412; Cohort 2: p = 0.0056) were significantly reduced in the Parkinson's disease group as compared to controls in both cohorts. This imaging approach robustly detects Parkinson's disease effects on these structures, indicating that it is a promising marker for neurodegenerative neuromelanin loss.</AbstractText
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We aimed to show that correcting image distortion significantly affects brain volumetry using voxel-based morphometry (VBM) and to assess whether the processing of distortion correction reduces system dependency.</AbstractText We obtained contiguous sagittal T(1)-weighted images of the brain from 22 healthy participants using 1.5- and 3-tesla magnetic resonance (MR) scanners, preprocessed images using Statistical Parametric Mapping 5, and tested the relation between distortion correction and brain volume using VBM.</AbstractText Local brain volume significantly increased or decreased on corrected images compared with uncorrected images. In addition, the method used to correct image distortion for gradient nonlinearity produced fewer volumetric errors from MR system variation.</AbstractText This is the first VBM study to show more precise volumetry using VBM with corrected images. These results indicate that multi-scanner or multi-site imaging trials require correction for distortion induced by gradient nonlinearity.</AbstractText
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Inflammatory response in macrophages on account of prostheses-derived wear particles is the leading cause of artificial joint failure. However, the mechanism by which wear particles initiate macrophage inflammation has not been fully elucidated. Previous research studies have identified TANK-binding kinase 1 (TBK1) and stimulator of interferon genes (STING) as potential factors in inflammation and autoimmune diseases. Here, we found that both TBK1 and STING were increased in synovium from aseptic loosening (AL) patients and were activated in titanium particles (TiPs)-stimulated macrophages. Lentivirus-mediated knockdown of TBK or STING significantly inhibited the inflammatory effects of macrophages, while overexpression of TBK or STING exerted opposite results. In concrete, STING/TBK1 promoted the activation of NF-κB and IRF3 pathways and macrophage M1 polarization. For further validation, a mice cranial osteolysis model was constructed for in vivo assays, and we found that STING-overexpressed lentivirus injection exacerbated osteolysis and inflammation, which was counteracted by TBK1-knockdown injection. In conclusion, STING/TBK1 enhanced TiP-induced macrophage inflammation and osteolysis via orchestrating the activation of NF-κB and IRF3 pathways and M1 polarization, which suggested STING/TBK1 as potential therapeutic targets for preventing AL of prostheses.</AbstractText
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In vivo detection of substantia nigra and locus coeruleus volume loss in Parkinson's disease using neuromelanin-sensitive MRI: Replication in two cohorts. Patients with Parkinson's disease undergo a loss of melanized neurons in substantia nigra pars compacta and locus coeruleus. Very few studies have assessed substantia nigra pars compacta and locus coeruleus pathology in Parkinson's disease simultaneously with magnetic resonance imaging (MRI). Neuromelanin-sensitive MRI measures of substantia nigra pars compacta and locus coeruleus volume based on explicit magnetization transfer contrast have been shown to have high scan-rescan reproducibility in controls, but no study has replicated detection of Parkinson's disease-associated volume loss in substantia nigra pars compacta and locus coeruleus in multiple cohorts with the same methodology. Two separate cohorts of Parkinson's disease patients and controls were recruited from the Emory Movement Disorders Clinic and scanned on two different MRI scanners. In cohort 1, imaging data from 19 controls and 22 Parkinson's disease patients were acquired with a Siemens Trio 3 Tesla scanner using a 2D gradient echo sequence with magnetization transfer preparation pulse. Cohort 2 consisted of 33 controls and 39 Parkinson's disease patients who were scanned on a Siemens Prisma 3 Tesla scanner with a similar imaging protocol. Locus coeruleus and substantia nigra pars compacta volumes were segmented in both cohorts. Substantia nigra pars compacta volume (Cohort 1: p = 0.0148; Cohort 2: p = 0.0011) and locus coeruleus volume (Cohort 1: p = 0.0412; Cohort 2: p = 0.0056) were significantly reduced in the Parkinson's disease group as compared to controls in both cohorts. This imaging approach robustly detects Parkinson's disease effects on these structures, indicating that it is a promising marker for neurodegenerative neuromelanin loss.</AbstractText
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Effects of image distortion correction on voxel-based morphometry. We aimed to show that correcting image distortion significantly affects brain volumetry using voxel-based morphometry (VBM) and to assess whether the processing of distortion correction reduces system dependency.</AbstractText We obtained contiguous sagittal T(1)-weighted images of the brain from 22 healthy participants using 1.5- and 3-tesla magnetic resonance (MR) scanners, preprocessed images using Statistical Parametric Mapping 5, and tested the relation between distortion correction and brain volume using VBM.</AbstractText Local brain volume significantly increased or decreased on corrected images compared with uncorrected images. In addition, the method used to correct image distortion for gradient nonlinearity produced fewer volumetric errors from MR system variation.</AbstractText This is the first VBM study to show more precise volumetry using VBM with corrected images. These results indicate that multi-scanner or multi-site imaging trials require correction for distortion induced by gradient nonlinearity.</AbstractText
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STING/TBK1 Regulates Inflammation in Macrophages and Titanium Particles-Induced Osteolysis. Inflammatory response in macrophages on account of prostheses-derived wear particles is the leading cause of artificial joint failure. However, the mechanism by which wear particles initiate macrophage inflammation has not been fully elucidated. Previous research studies have identified TANK-binding kinase 1 (TBK1) and stimulator of interferon genes (STING) as potential factors in inflammation and autoimmune diseases. Here, we found that both TBK1 and STING were increased in synovium from aseptic loosening (AL) patients and were activated in titanium particles (TiPs)-stimulated macrophages. Lentivirus-mediated knockdown of TBK or STING significantly inhibited the inflammatory effects of macrophages, while overexpression of TBK or STING exerted opposite results. In concrete, STING/TBK1 promoted the activation of NF-κB and IRF3 pathways and macrophage M1 polarization. For further validation, a mice cranial osteolysis model was constructed for in vivo assays, and we found that STING-overexpressed lentivirus injection exacerbated osteolysis and inflammation, which was counteracted by TBK1-knockdown injection. In conclusion, STING/TBK1 enhanced TiP-induced macrophage inflammation and osteolysis via orchestrating the activation of NF-κB and IRF3 pathways and M1 polarization, which suggested STING/TBK1 as potential therapeutic targets for preventing AL of prostheses.</AbstractText
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40694026
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24634081
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39477489
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Veteran and Brain-Computer Interfaces: The Duty to Care.
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Brain images, babies, and bathwater: critiquing critiques of functional neuroimaging.
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Impact of Obesity on Short-Term Outcomes Following Catheter Ablation for Atrial Fibrillation in Patients with Heart Failure.
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Anticipated by science fiction, the enhanced soldier crystallized in the United States at the dawn of the 21st century within the Pentagon's scientific agency, the Defense Advanced Research Projects Agency (DARPA). Fueled by the fear of being overtaken by the enemy, and then by its own technology, this agency's new vision produced a "bifurcation" within anthropotechnics: the modification of humans for war. The soldier is now at the heart of a process of radical innovation, with as yet unknown implications. Emblematic of this enhancement, the use of the brain-computer interfaces (BCIs) will not only expose the soldier to previously unknown psychocognitive and emotional effects, but also offer the enemy potential access to his/her inner self. By giving birth to a new kind of veteran, this hybridization will generate new responsibilities for military commanders and politicians, as well as a new type of care.</AbstractText
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Since the mid-1980s, psychologists and neuroscientists have used brain imaging to test hypotheses about human thought processes and their neural instantiation. In just three decades, functional neuroimaging has been transformed from a crude clinical tool to a widely used research method for understanding the human brain and mind. Such rapidly achieved success is bound to evoke skepticism. A degree of skepticism toward new methods and ideas is both inevitable and useful in any field. It is especially valuable in a science as young as cognitive neuroscience and its even younger siblings, social and affective neuroscience. Healthy skepticism encourages us to check our assumptions, recognize the limitations of our methods, and proceed thoughtfully. Skepticism itself, however, also must be examined. In this article, I review the most commonly voiced criticisms of functional neuroimaging. In the spirit of healthy skepticism, I will critically examine these criticisms themselves. Each contains at least a kernel of truth, although I will argue that in some cases the kernel has been over extended in ways that are inaccurate or misleading.</AbstractText
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This study aimed to evaluate the impact of obesity on in-hospital outcomes of patients with HF undergoing AF catheter ablation. This population-based, retrospective observational study extracted data from the US Nationwide Inpatient Sample (NIS) database 2005-2018. Patients ≥ 20 years with HF and undergoing catheter ablation for AF were eligible for inclusion. Propensity-score matching (PSM) was utilized to balance the baseline characteristics between obese and non-obese groups. Univariate and multivariable regression analyses were used to determine the associations between obese status and other variables with the in-hospital outcomes. These outcomes included non-home discharge, prolonged length of stay (LOS), complications, and a composite outcome that encompassed these outcomes along with in-hospital mortality. A total of 18,751 patients were included. After PSM, 8,014 patients remained in the study sample. The mean age was 64.6 ± 0.1 years. After adjustment, significant association was detected between obesity and greater odds of non-home discharge (adjusted odd ratio [aOR] = 1.18), prolonged LOS (aOR = 1.18), complications (aOR = 1.30), respiratory failure/mechanical ventilation (aOR = 1.56) and acute kidney injury (AKI) (aOR = 1.28), central nervous system and peripheral neuropathy (aOR = 1.33), and transient ischemic attack (aOR = 8.16), as well as poor composite outcome (aOR = 1.28) compared with non-obese patients. In US patients with HF undergoing AF catheter ablation, obesity is associated with a higher risk for non-home discharge, prolonged LOS, and several major complications. Clinicians should exercise heightened vigilance when administering therapy to this subgroup of patients.</AbstractText
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Veteran and Brain-Computer Interfaces: The Duty to Care. Anticipated by science fiction, the enhanced soldier crystallized in the United States at the dawn of the 21st century within the Pentagon's scientific agency, the Defense Advanced Research Projects Agency (DARPA). Fueled by the fear of being overtaken by the enemy, and then by its own technology, this agency's new vision produced a "bifurcation" within anthropotechnics: the modification of humans for war. The soldier is now at the heart of a process of radical innovation, with as yet unknown implications. Emblematic of this enhancement, the use of the brain-computer interfaces (BCIs) will not only expose the soldier to previously unknown psychocognitive and emotional effects, but also offer the enemy potential access to his/her inner self. By giving birth to a new kind of veteran, this hybridization will generate new responsibilities for military commanders and politicians, as well as a new type of care.</AbstractText
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Brain images, babies, and bathwater: critiquing critiques of functional neuroimaging. Since the mid-1980s, psychologists and neuroscientists have used brain imaging to test hypotheses about human thought processes and their neural instantiation. In just three decades, functional neuroimaging has been transformed from a crude clinical tool to a widely used research method for understanding the human brain and mind. Such rapidly achieved success is bound to evoke skepticism. A degree of skepticism toward new methods and ideas is both inevitable and useful in any field. It is especially valuable in a science as young as cognitive neuroscience and its even younger siblings, social and affective neuroscience. Healthy skepticism encourages us to check our assumptions, recognize the limitations of our methods, and proceed thoughtfully. Skepticism itself, however, also must be examined. In this article, I review the most commonly voiced criticisms of functional neuroimaging. In the spirit of healthy skepticism, I will critically examine these criticisms themselves. Each contains at least a kernel of truth, although I will argue that in some cases the kernel has been over extended in ways that are inaccurate or misleading.</AbstractText
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Impact of Obesity on Short-Term Outcomes Following Catheter Ablation for Atrial Fibrillation in Patients with Heart Failure. This study aimed to evaluate the impact of obesity on in-hospital outcomes of patients with HF undergoing AF catheter ablation. This population-based, retrospective observational study extracted data from the US Nationwide Inpatient Sample (NIS) database 2005-2018. Patients ≥ 20 years with HF and undergoing catheter ablation for AF were eligible for inclusion. Propensity-score matching (PSM) was utilized to balance the baseline characteristics between obese and non-obese groups. Univariate and multivariable regression analyses were used to determine the associations between obese status and other variables with the in-hospital outcomes. These outcomes included non-home discharge, prolonged length of stay (LOS), complications, and a composite outcome that encompassed these outcomes along with in-hospital mortality. A total of 18,751 patients were included. After PSM, 8,014 patients remained in the study sample. The mean age was 64.6 ± 0.1 years. After adjustment, significant association was detected between obesity and greater odds of non-home discharge (adjusted odd ratio [aOR] = 1.18), prolonged LOS (aOR = 1.18), complications (aOR = 1.30), respiratory failure/mechanical ventilation (aOR = 1.56) and acute kidney injury (AKI) (aOR = 1.28), central nervous system and peripheral neuropathy (aOR = 1.33), and transient ischemic attack (aOR = 8.16), as well as poor composite outcome (aOR = 1.28) compared with non-obese patients. In US patients with HF undergoing AF catheter ablation, obesity is associated with a higher risk for non-home discharge, prolonged LOS, and several major complications. Clinicians should exercise heightened vigilance when administering therapy to this subgroup of patients.</AbstractText
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37538852
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35066157
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37883030
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Otoferlin as a multirole Ca(2+) signaling protein: from inner ear synapses to cancer pathways.
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Hemodynamic and metabolic correspondence of resting-state voxel-based physiological metrics in healthy adults.
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The role of numerical and nonnumerical magnitudes in pigeons' conditional discrimination behavior.
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Humans have six members of the ferlin protein family: dysferlin, myoferlin, otoferlin, fer1L4, fer1L5, and fer1L6. These proteins share common features such as multiple Ca<sup
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Voxel-based physiological (VBP) variables derived from blood oxygen level dependent (BOLD) fMRI time-course variations include: amplitude of low frequency fluctuations (ALFF), fractional amplitude of low frequency fluctuations (fALFF) and regional homogeneity (ReHo). Although these BOLD-derived variables can detect between-group (e.g. disease vs control) spatial pattern differences, physiological interpretations are not well established. The primary objective of this study was to quantify spatial correspondences between BOLD VBP variables and PET measurements of cerebral metabolic rate and hemodynamics, being well-validated physiological standards. To this end, quantitative, whole-brain PET images of metabolic rate of glucose (MRGlu; <sup
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Research on approximate numerical estimation suggests that numerical representations can be influenced by nonnumerical magnitudes. Current theories of numerical cognition differ on the nature of this interaction. The present project evaluated the effect of task requirements on the stimulus control exerted by numerical and nonnumerical magnitudes on pigeons' numerical discrimination behavior. In a series of experiments, we explored the effects of cumulative area and item size on pigeons' numerical discrimination. The effect of cumulative area was assessed by presenting visual displays in which cumulative area and item number were either positively correlated, uncorrelated, or negatively correlated. The effect of item size was evaluated by presenting displays in which the size of individual items was varied across trials. Results confirmed that pigeons' numerical discrimination behavior accorded with Weber's law, a prime indicator of nonsymbolic numerical representation. The results further indicated that pigeons did not use numerical information when nonnumerical magnitudes also provided reliable information to solve the discrimination task. However, task manipulations that rendered the information provided by nonnumerical magnitudes unreliable successfully shifted stimulus control toward numerical magnitudes. (PsycInfo Database Record (c) 2023 APA, all rights reserved).</AbstractText
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Otoferlin as a multirole Ca(2+) signaling protein: from inner ear synapses to cancer pathways. Humans have six members of the ferlin protein family: dysferlin, myoferlin, otoferlin, fer1L4, fer1L5, and fer1L6. These proteins share common features such as multiple Ca<sup
|
Hemodynamic and metabolic correspondence of resting-state voxel-based physiological metrics in healthy adults. Voxel-based physiological (VBP) variables derived from blood oxygen level dependent (BOLD) fMRI time-course variations include: amplitude of low frequency fluctuations (ALFF), fractional amplitude of low frequency fluctuations (fALFF) and regional homogeneity (ReHo). Although these BOLD-derived variables can detect between-group (e.g. disease vs control) spatial pattern differences, physiological interpretations are not well established. The primary objective of this study was to quantify spatial correspondences between BOLD VBP variables and PET measurements of cerebral metabolic rate and hemodynamics, being well-validated physiological standards. To this end, quantitative, whole-brain PET images of metabolic rate of glucose (MRGlu; <sup
|
The role of numerical and nonnumerical magnitudes in pigeons' conditional discrimination behavior. Research on approximate numerical estimation suggests that numerical representations can be influenced by nonnumerical magnitudes. Current theories of numerical cognition differ on the nature of this interaction. The present project evaluated the effect of task requirements on the stimulus control exerted by numerical and nonnumerical magnitudes on pigeons' numerical discrimination behavior. In a series of experiments, we explored the effects of cumulative area and item size on pigeons' numerical discrimination. The effect of cumulative area was assessed by presenting visual displays in which cumulative area and item number were either positively correlated, uncorrelated, or negatively correlated. The effect of item size was evaluated by presenting displays in which the size of individual items was varied across trials. Results confirmed that pigeons' numerical discrimination behavior accorded with Weber's law, a prime indicator of nonsymbolic numerical representation. The results further indicated that pigeons did not use numerical information when nonnumerical magnitudes also provided reliable information to solve the discrimination task. However, task manipulations that rendered the information provided by nonnumerical magnitudes unreliable successfully shifted stimulus control toward numerical magnitudes. (PsycInfo Database Record (c) 2023 APA, all rights reserved).</AbstractText
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33490982
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33582224
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34400267
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Protocol for pressure-clamped patch-clamp recording at the node of Ranvier of rat myelinated nerves.
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Mitochondria and calcium defects correlate with axonal dysfunction in GDAP1-related Charcot-Marie-Tooth mouse model.
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Dosimetric Uncertainties Resulting From Interfractional Anatomic Variations for Patients Receiving Pancreas Stereotactic Body Radiation Therapy and Cone Beam Computed Tomography Image Guidance.
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The patch-clamp recording technique is indispensable for studying ion channel functions of cells but is challenging to apply to the node of Ranvier, a key site where action potentials are conducted along myelinated nerves. We have developed a pressure-clamped patch-clamp recording method applying to the node of Ranvier of rat myelinated nerves. The step-by-step protocol described here allows researchers to apply this approach to study mechanisms underlying saltatory conduction and information processing in myelinated nerves of mammals. For complete information on the generation and use of this protocol, please refer to Kanda et al. (2019).</AbstractText
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Ganglioside-induced differentiation associated protein 1 (GDAP1) gene encodes a protein of the mitochondrial outer membrane and of the mitochondrial membrane contacts with the endoplasmic reticulum (MAMs) and lysosomes. Since mutations in GDAP1 cause Charcot-Marie-Tooth, an inherited motor and sensory neuropathy, its function is essential for peripheral nerve physiology. Our previous studies showed structural and functional defects in mitochondria and their contacts when GDAP1 is depleted. Nevertheless, the underlying axonal pathophysiological events remain unclear. Here, we have used embryonic motor neurons (eMNs) cultures from Gdap1 knockout (Gdap1<sup
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To estimate the effects of interfractional anatomic changes on dose to organs at risk (OARs) and tumors, as measured with cone beam computed tomography (CBCT) image guidance for pancreatic stereotactic body radiation therapy.</AbstractText We evaluated 11 patients with pancreatic cancer whom were treated with stereotactic body radiation therapy (33-40 Gy in 5 fractions) using daily CT-on-rails (CTOR) image guidance immediately before treatment with breath-hold motion management. CBCT alignment was simulated in the treatment planning software by aligning the original planning CT to each fractional CTOR image set via fiducial markers. CTOR data sets were used to calculate fractional doses after alignment by applying the rigid shift of the planning CT and CTOR image sets to the planning treatment isocenter and recalculating the fractional dose. Accumulated dose to the gross tumor volume (GTV), tumor vessel interface, duodenum, small bowel, and stomach were calculated by summing the 5 fractional absolute dose-volume histograms into a single dose-volume histogram for comparison with the original planned dose.</AbstractText Four patients had a GTV D100% of at least 1.5 Gy less than the fractional planned value in several fractions; 4 patients had fractional underestimation of duodenum dose by 1.0 Gy per fraction. The D1.0 cm<sup For some patients, CBCT image guidance based on fiducial alignment may cause large dosimetric uncertainties for OARs and target structures, according to accumulated dose.</AbstractText
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Protocol for pressure-clamped patch-clamp recording at the node of Ranvier of rat myelinated nerves. The patch-clamp recording technique is indispensable for studying ion channel functions of cells but is challenging to apply to the node of Ranvier, a key site where action potentials are conducted along myelinated nerves. We have developed a pressure-clamped patch-clamp recording method applying to the node of Ranvier of rat myelinated nerves. The step-by-step protocol described here allows researchers to apply this approach to study mechanisms underlying saltatory conduction and information processing in myelinated nerves of mammals. For complete information on the generation and use of this protocol, please refer to Kanda et al. (2019).</AbstractText
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Mitochondria and calcium defects correlate with axonal dysfunction in GDAP1-related Charcot-Marie-Tooth mouse model. Ganglioside-induced differentiation associated protein 1 (GDAP1) gene encodes a protein of the mitochondrial outer membrane and of the mitochondrial membrane contacts with the endoplasmic reticulum (MAMs) and lysosomes. Since mutations in GDAP1 cause Charcot-Marie-Tooth, an inherited motor and sensory neuropathy, its function is essential for peripheral nerve physiology. Our previous studies showed structural and functional defects in mitochondria and their contacts when GDAP1 is depleted. Nevertheless, the underlying axonal pathophysiological events remain unclear. Here, we have used embryonic motor neurons (eMNs) cultures from Gdap1 knockout (Gdap1<sup
|
Dosimetric Uncertainties Resulting From Interfractional Anatomic Variations for Patients Receiving Pancreas Stereotactic Body Radiation Therapy and Cone Beam Computed Tomography Image Guidance. To estimate the effects of interfractional anatomic changes on dose to organs at risk (OARs) and tumors, as measured with cone beam computed tomography (CBCT) image guidance for pancreatic stereotactic body radiation therapy.</AbstractText We evaluated 11 patients with pancreatic cancer whom were treated with stereotactic body radiation therapy (33-40 Gy in 5 fractions) using daily CT-on-rails (CTOR) image guidance immediately before treatment with breath-hold motion management. CBCT alignment was simulated in the treatment planning software by aligning the original planning CT to each fractional CTOR image set via fiducial markers. CTOR data sets were used to calculate fractional doses after alignment by applying the rigid shift of the planning CT and CTOR image sets to the planning treatment isocenter and recalculating the fractional dose. Accumulated dose to the gross tumor volume (GTV), tumor vessel interface, duodenum, small bowel, and stomach were calculated by summing the 5 fractional absolute dose-volume histograms into a single dose-volume histogram for comparison with the original planned dose.</AbstractText Four patients had a GTV D100% of at least 1.5 Gy less than the fractional planned value in several fractions; 4 patients had fractional underestimation of duodenum dose by 1.0 Gy per fraction. The D1.0 cm<sup For some patients, CBCT image guidance based on fiducial alignment may cause large dosimetric uncertainties for OARs and target structures, according to accumulated dose.</AbstractText
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35903637
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29278773
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35203050
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Resting-State Brain Variability in Youth With Attention-Deficit/Hyperactivity Disorder.
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An evaluation of the efficacy, reliability, and sensitivity of motion correction strategies for resting-state functional MRI.
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Generation of a human iPSC line (UUIGPi015-A) from a patient with Dravet syndrome and a 2.9 Mb deletion spanning SCN1A on chromosome 2.
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In this study, we sought to determine the nature of the abnormality in resting-state default mode network (DMN) activation and explore its correlation with functional connectivity in attention-deficit/hyperactivity disorder (ADHD). We obtained resting-state functional magnetic resonance images of youth with ADHD and typically developing counterparts from the publicly available ADHD-200 database. We used data from Peking University (232 scans) and New York University (172 scans); the scan repetition time was 2 s for both data collection sites. We applied generalized estimating equations to estimate the variability of the averaged blood-oxygen-level-dependent (BOLD) time series extracted from the DMN at rest. We performed network-based statistics to determine the association between the observed differences in BOLD signal variability and altered functional connectivity. We analyzed data from 105 youth with ADHD (age: mean 12.17, standard deviation 2.31, median 12.25; 15.2% female, 84.8% male) and 140 typically developing youth (age: mean 11.99, standard deviation 2.28, median 11.85; 47.1% female, 52.9% male), who aged 7-17 years. The imaging data were cross-sectionally collected for each participant at one time point. We observed a greater number of significant BOLD signal changes and higher-order polynomial significant associations in youth with ADHD. Moreover, there were significant between-group differences in BOLD signal change after the first 140 s, which coincided with decreased resting-state functional connectivity within the DMN in youth with ADHD. Increased variability of neural signaling was intermittently observed in the brains of youth with ADHD at rest, thereby indicating their default mode state was more unstable than that of typically developing youth.</AbstractText
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Estimates of functional connectivity derived from resting-state functional magnetic resonance imaging (rs-fMRI) are sensitive to artefacts caused by in-scanner head motion. This susceptibility has motivated the development of numerous denoising methods designed to mitigate motion-related artefacts. Here, we compare popular retrospective rs-fMRI denoising methods, such as regression of head motion parameters and mean white matter (WM) and cerebrospinal fluid (CSF) (with and without expansion terms), aCompCor, volume censoring (e.g., scrubbing and spike regression), global signal regression and ICA-AROMA, combined into 19 different pipelines. These pipelines were evaluated across five different quality control benchmarks in four independent datasets associated with varying levels of motion. Pipelines were benchmarked by examining the residual relationship between in-scanner movement and functional connectivity after denoising; the effect of distance on this residual relationship; whole-brain differences in functional connectivity between high- and low-motion healthy controls (HC); the temporal degrees of freedom lost during denoising; and the test-retest reliability of functional connectivity estimates. We also compared the sensitivity of each pipeline to clinical differences in functional connectivity in independent samples of people with schizophrenia and obsessive-compulsive disorder. Our results indicate that (1) simple linear regression of regional fMRI time series against head motion parameters and WM/CSF signals (with or without expansion terms) is not sufficient to remove head motion artefacts; (2) aCompCor pipelines may only be viable in low-motion data; (3) volume censoring performs well at minimising motion-related artefact but a major benefit of this approach derives from the exclusion of high-motion individuals; (4) while not as effective as volume censoring, ICA-AROMA performed well across our benchmarks for relatively low cost in terms of data loss; (5) the addition of global signal regression improved the performance of nearly all pipelines on most benchmarks, but exacerbated the distance-dependence of correlations between motion and functional connectivity; and (6) group comparisons in functional connectivity between healthy controls and schizophrenia patients are highly dependent on preprocessing strategy. We offer some recommendations for best practice and outline simple analyses to facilitate transparent reporting of the degree to which a given set of findings may be affected by motion-related artefact.</AbstractText
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Dravet syndrome is an early onset devastating epilepsy syndrome usually caused by heterozygous mutations in SCN1A. We generated a human iPSC line (UUIGPi015-A) from dermal fibroblasts of a patient with Dravet syndrome carrying a deletion on chromosome 2 encompassing SCN1A and 9 flanking genes. Characterization of the iPSC line confirmed expression of pluripotency markers, tri-lineage differentiation capacity and absence of exogenous reprogramming factors. The iPSC line retained the deletion and was genomically stable. The iPSC line UUIGPi015-A provides a useful resource for studies on the pathophysiology of Dravet syndrome and seizures caused by haploinsufficiency of SCN1A and flanking gene products.</AbstractText
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Resting-State Brain Variability in Youth With Attention-Deficit/Hyperactivity Disorder. In this study, we sought to determine the nature of the abnormality in resting-state default mode network (DMN) activation and explore its correlation with functional connectivity in attention-deficit/hyperactivity disorder (ADHD). We obtained resting-state functional magnetic resonance images of youth with ADHD and typically developing counterparts from the publicly available ADHD-200 database. We used data from Peking University (232 scans) and New York University (172 scans); the scan repetition time was 2 s for both data collection sites. We applied generalized estimating equations to estimate the variability of the averaged blood-oxygen-level-dependent (BOLD) time series extracted from the DMN at rest. We performed network-based statistics to determine the association between the observed differences in BOLD signal variability and altered functional connectivity. We analyzed data from 105 youth with ADHD (age: mean 12.17, standard deviation 2.31, median 12.25; 15.2% female, 84.8% male) and 140 typically developing youth (age: mean 11.99, standard deviation 2.28, median 11.85; 47.1% female, 52.9% male), who aged 7-17 years. The imaging data were cross-sectionally collected for each participant at one time point. We observed a greater number of significant BOLD signal changes and higher-order polynomial significant associations in youth with ADHD. Moreover, there were significant between-group differences in BOLD signal change after the first 140 s, which coincided with decreased resting-state functional connectivity within the DMN in youth with ADHD. Increased variability of neural signaling was intermittently observed in the brains of youth with ADHD at rest, thereby indicating their default mode state was more unstable than that of typically developing youth.</AbstractText
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An evaluation of the efficacy, reliability, and sensitivity of motion correction strategies for resting-state functional MRI. Estimates of functional connectivity derived from resting-state functional magnetic resonance imaging (rs-fMRI) are sensitive to artefacts caused by in-scanner head motion. This susceptibility has motivated the development of numerous denoising methods designed to mitigate motion-related artefacts. Here, we compare popular retrospective rs-fMRI denoising methods, such as regression of head motion parameters and mean white matter (WM) and cerebrospinal fluid (CSF) (with and without expansion terms), aCompCor, volume censoring (e.g., scrubbing and spike regression), global signal regression and ICA-AROMA, combined into 19 different pipelines. These pipelines were evaluated across five different quality control benchmarks in four independent datasets associated with varying levels of motion. Pipelines were benchmarked by examining the residual relationship between in-scanner movement and functional connectivity after denoising; the effect of distance on this residual relationship; whole-brain differences in functional connectivity between high- and low-motion healthy controls (HC); the temporal degrees of freedom lost during denoising; and the test-retest reliability of functional connectivity estimates. We also compared the sensitivity of each pipeline to clinical differences in functional connectivity in independent samples of people with schizophrenia and obsessive-compulsive disorder. Our results indicate that (1) simple linear regression of regional fMRI time series against head motion parameters and WM/CSF signals (with or without expansion terms) is not sufficient to remove head motion artefacts; (2) aCompCor pipelines may only be viable in low-motion data; (3) volume censoring performs well at minimising motion-related artefact but a major benefit of this approach derives from the exclusion of high-motion individuals; (4) while not as effective as volume censoring, ICA-AROMA performed well across our benchmarks for relatively low cost in terms of data loss; (5) the addition of global signal regression improved the performance of nearly all pipelines on most benchmarks, but exacerbated the distance-dependence of correlations between motion and functional connectivity; and (6) group comparisons in functional connectivity between healthy controls and schizophrenia patients are highly dependent on preprocessing strategy. We offer some recommendations for best practice and outline simple analyses to facilitate transparent reporting of the degree to which a given set of findings may be affected by motion-related artefact.</AbstractText
|
Generation of a human iPSC line (UUIGPi015-A) from a patient with Dravet syndrome and a 2.9 Mb deletion spanning SCN1A on chromosome 2. Dravet syndrome is an early onset devastating epilepsy syndrome usually caused by heterozygous mutations in SCN1A. We generated a human iPSC line (UUIGPi015-A) from dermal fibroblasts of a patient with Dravet syndrome carrying a deletion on chromosome 2 encompassing SCN1A and 9 flanking genes. Characterization of the iPSC line confirmed expression of pluripotency markers, tri-lineage differentiation capacity and absence of exogenous reprogramming factors. The iPSC line retained the deletion and was genomically stable. The iPSC line UUIGPi015-A provides a useful resource for studies on the pathophysiology of Dravet syndrome and seizures caused by haploinsufficiency of SCN1A and flanking gene products.</AbstractText
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40149575
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37061720
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40721529
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The Impact of Visualization on Stroke Rehabilitation in Adults: A Systematic Review of Randomized Controlled Trials on Guided and Motor Imagery.
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Recommendations for progression criteria during external randomised pilot trial design, conduct, analysis and reporting.
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The LISTEN principles for genetic sequence data governance and database engineering.
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<b
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External randomised pilot trials aim to assess whether a future definitive Randomised Controlled Trial (RCT) is feasible. Prespecified progression criteria help guide the interpretation of pilot trial findings to decide whether, and how, a definitive RCT should be conducted. This commentary presents a set of proposed recommendations for progression criteria to guide researchers when (i) designing, (ii) conducting, (iii) analysing and (iv) reporting external randomised pilot trials.</AbstractText Recommendations were developed following a mixed methods approach. This involved (i) a methodological review of pilot trial publications, (ii) a cross-sectional study of pilot trial research funding applications, (iii) qualitative interviews with pilot trial researchers and (iv) a survey of corresponding authors of identified pilot trial publications. Initial recommendations were refined following two consultation stakeholder workshops held in July 2022. Recommendations for progression criteria for external randomised pilot trials: i.</AbstractText consider progression criteria from the earliest opportunity; map progression criteria to feasibility objectives; consider quantitative and qualitative interpretations of feasibility; provide justification; develop guidelines rather than rules; seek input from relevant stakeholders. ii. Conduct: regularly monitor pilot trial data against progression criteria. iii.</AbstractText avoid considering each progression criterion in isolation; engage in discussion with relevant stakeholders; consider context and other factors external to the pilot trial; consider feasibility (can we?) and progression (will we?). iv. Reporting: we propose a reporting checklist in relation to progression criteria and recommend reporting in a table format for clarity.</AbstractText These recommendations provide a helpful resource for researchers to consider progression criteria at different stages of external randomised pilot trials. We have produced a simple infographic tool to summarise these recommendations for researchers to refer to. Further research is needed to evaluate whether these proposed recommendations should inform future development, or update, of established guidelines for the design, conduct, analysis and reporting of external randomised pilot trials.</AbstractText
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Several international legal agreements include an 'access and benefit-sharing' (ABS) mechanism that attaches obligations to the use of genetic sequence data. These agreements are frequently subject to critique on the grounds that ABS is either fundamentally incompatible with the principles of open science, or technically challenging to implement in open scientific databases. Here, we argue that these critiques arise from a misinterpretation of the principles of open science and that both considerations can be addressed by a set of simple principles that link database engineering and governance. We introduce a checklist of six database design considerations, LISTEN: licensed, identified, supervised, transparent, enforced and non-exclusive, which can be readily adopted by both new and existing platforms participating in ABS systems. We also highlight how these principles can act in concert with familiar principles of open science, such as findable, accessible, interoperable and reusable (FAIR) data sharing.</AbstractText
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The Impact of Visualization on Stroke Rehabilitation in Adults: A Systematic Review of Randomized Controlled Trials on Guided and Motor Imagery. <b
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Recommendations for progression criteria during external randomised pilot trial design, conduct, analysis and reporting. External randomised pilot trials aim to assess whether a future definitive Randomised Controlled Trial (RCT) is feasible. Prespecified progression criteria help guide the interpretation of pilot trial findings to decide whether, and how, a definitive RCT should be conducted. This commentary presents a set of proposed recommendations for progression criteria to guide researchers when (i) designing, (ii) conducting, (iii) analysing and (iv) reporting external randomised pilot trials.</AbstractText Recommendations were developed following a mixed methods approach. This involved (i) a methodological review of pilot trial publications, (ii) a cross-sectional study of pilot trial research funding applications, (iii) qualitative interviews with pilot trial researchers and (iv) a survey of corresponding authors of identified pilot trial publications. Initial recommendations were refined following two consultation stakeholder workshops held in July 2022. Recommendations for progression criteria for external randomised pilot trials: i.</AbstractText consider progression criteria from the earliest opportunity; map progression criteria to feasibility objectives; consider quantitative and qualitative interpretations of feasibility; provide justification; develop guidelines rather than rules; seek input from relevant stakeholders. ii. Conduct: regularly monitor pilot trial data against progression criteria. iii.</AbstractText avoid considering each progression criterion in isolation; engage in discussion with relevant stakeholders; consider context and other factors external to the pilot trial; consider feasibility (can we?) and progression (will we?). iv. Reporting: we propose a reporting checklist in relation to progression criteria and recommend reporting in a table format for clarity.</AbstractText These recommendations provide a helpful resource for researchers to consider progression criteria at different stages of external randomised pilot trials. We have produced a simple infographic tool to summarise these recommendations for researchers to refer to. Further research is needed to evaluate whether these proposed recommendations should inform future development, or update, of established guidelines for the design, conduct, analysis and reporting of external randomised pilot trials.</AbstractText
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The LISTEN principles for genetic sequence data governance and database engineering. Several international legal agreements include an 'access and benefit-sharing' (ABS) mechanism that attaches obligations to the use of genetic sequence data. These agreements are frequently subject to critique on the grounds that ABS is either fundamentally incompatible with the principles of open science, or technically challenging to implement in open scientific databases. Here, we argue that these critiques arise from a misinterpretation of the principles of open science and that both considerations can be addressed by a set of simple principles that link database engineering and governance. We introduce a checklist of six database design considerations, LISTEN: licensed, identified, supervised, transparent, enforced and non-exclusive, which can be readily adopted by both new and existing platforms participating in ABS systems. We also highlight how these principles can act in concert with familiar principles of open science, such as findable, accessible, interoperable and reusable (FAIR) data sharing.</AbstractText
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38009961
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25867615
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38569727
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Prolonged neural encoding of visual information in autism.
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Central and peripheral vision loss differentially affects contextual cueing in visual search.
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Bulky malignant peripheral nerve sheath tumour of the left thigh in a pregnant woman presenting with a pathological fracture of the proximal femur.
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Autism spectrum disorder (ASD) is associated with a hyper-focused visual attentional style, impacting higher-order social and affective domains. The understanding of such peculiarity can benefit from the use of multivariate pattern analysis (MVPA) of high-resolution electroencephalography (EEG) data, which has proved to be a powerful technique to investigate the hidden neural dynamics orchestrating sensory and cognitive processes. Here, we recorded EEG in typically developing (TD) children and in children with ASD during a visuo-spatial attentional task where attention was exogenously captured by a small (zoom-in) or large (zoom-out) cue in the visual field before the appearance of a target at different eccentricities. MVPA was performed both in the cue-locked period, to reveal potential differences in the modulation of the attentional focus, and in the target-locked period, to reveal potential cascade effects on stimulus processing. Cue-locked MVPA revealed that while in the TD group the pattern of neural activity contained information about the cue mainly before the target appearance, the ASD group showed a temporally sustained and topographically diffuse significant decoding of the cue neural response even after the target onset, suggesting a delayed extinction of cue-related neural activity. Crucially, this delayed extinction positively correlated with behavioral measures of attentional hyperfocusing. Results of target-locked MVPA were coherent with a hyper-focused attentional profile, highlighting an earlier and stronger decoding of target neural responses in small cue trials in the ASD group. The present findings document a spatially and temporally overrepresented encoding of visual information in ASD, which can constitute one of the main reasons behind their peculiar cognitive style.</AbstractText
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Visual search for targets in repeated displays is more efficient than search for the same targets in random distractor layouts. Previous work has shown that this contextual cueing is severely impaired under central vision loss. Here, we investigated whether central vision loss, simulated with gaze-contingent displays, prevents the incidental learning of contextual cues or the expression of learning, that is, the guidance of search by learned target-distractor configurations. Visual search with a central scotoma reduced contextual cueing both with respect to search times and gaze parameters. However, when the scotoma was subsequently removed, contextual cueing was observed in a comparable magnitude as for controls who had searched without scotoma simulation throughout the experiment. This indicated that search with a central scotoma did not prevent incidental context learning, but interfered with search guidance by learned contexts. We discuss the role of visuospatial working memory load as source of this interference. In contrast to central vision loss, peripheral vision loss was expected to prevent spatial configuration learning itself, because the restricted search window did not allow the integration of invariant local configurations with the global display layout. This expectation was confirmed in that visual search with a simulated peripheral scotoma eliminated contextual cueing not only in the initial learning phase with scotoma, but also in the subsequent test phase without scotoma.</AbstractText
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Malignant peripheral nerve sheath tumour (MPNST) is an aggressive soft tissue sarcoma with a poor prognosis, affecting most commonly the extremities. The lungs constitute the most frequent location for distant metastases. Half of all MPNSTs arise in patients with neurofibromatosis type 1, while approximately 10% are radiation induced and the rest are sporadic.The authors present a pregnant woman in her 40s with a sporadic MPNST of the lower limb and with lung metastases at diagnosis. Treatment consisted of interilioabdominal amputation, followed by adjuvant chemotherapy. Partial response and disease stabilisation were achieved with chemotherapy.Surgical resection with negative margins is the only potentially curative therapy, while radiation therapy and chemotherapy might be useful in the neoadjuvant or adjuvant setting, but their advantage in survival is not demonstrated. In the reported case, chemotherapy permitted the achievement of partial response and stabilisation of the disease.</AbstractText
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Prolonged neural encoding of visual information in autism. Autism spectrum disorder (ASD) is associated with a hyper-focused visual attentional style, impacting higher-order social and affective domains. The understanding of such peculiarity can benefit from the use of multivariate pattern analysis (MVPA) of high-resolution electroencephalography (EEG) data, which has proved to be a powerful technique to investigate the hidden neural dynamics orchestrating sensory and cognitive processes. Here, we recorded EEG in typically developing (TD) children and in children with ASD during a visuo-spatial attentional task where attention was exogenously captured by a small (zoom-in) or large (zoom-out) cue in the visual field before the appearance of a target at different eccentricities. MVPA was performed both in the cue-locked period, to reveal potential differences in the modulation of the attentional focus, and in the target-locked period, to reveal potential cascade effects on stimulus processing. Cue-locked MVPA revealed that while in the TD group the pattern of neural activity contained information about the cue mainly before the target appearance, the ASD group showed a temporally sustained and topographically diffuse significant decoding of the cue neural response even after the target onset, suggesting a delayed extinction of cue-related neural activity. Crucially, this delayed extinction positively correlated with behavioral measures of attentional hyperfocusing. Results of target-locked MVPA were coherent with a hyper-focused attentional profile, highlighting an earlier and stronger decoding of target neural responses in small cue trials in the ASD group. The present findings document a spatially and temporally overrepresented encoding of visual information in ASD, which can constitute one of the main reasons behind their peculiar cognitive style.</AbstractText
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Central and peripheral vision loss differentially affects contextual cueing in visual search. Visual search for targets in repeated displays is more efficient than search for the same targets in random distractor layouts. Previous work has shown that this contextual cueing is severely impaired under central vision loss. Here, we investigated whether central vision loss, simulated with gaze-contingent displays, prevents the incidental learning of contextual cues or the expression of learning, that is, the guidance of search by learned target-distractor configurations. Visual search with a central scotoma reduced contextual cueing both with respect to search times and gaze parameters. However, when the scotoma was subsequently removed, contextual cueing was observed in a comparable magnitude as for controls who had searched without scotoma simulation throughout the experiment. This indicated that search with a central scotoma did not prevent incidental context learning, but interfered with search guidance by learned contexts. We discuss the role of visuospatial working memory load as source of this interference. In contrast to central vision loss, peripheral vision loss was expected to prevent spatial configuration learning itself, because the restricted search window did not allow the integration of invariant local configurations with the global display layout. This expectation was confirmed in that visual search with a simulated peripheral scotoma eliminated contextual cueing not only in the initial learning phase with scotoma, but also in the subsequent test phase without scotoma.</AbstractText
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Bulky malignant peripheral nerve sheath tumour of the left thigh in a pregnant woman presenting with a pathological fracture of the proximal femur. Malignant peripheral nerve sheath tumour (MPNST) is an aggressive soft tissue sarcoma with a poor prognosis, affecting most commonly the extremities. The lungs constitute the most frequent location for distant metastases. Half of all MPNSTs arise in patients with neurofibromatosis type 1, while approximately 10% are radiation induced and the rest are sporadic.The authors present a pregnant woman in her 40s with a sporadic MPNST of the lower limb and with lung metastases at diagnosis. Treatment consisted of interilioabdominal amputation, followed by adjuvant chemotherapy. Partial response and disease stabilisation were achieved with chemotherapy.Surgical resection with negative margins is the only potentially curative therapy, while radiation therapy and chemotherapy might be useful in the neoadjuvant or adjuvant setting, but their advantage in survival is not demonstrated. In the reported case, chemotherapy permitted the achievement of partial response and stabilisation of the disease.</AbstractText
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35665225
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23994479
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35438398
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Inhibitory Spike-Timing-Dependent Plasticity Can Account for Pathological Strengthening of Pallido-Subthalamic Synapses in Parkinson's Disease.
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Preconfigured, skewed distribution of firing rates in the hippocampus and entorhinal cortex.
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Impact of financial inclusion and globalization on environmental quality: evidence from G20 economies.
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Parkinson's disease (PD) is a neurodegenerative brain disorder associated with dysfunction of the basal ganglia (BG) circuitry. Dopamine (DA) depletion in experimental PD models leads to the pathological strengthening of pallido-subthalamic synaptic connections, contributing to the emergence of abnormally synchronized neuronal activity in the external segment of the globus pallidus (GPe) and subthalamic nucleus (STN). Augmented GPe-STN transmission following loss of DA was attributed to heterosynaptic plasticity mechanisms induced by cortico-subthalamic inputs. However, synaptic plasticity may play a role in this process. Here, by employing computational modeling we show that assuming inhibitory spike-timing-dependent plasticity (iSTDP) at pallido-subthalamic synapses can account for pathological strengthening of pallido-subthalamic synapses in PD by further promoting correlated neuronal activity in the GPe-STN network. In addition, we show that GPe-STN transmission delays can shape bistable activity-connectivity states due to iSTDP, characterized by strong connectivity and strong synchronized activity (pathological states) as opposed to weak connectivity and desynchronized activity (physiological states). Our results may shed light on how abnormal reshaping of GPe-STN connectivity by synaptic plasticity during parkinsonism is related to the PD pathophysiology and contribute to the development of therapeutic brain stimulation techniques targeting plasticity-induced rewiring of network connectivity.</AbstractText
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Despite the importance of the discharge frequency in neuronal communication, little is known about the firing-rate patterns of cortical populations. Using large-scale recordings from multiple layers of the entorhinal-hippocampal loop, we found that the firing rates of principal neurons showed a lognormal-like distribution in all brain states. Mean and peak rates within place fields of hippocampal neurons were also strongly skewed. Importantly, firing rates of the same neurons showed reliable correlations in different brain states and testing situations, as well as across familiar and novel environments. The fraction of neurons that participated in population oscillations displayed a lognormal pattern. Such skewed firing rates of individual neurons may be due to a skewed distribution of synaptic weights, which is supported by our observation of a lognormal distribution of the efficacy of spike transfer from principal neurons to interneurons. The persistent skewed distribution of firing rates implies that a preconfigured, highly active minority dominates information transmission in cortical networks.</AbstractText
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Sustainable development and addressing climate change are among the most pressing issues faced by countries around the world. This research investigates the dynamic associations between financial inclusion, globalization and CO<sub
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Inhibitory Spike-Timing-Dependent Plasticity Can Account for Pathological Strengthening of Pallido-Subthalamic Synapses in Parkinson's Disease. Parkinson's disease (PD) is a neurodegenerative brain disorder associated with dysfunction of the basal ganglia (BG) circuitry. Dopamine (DA) depletion in experimental PD models leads to the pathological strengthening of pallido-subthalamic synaptic connections, contributing to the emergence of abnormally synchronized neuronal activity in the external segment of the globus pallidus (GPe) and subthalamic nucleus (STN). Augmented GPe-STN transmission following loss of DA was attributed to heterosynaptic plasticity mechanisms induced by cortico-subthalamic inputs. However, synaptic plasticity may play a role in this process. Here, by employing computational modeling we show that assuming inhibitory spike-timing-dependent plasticity (iSTDP) at pallido-subthalamic synapses can account for pathological strengthening of pallido-subthalamic synapses in PD by further promoting correlated neuronal activity in the GPe-STN network. In addition, we show that GPe-STN transmission delays can shape bistable activity-connectivity states due to iSTDP, characterized by strong connectivity and strong synchronized activity (pathological states) as opposed to weak connectivity and desynchronized activity (physiological states). Our results may shed light on how abnormal reshaping of GPe-STN connectivity by synaptic plasticity during parkinsonism is related to the PD pathophysiology and contribute to the development of therapeutic brain stimulation techniques targeting plasticity-induced rewiring of network connectivity.</AbstractText
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Preconfigured, skewed distribution of firing rates in the hippocampus and entorhinal cortex. Despite the importance of the discharge frequency in neuronal communication, little is known about the firing-rate patterns of cortical populations. Using large-scale recordings from multiple layers of the entorhinal-hippocampal loop, we found that the firing rates of principal neurons showed a lognormal-like distribution in all brain states. Mean and peak rates within place fields of hippocampal neurons were also strongly skewed. Importantly, firing rates of the same neurons showed reliable correlations in different brain states and testing situations, as well as across familiar and novel environments. The fraction of neurons that participated in population oscillations displayed a lognormal pattern. Such skewed firing rates of individual neurons may be due to a skewed distribution of synaptic weights, which is supported by our observation of a lognormal distribution of the efficacy of spike transfer from principal neurons to interneurons. The persistent skewed distribution of firing rates implies that a preconfigured, highly active minority dominates information transmission in cortical networks.</AbstractText
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Impact of financial inclusion and globalization on environmental quality: evidence from G20 economies. Sustainable development and addressing climate change are among the most pressing issues faced by countries around the world. This research investigates the dynamic associations between financial inclusion, globalization and CO<sub
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34089103
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29354050
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36162735
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Intra- and interhemispheric symmetry of subcortical brain structures: a volumetric analysis in the aging human brain.
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Brain Network Modularity Predicts Exercise-Related Executive Function Gains in Older Adults.
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Phldb2 is essential for regulating hippocampal dendritic spine morphology through drebrin in an adult-type isoform-specific manner.
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Here, we address the hemispheric interdependency of subcortical structures in the aging human brain. In particular, we investigated whether subcortical volume variations can be explained by the adjacency of structures in the same hemisphere or are due to the interhemispheric development of mirror subcortical structures in the brain. Seven subcortical structures in each hemisphere were automatically segmented in a large sample of 3312 magnetic resonance imaging (MRI) studies of elderly individuals in their 70s and 80s. We performed Eigenvalue analysis, and found that anatomic volumes in the limbic system and basal ganglia show similar statistical dependency whether considered in the same hemisphere (intrahemispherically) or different hemispheres (interhemispherically). Our results indicate that anatomic bilaterality of subcortical volumes is preserved in the aging human brain, supporting the hypothesis that coupling between non-adjacent subcortical structures might act as a mechanism to compensate for the deleterious effects of aging.</AbstractText
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Recent work suggests that the brain can be conceptualized as a network comprised of groups of sub-networks or modules. The extent of segregation between modules can be quantified with a modularity metric, where networks with high modularity have dense connections within modules and sparser connections between modules. Previous work has shown that higher modularity predicts greater improvements after cognitive training in patients with traumatic brain injury and in healthy older and young adults. It is not known, however, whether modularity can also predict cognitive gains after a physical exercise intervention. Here, we quantified modularity in older adults (<i
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Morphologically dynamic dendritic spines are the major sites of neuronal plasticity in the brain; however, the molecular mechanisms underlying their morphological dynamics have not been fully elucidated. Phldb2 is a protein that contains two predicted coiled-coil domains and the pleckstrin homology domain, whose binding is highly sensitive to PIP<sub
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Intra- and interhemispheric symmetry of subcortical brain structures: a volumetric analysis in the aging human brain. Here, we address the hemispheric interdependency of subcortical structures in the aging human brain. In particular, we investigated whether subcortical volume variations can be explained by the adjacency of structures in the same hemisphere or are due to the interhemispheric development of mirror subcortical structures in the brain. Seven subcortical structures in each hemisphere were automatically segmented in a large sample of 3312 magnetic resonance imaging (MRI) studies of elderly individuals in their 70s and 80s. We performed Eigenvalue analysis, and found that anatomic volumes in the limbic system and basal ganglia show similar statistical dependency whether considered in the same hemisphere (intrahemispherically) or different hemispheres (interhemispherically). Our results indicate that anatomic bilaterality of subcortical volumes is preserved in the aging human brain, supporting the hypothesis that coupling between non-adjacent subcortical structures might act as a mechanism to compensate for the deleterious effects of aging.</AbstractText
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Brain Network Modularity Predicts Exercise-Related Executive Function Gains in Older Adults. Recent work suggests that the brain can be conceptualized as a network comprised of groups of sub-networks or modules. The extent of segregation between modules can be quantified with a modularity metric, where networks with high modularity have dense connections within modules and sparser connections between modules. Previous work has shown that higher modularity predicts greater improvements after cognitive training in patients with traumatic brain injury and in healthy older and young adults. It is not known, however, whether modularity can also predict cognitive gains after a physical exercise intervention. Here, we quantified modularity in older adults (<i
|
Phldb2 is essential for regulating hippocampal dendritic spine morphology through drebrin in an adult-type isoform-specific manner. Morphologically dynamic dendritic spines are the major sites of neuronal plasticity in the brain; however, the molecular mechanisms underlying their morphological dynamics have not been fully elucidated. Phldb2 is a protein that contains two predicted coiled-coil domains and the pleckstrin homology domain, whose binding is highly sensitive to PIP<sub
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36182711
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31649571
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36069044
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The Flow-Clutch Scale: Translation and validation study of the Chinese version.
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Can We Motivate Students to Practice Physical Activities and Sports Through Models-Based Practice? A Systematic Review and Meta-Analysis of Psychosocial Factors Related to Physical Education.
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Pilot Study of Associations Among Functional Connectivity and Neurocognition in Survivors of Pediatric Brain Tumor and Healthy Peers.
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The integrated model of flow and clutch provides a multistate perspective to the optimal experiences during physical exercises. Based on this model, the Flow-Clutch Scale (FCS) was developed. The current study is the first step to test the psychometric properties of a Chinese version of the FCS (FCS-C).</AbstractText A confirmatory factor analysis (CFA) with Maximum Likelihood estimate was performed in Chinese athletes (N = 426) to explore the structural validity of the FCS-C . The Pearson correlations between the subscales of the FCS-C and "non-reactivity to inner experiences", "cognitive flexibility", and "self-consciousness" were explored to examine the concurrent validity. Cronbach's alpha coefficients were used to assess the internal consistency of the total scale and subscales. Moreover, the test-retest reliability was examined in a subsample (N = 53) using a two-week interval.</AbstractText The results of CFA suggested that the three-factor model showed an acceptable model fit (χ<sup Results indicated that the three-factor model of FCS-C is acceptable, whereas its validity is not satisfactory to appropriately examine flow and/or clutch states in Chinese athletes. In summary, the current translation and validation study of the FCS-C allows for future research on optimal exercise experiences in Chinese-speaking cohorts including a further cultural adaptation of the questionnaire.</AbstractText
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Adults (more than 18 years old) are likely to reproduce the habits that they acquired during childhood and adolescence (from 6 to 16 years old). For that reason, teachers and parents have the responsibility to promote an active and healthy lifestyle in children and adolescents. Even though every school subject should promote healthy activities, Physical Education (PE) is the most important subject to foster well-being habits associated to healthy lifestyle during sport practice and other kinds of active tasks. Indeed, there are many factors that influence the acquisition of healthy habits that should be taken into account when programs and activities are implemented in both educational and extracurricular context. In this sense, psychological and social factors are of utmost importance to achieve optimal experiences for an active and healthy lifestyle. However, due to the myriad of studies analyzing different factors in different contexts, there could be confusion when programs and pedagogical strategies are applied in educational or extracurricular contexts. The objective of this investigation is to analyse the state of art of the psychosocial factors which influence the engagement in physical activities and sport practice. The keywords used in this review were mainly: "Self-Determination Theory," "(intrinsic) motivation," "Psychological need satisfaction," "physical activity and sport engagement," "Elementary Education," "Secondary Education," "Physical Education." In addition, the Boolean data type "and," "or," and "not" were also used. The articles were selected according to the following criteria: (a) peer-reviewed original research published in international journals indexed in JCR or SJR, (b) published in English or Spanish, (c) about psychosocial factors which influence the physical activity and sport engagement, (d) in educational or extracurricular context. Research articles selected were found through Web of Science, Scopus, Google Scholar, SportDiscus (EBSCO-host), ERIC, PubMed, Medline, and PsycInfo databases. It was observed that physical activities and sport practice engagement are closely related to psychological factors. In particularly, intrinsic motivation was able to determine the active participation in any activity, including physical activity and sport practice during the implementation of Small-Sided Games and other kinds of pedagogical strategies (e.g., Pedagogical Models). Motivation was also closely related to flow state. Finally, these variables should be considered in order to organize effective programs to promote an active and healthy lifestyle in Physical Education classes.</AbstractText
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This pilot study examined the associations among functional connectivity in the salience, central executive, and default mode networks, and neurocognition in pediatric brain tumor survivors and healthy children. Thirteen pediatric brain tumor survivors (9 boys, M = 12.76 years) and 10 healthy children (6 boys, M = 12.70 years) completed magnetic resonance imaging (MRI) and assessment of processing speed and executive function. Pediatric brain tumor survivors performed more poorly than healthy children on measures of processing speed, divided attention, and working memory; parent ratings of day-to-day executive function did not differ significantly by group, though both pediatric brain tumor survivors who underwent only surgical resection and healthy children were rated by parents as having difficulties approaching a standard deviation above the normative mean. Connectivity was lower in the salience network and greater in the default mode network in pediatric brain tumor survivors. Cross-method correlations showed that increased salience network and default mode network connectivity were associated with better task performance and parent-rated executive skills and higher central executive network connectivity with poorer parent-rated executive skills. This perhaps reflects an adaptive pattern of hyperconnectivity in pediatric brain tumor survivors.</AbstractText
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The Flow-Clutch Scale: Translation and validation study of the Chinese version. The integrated model of flow and clutch provides a multistate perspective to the optimal experiences during physical exercises. Based on this model, the Flow-Clutch Scale (FCS) was developed. The current study is the first step to test the psychometric properties of a Chinese version of the FCS (FCS-C).</AbstractText A confirmatory factor analysis (CFA) with Maximum Likelihood estimate was performed in Chinese athletes (N = 426) to explore the structural validity of the FCS-C . The Pearson correlations between the subscales of the FCS-C and "non-reactivity to inner experiences", "cognitive flexibility", and "self-consciousness" were explored to examine the concurrent validity. Cronbach's alpha coefficients were used to assess the internal consistency of the total scale and subscales. Moreover, the test-retest reliability was examined in a subsample (N = 53) using a two-week interval.</AbstractText The results of CFA suggested that the three-factor model showed an acceptable model fit (χ<sup Results indicated that the three-factor model of FCS-C is acceptable, whereas its validity is not satisfactory to appropriately examine flow and/or clutch states in Chinese athletes. In summary, the current translation and validation study of the FCS-C allows for future research on optimal exercise experiences in Chinese-speaking cohorts including a further cultural adaptation of the questionnaire.</AbstractText
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Can We Motivate Students to Practice Physical Activities and Sports Through Models-Based Practice? A Systematic Review and Meta-Analysis of Psychosocial Factors Related to Physical Education. Adults (more than 18 years old) are likely to reproduce the habits that they acquired during childhood and adolescence (from 6 to 16 years old). For that reason, teachers and parents have the responsibility to promote an active and healthy lifestyle in children and adolescents. Even though every school subject should promote healthy activities, Physical Education (PE) is the most important subject to foster well-being habits associated to healthy lifestyle during sport practice and other kinds of active tasks. Indeed, there are many factors that influence the acquisition of healthy habits that should be taken into account when programs and activities are implemented in both educational and extracurricular context. In this sense, psychological and social factors are of utmost importance to achieve optimal experiences for an active and healthy lifestyle. However, due to the myriad of studies analyzing different factors in different contexts, there could be confusion when programs and pedagogical strategies are applied in educational or extracurricular contexts. The objective of this investigation is to analyse the state of art of the psychosocial factors which influence the engagement in physical activities and sport practice. The keywords used in this review were mainly: "Self-Determination Theory," "(intrinsic) motivation," "Psychological need satisfaction," "physical activity and sport engagement," "Elementary Education," "Secondary Education," "Physical Education." In addition, the Boolean data type "and," "or," and "not" were also used. The articles were selected according to the following criteria: (a) peer-reviewed original research published in international journals indexed in JCR or SJR, (b) published in English or Spanish, (c) about psychosocial factors which influence the physical activity and sport engagement, (d) in educational or extracurricular context. Research articles selected were found through Web of Science, Scopus, Google Scholar, SportDiscus (EBSCO-host), ERIC, PubMed, Medline, and PsycInfo databases. It was observed that physical activities and sport practice engagement are closely related to psychological factors. In particularly, intrinsic motivation was able to determine the active participation in any activity, including physical activity and sport practice during the implementation of Small-Sided Games and other kinds of pedagogical strategies (e.g., Pedagogical Models). Motivation was also closely related to flow state. Finally, these variables should be considered in order to organize effective programs to promote an active and healthy lifestyle in Physical Education classes.</AbstractText
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Pilot Study of Associations Among Functional Connectivity and Neurocognition in Survivors of Pediatric Brain Tumor and Healthy Peers. This pilot study examined the associations among functional connectivity in the salience, central executive, and default mode networks, and neurocognition in pediatric brain tumor survivors and healthy children. Thirteen pediatric brain tumor survivors (9 boys, M = 12.76 years) and 10 healthy children (6 boys, M = 12.70 years) completed magnetic resonance imaging (MRI) and assessment of processing speed and executive function. Pediatric brain tumor survivors performed more poorly than healthy children on measures of processing speed, divided attention, and working memory; parent ratings of day-to-day executive function did not differ significantly by group, though both pediatric brain tumor survivors who underwent only surgical resection and healthy children were rated by parents as having difficulties approaching a standard deviation above the normative mean. Connectivity was lower in the salience network and greater in the default mode network in pediatric brain tumor survivors. Cross-method correlations showed that increased salience network and default mode network connectivity were associated with better task performance and parent-rated executive skills and higher central executive network connectivity with poorer parent-rated executive skills. This perhaps reflects an adaptive pattern of hyperconnectivity in pediatric brain tumor survivors.</AbstractText
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33989467
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32733110
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33619879
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How to Evaluate Patients and Educate Them About Self-Examinations for Tardive Dyskinesia Between Appointments.
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Assesment of Risk Factors for Tardive Dyskinesia.
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External validation and comparison of current scoring systems in retrograde intrarenal surgery: Multi-institutional study with 949 patients.
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Patients taking dopamine-blocking agents such as antipsychotics are at risk for developing tardive dyskinesia. In this webcast, Drs McEvoy and Nierenberg discuss symptoms of tardive dyskinesia, how to observe patients (whether in person or via telemedicine), and how to educate patients and families about TD.</AbstractText
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Aim of the study is to evaluate sociodemographic and clinical features that may be associated with the development of Tardive dyskinesia (TD).</AbstractText 80 patients attending an outpatient psychiatry clinic in Istanbul, Turkey were divided into TD (n = 50) and control groups (CG) (n = 30). Sociodemographic and clinical data was collected through face-to-face interviews and a retrospective search of medical records.</AbstractText There was a significant difference between TD and control group (CG) in terms of mean; onset of psychiatric disease at or after 35 years of age; first use of APD at or after 35 years of age; use of long-acting injectable APD; history of extrapyramidal side-effects; history of akathisia and family history of psychiatric disease. There was no significant difference between the two groups in terms of DSM- IV-based psychiatric diagnosis distributions, the existence of complete recovery periods during the course of the disease; total duration of APD use for at least 10 years; APD holidays; regular APD use; history of ECT and smoking or alcohol and substance abuse/addiction.</AbstractText Advancing age seemed to be the most significant risk factor in the development of TD. Clinicians need to be cautious about TD when prescribing APD for elderly patients.</AbstractText
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To externally validate and compare Resorlu-Unsal stone score (RUSS), modified Seoul National University Renal Stone Complexity Score(S-ReSC), Ito's nomogram, and Retrograde Intra-Renal Surgery (R.I.R.S.) scoring systems for predicting capabilities of both the stone-free status and complications in a multi-institutional study.</AbstractText We performed a retrospective analysis of 949 patients who underwent flexible ureterorenoscopy (f-URS) and laser lithotripsy for renal stones in two institutions between March-2015 and June-2020. The RUSS, modified S-ReSC, Ito's nomogram, and R.I.R.S. scores were calculated for each patient by the same surgeon on imaging methods. Results were compared for their predictive capability of stone-free status and complications.</AbstractText Of 949 patients 603 were male and 346 were female with a mean age of 47.2 ± 14.3 (range 2-84 years). Mean stone burden was 102.6 ± 42.2 (48-270 mm<sup All four scoring systems (RUSS, modified S-ReSC, Ito's nomogram, and R.I.R.S.) could predict stone-free status after f-URS, however, the AUC values are not satisfactory in our large patient cohort. Although these scoring systems were not developed for predicting post-operative complications, they were associated with complications in our study. However, these four scoring systems have some significant limitations. The ideal scoring system is yet to be developed.</AbstractText
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How to Evaluate Patients and Educate Them About Self-Examinations for Tardive Dyskinesia Between Appointments. Patients taking dopamine-blocking agents such as antipsychotics are at risk for developing tardive dyskinesia. In this webcast, Drs McEvoy and Nierenberg discuss symptoms of tardive dyskinesia, how to observe patients (whether in person or via telemedicine), and how to educate patients and families about TD.</AbstractText
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Assesment of Risk Factors for Tardive Dyskinesia. Aim of the study is to evaluate sociodemographic and clinical features that may be associated with the development of Tardive dyskinesia (TD).</AbstractText 80 patients attending an outpatient psychiatry clinic in Istanbul, Turkey were divided into TD (n = 50) and control groups (CG) (n = 30). Sociodemographic and clinical data was collected through face-to-face interviews and a retrospective search of medical records.</AbstractText There was a significant difference between TD and control group (CG) in terms of mean; onset of psychiatric disease at or after 35 years of age; first use of APD at or after 35 years of age; use of long-acting injectable APD; history of extrapyramidal side-effects; history of akathisia and family history of psychiatric disease. There was no significant difference between the two groups in terms of DSM- IV-based psychiatric diagnosis distributions, the existence of complete recovery periods during the course of the disease; total duration of APD use for at least 10 years; APD holidays; regular APD use; history of ECT and smoking or alcohol and substance abuse/addiction.</AbstractText Advancing age seemed to be the most significant risk factor in the development of TD. Clinicians need to be cautious about TD when prescribing APD for elderly patients.</AbstractText
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External validation and comparison of current scoring systems in retrograde intrarenal surgery: Multi-institutional study with 949 patients. To externally validate and compare Resorlu-Unsal stone score (RUSS), modified Seoul National University Renal Stone Complexity Score(S-ReSC), Ito's nomogram, and Retrograde Intra-Renal Surgery (R.I.R.S.) scoring systems for predicting capabilities of both the stone-free status and complications in a multi-institutional study.</AbstractText We performed a retrospective analysis of 949 patients who underwent flexible ureterorenoscopy (f-URS) and laser lithotripsy for renal stones in two institutions between March-2015 and June-2020. The RUSS, modified S-ReSC, Ito's nomogram, and R.I.R.S. scores were calculated for each patient by the same surgeon on imaging methods. Results were compared for their predictive capability of stone-free status and complications.</AbstractText Of 949 patients 603 were male and 346 were female with a mean age of 47.2 ± 14.3 (range 2-84 years). Mean stone burden was 102.6 ± 42.2 (48-270 mm<sup All four scoring systems (RUSS, modified S-ReSC, Ito's nomogram, and R.I.R.S.) could predict stone-free status after f-URS, however, the AUC values are not satisfactory in our large patient cohort. Although these scoring systems were not developed for predicting post-operative complications, they were associated with complications in our study. However, these four scoring systems have some significant limitations. The ideal scoring system is yet to be developed.</AbstractText
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39199438
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17610823
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39173841
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Multiple Types of Developmental Dyslexias in a Shallow Orthography: Principles for Diagnostic Screening in Italian.
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Hierarchical coding of letter strings in the ventral stream: dissecting the inner organization of the visual word-form system.
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Acute exercise might not affect subsequent appetite responses to a fixed meal in adolescents with obesity: The SMASH exploratory study.
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A new dyslexia screening test for Italian, <i
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Visual word recognition has been proposed to rely on a hierarchy of increasingly complex neuronal detectors, from individual letters to bigrams and morphemes. We used fMRI to test whether such a hierarchy is present in the left occipitotemporal cortex, at the site of the visual word-form area, and with an anterior-to-posterior progression. We exposed adult readers to (1) false-font strings; (2) strings of infrequent letters; (3) strings of frequent letters but rare bigrams; (4) strings with frequent bigrams but rare quadrigrams; (5) strings with frequent quadrigrams; (6) real words. A gradient of selectivity was observed through the entire span of the occipitotemporal cortex, with activation becoming more selective for higher-level stimuli toward the anterior fusiform region. A similar gradient was also seen in left inferior frontoinsular cortex. Those gradients were asymmetrical in favor of the left hemisphere. We conclude that the left occipitotemporal visual word-form area, far from being a homogeneous structure, presents a high degree of functional and spatial hierarchical organization which must result from a tuning process during reading acquisition.</AbstractText
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While an intensity-dependent post-exercise decrease in energy intake (EI) has been described in adolescents with obesity, studies invariably used ad libitum meals, limiting then any conclusions regarding the effect of exercise on post-meal appetitive responses that can be also impacted by the ad libitum nature of the meal. This study analyses appetite and food-reward related responses to a fixed meal after an acute exercise, also exploring the associations between substrate use during exercise and overall daily EI in adolescents with obesity. Thirteen adolescents with obesity (12-16 years, 5 males) randomly complete 2 experimental sessions: (i) a control condition (CON); (ii) a 30-min moderate intensity (65% VO<sub
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Multiple Types of Developmental Dyslexias in a Shallow Orthography: Principles for Diagnostic Screening in Italian. A new dyslexia screening test for Italian, <i
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Hierarchical coding of letter strings in the ventral stream: dissecting the inner organization of the visual word-form system. Visual word recognition has been proposed to rely on a hierarchy of increasingly complex neuronal detectors, from individual letters to bigrams and morphemes. We used fMRI to test whether such a hierarchy is present in the left occipitotemporal cortex, at the site of the visual word-form area, and with an anterior-to-posterior progression. We exposed adult readers to (1) false-font strings; (2) strings of infrequent letters; (3) strings of frequent letters but rare bigrams; (4) strings with frequent bigrams but rare quadrigrams; (5) strings with frequent quadrigrams; (6) real words. A gradient of selectivity was observed through the entire span of the occipitotemporal cortex, with activation becoming more selective for higher-level stimuli toward the anterior fusiform region. A similar gradient was also seen in left inferior frontoinsular cortex. Those gradients were asymmetrical in favor of the left hemisphere. We conclude that the left occipitotemporal visual word-form area, far from being a homogeneous structure, presents a high degree of functional and spatial hierarchical organization which must result from a tuning process during reading acquisition.</AbstractText
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Acute exercise might not affect subsequent appetite responses to a fixed meal in adolescents with obesity: The SMASH exploratory study. While an intensity-dependent post-exercise decrease in energy intake (EI) has been described in adolescents with obesity, studies invariably used ad libitum meals, limiting then any conclusions regarding the effect of exercise on post-meal appetitive responses that can be also impacted by the ad libitum nature of the meal. This study analyses appetite and food-reward related responses to a fixed meal after an acute exercise, also exploring the associations between substrate use during exercise and overall daily EI in adolescents with obesity. Thirteen adolescents with obesity (12-16 years, 5 males) randomly complete 2 experimental sessions: (i) a control condition (CON); (ii) a 30-min moderate intensity (65% VO<sub
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40213932
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29862158
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40415631
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Evolution of Brain Magnetic Resonance Imaging Lesions in Dogs Treated for Meningoencephalomyelitis of Unknown Origin Between Initial Diagnosis and Relapse.
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Severe bacterial sepsis results in delayed diagnosis of tuberculous lymphadenitis in a rheumatoid arthritis patient treated with adalimumab.
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Centering U.S. Rural, Immigrant Latinx Adolescent Voices Through Narrative Mapping: Exploring a Novel Approach to Communicated Narrative Sense-Making.
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The response of meningoencephalitis of unknown origin (MUO) in dogs to immunosuppressive treatment is unpredictable, and relapses frequently occur.</AbstractText Our aim was to describe the evolution of brain magnetic resonance imaging (MRI) lesions in dogs treated for MUO from diagnosis to relapse and to define the diagnostic and clinical value of repeat MRI at relapse.</AbstractText Eighteen dogs treated for MUO that experienced relapse and underwent MRI both at disease onset and relapse.</AbstractText Retrospective, descriptive, longitudinal, case series study. Dogs were identified from medical records between 2015 and 2024. The MR images were reviewed by radiologists for lesion number, location, size, pre- and post-contrast signal aspect, meningeal enhancement, mass effect, perilesional edema, and evidence of intracranial hypertension.</AbstractText Median interval between MRIs was 259 days (range, 31-876 days). In dogs with relapse delay < 157 days, lesion number tended to decrease. Residual lesions tended to enlarge and exhibit contrast enhancement and perilesional edema (suggesting an active pathologic process), but without development of new lesions. After 233 days, all dogs had developed new lesions. Half exhibited enlarged active residual lesions, whereas the others showed either remission or smaller inactive lesions.</AbstractText Before a clinical relapse at approximately 6 months, remission of the initial pathologic process and development of new lesions appear unlikely. Beyond this period, new lesions may occur with or without remission of the initial pathologic process, and repeat MRI is of high diagnostic and clinical value in detecting new lesions and characterizing the underlying pathologic process.</AbstractText
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Although tumor necrosis factor (TNF)-α inhibitors are effective in patients with rheumatoid arthritis (RA), an increased risk of infections often becomes a serious problem. It is well known that TNF-α inhibitors increase the risk of tuberculosis, but extrapulmonary tuberculosis often induced by them is difficult to diagnose using routine imaging examinations. We described a case of delayed diagnosis of a tuberculous lymphadenitis in a patient with RA treated with TNF-α inhibitor because of the complications of severe bacterial sepsis. In this case, rescreening with the interferon-γ release assay and excisional biopsy were useful in confirming the diagnosis of extrapulmonary tuberculosis. In the case we presented, she had other risk factors, that is, advanced age at the start of anti- TNF-α treatment or concomitant use of corticosteroid, might contribute to the development of complex infections. We should keep in mind that careful follow-up and appropriate examinations are necessary in caring for patients administering immunosuppressive treatments including anti- TNF-α drugs.</AbstractText
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In the current study, we explore how rural immigrant Latinx adolescents make sense of and cope with their experiences through narrative mapping. Narrative mapping is an arts-based research method consisting of intrapersonal sensemaking through drawing and interpersonal sensemaking through discussion with others. We theoretically ground our study in narrative resilience via communicated narrative sense-making (CNSM) theory's translational storytelling heuristic. We asked 20 immigrant Latinx adolescents, ages 15-18, from a small rural Nebraskan community, in which 70% identify as Hispanic/Latinx, to draw and discuss a story about their health, education, and/or stress. We found that students drew and explained their drawings and experiences to their peers through two narrative sense-making devices: <i
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Evolution of Brain Magnetic Resonance Imaging Lesions in Dogs Treated for Meningoencephalomyelitis of Unknown Origin Between Initial Diagnosis and Relapse. The response of meningoencephalitis of unknown origin (MUO) in dogs to immunosuppressive treatment is unpredictable, and relapses frequently occur.</AbstractText Our aim was to describe the evolution of brain magnetic resonance imaging (MRI) lesions in dogs treated for MUO from diagnosis to relapse and to define the diagnostic and clinical value of repeat MRI at relapse.</AbstractText Eighteen dogs treated for MUO that experienced relapse and underwent MRI both at disease onset and relapse.</AbstractText Retrospective, descriptive, longitudinal, case series study. Dogs were identified from medical records between 2015 and 2024. The MR images were reviewed by radiologists for lesion number, location, size, pre- and post-contrast signal aspect, meningeal enhancement, mass effect, perilesional edema, and evidence of intracranial hypertension.</AbstractText Median interval between MRIs was 259 days (range, 31-876 days). In dogs with relapse delay < 157 days, lesion number tended to decrease. Residual lesions tended to enlarge and exhibit contrast enhancement and perilesional edema (suggesting an active pathologic process), but without development of new lesions. After 233 days, all dogs had developed new lesions. Half exhibited enlarged active residual lesions, whereas the others showed either remission or smaller inactive lesions.</AbstractText Before a clinical relapse at approximately 6 months, remission of the initial pathologic process and development of new lesions appear unlikely. Beyond this period, new lesions may occur with or without remission of the initial pathologic process, and repeat MRI is of high diagnostic and clinical value in detecting new lesions and characterizing the underlying pathologic process.</AbstractText
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Severe bacterial sepsis results in delayed diagnosis of tuberculous lymphadenitis in a rheumatoid arthritis patient treated with adalimumab. Although tumor necrosis factor (TNF)-α inhibitors are effective in patients with rheumatoid arthritis (RA), an increased risk of infections often becomes a serious problem. It is well known that TNF-α inhibitors increase the risk of tuberculosis, but extrapulmonary tuberculosis often induced by them is difficult to diagnose using routine imaging examinations. We described a case of delayed diagnosis of a tuberculous lymphadenitis in a patient with RA treated with TNF-α inhibitor because of the complications of severe bacterial sepsis. In this case, rescreening with the interferon-γ release assay and excisional biopsy were useful in confirming the diagnosis of extrapulmonary tuberculosis. In the case we presented, she had other risk factors, that is, advanced age at the start of anti- TNF-α treatment or concomitant use of corticosteroid, might contribute to the development of complex infections. We should keep in mind that careful follow-up and appropriate examinations are necessary in caring for patients administering immunosuppressive treatments including anti- TNF-α drugs.</AbstractText
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Centering U.S. Rural, Immigrant Latinx Adolescent Voices Through Narrative Mapping: Exploring a Novel Approach to Communicated Narrative Sense-Making. In the current study, we explore how rural immigrant Latinx adolescents make sense of and cope with their experiences through narrative mapping. Narrative mapping is an arts-based research method consisting of intrapersonal sensemaking through drawing and interpersonal sensemaking through discussion with others. We theoretically ground our study in narrative resilience via communicated narrative sense-making (CNSM) theory's translational storytelling heuristic. We asked 20 immigrant Latinx adolescents, ages 15-18, from a small rural Nebraskan community, in which 70% identify as Hispanic/Latinx, to draw and discuss a story about their health, education, and/or stress. We found that students drew and explained their drawings and experiences to their peers through two narrative sense-making devices: <i
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40464467
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22086977
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39466625
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Lamotrigine Enhances Autophagy and Reduces Post-Traumatic Spinal Neural Injury in Mice.
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Homeostatic synaptic plasticity: local and global mechanisms for stabilizing neuronal function.
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Accumbal serotonin hypofunction and dopamine hyperfunction due to chronic stress and palatable food intake in rats.
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Lamotrigine (LTG) is an antiepileptic drug that stabilizes the presynaptic membrane by blocking sodium channels and inhibiting excessive glutamate release. Its neuroprotective effects have been demonstrated in various pathological states. However, the role of LTG in spinal cord injury (SCI) and its relationship with autophagy, which is essential for cellular homeostasis, warrant further investigation.</AbstractText We established a mouse model of SCI using complete spinal transection. The neuroprotective effects of LTG were assessed using immunostaining and functional assessments, including Basso Mouse Scale (BMS) scores, lesion site area, and synapse survival. Western blot analyses were also performed to further examine the underlying cellular and molecular mechanisms of autophagy.</AbstractText LTG treatment promoted the post-traumatic survival of spinal neurons, improved BMS scores, reduced lesion site area, and enhanced synapse survival in a mouse model of SCI. Furthermore, LTG attenuated apoptosis following SCI by activating autophagy during the secondary injury phase. These findings indicate that LTG-enhanced autophagosome formation and autolysosome degradation play a key role in reducing neuronal loss after SCI.</AbstractText LTG appears to attenuate post-traumatic spinal neural injury by enhancing autophagy flux.</AbstractText
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Neural circuits must maintain stable function in the face of many plastic challenges, including changes in synapse number and strength, during learning and development. Recent work has shown that these destabilizing influences are counterbalanced by homeostatic plasticity mechanisms that act to stabilize neuronal and circuit activity. One such mechanism is synaptic scaling, which allows neurons to detect changes in their own firing rates through a set of calcium-dependent sensors that then regulate receptor trafficking to increase or decrease the accumulation of glutamate receptors at synaptic sites. Additional homeostatic mechanisms may allow local changes in synaptic activation to generate local synaptic adaptations, and network-wide changes in activity to generate network-wide adjustments in the balance between excitation and inhibition. The signaling pathways underlying these various forms of homeostatic plasticity are currently under intense scrutiny, and although dozens of molecular pathways have now been implicated in homeostatic plasticity, a clear picture of how homeostatic feedback is structured at the molecular level has not yet emerged. On a functional level, neuronal networks likely use this complex set of regulatory mechanisms to achieve homeostasis over a wide range of temporal and spatial scales.</AbstractText
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<b
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Lamotrigine Enhances Autophagy and Reduces Post-Traumatic Spinal Neural Injury in Mice. Lamotrigine (LTG) is an antiepileptic drug that stabilizes the presynaptic membrane by blocking sodium channels and inhibiting excessive glutamate release. Its neuroprotective effects have been demonstrated in various pathological states. However, the role of LTG in spinal cord injury (SCI) and its relationship with autophagy, which is essential for cellular homeostasis, warrant further investigation.</AbstractText We established a mouse model of SCI using complete spinal transection. The neuroprotective effects of LTG were assessed using immunostaining and functional assessments, including Basso Mouse Scale (BMS) scores, lesion site area, and synapse survival. Western blot analyses were also performed to further examine the underlying cellular and molecular mechanisms of autophagy.</AbstractText LTG treatment promoted the post-traumatic survival of spinal neurons, improved BMS scores, reduced lesion site area, and enhanced synapse survival in a mouse model of SCI. Furthermore, LTG attenuated apoptosis following SCI by activating autophagy during the secondary injury phase. These findings indicate that LTG-enhanced autophagosome formation and autolysosome degradation play a key role in reducing neuronal loss after SCI.</AbstractText LTG appears to attenuate post-traumatic spinal neural injury by enhancing autophagy flux.</AbstractText
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Homeostatic synaptic plasticity: local and global mechanisms for stabilizing neuronal function. Neural circuits must maintain stable function in the face of many plastic challenges, including changes in synapse number and strength, during learning and development. Recent work has shown that these destabilizing influences are counterbalanced by homeostatic plasticity mechanisms that act to stabilize neuronal and circuit activity. One such mechanism is synaptic scaling, which allows neurons to detect changes in their own firing rates through a set of calcium-dependent sensors that then regulate receptor trafficking to increase or decrease the accumulation of glutamate receptors at synaptic sites. Additional homeostatic mechanisms may allow local changes in synaptic activation to generate local synaptic adaptations, and network-wide changes in activity to generate network-wide adjustments in the balance between excitation and inhibition. The signaling pathways underlying these various forms of homeostatic plasticity are currently under intense scrutiny, and although dozens of molecular pathways have now been implicated in homeostatic plasticity, a clear picture of how homeostatic feedback is structured at the molecular level has not yet emerged. On a functional level, neuronal networks likely use this complex set of regulatory mechanisms to achieve homeostasis over a wide range of temporal and spatial scales.</AbstractText
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Accumbal serotonin hypofunction and dopamine hyperfunction due to chronic stress and palatable food intake in rats. <b
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35911892
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25043498
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36179465
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Clinical Spectrum of Tauopathies.
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Voxelwise meta-analysis of gray matter abnormalities in dementia with Lewy bodies.
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Ultrafast cervcial spine MRI protocol using deep learning-based reconstruction: Diagnostic equivalence to a conventional protocol.
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Tauopathies are both clinical and pathological heterogeneous disorders characterized by neuronal and/or glial accumulation of misfolded tau protein. It is now well understood that every pathologic tauopathy may present with various clinical phenotypes based on the primary site of involvement and the spread and distribution of the pathology in the nervous system making clinicopathological correlation more and more challenging. The clinical spectrum of tauopathies includes syndromes with a strong association with an underlying primary tauopathy, including Richardson syndrome (RS), corticobasal syndrome (CBS), non-fluent agrammatic primary progressive aphasia (nfaPPA)/apraxia of speech, pure akinesia with gait freezing (PAGF), and behavioral variant frontotemporal dementia (bvFTD), or weak association with an underlying primary tauopathy, including Parkinsonian syndrome, late-onset cerebellar ataxia, primary lateral sclerosis, semantic variant PPA (svPPA), and amnestic syndrome. Here, we discuss clinical syndromes associated with various primary tauopathies and their distinguishing clinical features and new biomarkers becoming available to improve <i
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Increasing neuroimaging studies have revealed brain gray matter (GM) atrophy by voxel-based morphometry (VBM) studies in patients with dementia with Lewy bodies (DLB) relative to healthy controls. However, the spatial localization of GM abnormalities reported in the existing studies is heterogeneous. Here, we aimed to investigate concurrence across VBM studies to help clarify the structural abnormalities underpinning this condition.</AbstractText A systematic search for VBM studies of DLB patients and healthy controls published in PubMed database from January 2000 to March 2014 was conducted. A quantitative meta-analysis of whole-brain VBM studies in DLB patients and healthy controls was performed by means of Anisotropic Effect Size version of Signed Differential Mapping (AES-SDM) software package.</AbstractText Seven studies comprising 218 DLB patients and 219 healthy controls were included in the present study. Compared to healthy subjects, the patients group showed consistent decreased GM in right lateral temporal/insular cortex and left lenticular nucleus/insular cortex. The results remained largely unchanged in the following jackknife sensitivity analyses. Meta-regression analysis indicated an increased probability of finding brain atrophy in left superior temporal gyrus in patients with lower MMSE scores.</AbstractText The present meta-analysis quantitatively demonstrates a characteristic pattern of GM alternations that contributed to the understanding of pathophysiology underlying DLB. Future studies will benefit from employing meta-analytical comparisons to other dementia subtypes with solid evidence to extend these findings.</AbstractText
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A major drawback of magnetic resonance imaging (MRI) is its limited imaging speed. This study proposed an ultrafast cervical spine MRI protocol (2 min 57 s) using deep learning-based reconstruction (DLR) and compared the diagnostic results to those of conventional MRI protocols (12 min 54 s).</AbstractText Fifty patients who underwent cervical spine MRI using both conventional and ultrafast protocols, including sagittal T1-weighted, T2-weighted, short-TI inversion recovery, and axial T2*-weighted imaging were included in this study. The ultrafast protocol shortened the acquisition time to approximately-one-fourth of that of the conventional protocol by reducing the phase matrix, oversampling rate, and number of excitations, and by applying compressed sensing. To compensate for the decreased signal-to-noise ratio caused by acceleration, noise reduction using DLR was performed. For image interpretation, three neuroradiologists graded or classified degenerative changes, including central canal stenosis, foraminal stenosis, endplate degeneration, disc degeneration, and disc hernia. The presence of other pathologies was also recorded. Given the absence of a reference standard, we tested the interchangeability of the two protocols by calculating the 95% confidence interval (CI) of the individual equivalence index. We also assessed the inter-protocol intra-reader agreement using kappa statistics.</AbstractText Except for endplate degeneration, the 95 % CI of the individual equivalence index for all variables did not exceed 5 %, indicating interchangeability between the two protocols. The kappa values ranged from 0.600 to 0.977, indicating substantial to almost perfect agreement.</AbstractText The proposed ultrafast MRI protocol yielded almost equivalent diagnostic results compared as the conventional protocol.</AbstractText
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Clinical Spectrum of Tauopathies. Tauopathies are both clinical and pathological heterogeneous disorders characterized by neuronal and/or glial accumulation of misfolded tau protein. It is now well understood that every pathologic tauopathy may present with various clinical phenotypes based on the primary site of involvement and the spread and distribution of the pathology in the nervous system making clinicopathological correlation more and more challenging. The clinical spectrum of tauopathies includes syndromes with a strong association with an underlying primary tauopathy, including Richardson syndrome (RS), corticobasal syndrome (CBS), non-fluent agrammatic primary progressive aphasia (nfaPPA)/apraxia of speech, pure akinesia with gait freezing (PAGF), and behavioral variant frontotemporal dementia (bvFTD), or weak association with an underlying primary tauopathy, including Parkinsonian syndrome, late-onset cerebellar ataxia, primary lateral sclerosis, semantic variant PPA (svPPA), and amnestic syndrome. Here, we discuss clinical syndromes associated with various primary tauopathies and their distinguishing clinical features and new biomarkers becoming available to improve <i
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Voxelwise meta-analysis of gray matter abnormalities in dementia with Lewy bodies. Increasing neuroimaging studies have revealed brain gray matter (GM) atrophy by voxel-based morphometry (VBM) studies in patients with dementia with Lewy bodies (DLB) relative to healthy controls. However, the spatial localization of GM abnormalities reported in the existing studies is heterogeneous. Here, we aimed to investigate concurrence across VBM studies to help clarify the structural abnormalities underpinning this condition.</AbstractText A systematic search for VBM studies of DLB patients and healthy controls published in PubMed database from January 2000 to March 2014 was conducted. A quantitative meta-analysis of whole-brain VBM studies in DLB patients and healthy controls was performed by means of Anisotropic Effect Size version of Signed Differential Mapping (AES-SDM) software package.</AbstractText Seven studies comprising 218 DLB patients and 219 healthy controls were included in the present study. Compared to healthy subjects, the patients group showed consistent decreased GM in right lateral temporal/insular cortex and left lenticular nucleus/insular cortex. The results remained largely unchanged in the following jackknife sensitivity analyses. Meta-regression analysis indicated an increased probability of finding brain atrophy in left superior temporal gyrus in patients with lower MMSE scores.</AbstractText The present meta-analysis quantitatively demonstrates a characteristic pattern of GM alternations that contributed to the understanding of pathophysiology underlying DLB. Future studies will benefit from employing meta-analytical comparisons to other dementia subtypes with solid evidence to extend these findings.</AbstractText
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Ultrafast cervcial spine MRI protocol using deep learning-based reconstruction: Diagnostic equivalence to a conventional protocol. A major drawback of magnetic resonance imaging (MRI) is its limited imaging speed. This study proposed an ultrafast cervical spine MRI protocol (2 min 57 s) using deep learning-based reconstruction (DLR) and compared the diagnostic results to those of conventional MRI protocols (12 min 54 s).</AbstractText Fifty patients who underwent cervical spine MRI using both conventional and ultrafast protocols, including sagittal T1-weighted, T2-weighted, short-TI inversion recovery, and axial T2*-weighted imaging were included in this study. The ultrafast protocol shortened the acquisition time to approximately-one-fourth of that of the conventional protocol by reducing the phase matrix, oversampling rate, and number of excitations, and by applying compressed sensing. To compensate for the decreased signal-to-noise ratio caused by acceleration, noise reduction using DLR was performed. For image interpretation, three neuroradiologists graded or classified degenerative changes, including central canal stenosis, foraminal stenosis, endplate degeneration, disc degeneration, and disc hernia. The presence of other pathologies was also recorded. Given the absence of a reference standard, we tested the interchangeability of the two protocols by calculating the 95% confidence interval (CI) of the individual equivalence index. We also assessed the inter-protocol intra-reader agreement using kappa statistics.</AbstractText Except for endplate degeneration, the 95 % CI of the individual equivalence index for all variables did not exceed 5 %, indicating interchangeability between the two protocols. The kappa values ranged from 0.600 to 0.977, indicating substantial to almost perfect agreement.</AbstractText The proposed ultrafast MRI protocol yielded almost equivalent diagnostic results compared as the conventional protocol.</AbstractText
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39846186
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33971241
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39494983
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Infarct core segmentation using U-Net in CT perfusion imaging: a feasibility study.
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Diffusion kurtosis imaging for the assessment of renal fibrosis of chronic kidney disease: A preliminary study.
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Dopaminergic Axon Tracts Within a Hyaluronic Acid Hydrogel Encasement to Restore the Nigrostriatal Pathway.
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BackgroundThe wide variability in thresholds on computed tomography (CT) perfusion parametric maps has led to controversy in the stroke imaging community about the most accurate measurement of core infarction.PurposeTo investigate the feasibility of using U-Net to perform infarct core segmentation in CT perfusion imaging.Material and MethodsCT perfusion parametric maps were the input of U-Net, while the ground truth segmentation was determined based on diffusion-weighted imaging (DWI). The dataset used in this study was from the ISLES2018 challenge, which contains 63 acute stroke patients receiving CT perfusion imaging and DWI within 8 h of stroke onset. The segmentation accuracy of model outputs was assessed by calculating Dice similarity coefficient (DSC), sensitivity, and intersection over union (IoU).ResultsThe highest DSC was observed in U-Net taking mean transit time (MTT) or time-to-maximum (Tmax) as input. Meanwhile, the highest sensitivity and IoU were observed in U-Net taking Tmax as input. A DSC in the range of 0.2-0.4 was found in U-Net taking Tmax as input when the infarct area contains < 1000 pixels. A DSC of 0.4-0.6 was found in U-Net taking Tmax as input when the infarct area contains 1000-1999 pixels. A DSC value of 0.6-0.8 was found in U-Net taking Tmax as input when the infarct area contains ≥ 2000 pixels.ConclusionOur model achieved good performance for infarct area containing ≥ 2000 pixels, so it may assist in identifying patients who are contraindicated for intravenous thrombolysis.</AbstractText
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To investigate the potential of diffusion kurtosis imaging (DKI) for the assessment of renal fibrosis in chronic kidney disease (CKD), using histopathology as the reference standard.</AbstractText Eighty-nine CKD patients and twenty healthy volunteers were recruited in this study. DKI was performed in all participants and all CKD patients received renal biopsy. The values of mean diffusivity (MD) and mean kurtosis (MK) in the renal cortex and medulla were compared between CKD patients and healthy volunteers. The Spearman correlation coefficient was calculated to assess the relationship between MD, MK values and the estimated glomerular filtration rate (eGFR), serum creatinine (SCr), 24 h urinary protein (24 h-UPRO), histopathological fibrosis score.</AbstractText The medullary MD values were significantly lower than cortex, while the cortical MK values were significantly lower than medulla for all participants. Renal parenchymal MD values were significantly lower in the CKD patients than healthy controls, whereas MK values were significantly higher in the CKD patients than healthy controls. In the CKD patients, the significantly negative correlation was observed between the renal parenchymal MD values and the 24 h-UPRO, SCr, histopathological fibrosis score, as well as between the renal parenchymal MK values and the eGFR, while the significantly positive correlation was found between the renal parenchymal MD values and the eGFR, as well as between the renal parenchymal MK values and the 24 h-UPRO, SCr, histopathological fibrosis score.</AbstractText DKI shows great potential in the noninvasive assessment of renal fibrosis in CKD.</AbstractText
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Parkinson's disease is characterized by motor deficits emerging from insufficient dopamine in the striatum after degeneration of dopaminergic neurons and their long-projecting axons comprising the nigrostriatal pathway. To address this, a tissue-engineered nigrostriatal pathway (TE-NSP) featuring a tubular hydrogel with a collagen/laminin core that encases aggregated dopaminergic neurons and their axonal tracts is developed. This engineered microtissue can be implanted to replace neurons and axons with fidelity to the lost pathway and thus may provide dopamine according to feedback from host circuitry. While TE-NSPs have traditionally been fabricated with agarose, here a hyaluronic acid (HA) hydrogel is utilized to have a more bioactive encasement while expanding control over physical and biochemical properties. Using rat ventral midbrain neurons, it is found that TE-NSPs exhibited improved neurite growth with HA relative to agarose, with no differences in electrically-evoked dopamine release. When transplanted, HA hydrogels reduced average host neuron loss and inflammation around the implant compared to agarose, and TE-NSP neurons and axonal tracts survived for at least 2 weeks to structurally emulate the lost pathway. This study represents an innovative use of HA hydrogels for neuroregenerative medicine and enables future studies expanding the control and functionality of TE-NSPs.</AbstractText
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Infarct core segmentation using U-Net in CT perfusion imaging: a feasibility study. BackgroundThe wide variability in thresholds on computed tomography (CT) perfusion parametric maps has led to controversy in the stroke imaging community about the most accurate measurement of core infarction.PurposeTo investigate the feasibility of using U-Net to perform infarct core segmentation in CT perfusion imaging.Material and MethodsCT perfusion parametric maps were the input of U-Net, while the ground truth segmentation was determined based on diffusion-weighted imaging (DWI). The dataset used in this study was from the ISLES2018 challenge, which contains 63 acute stroke patients receiving CT perfusion imaging and DWI within 8 h of stroke onset. The segmentation accuracy of model outputs was assessed by calculating Dice similarity coefficient (DSC), sensitivity, and intersection over union (IoU).ResultsThe highest DSC was observed in U-Net taking mean transit time (MTT) or time-to-maximum (Tmax) as input. Meanwhile, the highest sensitivity and IoU were observed in U-Net taking Tmax as input. A DSC in the range of 0.2-0.4 was found in U-Net taking Tmax as input when the infarct area contains < 1000 pixels. A DSC of 0.4-0.6 was found in U-Net taking Tmax as input when the infarct area contains 1000-1999 pixels. A DSC value of 0.6-0.8 was found in U-Net taking Tmax as input when the infarct area contains ≥ 2000 pixels.ConclusionOur model achieved good performance for infarct area containing ≥ 2000 pixels, so it may assist in identifying patients who are contraindicated for intravenous thrombolysis.</AbstractText
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Diffusion kurtosis imaging for the assessment of renal fibrosis of chronic kidney disease: A preliminary study. To investigate the potential of diffusion kurtosis imaging (DKI) for the assessment of renal fibrosis in chronic kidney disease (CKD), using histopathology as the reference standard.</AbstractText Eighty-nine CKD patients and twenty healthy volunteers were recruited in this study. DKI was performed in all participants and all CKD patients received renal biopsy. The values of mean diffusivity (MD) and mean kurtosis (MK) in the renal cortex and medulla were compared between CKD patients and healthy volunteers. The Spearman correlation coefficient was calculated to assess the relationship between MD, MK values and the estimated glomerular filtration rate (eGFR), serum creatinine (SCr), 24 h urinary protein (24 h-UPRO), histopathological fibrosis score.</AbstractText The medullary MD values were significantly lower than cortex, while the cortical MK values were significantly lower than medulla for all participants. Renal parenchymal MD values were significantly lower in the CKD patients than healthy controls, whereas MK values were significantly higher in the CKD patients than healthy controls. In the CKD patients, the significantly negative correlation was observed between the renal parenchymal MD values and the 24 h-UPRO, SCr, histopathological fibrosis score, as well as between the renal parenchymal MK values and the eGFR, while the significantly positive correlation was found between the renal parenchymal MD values and the eGFR, as well as between the renal parenchymal MK values and the 24 h-UPRO, SCr, histopathological fibrosis score.</AbstractText DKI shows great potential in the noninvasive assessment of renal fibrosis in CKD.</AbstractText
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Dopaminergic Axon Tracts Within a Hyaluronic Acid Hydrogel Encasement to Restore the Nigrostriatal Pathway. Parkinson's disease is characterized by motor deficits emerging from insufficient dopamine in the striatum after degeneration of dopaminergic neurons and their long-projecting axons comprising the nigrostriatal pathway. To address this, a tissue-engineered nigrostriatal pathway (TE-NSP) featuring a tubular hydrogel with a collagen/laminin core that encases aggregated dopaminergic neurons and their axonal tracts is developed. This engineered microtissue can be implanted to replace neurons and axons with fidelity to the lost pathway and thus may provide dopamine according to feedback from host circuitry. While TE-NSPs have traditionally been fabricated with agarose, here a hyaluronic acid (HA) hydrogel is utilized to have a more bioactive encasement while expanding control over physical and biochemical properties. Using rat ventral midbrain neurons, it is found that TE-NSPs exhibited improved neurite growth with HA relative to agarose, with no differences in electrically-evoked dopamine release. When transplanted, HA hydrogels reduced average host neuron loss and inflammation around the implant compared to agarose, and TE-NSP neurons and axonal tracts survived for at least 2 weeks to structurally emulate the lost pathway. This study represents an innovative use of HA hydrogels for neuroregenerative medicine and enables future studies expanding the control and functionality of TE-NSPs.</AbstractText
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39600178
|
20198109
|
40396896
|
Organic NMR crystallography: enabling progress for applications to pharmaceuticals and plant cell walls.
|
DNP-Hyperpolarized C Magnetic Resonance Metabolic Imaging for Cancer Applications.
|
A Dyad Approach to Understanding Intimate Partner and Family Distress as Risk Factors for Poor Warfighter Brain Health Following Mild Traumatic Brain Injury in Military Couples.
|
The application of NMR crystallography to organic molecules is exemplified by two case studies. For the tosylate salt of the active pharmaceutical ingredient, Ritlectinib, solid-state NMR spectra are presented at a <sup
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Critical factors in characterizing the aggressiveness and response to therapy for tumors are the availability of noninvasive biomarkers that can be combined with other clinical parameters to tailor treatment regimens to each individual patient. While conventional magnetic resonance (MR) images are widely used to estimate changes in tumor size, they do not provide the rapid readout that is required to make an early decision on whether a change in therapy is required. The use of hyperpolarized (13)C agents to obtain metabolic imaging data is of great interest for in vivo assessment of tumors. One of the first agents being considered for in vivo studies with dynamic nuclear polarization (DNP) is 1-(13)C-labeled pyruvate, which is converted to lactate or alanine, dependent upon the needs of the tissue in question. The development of this new technology and its implementation in preclinical cancer model systems has clearly demonstrated the potential for highlighting tumor aggressiveness and for monitoring changes associated with disease progression. While there is further work to do in terms of studying new agents, improving the DNP process itself and developing efficient MR methods for acquiring and analyzing the data, the preliminary results are extremely promising and provide strong motivation for considering cancer as one of the first applications of the technology.</AbstractText
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Using a dyadic approach with military couples, the current study examined family risk factors for chronic neurobehavioral symptoms in service members and veterans (SMVs) following a mild traumatic brain injury (MTBI).</AbstractText Military Treatment Facility.</AbstractText SMV (n = 122) and intimate partner (IPs, n = 122) dyads (N = 244).</AbstractText Prospective cohort.</AbstractText SMVs completed seven neurobehavioral outcome measures. Their intimate partners completed 12 health-related quality of life (HRQOL) risk factor measures. Both members of the dyad completed three family relationships risk factor measures.</AbstractText The number of neurobehavioral measures that were clinically elevated (≥60 T) were summed and used to classify SMVs into three outcome groups: (1) None/Few Symptoms [0-1 elevated scores]; (2) Several Symptoms [2-3 elevated scores]; and (3) Many Symptoms [4-7 elevated scores]. SMVs in the Many Symptoms group had significantly higher scores on nine family risk factor measures compared to the None/Few Symptoms group, and seven family risk factor measures compared to the Several Symptoms group. The Several Symptoms group had higher scores on one risk factor measure compared to the None/Few Symptoms group. The largest effect sizes were found for the SMV family relationships risk factor measures. SMVs were 4.2 to 13.0 times more likely to have poor neurobehavioral outcomes when they had negative versus positive family relationships.</AbstractText An important and unique addition to the literature was the finding that a range of risk factors in the SMV's family environment were strongly associated with clinically elevated chronic neurobehavioral symptoms following an MTBI. The establishment of the Family Wellness Program within the Defense Intrepid Network will open the door for family wellness to have a long-term place in military TBI treatment programs as a holistic, family-centered interdisciplinary model of care for warfighter brain health and return to duty following a TBI, and healthy, resilient, and military ready families.</AbstractText
|
Organic NMR crystallography: enabling progress for applications to pharmaceuticals and plant cell walls. The application of NMR crystallography to organic molecules is exemplified by two case studies. For the tosylate salt of the active pharmaceutical ingredient, Ritlectinib, solid-state NMR spectra are presented at a <sup
|
DNP-Hyperpolarized C Magnetic Resonance Metabolic Imaging for Cancer Applications. Critical factors in characterizing the aggressiveness and response to therapy for tumors are the availability of noninvasive biomarkers that can be combined with other clinical parameters to tailor treatment regimens to each individual patient. While conventional magnetic resonance (MR) images are widely used to estimate changes in tumor size, they do not provide the rapid readout that is required to make an early decision on whether a change in therapy is required. The use of hyperpolarized (13)C agents to obtain metabolic imaging data is of great interest for in vivo assessment of tumors. One of the first agents being considered for in vivo studies with dynamic nuclear polarization (DNP) is 1-(13)C-labeled pyruvate, which is converted to lactate or alanine, dependent upon the needs of the tissue in question. The development of this new technology and its implementation in preclinical cancer model systems has clearly demonstrated the potential for highlighting tumor aggressiveness and for monitoring changes associated with disease progression. While there is further work to do in terms of studying new agents, improving the DNP process itself and developing efficient MR methods for acquiring and analyzing the data, the preliminary results are extremely promising and provide strong motivation for considering cancer as one of the first applications of the technology.</AbstractText
|
A Dyad Approach to Understanding Intimate Partner and Family Distress as Risk Factors for Poor Warfighter Brain Health Following Mild Traumatic Brain Injury in Military Couples. Using a dyadic approach with military couples, the current study examined family risk factors for chronic neurobehavioral symptoms in service members and veterans (SMVs) following a mild traumatic brain injury (MTBI).</AbstractText Military Treatment Facility.</AbstractText SMV (n = 122) and intimate partner (IPs, n = 122) dyads (N = 244).</AbstractText Prospective cohort.</AbstractText SMVs completed seven neurobehavioral outcome measures. Their intimate partners completed 12 health-related quality of life (HRQOL) risk factor measures. Both members of the dyad completed three family relationships risk factor measures.</AbstractText The number of neurobehavioral measures that were clinically elevated (≥60 T) were summed and used to classify SMVs into three outcome groups: (1) None/Few Symptoms [0-1 elevated scores]; (2) Several Symptoms [2-3 elevated scores]; and (3) Many Symptoms [4-7 elevated scores]. SMVs in the Many Symptoms group had significantly higher scores on nine family risk factor measures compared to the None/Few Symptoms group, and seven family risk factor measures compared to the Several Symptoms group. The Several Symptoms group had higher scores on one risk factor measure compared to the None/Few Symptoms group. The largest effect sizes were found for the SMV family relationships risk factor measures. SMVs were 4.2 to 13.0 times more likely to have poor neurobehavioral outcomes when they had negative versus positive family relationships.</AbstractText An important and unique addition to the literature was the finding that a range of risk factors in the SMV's family environment were strongly associated with clinically elevated chronic neurobehavioral symptoms following an MTBI. The establishment of the Family Wellness Program within the Defense Intrepid Network will open the door for family wellness to have a long-term place in military TBI treatment programs as a holistic, family-centered interdisciplinary model of care for warfighter brain health and return to duty following a TBI, and healthy, resilient, and military ready families.</AbstractText
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37802314
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35549404
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36754227
|
A PrP EGFR signaling axis controls neural stem cell senescence through modulating cellular energy pathways.
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The Tabula Sapiens: A multiple-organ, single-cell transcriptomic atlas of humans.
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Structural basis of botulinum neurotoxin serotype A1 binding to human SV2A or SV2C receptors.
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Mis-folding of the prion protein (PrP) is known to cause neurodegenerative disease; however, the native function of this protein remains poorly defined. PrP has been linked with many cellular functions, including cellular proliferation and senescence. It is also known to influence epidermal growth factor receptor (EGFR) signaling, a pathway that is itself linked with both cell growth and senescence. Adult neural stem cells (NSCs) persist at low levels in the brain throughout life and retain the ability to proliferate and differentiate into new neural lineage cells. KO of PrP has previously been shown to reduce NSC proliferative capacity. We used PrP KO and WT NSCs from adult mouse brain to examine the influence of PrP on cellular senescence, EGFR signaling, and the downstream cellular processes. PrP KO NSCs showed decreased cell proliferation and increased senescence in in vitro cultures. Expression of EGFR was decreased in PrP KO NSCs compared with WT NSCs and additional supplementation of EGF was sufficient to reduce senescence. RNA-seq analysis confirmed that significant changes were occurring at the mRNA level within the EGFR signaling pathway and these were associated with reduced expression of mitochondrial components and correspondingly reduced mitochondrial function. Metabolomic analysis of cellular energy pathways showed that blockages were occurring at critical sites for production of energy and biomass, including catabolism of pyruvate. We conclude that, in the absence of PrP, NSC growth pathways are downregulated as a consequence of insufficient energy and growth intermediates.</AbstractText
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Molecular characterization of cell types using single-cell transcriptome sequencing is revolutionizing cell biology and enabling new insights into the physiology of human organs. We created a human reference atlas comprising nearly 500,000 cells from 24 different tissues and organs, many from the same donor. This atlas enabled molecular characterization of more than 400 cell types, their distribution across tissues, and tissue-specific variation in gene expression. Using multiple tissues from a single donor enabled identification of the clonal distribution of T cells between tissues, identification of the tissue-specific mutation rate in B cells, and analysis of the cell cycle state and proliferative potential of shared cell types across tissues. Cell type-specific RNA splicing was discovered and analyzed across tissues within an individual.</AbstractText
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Botulinum neurotoxin A1 (BoNT/A1) is the most potent natural poison in human. BoNT/A1 recognize the luminal domain of SV2A (LD-SV2A) and its glycosylation at position N573 (N573g) or the luminal domain of SV2C (LD-SV2C) and its glycosylation at position N559 (N559g) to bind neural membrane. Our computational data suggest that the N-glycan at position 480 (N480g) in the luminal domain of SV2C (LD-SV2C) indirectly enhanced the contacts of the neurotoxin surface with the second N-glycan at position 559 (N559g) by acting as a shield to prevent N559g to interact with residues of LD-SV2C. The absence of an N-glycan homologous to N480g in LD-SV2A leads to a decrease of the binding of N573g to the surface of BoNT/A1. Concerning the intermolecular interactions between BoNT/A and the protein part of LD-SV2A or LD-SV2C, we showed that the high affinity of the neurotoxin for binding LD-SV2C are mediated by a better compaction of its F557-F562 part provided by a π-π network mediated by residues F547, F552, F557 and F562 coupled with the presence of two aromatic residues at position 563 and 564 that optimize the binding of BoNT/A1 via cation-pi and CH-pi interaction. Finally, in addition to the well-known ganglioside binding site which accommodates a ganglioside on the surface of BoNT/A1, we identified a structure we coined the ganglioside binding loop defined by the sequence 1253-HQFNNIAK-1260 that is conserved across all subtypes of BoNT/A and is predicted to has a high affinity to interact with gangliosides. These data solved the puzzle generated by mutational studies that could be only partially understood with crystallographic data that lack both a biologically relevant membrane environment and a full glycosylation of SV2.</AbstractText
|
A PrP EGFR signaling axis controls neural stem cell senescence through modulating cellular energy pathways. Mis-folding of the prion protein (PrP) is known to cause neurodegenerative disease; however, the native function of this protein remains poorly defined. PrP has been linked with many cellular functions, including cellular proliferation and senescence. It is also known to influence epidermal growth factor receptor (EGFR) signaling, a pathway that is itself linked with both cell growth and senescence. Adult neural stem cells (NSCs) persist at low levels in the brain throughout life and retain the ability to proliferate and differentiate into new neural lineage cells. KO of PrP has previously been shown to reduce NSC proliferative capacity. We used PrP KO and WT NSCs from adult mouse brain to examine the influence of PrP on cellular senescence, EGFR signaling, and the downstream cellular processes. PrP KO NSCs showed decreased cell proliferation and increased senescence in in vitro cultures. Expression of EGFR was decreased in PrP KO NSCs compared with WT NSCs and additional supplementation of EGF was sufficient to reduce senescence. RNA-seq analysis confirmed that significant changes were occurring at the mRNA level within the EGFR signaling pathway and these were associated with reduced expression of mitochondrial components and correspondingly reduced mitochondrial function. Metabolomic analysis of cellular energy pathways showed that blockages were occurring at critical sites for production of energy and biomass, including catabolism of pyruvate. We conclude that, in the absence of PrP, NSC growth pathways are downregulated as a consequence of insufficient energy and growth intermediates.</AbstractText
|
The Tabula Sapiens: A multiple-organ, single-cell transcriptomic atlas of humans. Molecular characterization of cell types using single-cell transcriptome sequencing is revolutionizing cell biology and enabling new insights into the physiology of human organs. We created a human reference atlas comprising nearly 500,000 cells from 24 different tissues and organs, many from the same donor. This atlas enabled molecular characterization of more than 400 cell types, their distribution across tissues, and tissue-specific variation in gene expression. Using multiple tissues from a single donor enabled identification of the clonal distribution of T cells between tissues, identification of the tissue-specific mutation rate in B cells, and analysis of the cell cycle state and proliferative potential of shared cell types across tissues. Cell type-specific RNA splicing was discovered and analyzed across tissues within an individual.</AbstractText
|
Structural basis of botulinum neurotoxin serotype A1 binding to human SV2A or SV2C receptors. Botulinum neurotoxin A1 (BoNT/A1) is the most potent natural poison in human. BoNT/A1 recognize the luminal domain of SV2A (LD-SV2A) and its glycosylation at position N573 (N573g) or the luminal domain of SV2C (LD-SV2C) and its glycosylation at position N559 (N559g) to bind neural membrane. Our computational data suggest that the N-glycan at position 480 (N480g) in the luminal domain of SV2C (LD-SV2C) indirectly enhanced the contacts of the neurotoxin surface with the second N-glycan at position 559 (N559g) by acting as a shield to prevent N559g to interact with residues of LD-SV2C. The absence of an N-glycan homologous to N480g in LD-SV2A leads to a decrease of the binding of N573g to the surface of BoNT/A1. Concerning the intermolecular interactions between BoNT/A and the protein part of LD-SV2A or LD-SV2C, we showed that the high affinity of the neurotoxin for binding LD-SV2C are mediated by a better compaction of its F557-F562 part provided by a π-π network mediated by residues F547, F552, F557 and F562 coupled with the presence of two aromatic residues at position 563 and 564 that optimize the binding of BoNT/A1 via cation-pi and CH-pi interaction. Finally, in addition to the well-known ganglioside binding site which accommodates a ganglioside on the surface of BoNT/A1, we identified a structure we coined the ganglioside binding loop defined by the sequence 1253-HQFNNIAK-1260 that is conserved across all subtypes of BoNT/A and is predicted to has a high affinity to interact with gangliosides. These data solved the puzzle generated by mutational studies that could be only partially understood with crystallographic data that lack both a biologically relevant membrane environment and a full glycosylation of SV2.</AbstractText
|
40595725
|
36924923
|
40782980
|
Dopaminergic and serotonergic genetic variants predict actions and expectations of cooperation and punishment.
|
The gut-brain connection: Exploring the influence of the gut microbiota on neuroplasticity and neurodevelopmental disorders.
|
Antibiotic Resistance, Biofilm Formation, and Virulence Gene Profiling of Multidrug-Resistant Pseudomonas aeruginosa Isolates from a Multi-Speciality Hospital in Sikkim, India.
|
Genetic variants in dopaminergic and serotonergic pathways have been linked to individual differences in social behavior. In this study, we investigated the relationship between eight allelic variants within these pathways and both behavior and beliefs in 99 participants playing an online Public Goods Game (PGG) with and without punishment. Our results show that individuals with the 5-HTTLPR L/L genotype contributed less and had lower expectations of others' contributions in the absence of punishment; the 5-HTR1B-rs13212041 T/T genotype was associated with lower expectations of antisocial and spiteful punishment; the COMT-rs4680 A/A (Met/Met) genotype was linked to lower expectations of contributions in the presence of punishment. These findings suggest that specific alleles modulate both cooperative behavior and social expectations, suggesting a genetic contribution to individual variability in responses to social dilemmas.</AbstractText
|
Neuroplasticity refers to the ability of brain circuits to reorganize and change the properties of the network, resulting in alterations in brain function and behavior. It is traditionally believed that neuroplasticity is influenced by external stimuli, learning, and experience. Intriguingly, there is new evidence suggesting that endogenous signals from the body's periphery may play a role. The gut microbiota, a diverse community of microorganisms living in harmony with their host, may be able to influence plasticity through its modulation of the gut-brain axis. Interestingly, the maturation of the gut microbiota coincides with critical periods of neurodevelopment, during which neural circuits are highly plastic and potentially vulnerable. As such, dysbiosis (an imbalance in the gut microbiota composition) during early life may contribute to the disruption of normal developmental trajectories, leading to neurodevelopmental disorders. This review aims to examine the ways in which the gut microbiota can affect neuroplasticity. It will also discuss recent research linking gastrointestinal issues and bacterial dysbiosis to various neurodevelopmental disorders and their potential impact on neurological outcomes. This article is part of the Special Issue on "Microbiome & the Brain: Mechanisms & Maladies".</AbstractText
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Effective antibiotic stewardship and monitoring of antimicrobial resistance are crucial for mitigating the emergence and spread of opportunistic nosocomial pathogens, such as Pseudomonas aeruginosa. This study aimed to identify antibiotic resistance patterns, the ability to form biofilms, and the presence of virulence-associated genes in multidrug-resistant (MDR) P. aeruginosa isolates from a multi-speciality government hospital in Sikkim, India.</AbstractText Forty clinical isolates of P. aeruginosa were characterised through antimicrobial susceptibility testing (AST). MDR isolates were evaluated for biofilm formation and the presence of carbapenemase genes (bla<sub The ecfX gene specific to P. aeruginosa was detected in all isolates, confirming their identification. Among the isolates, 37.5% were MDR, and 7.5% were extensively drug-resistant (XDR), with a multiple antibiotic resistance (MAR) index ranging from 0.210 to 0.894. Some MDR isolates demonstrated resistance to meropenem (MIC 15.62 to 125 μg/mL), indicating carbapenem resistance. All isolates showed a MIC of ≤ 2 μg/mL to colistin. These MDR isolates formed biofilms and harboured lasR, mexAB-oprM, along with the majority of virulence-related genes (toxA, lasA, popB, phzM, and algD). However, only two carbapenemase genes were detected: bla<sub This study highlights the occurrence of biofilm-forming, MDR, and carbapenem-resistant clinical isolates of P. aeruginosa. These isolates harbour several virulence-associated genes and are fully susceptible to colistin, suggesting its potential role in treating such infections. The findings emphasise the need for continued surveillance and targeted antimicrobial stewardship in hospital settings.</AbstractText
|
Dopaminergic and serotonergic genetic variants predict actions and expectations of cooperation and punishment. Genetic variants in dopaminergic and serotonergic pathways have been linked to individual differences in social behavior. In this study, we investigated the relationship between eight allelic variants within these pathways and both behavior and beliefs in 99 participants playing an online Public Goods Game (PGG) with and without punishment. Our results show that individuals with the 5-HTTLPR L/L genotype contributed less and had lower expectations of others' contributions in the absence of punishment; the 5-HTR1B-rs13212041 T/T genotype was associated with lower expectations of antisocial and spiteful punishment; the COMT-rs4680 A/A (Met/Met) genotype was linked to lower expectations of contributions in the presence of punishment. These findings suggest that specific alleles modulate both cooperative behavior and social expectations, suggesting a genetic contribution to individual variability in responses to social dilemmas.</AbstractText
|
The gut-brain connection: Exploring the influence of the gut microbiota on neuroplasticity and neurodevelopmental disorders. Neuroplasticity refers to the ability of brain circuits to reorganize and change the properties of the network, resulting in alterations in brain function and behavior. It is traditionally believed that neuroplasticity is influenced by external stimuli, learning, and experience. Intriguingly, there is new evidence suggesting that endogenous signals from the body's periphery may play a role. The gut microbiota, a diverse community of microorganisms living in harmony with their host, may be able to influence plasticity through its modulation of the gut-brain axis. Interestingly, the maturation of the gut microbiota coincides with critical periods of neurodevelopment, during which neural circuits are highly plastic and potentially vulnerable. As such, dysbiosis (an imbalance in the gut microbiota composition) during early life may contribute to the disruption of normal developmental trajectories, leading to neurodevelopmental disorders. This review aims to examine the ways in which the gut microbiota can affect neuroplasticity. It will also discuss recent research linking gastrointestinal issues and bacterial dysbiosis to various neurodevelopmental disorders and their potential impact on neurological outcomes. This article is part of the Special Issue on "Microbiome & the Brain: Mechanisms & Maladies".</AbstractText
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Antibiotic Resistance, Biofilm Formation, and Virulence Gene Profiling of Multidrug-Resistant Pseudomonas aeruginosa Isolates from a Multi-Speciality Hospital in Sikkim, India. Effective antibiotic stewardship and monitoring of antimicrobial resistance are crucial for mitigating the emergence and spread of opportunistic nosocomial pathogens, such as Pseudomonas aeruginosa. This study aimed to identify antibiotic resistance patterns, the ability to form biofilms, and the presence of virulence-associated genes in multidrug-resistant (MDR) P. aeruginosa isolates from a multi-speciality government hospital in Sikkim, India.</AbstractText Forty clinical isolates of P. aeruginosa were characterised through antimicrobial susceptibility testing (AST). MDR isolates were evaluated for biofilm formation and the presence of carbapenemase genes (bla<sub The ecfX gene specific to P. aeruginosa was detected in all isolates, confirming their identification. Among the isolates, 37.5% were MDR, and 7.5% were extensively drug-resistant (XDR), with a multiple antibiotic resistance (MAR) index ranging from 0.210 to 0.894. Some MDR isolates demonstrated resistance to meropenem (MIC 15.62 to 125 μg/mL), indicating carbapenem resistance. All isolates showed a MIC of ≤ 2 μg/mL to colistin. These MDR isolates formed biofilms and harboured lasR, mexAB-oprM, along with the majority of virulence-related genes (toxA, lasA, popB, phzM, and algD). However, only two carbapenemase genes were detected: bla<sub This study highlights the occurrence of biofilm-forming, MDR, and carbapenem-resistant clinical isolates of P. aeruginosa. These isolates harbour several virulence-associated genes and are fully susceptible to colistin, suggesting its potential role in treating such infections. The findings emphasise the need for continued surveillance and targeted antimicrobial stewardship in hospital settings.</AbstractText
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31954173
|
33192479
|
32811699
|
Denoising arterial spin labeling perfusion MRI with deep machine learning.
|
Detection of Cerebrovascular Loss in the Normal Aging C57BL/6 Mouse Brain Using in vivo Contrast-Enhanced Magnetic Resonance Angiography.
|
Blood microRNA expressions in patients with mild to moderate psoriasis and the relationship between microRNAs and psoriasis activity.
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Arterial spin labeling (ASL) perfusion MRI is a noninvasive technique for measuring cerebral blood flow (CBF) in a quantitative manner. A technical challenge in ASL MRI is data processing because of the inherently low signal-to-noise-ratio (SNR). Deep learning (DL) is an emerging machine learning technique that can learn a nonlinear transform from acquired data without using any explicit hypothesis. Such a high flexibility may be particularly beneficial for ASL denoising. In this paper, we proposed and validated a DL-based ASL MRI denoising algorithm (DL-ASL).</AbstractText The DL-ASL network was constructed using convolutional neural networks (CNNs) with dilated convolution and wide activation residual blocks to explicitly take the inter-voxel correlations into account, and preserve spatial resolution of input image during model learning.</AbstractText DL-ASL substantially improved the quality of ASL CBF in terms of SNR. Based on retrospective analyses, DL-ASL showed a high potential of reducing 75% of the original acquisition time without sacrificing CBF measurement quality.</AbstractText DL-ASL achieved improved denoising performance for ASL MRI as compared with current routine methods in terms of higher PSNR, SSIM and Radiologic scores. With the help of DL-ASL, much fewer repetitions may be prescribed in ASL MRI, resulting in a great reduction of the total acquisition time.</AbstractText
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Microvascular rarefaction, or the decrease in vascular density, has been described in the cerebrovasculature of aging humans, rats, and, more recently, mice in the presence and absence of age-dependent diseases. Given the wide use of mice in modeling age-dependent human diseases of the cerebrovasculature, visualization, and quantification of the global murine cerebrovasculature is necessary for establishing the baseline changes that occur with aging. To provide <i
|
In recent studies, microRNAs (mi-RNAs) have been shown to play an important role in psoriasis pathogenesis. However, studies evaluating mi-RNAs in the blood of psoriasis patients including a large number of mi-RNA panels are scarce.</AbstractText The authors aimed to assess mi-RNA expressions in blood samples of psoriasis patients, as well as to evaluate the association between mi-RNA expression and psoriasis severity.</AbstractText This was a case-control study on 52 patients with psoriasis vulgaris and 54 controls. Patients' medical history, psoriasis area and severity index (PASI) scores, and dermatology life quality index (DLQI) scores were recorded. The 42 disease-related mi-RNA primers were assessed by real-time PCR.</AbstractText In the patient group, 13.4% presented nail involvement and 8.2% had psoriatic arthritis. The mean PASI and DLQI scores were 7.90±8.83 and 8.13±5.50, respectively. Among 42 mi-RNA primers; hsa-miR-155-5p, hsa-miR-369-3p, hsa-miR-193b-3p, hsa-miR-498, hsa-miR-1266-5p, hsa-let-7d-5p, hsa-miR-205-5p, hsa-let-7c-5p, hsa-miR-30b-3p, and hsa-miR-515-3p expressions were significantly up-regulated, whereas hsa-miR-21-5p, hsa-miR-142-3p, hsa-miR-424-5p, hsa-miR-223-3p, hsa-miR-26a-5p, hsa-miR-106b-5p, hsa-miR-126-5p, hsa-miR-181a-5p, hsa-miR-222-3p, hsa-miR-22-3p, hsa-miR-24-3p, hsa-miR-17-3p, hsa-miR-30b-5p, hsa-miR-130a-3p, hsa-miR-30e-5p, and hsa-miR-16-5p were significantly down-regulated in psoriasis patients when compared with the control group (p<0.05).</AbstractText As the study included patients with mild to moderate psoriasis who mostly only received topical treatments, changes in miRNA before and after systemic treatments were not assessed.</AbstractText The detection of 24 mi-RNA expressions up- or down-regulated in psoriasis patients, even in those with milder disease, further supports the role of mi-RNAs in the psoriasis pathogenesis. Future studies should clarify whether mi-RNAs can be used as a marker for psoriasis prognosis or as a therapeutic agent in the treatment of psoriasis.</AbstractText
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Denoising arterial spin labeling perfusion MRI with deep machine learning. Arterial spin labeling (ASL) perfusion MRI is a noninvasive technique for measuring cerebral blood flow (CBF) in a quantitative manner. A technical challenge in ASL MRI is data processing because of the inherently low signal-to-noise-ratio (SNR). Deep learning (DL) is an emerging machine learning technique that can learn a nonlinear transform from acquired data without using any explicit hypothesis. Such a high flexibility may be particularly beneficial for ASL denoising. In this paper, we proposed and validated a DL-based ASL MRI denoising algorithm (DL-ASL).</AbstractText The DL-ASL network was constructed using convolutional neural networks (CNNs) with dilated convolution and wide activation residual blocks to explicitly take the inter-voxel correlations into account, and preserve spatial resolution of input image during model learning.</AbstractText DL-ASL substantially improved the quality of ASL CBF in terms of SNR. Based on retrospective analyses, DL-ASL showed a high potential of reducing 75% of the original acquisition time without sacrificing CBF measurement quality.</AbstractText DL-ASL achieved improved denoising performance for ASL MRI as compared with current routine methods in terms of higher PSNR, SSIM and Radiologic scores. With the help of DL-ASL, much fewer repetitions may be prescribed in ASL MRI, resulting in a great reduction of the total acquisition time.</AbstractText
|
Detection of Cerebrovascular Loss in the Normal Aging C57BL/6 Mouse Brain Using in vivo Contrast-Enhanced Magnetic Resonance Angiography. Microvascular rarefaction, or the decrease in vascular density, has been described in the cerebrovasculature of aging humans, rats, and, more recently, mice in the presence and absence of age-dependent diseases. Given the wide use of mice in modeling age-dependent human diseases of the cerebrovasculature, visualization, and quantification of the global murine cerebrovasculature is necessary for establishing the baseline changes that occur with aging. To provide <i
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Blood microRNA expressions in patients with mild to moderate psoriasis and the relationship between microRNAs and psoriasis activity. In recent studies, microRNAs (mi-RNAs) have been shown to play an important role in psoriasis pathogenesis. However, studies evaluating mi-RNAs in the blood of psoriasis patients including a large number of mi-RNA panels are scarce.</AbstractText The authors aimed to assess mi-RNA expressions in blood samples of psoriasis patients, as well as to evaluate the association between mi-RNA expression and psoriasis severity.</AbstractText This was a case-control study on 52 patients with psoriasis vulgaris and 54 controls. Patients' medical history, psoriasis area and severity index (PASI) scores, and dermatology life quality index (DLQI) scores were recorded. The 42 disease-related mi-RNA primers were assessed by real-time PCR.</AbstractText In the patient group, 13.4% presented nail involvement and 8.2% had psoriatic arthritis. The mean PASI and DLQI scores were 7.90±8.83 and 8.13±5.50, respectively. Among 42 mi-RNA primers; hsa-miR-155-5p, hsa-miR-369-3p, hsa-miR-193b-3p, hsa-miR-498, hsa-miR-1266-5p, hsa-let-7d-5p, hsa-miR-205-5p, hsa-let-7c-5p, hsa-miR-30b-3p, and hsa-miR-515-3p expressions were significantly up-regulated, whereas hsa-miR-21-5p, hsa-miR-142-3p, hsa-miR-424-5p, hsa-miR-223-3p, hsa-miR-26a-5p, hsa-miR-106b-5p, hsa-miR-126-5p, hsa-miR-181a-5p, hsa-miR-222-3p, hsa-miR-22-3p, hsa-miR-24-3p, hsa-miR-17-3p, hsa-miR-30b-5p, hsa-miR-130a-3p, hsa-miR-30e-5p, and hsa-miR-16-5p were significantly down-regulated in psoriasis patients when compared with the control group (p<0.05).</AbstractText As the study included patients with mild to moderate psoriasis who mostly only received topical treatments, changes in miRNA before and after systemic treatments were not assessed.</AbstractText The detection of 24 mi-RNA expressions up- or down-regulated in psoriasis patients, even in those with milder disease, further supports the role of mi-RNAs in the psoriasis pathogenesis. Future studies should clarify whether mi-RNAs can be used as a marker for psoriasis prognosis or as a therapeutic agent in the treatment of psoriasis.</AbstractText
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40618043
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29856543
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39838948
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Cross-cultural adaptation of the family coping questionnaire and psychometric evaluation among caregivers of schizophrenic patients in China.
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What is the risk-benefit ratio of long-term antipsychotic treatment in people with schizophrenia?
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Mass production of robust hydrogel electrolytes for high-performance zinc-ion batteries.
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Schizophrenia is a significant public health concern in China, imposing a heavy burden on patients' families and the healthcare system. However, there is a lack of a specific questionnaire for family caregivers of schizophrenia patients in China. This study aimed to introduce and culturally adapt the Family Coping Questionnaire (FCQ) to develop an assessment tool suitable for the Chinese cultural context.</AbstractText With the permission of the original author, the FCQ was culturally adapted following the Brislin translation model, which involved forward translation, target harmonization, back translation, and reconciliation. A pilot test with 15 caregivers was conducted to refine the questionnaire, followed by a cross-sectional survey of 242 participants from the psychiatric clinic and ward at the Third Xiangya Hospital of Central South University, Changsha, Hunan, China. Data analysis was performed using SPSS 22.0 to evaluate the scale's properties.</AbstractText The Chinese version of the FCQ demonstrated good reliability, with a Cronbach's α of 0.714 for the overall questionnaire and ranging from 0.57 to 0.79 for individual scales. The split-half reliability was 0.654, and test-retest reliability ranged from 0.52 to 0.88 for individual scales, with an overall FCQ reliability of 0.89. The content validity index was 1.0, and the FCQ accounted for 62.97% of the variance, indicating satisfactory construct validity.</AbstractText The culturally adapted Chinese version of the FCQ questionnaire has demonstrated good reliability and validity, serving as an effective tool for assessing the coping styles of caregivers of schizophrenia patients in China. However, this study has limitations. The sample was mainly composed of caregivers of patients in mild wards, and future research needs to expand the sample range.</AbstractText Not applicable.</AbstractText
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The long-term benefit-to-risk ratio of sustained antipsychotic treatment for schizophrenia has recently been questioned. In this paper, we critically examine the literature on the long-term efficacy and effectiveness of this treatment. We also review the evidence on the undesired effects, the impact on physical morbidity and mortality, as well as the neurobiological correlates of chronic exposure to antipsychotics. Finally, we summarize factors that affect the risk-benefit ratio. There is consistent evidence supporting the efficacy of antipsychotics in the short term and mid term following stabilization of acute psychotic symptoms. There is insufficient evidence supporting the notion that this effect changes in the long term. Most, but not all, of the long-term cohort studies find a decrease in efficacy during chronic treatment with antipsychotics. However, these results are inconclusive, given the extensive risk of bias, including increasing non-adherence. On the other hand, long-term studies based on national registries, which have lower risk of bias, find an advantage in terms of effectiveness during sustained antipsychotic treatment. Sustained antipsychotic treatment has been also consistently associated with lower mortality in people with schizophrenia compared to no antipsychotic treatment. Nevertheless, chronic antipsychotic use is associated with metabolic disturbance and tardive dyskinesia. The latter is the clearest undesired clinical consequence of brain functioning as a potential result of chronic antipsychotic exposure, likely from dopaminergic hypersensitivity, without otherwise clear evidence of other irreversible neurobiological changes. Adjunctive psychosocial interventions seem critical for achieving recovery. However, overall, the current literature does not support the safe reduction of antipsychotic dosages by 50% or more in stabilized individuals receiving adjunctive psychosocial interventions. In conclusion, the critical appraisal of the literature indicates that, although chronic antipsychotic use can be associated with undesirable neurologic and metabolic side effects, the evidence supporting its long-term efficacy and effectiveness, including impact on life expectancy, outweighs the evidence against this practice, overall indicating a favorable benefit-to-risk ratio. However, the finding that a minority of individuals diagnosed initially with schizophrenia appear to be relapse free for long periods, despite absence of sustained antipsychotic treatment, calls for further research on patient-level predictors of positive outcomes in people with an initial psychotic presentation.</AbstractText
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Hydrogel electrolytes are crucial for solving the problems of random zinc dendrite growth, hydrogen evolution reactions, and uncontrollable passivation. However, their complex fabrication processes pose challenges to achieving large-scale production with excellent mechanical properties required to withstand multiple cycles of mechanical loads while maintaining high electrochemical performance needed for the new-generation flexible zinc-ion batteries. Herein, we present a superspreading-based strategy to produce robust hydrogel electrolytes consisting of polyvinyl alcohol, sodium alginate and sodium acetate. The hydrogel electrolytes have a tensile strength of 54.1 ± 2.5 MPa, a fracture strain of up to 1113 ± 37%, and a fracture toughness of 374.1 ± 6.1 MJ m<sup
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Cross-cultural adaptation of the family coping questionnaire and psychometric evaluation among caregivers of schizophrenic patients in China. Schizophrenia is a significant public health concern in China, imposing a heavy burden on patients' families and the healthcare system. However, there is a lack of a specific questionnaire for family caregivers of schizophrenia patients in China. This study aimed to introduce and culturally adapt the Family Coping Questionnaire (FCQ) to develop an assessment tool suitable for the Chinese cultural context.</AbstractText With the permission of the original author, the FCQ was culturally adapted following the Brislin translation model, which involved forward translation, target harmonization, back translation, and reconciliation. A pilot test with 15 caregivers was conducted to refine the questionnaire, followed by a cross-sectional survey of 242 participants from the psychiatric clinic and ward at the Third Xiangya Hospital of Central South University, Changsha, Hunan, China. Data analysis was performed using SPSS 22.0 to evaluate the scale's properties.</AbstractText The Chinese version of the FCQ demonstrated good reliability, with a Cronbach's α of 0.714 for the overall questionnaire and ranging from 0.57 to 0.79 for individual scales. The split-half reliability was 0.654, and test-retest reliability ranged from 0.52 to 0.88 for individual scales, with an overall FCQ reliability of 0.89. The content validity index was 1.0, and the FCQ accounted for 62.97% of the variance, indicating satisfactory construct validity.</AbstractText The culturally adapted Chinese version of the FCQ questionnaire has demonstrated good reliability and validity, serving as an effective tool for assessing the coping styles of caregivers of schizophrenia patients in China. However, this study has limitations. The sample was mainly composed of caregivers of patients in mild wards, and future research needs to expand the sample range.</AbstractText Not applicable.</AbstractText
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What is the risk-benefit ratio of long-term antipsychotic treatment in people with schizophrenia? The long-term benefit-to-risk ratio of sustained antipsychotic treatment for schizophrenia has recently been questioned. In this paper, we critically examine the literature on the long-term efficacy and effectiveness of this treatment. We also review the evidence on the undesired effects, the impact on physical morbidity and mortality, as well as the neurobiological correlates of chronic exposure to antipsychotics. Finally, we summarize factors that affect the risk-benefit ratio. There is consistent evidence supporting the efficacy of antipsychotics in the short term and mid term following stabilization of acute psychotic symptoms. There is insufficient evidence supporting the notion that this effect changes in the long term. Most, but not all, of the long-term cohort studies find a decrease in efficacy during chronic treatment with antipsychotics. However, these results are inconclusive, given the extensive risk of bias, including increasing non-adherence. On the other hand, long-term studies based on national registries, which have lower risk of bias, find an advantage in terms of effectiveness during sustained antipsychotic treatment. Sustained antipsychotic treatment has been also consistently associated with lower mortality in people with schizophrenia compared to no antipsychotic treatment. Nevertheless, chronic antipsychotic use is associated with metabolic disturbance and tardive dyskinesia. The latter is the clearest undesired clinical consequence of brain functioning as a potential result of chronic antipsychotic exposure, likely from dopaminergic hypersensitivity, without otherwise clear evidence of other irreversible neurobiological changes. Adjunctive psychosocial interventions seem critical for achieving recovery. However, overall, the current literature does not support the safe reduction of antipsychotic dosages by 50% or more in stabilized individuals receiving adjunctive psychosocial interventions. In conclusion, the critical appraisal of the literature indicates that, although chronic antipsychotic use can be associated with undesirable neurologic and metabolic side effects, the evidence supporting its long-term efficacy and effectiveness, including impact on life expectancy, outweighs the evidence against this practice, overall indicating a favorable benefit-to-risk ratio. However, the finding that a minority of individuals diagnosed initially with schizophrenia appear to be relapse free for long periods, despite absence of sustained antipsychotic treatment, calls for further research on patient-level predictors of positive outcomes in people with an initial psychotic presentation.</AbstractText
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Mass production of robust hydrogel electrolytes for high-performance zinc-ion batteries. Hydrogel electrolytes are crucial for solving the problems of random zinc dendrite growth, hydrogen evolution reactions, and uncontrollable passivation. However, their complex fabrication processes pose challenges to achieving large-scale production with excellent mechanical properties required to withstand multiple cycles of mechanical loads while maintaining high electrochemical performance needed for the new-generation flexible zinc-ion batteries. Herein, we present a superspreading-based strategy to produce robust hydrogel electrolytes consisting of polyvinyl alcohol, sodium alginate and sodium acetate. The hydrogel electrolytes have a tensile strength of 54.1 ± 2.5 MPa, a fracture strain of up to 1113 ± 37%, and a fracture toughness of 374.1 ± 6.1 MJ m<sup
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20955933
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20546078
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20028933
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The genetics of child psychiatric disorders: focus on autism and Tourette syndrome.
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Research review: the neurobiology and genetics of maltreatment and adversity.
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Leiomyoma shrinkage after MRI-guided focused ultrasound treatment: report of 80 patients.
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Investigations into the genetics of child psychiatric disorders have finally begun to shed light on molecular and cellular mechanisms of psychopathology. The first strains of success in this notoriously difficult area of inquiry are the result of an increasingly sophisticated appreciation of the allelic architecture of common neuropsychiatric and neurodevelopmental disorders, the consolidation of large patient cohorts now beginning to reach sufficient size to power reliable studies, the emergence of genomic tools enabling comprehensive investigations of rare as well as common genetic variation, and advances in developmental neuroscience that are fueling the rapid translation of genetic findings.</AbstractText
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The neurobiological mechanisms by which childhood maltreatment heightens vulnerability to psychopathology remain poorly understood. It is likely that a complex interaction between environmental experiences (including poor caregiving) and an individual's genetic make-up influence neurobiological development across infancy and childhood, which in turn sets the stage for a child's psychological and emotional development. This review provides a concise synopsis of those studies investigating the neurobiological and genetic factors associated with childhood maltreatment and adversity. We first provide an overview of the neuroendocrine findings, drawing from animal and human studies. These studies indicate an association between early adversity and atypical development of the hypothalamic-pituitary-adrenal (HPA) axis stress response, which can predispose to psychiatric vulnerability in adulthood. We then review the neuroimaging findings of structural and functional brain differences in children and adults who have experienced childhood maltreatment. These studies offer evidence of several structural differences associated with early stress, most notably in the corpus callosum in children and the hippocampus in adults; functional studies have reported atypical activation of several brain regions, including decreased activity of the prefrontal cortex. Next we consider studies that suggest that the effect of environmental adversity may be conditional on an individual's genotype. We also briefly consider the possible role that epigenetic mechanisms might play in mediating the impact of early adversity. Finally we consider several ways in which the neurobiological and genetic research may be relevant to clinical practice and intervention.</AbstractText
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The purpose of this study was to assess the degree of leiomyoma ablation and shrinkage after MRI-guided focused ultrasound treatment performed according to U.S. Food and Drug Administration protocols for commercial trials.</AbstractText A total of 147 symptomatic leiomyomas in 80 women (average age, 46 years; range, 34-55 years) were managed with MRI-guided focused ultrasound. The average volume of treated fibroids was 175+/-201 (SD) cm3. Before treatment, T2-weighted MR images in three planes were obtained to measure leiomyoma volume. Immediately after treatment, T1-weighted contrast-enhanced fat-suppressed MR images in three planes were used to measure nonperfused volume ratio. Similar images obtained 6 months after treatment were used to determine leiomyoma shrinkage. Qualitative and quantitative relations between fibroid volume, nonperfused volume ratio at treatment, and 6-month shrinkage were measured.</AbstractText The average nonperfused volume ratio was 55%+/-25% immediately after treatment. Six months after treatment, the average volume of treated fibroids had decreased to 112+/-141 cm3 (n=81) (p<0.0001) with an average volume reduction of 31%+/-28%. A linear regression model showed highly significant correlation between posttreatment nonperfused volume ratio and shrinkage at 6 months (p<0.0001).</AbstractText MRI-guided focused ultrasound therapy for leiomyoma can result in nonperfused volume ratio and shrinkage that exceed those in previous clinical trials because the treatment guidelines have been relaxed to allow a greater amount of tissue ablation. The results suggest that a larger nonperfused volume ratio can be achieved, resulting in greater shrinkage and improved relief of symptoms.</AbstractText
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The genetics of child psychiatric disorders: focus on autism and Tourette syndrome. Investigations into the genetics of child psychiatric disorders have finally begun to shed light on molecular and cellular mechanisms of psychopathology. The first strains of success in this notoriously difficult area of inquiry are the result of an increasingly sophisticated appreciation of the allelic architecture of common neuropsychiatric and neurodevelopmental disorders, the consolidation of large patient cohorts now beginning to reach sufficient size to power reliable studies, the emergence of genomic tools enabling comprehensive investigations of rare as well as common genetic variation, and advances in developmental neuroscience that are fueling the rapid translation of genetic findings.</AbstractText
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Research review: the neurobiology and genetics of maltreatment and adversity. The neurobiological mechanisms by which childhood maltreatment heightens vulnerability to psychopathology remain poorly understood. It is likely that a complex interaction between environmental experiences (including poor caregiving) and an individual's genetic make-up influence neurobiological development across infancy and childhood, which in turn sets the stage for a child's psychological and emotional development. This review provides a concise synopsis of those studies investigating the neurobiological and genetic factors associated with childhood maltreatment and adversity. We first provide an overview of the neuroendocrine findings, drawing from animal and human studies. These studies indicate an association between early adversity and atypical development of the hypothalamic-pituitary-adrenal (HPA) axis stress response, which can predispose to psychiatric vulnerability in adulthood. We then review the neuroimaging findings of structural and functional brain differences in children and adults who have experienced childhood maltreatment. These studies offer evidence of several structural differences associated with early stress, most notably in the corpus callosum in children and the hippocampus in adults; functional studies have reported atypical activation of several brain regions, including decreased activity of the prefrontal cortex. Next we consider studies that suggest that the effect of environmental adversity may be conditional on an individual's genotype. We also briefly consider the possible role that epigenetic mechanisms might play in mediating the impact of early adversity. Finally we consider several ways in which the neurobiological and genetic research may be relevant to clinical practice and intervention.</AbstractText
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Leiomyoma shrinkage after MRI-guided focused ultrasound treatment: report of 80 patients. The purpose of this study was to assess the degree of leiomyoma ablation and shrinkage after MRI-guided focused ultrasound treatment performed according to U.S. Food and Drug Administration protocols for commercial trials.</AbstractText A total of 147 symptomatic leiomyomas in 80 women (average age, 46 years; range, 34-55 years) were managed with MRI-guided focused ultrasound. The average volume of treated fibroids was 175+/-201 (SD) cm3. Before treatment, T2-weighted MR images in three planes were obtained to measure leiomyoma volume. Immediately after treatment, T1-weighted contrast-enhanced fat-suppressed MR images in three planes were used to measure nonperfused volume ratio. Similar images obtained 6 months after treatment were used to determine leiomyoma shrinkage. Qualitative and quantitative relations between fibroid volume, nonperfused volume ratio at treatment, and 6-month shrinkage were measured.</AbstractText The average nonperfused volume ratio was 55%+/-25% immediately after treatment. Six months after treatment, the average volume of treated fibroids had decreased to 112+/-141 cm3 (n=81) (p<0.0001) with an average volume reduction of 31%+/-28%. A linear regression model showed highly significant correlation between posttreatment nonperfused volume ratio and shrinkage at 6 months (p<0.0001).</AbstractText MRI-guided focused ultrasound therapy for leiomyoma can result in nonperfused volume ratio and shrinkage that exceed those in previous clinical trials because the treatment guidelines have been relaxed to allow a greater amount of tissue ablation. The results suggest that a larger nonperfused volume ratio can be achieved, resulting in greater shrinkage and improved relief of symptoms.</AbstractText
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28862362
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23584259
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29889085
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Controlling the object phase for g-factor reduction in phase-Constrained parallel MRI using spatially selective RF pulses.
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Sparsity-promoting calibration for GRAPPA accelerated parallel MRI reconstruction.
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T-cell infiltration into the perilesional cortex is long-lasting and associates with poor somatomotor recovery after experimental traumatic brain injury.
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Parallel imaging generally entails a reduction in the signal-to-noise ratio of the final image. Phase-constrained methods aim to improve reconstruction quality by using symmetry properties of k-space. Noise amplification in phase-constrained reconstruction depends heavily on the object background phase. The purpose of this work is to present a new approach of using tailored radiofrequency pulses to optimize the object phase distribution in order to maximize the benefit of phase-constrained reconstruction, and to minimize the noise amplification.</AbstractText Intrinsic object phase and coil sensitivity profiles are measured in a prescan. Optimal phase distribution is computed to maximize signal-to-noise ratio in the given setup. Tailored radiofrequency pulses are designed to introduce the optimal phase map in the following accelerated acquisitions, subsequently reconstructed by phase-constrained methods. The potential of the method is demonstrated in vivo with in-plane accelerated (8x) and simultaneous multislice (3x) acquisitions.</AbstractText Mean g-factors are reduced by up to a factor of 2 compared with conventional techniques when an appropriate phase-constrained reconstruction is applied to phase-optimized acquisitions, enhancing the signal-to-noise ratio of the final images and the visibility of small details.</AbstractText Combining phase-constrained reconstruction and phase optimization by tailored radiofrequency pulses can provide notable improvement in the signal-to-noise ratio and reconstruction quality of accelerated MRI. Magn Reson Med 79:2113-2125, 2018. © 2017 International Society for Magnetic Resonance in Medicine.</AbstractText
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The amount of calibration data needed to produce images of adequate quality can prevent auto-calibrating parallel imaging reconstruction methods like generalized autocalibrating partially parallel acquisitions (GRAPPA) from achieving a high total acceleration factor. To improve the quality of calibration when the number of auto-calibration signal (ACS) lines is restricted, we propose a sparsity-promoting regularized calibration method that finds a GRAPPA kernel consistent with the ACS fit equations that yields jointly sparse reconstructed coil channel images. Several experiments evaluate the performance of the proposed method relative to unregularized and existing regularized calibration methods for both low-quality and underdetermined fits from the ACS lines. These experiments demonstrate that the proposed method, like other regularization methods, is capable of mitigating noise amplification, and in addition, the proposed method is particularly effective at minimizing coherent aliasing artifacts caused by poor kernel calibration in real data. Using the proposed method, we can increase the total achievable acceleration while reducing degradation of the reconstructed image better than existing regularized calibration methods.</AbstractText
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T-lymphocyte (T-cell) invasion into the brain parenchyma is a major consequence of traumatic brain injury (TBI). However, the role of T-cells in the post-TBI functional outcome and secondary inflammatory processes is unknown. We explored the dynamics of T-cell infiltration into the cortex after TBI to establish whether the infiltration relates to post-injury functional impairment/recovery and progression of the secondary injury.</AbstractText TBI was induced in rats by lateral fluid-percussion injury, and the acute functional impairment was assessed using the neuroscore. Animals were killed between 1-90 d post-TBI for immunohistochemical analysis of T-cell infiltration (CD3), chronic macrophage/microglial reaction (CD68), blood-brain barrier (BBB) dysfunction (IgG), and endophenotype of the cortical injury. Furthermore, the occurrence of spontaneous seizures and spike-and-wave discharges were assessed using video-electroencephalography.</AbstractText The number of T-cells peaked at 2-d post-TBI, and then dramatically decreased by 7-d post-TBI (5% of 2-d value). Unexpectedly, chronic T-cell infiltration at 1 or 3 months post-TBI did not correlate with the severity of chronic inflammation (p > 0.05) or BBB dysfunction (p > 0.05). Multiple regression analysis indicated that inflammation and BBB dysfunction is associated with 48% of the perilesional T-cell infiltration even at the chronic time-point (r = 0.695, F = 6.54, p < 0.05). The magnitude of T-cell infiltration did not predict the pathologic endophenotype of cortical injury, but the higher the number of T-cells in the cortex, the poorer the recovery index based on the neuroscore (r = - 0.538, p < 0.05). T-cell infiltration was not associated with the number or duration of age-related spike-and-wave discharges (SWD). Nevertheless, the higher the number of SWD, the poorer the recovery index (r = - 0.767, p < 0.5).</AbstractText These findings suggest that acute infiltration of T-cells into the brain parenchyma after TBI is a contributing factor to poor post-injury recovery.</AbstractText
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Controlling the object phase for g-factor reduction in phase-Constrained parallel MRI using spatially selective RF pulses. Parallel imaging generally entails a reduction in the signal-to-noise ratio of the final image. Phase-constrained methods aim to improve reconstruction quality by using symmetry properties of k-space. Noise amplification in phase-constrained reconstruction depends heavily on the object background phase. The purpose of this work is to present a new approach of using tailored radiofrequency pulses to optimize the object phase distribution in order to maximize the benefit of phase-constrained reconstruction, and to minimize the noise amplification.</AbstractText Intrinsic object phase and coil sensitivity profiles are measured in a prescan. Optimal phase distribution is computed to maximize signal-to-noise ratio in the given setup. Tailored radiofrequency pulses are designed to introduce the optimal phase map in the following accelerated acquisitions, subsequently reconstructed by phase-constrained methods. The potential of the method is demonstrated in vivo with in-plane accelerated (8x) and simultaneous multislice (3x) acquisitions.</AbstractText Mean g-factors are reduced by up to a factor of 2 compared with conventional techniques when an appropriate phase-constrained reconstruction is applied to phase-optimized acquisitions, enhancing the signal-to-noise ratio of the final images and the visibility of small details.</AbstractText Combining phase-constrained reconstruction and phase optimization by tailored radiofrequency pulses can provide notable improvement in the signal-to-noise ratio and reconstruction quality of accelerated MRI. Magn Reson Med 79:2113-2125, 2018. © 2017 International Society for Magnetic Resonance in Medicine.</AbstractText
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Sparsity-promoting calibration for GRAPPA accelerated parallel MRI reconstruction. The amount of calibration data needed to produce images of adequate quality can prevent auto-calibrating parallel imaging reconstruction methods like generalized autocalibrating partially parallel acquisitions (GRAPPA) from achieving a high total acceleration factor. To improve the quality of calibration when the number of auto-calibration signal (ACS) lines is restricted, we propose a sparsity-promoting regularized calibration method that finds a GRAPPA kernel consistent with the ACS fit equations that yields jointly sparse reconstructed coil channel images. Several experiments evaluate the performance of the proposed method relative to unregularized and existing regularized calibration methods for both low-quality and underdetermined fits from the ACS lines. These experiments demonstrate that the proposed method, like other regularization methods, is capable of mitigating noise amplification, and in addition, the proposed method is particularly effective at minimizing coherent aliasing artifacts caused by poor kernel calibration in real data. Using the proposed method, we can increase the total achievable acceleration while reducing degradation of the reconstructed image better than existing regularized calibration methods.</AbstractText
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T-cell infiltration into the perilesional cortex is long-lasting and associates with poor somatomotor recovery after experimental traumatic brain injury. T-lymphocyte (T-cell) invasion into the brain parenchyma is a major consequence of traumatic brain injury (TBI). However, the role of T-cells in the post-TBI functional outcome and secondary inflammatory processes is unknown. We explored the dynamics of T-cell infiltration into the cortex after TBI to establish whether the infiltration relates to post-injury functional impairment/recovery and progression of the secondary injury.</AbstractText TBI was induced in rats by lateral fluid-percussion injury, and the acute functional impairment was assessed using the neuroscore. Animals were killed between 1-90 d post-TBI for immunohistochemical analysis of T-cell infiltration (CD3), chronic macrophage/microglial reaction (CD68), blood-brain barrier (BBB) dysfunction (IgG), and endophenotype of the cortical injury. Furthermore, the occurrence of spontaneous seizures and spike-and-wave discharges were assessed using video-electroencephalography.</AbstractText The number of T-cells peaked at 2-d post-TBI, and then dramatically decreased by 7-d post-TBI (5% of 2-d value). Unexpectedly, chronic T-cell infiltration at 1 or 3 months post-TBI did not correlate with the severity of chronic inflammation (p > 0.05) or BBB dysfunction (p > 0.05). Multiple regression analysis indicated that inflammation and BBB dysfunction is associated with 48% of the perilesional T-cell infiltration even at the chronic time-point (r = 0.695, F = 6.54, p < 0.05). The magnitude of T-cell infiltration did not predict the pathologic endophenotype of cortical injury, but the higher the number of T-cells in the cortex, the poorer the recovery index based on the neuroscore (r = - 0.538, p < 0.05). T-cell infiltration was not associated with the number or duration of age-related spike-and-wave discharges (SWD). Nevertheless, the higher the number of SWD, the poorer the recovery index (r = - 0.767, p < 0.5).</AbstractText These findings suggest that acute infiltration of T-cells into the brain parenchyma after TBI is a contributing factor to poor post-injury recovery.</AbstractText
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32816570
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25081016
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36148712
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Uveal Effusion Associated with Presumed Viral Encephalitis.
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Glutamate receptor antibodies in neurological diseases: anti-AMPA-GluR3 antibodies, anti-NMDA-NR1 antibodies, anti-NMDA-NR2A/B antibodies, anti-mGluR1 antibodies or anti-mGluR5 antibodies are present in subpopulations of patients with either: epilepsy, encephalitis, cerebellar ataxia, systemic lupus erythematosus (SLE) and neuropsychiatric SLE, Sjogren's syndrome, schizophrenia, mania or stroke. These autoimmune anti-glutamate receptor antibodies can bind neurons in few brain regions, activate glutamate receptors, decrease glutamate receptor's expression, impair glutamate-induced signaling and function, activate blood brain barrier endothelial cells, kill neurons, damage the brain, induce behavioral/psychiatric/cognitive abnormalities and ataxia in animal models, and can be removed or silenced in some patients by immunotherapy.
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Non-essential heavy metals and protective effects of selenium against mercury toxicity in endangered Australian sea lion (Neophoca cinerea) pups with hookworm disease.
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Uveal effusion is a rare disease that is characterized by exudative detachment of the ciliary body and choroid. Herein, we report a rare case of uveal effusion associated with viral encephalitis, which resolved following the treatment of the viral encephalitis and administration of corticosteroids.</AbstractText A 67-year-old man who was hospitalized for viral encephalitis was referred to our clinic. He had been treated for herpes zoster ophthalmicus in his left eye 3 weeks previously. Choroidal detachment and uveal effusion between the ciliary body and sclera were observed. He was prescribed oral and topical steroids and cycloplegics to treat uveal effusion, and an antiviral agent (Acyclovir) to treat viral encephalitis. After 4 weeks, the choroidal detachment resolved completely.</AbstractText Uveal effusion syndrome can develop in association with viral encephalitis and be treated successfully with oral and topical steroids; we suggest that medical treatment should be attempted prior to surgery.</AbstractText ADEM: Acute disseminated encephalomyelitis; BCVA: Best corrected visual acuity; CSF: Cerebrospinal fluid; CT: Computed tomography; MRI: Magnetic resonance imaging; WBC: White blood cell.</AbstractText
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Glutamate is the major excitatory neurotransmitter of the Central Nervous System (CNS), and it is crucially needed for numerous key neuronal functions. Yet, excess glutamate causes massive neuronal death and brain damage by excitotoxicity--detrimental over activation of glutamate receptors. Glutamate-mediated excitotoxicity is the main pathological process taking place in many types of acute and chronic CNS diseases and injuries. In recent years, it became clear that not only excess glutamate can cause massive brain damage, but that several types of anti-glutamate receptor antibodies, that are present in the serum and CSF of subpopulations of patients with a kaleidoscope of human neurological diseases, can undoubtedly do so too, by inducing several very potent pathological effects in the CNS. Collectively, the family of anti-glutamate receptor autoimmune antibodies seem to be the most widespread, potent, dangerous and interesting anti-brain autoimmune antibodies discovered up to now. This impression stems from taking together the presence of various types of anti-glutamate receptor antibodies in a kaleidoscope of human neurological and autoimmune diseases, their high levels in the CNS due to intrathecal production, their multiple pathological effects in the brain, and the unique and diverse mechanisms of action by which they can affect glutamate receptors, signaling and effects, and subsequently impair neuronal signaling and induce brain damage. The two main families of autoimmune anti-glutamate receptor antibodies that were already found in patients with neurological and/or autoimmune diseases, and that were already shown to be detrimental to the CNS, include the antibodies directed against ionotorpic glutamate receptors: the anti-AMPA-GluR3 antibodies, anti-NMDA-NR1 antibodies and anti-NMDA-NR2 antibodies, and the antibodies directed against Metabotropic glutamate receptors: the anti-mGluR1 antibodies and the anti-mGluR5 antibodies. Each type of these anti-glutamate receptor antibodies is discussed separately in this very comprehensive review, with regards to: the human diseases in which these anti-glutamate receptor antibodies were found thus far, their presence and production in the nervous system, their association with various psychiatric/behavioral/cognitive/motor impairments, their possible association with certain infectious organisms, their detrimental effects in vitro as well as in vivo in animal models in mice, rats or rabbits, and their diverse and unique mechanisms of action. The review also covers the very encouraging positive responses to immunotherapy of some patients that have either of the above-mentioned anti-glutamate receptor antibodies, and that suffer from various neurological diseases/problems. All the above are also summarized in the review's five schematic and useful figures, for each type of anti-glutamate receptor antibodies separately. The review ends with a summary of all the main findings, and with recommended guidelines for diagnosis, therapy, drug design and future investigations. In the nut shell, the human studies, the in vitro studies, as well as the in vivo studies in animal models in mice, rats and rabbit revealed the following findings regarding the five different types of anti-glutamate receptor antibodies: (1) Anti-AMPA-GluR3B antibodies are present in ~25-30% of patients with different types of Epilepsy. When these anti-glutamate receptor antibodies (or other types of autoimmune antibodies) are found in Epilepsy patients, and when these autoimmune antibodies are suspected to induce or aggravate the seizures and/or the cognitive/psychiatric/behavioral impairments that sometimes accompany the seizures, the Epilepsy is called 'Autoimmune Epilepsy'. In some patients with 'Autoimmune Epilepsy' the anti-AMPA-GluR3B antibodies associate significantly with psychiatric/cognitive/behavior abnormalities. In vitro and/or in animal models, the anti-AMPA-GluR3B antibodies by themselves induce many pathological effects: they activate glutamate/AMPA receptors, kill neurons by 'Excitotoxicity', and/or by complement activation modulated by complement regulatory proteins, cause multiple brain damage, aggravate chemoconvulsant-induced seizures, and also induce behavioral/motor impairments. Some patients with 'Autoimmune Epilepsy' that have anti-AMPA-GluR3B antibodies respond well (although sometimes transiently) to immunotherapy, and thanks to that have reduced seizures and overall improved neurological functions. (2) Anti-NMDA-NR1 antibodies are present in patients with autoimmune 'Anti-NMDA-receptor Encephalitis'. In humans, in animal models and in vitro the anti-NMDA-NR1 antibodies can be very pathogenic since they can cause a pronounced decrease of surface NMDA receptors expressed in hippocampal neurons, and also decrease the cluster density and synaptic localization of the NMDA receptors. The anti-NMDA-NR1 antibodies induce these effects by crosslinking and internalization of the NMDA receptors. Such changes can impair glutamate signaling via the NMDA receptors and lead to various neuronal/behavior/cognitive/psychiatric abnormalities. Anti-NMDA-NR1 antibodies are frequently present in high levels in the CSF of the patients with 'Anti-NMDA-receptor encephalitis' due to their intrathecal production. Many patients with 'Anti-NMDA receptor Encephalitis' respond well to several modes of immunotherapy. (3) Anti-NMDA-NR2A/B antibodies are present in a substantial number of patients with Systemic Lupus Erythematosus (SLE) with or without neuropsychiatric problems. The exact percentage of SLE patients having anti-NMDA-NR2A/B antibodies varies in different studies from 14 to 35%, and in one study such antibodies were found in 81% of patients with diffuse 'Neuropshychiatric SLE', and in 44% of patients with focal 'Neuropshychiatric SLE'. Anti-NMDA-NR2A/B antibodies are also present in subpopulations of patients with Epilepsy of several types, Encephalitis of several types (e.g., chronic progressive limbic Encephalitis, Paraneoplastic Encephalitis or Herpes Simplex Virus Encephalitis), Schizophrenia, Mania, Stroke, or Sjorgen syndrome. In some patients, the anti-NMDA-NR2A/B antibodies are present in both the serum and the CSF. Some of the anti-NMDA-NR2A/B antibodies cross-react with dsDNA, while others do not. Some of the anti-NMDA-NR2A/B antibodies associate with neuropsychiatric/cognitive/behavior/mood impairments in SLE patients, while others do not. The anti-NMDA-NR2A/B antibodies can undoubtedly be very pathogenic, since they can kill neurons by activating NMDA receptors and inducing 'Excitotoxicity', damage the brain, cause dramatic decrease of membranal NMDA receptors expressed in hippocampal neurons, and also induce behavioral cognitive impairments in animal models. Yet, the concentration of the anti-NMDA-NR2A/B antibodies seems to determine if they have positive or negative effects on the activity of glutamate receptors and on the survival of neurons. Thus, at low concentration, the anti-NMDA-NR2A/B antibodies were found to be positive modulators of receptor function and increase the size of NMDA receptor-mediated excitatory postsynaptic potentials, whereas at high concentration they are pathogenic as they promote 'Excitotoxcity' through enhanced mitochondrial permeability transition. (4) Anti-mGluR1 antibodies were found thus far in very few patients with Paraneoplastic Cerebellar Ataxia, and in these patients they are produced intrathecally and therefore present in much higher levels in the CSF than in the serum. The anti-mGluR1 antibodies can be very pathogenic in the brain since they can reduce the basal neuronal activity, block the induction of long-term depression of Purkinje cells, and altogether cause cerebellar motor coordination deficits by a combination of rapid effects on both the acute and the plastic responses of Purkinje cells, and by chronic degenerative effects. Strikingly, within 30 min after injection of anti-mGluR1 antibodies into the brain of mice, the mice became ataxic. Anti-mGluR1 antibodies derived from patients with Ataxia also caused disturbance of eye movements in animal models. Immunotherapy can be very effective for some Cerebellar Ataxia patients that have anti-mGluR1 antibodies. (5) Anti-mGluR5 antibodies were found thus far in the serum and CSF of very few patients with Hodgkin lymphoma and Limbic Encephalopathy (Ophelia syndrome). The sera of these patients that contained anti-GluR5 antibodies reacted with the neuropil of the hippocampus and cell surface of live rat hippocampal neurons, and immunoprecipitation from cultured neurons and mass spectrometry demonstrated that the antigen was indeed mGluR5. Taken together, all these evidences show that anti-glutamate receptor antibodies are much more frequent among various neurological diseases than ever realized before, and that they are very detrimental to the nervous system. As such, they call for diagnosis, therapeutic removal or silencing and future studies. What we have learned by now about the broad family of anti-glutamate receptor antibodies is so exciting, novel, unique and important, that it makes all future efforts worthy and essential.</AbstractText
|
The endangered Australian sea lion, Neophoca cinerea, faces ongoing population decline. Identification of key threats to N. cinerea population recovery, including disease and pollutants, is an objective of the species' recovery plan. Previous studies have identified Uncinaria sanguinis, an intestinal nematode, as a significant cause of disease and mortality in N. cinerea pups. Given the impact of heavy metals on the immune response, investigation of these pollutants is critical. To this end, the concentrations of arsenic (As), total mercury (Hg), cadmium (Cd), chromium (Cr), lead (Pb) and selenium (Se) were determined in blood collected from N. cinerea pups sampled during the 2017/18, 2019 and 2020/21 breeding seasons at Seal Bay Conservation Park, South Australia. Significant differences (p < 0.05) in Hg, As, Cr, and Se concentrations and molar ratio of Se:Hg were seen between breeding seasons. Pup age, maternal parity and inter-individual foraging behaviour were considered factors driving these differences. The concentrations of Hg (357, 198 and 241 µg/L) and As (225, 834 and 608 µg/L) were high in 2017/18, 2019 and 2020/21 respectively with Hg concentrations in the blood of N. cinerea pups above toxicological thresholds reported for marine mammals. The concentration of Se (1332, 647, 763 µg/L) and molar ratio of Se:Hg (9.47, 7.98 and 6.82) were low compared to other pinniped pups, indicating potential vulnerability of pups to the toxic effects of Hg. Significant (p < 0.05) negative associations for Pb and Cd with several red blood cell parameters suggest they could be exacerbating the anaemia caused by hookworm disease. Temporal (age-related) changes in element concentrations were also seen, such that pup age needs to be considered when interpreting bioaccumulation patterns. Further investigation of the role of elevated heavy metal concentrations on N. cinerea pup health, disease and development is recommended, particularly with respect to immunological impacts.</AbstractText
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Uveal Effusion Associated with Presumed Viral Encephalitis. Uveal effusion is a rare disease that is characterized by exudative detachment of the ciliary body and choroid. Herein, we report a rare case of uveal effusion associated with viral encephalitis, which resolved following the treatment of the viral encephalitis and administration of corticosteroids.</AbstractText A 67-year-old man who was hospitalized for viral encephalitis was referred to our clinic. He had been treated for herpes zoster ophthalmicus in his left eye 3 weeks previously. Choroidal detachment and uveal effusion between the ciliary body and sclera were observed. He was prescribed oral and topical steroids and cycloplegics to treat uveal effusion, and an antiviral agent (Acyclovir) to treat viral encephalitis. After 4 weeks, the choroidal detachment resolved completely.</AbstractText Uveal effusion syndrome can develop in association with viral encephalitis and be treated successfully with oral and topical steroids; we suggest that medical treatment should be attempted prior to surgery.</AbstractText ADEM: Acute disseminated encephalomyelitis; BCVA: Best corrected visual acuity; CSF: Cerebrospinal fluid; CT: Computed tomography; MRI: Magnetic resonance imaging; WBC: White blood cell.</AbstractText
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Glutamate receptor antibodies in neurological diseases: anti-AMPA-GluR3 antibodies, anti-NMDA-NR1 antibodies, anti-NMDA-NR2A/B antibodies, anti-mGluR1 antibodies or anti-mGluR5 antibodies are present in subpopulations of patients with either: epilepsy, encephalitis, cerebellar ataxia, systemic lupus erythematosus (SLE) and neuropsychiatric SLE, Sjogren's syndrome, schizophrenia, mania or stroke. These autoimmune anti-glutamate receptor antibodies can bind neurons in few brain regions, activate glutamate receptors, decrease glutamate receptor's expression, impair glutamate-induced signaling and function, activate blood brain barrier endothelial cells, kill neurons, damage the brain, induce behavioral/psychiatric/cognitive abnormalities and ataxia in animal models, and can be removed or silenced in some patients by immunotherapy. Glutamate is the major excitatory neurotransmitter of the Central Nervous System (CNS), and it is crucially needed for numerous key neuronal functions. Yet, excess glutamate causes massive neuronal death and brain damage by excitotoxicity--detrimental over activation of glutamate receptors. Glutamate-mediated excitotoxicity is the main pathological process taking place in many types of acute and chronic CNS diseases and injuries. In recent years, it became clear that not only excess glutamate can cause massive brain damage, but that several types of anti-glutamate receptor antibodies, that are present in the serum and CSF of subpopulations of patients with a kaleidoscope of human neurological diseases, can undoubtedly do so too, by inducing several very potent pathological effects in the CNS. Collectively, the family of anti-glutamate receptor autoimmune antibodies seem to be the most widespread, potent, dangerous and interesting anti-brain autoimmune antibodies discovered up to now. This impression stems from taking together the presence of various types of anti-glutamate receptor antibodies in a kaleidoscope of human neurological and autoimmune diseases, their high levels in the CNS due to intrathecal production, their multiple pathological effects in the brain, and the unique and diverse mechanisms of action by which they can affect glutamate receptors, signaling and effects, and subsequently impair neuronal signaling and induce brain damage. The two main families of autoimmune anti-glutamate receptor antibodies that were already found in patients with neurological and/or autoimmune diseases, and that were already shown to be detrimental to the CNS, include the antibodies directed against ionotorpic glutamate receptors: the anti-AMPA-GluR3 antibodies, anti-NMDA-NR1 antibodies and anti-NMDA-NR2 antibodies, and the antibodies directed against Metabotropic glutamate receptors: the anti-mGluR1 antibodies and the anti-mGluR5 antibodies. Each type of these anti-glutamate receptor antibodies is discussed separately in this very comprehensive review, with regards to: the human diseases in which these anti-glutamate receptor antibodies were found thus far, their presence and production in the nervous system, their association with various psychiatric/behavioral/cognitive/motor impairments, their possible association with certain infectious organisms, their detrimental effects in vitro as well as in vivo in animal models in mice, rats or rabbits, and their diverse and unique mechanisms of action. The review also covers the very encouraging positive responses to immunotherapy of some patients that have either of the above-mentioned anti-glutamate receptor antibodies, and that suffer from various neurological diseases/problems. All the above are also summarized in the review's five schematic and useful figures, for each type of anti-glutamate receptor antibodies separately. The review ends with a summary of all the main findings, and with recommended guidelines for diagnosis, therapy, drug design and future investigations. In the nut shell, the human studies, the in vitro studies, as well as the in vivo studies in animal models in mice, rats and rabbit revealed the following findings regarding the five different types of anti-glutamate receptor antibodies: (1) Anti-AMPA-GluR3B antibodies are present in ~25-30% of patients with different types of Epilepsy. When these anti-glutamate receptor antibodies (or other types of autoimmune antibodies) are found in Epilepsy patients, and when these autoimmune antibodies are suspected to induce or aggravate the seizures and/or the cognitive/psychiatric/behavioral impairments that sometimes accompany the seizures, the Epilepsy is called 'Autoimmune Epilepsy'. In some patients with 'Autoimmune Epilepsy' the anti-AMPA-GluR3B antibodies associate significantly with psychiatric/cognitive/behavior abnormalities. In vitro and/or in animal models, the anti-AMPA-GluR3B antibodies by themselves induce many pathological effects: they activate glutamate/AMPA receptors, kill neurons by 'Excitotoxicity', and/or by complement activation modulated by complement regulatory proteins, cause multiple brain damage, aggravate chemoconvulsant-induced seizures, and also induce behavioral/motor impairments. Some patients with 'Autoimmune Epilepsy' that have anti-AMPA-GluR3B antibodies respond well (although sometimes transiently) to immunotherapy, and thanks to that have reduced seizures and overall improved neurological functions. (2) Anti-NMDA-NR1 antibodies are present in patients with autoimmune 'Anti-NMDA-receptor Encephalitis'. In humans, in animal models and in vitro the anti-NMDA-NR1 antibodies can be very pathogenic since they can cause a pronounced decrease of surface NMDA receptors expressed in hippocampal neurons, and also decrease the cluster density and synaptic localization of the NMDA receptors. The anti-NMDA-NR1 antibodies induce these effects by crosslinking and internalization of the NMDA receptors. Such changes can impair glutamate signaling via the NMDA receptors and lead to various neuronal/behavior/cognitive/psychiatric abnormalities. Anti-NMDA-NR1 antibodies are frequently present in high levels in the CSF of the patients with 'Anti-NMDA-receptor encephalitis' due to their intrathecal production. Many patients with 'Anti-NMDA receptor Encephalitis' respond well to several modes of immunotherapy. (3) Anti-NMDA-NR2A/B antibodies are present in a substantial number of patients with Systemic Lupus Erythematosus (SLE) with or without neuropsychiatric problems. The exact percentage of SLE patients having anti-NMDA-NR2A/B antibodies varies in different studies from 14 to 35%, and in one study such antibodies were found in 81% of patients with diffuse 'Neuropshychiatric SLE', and in 44% of patients with focal 'Neuropshychiatric SLE'. Anti-NMDA-NR2A/B antibodies are also present in subpopulations of patients with Epilepsy of several types, Encephalitis of several types (e.g., chronic progressive limbic Encephalitis, Paraneoplastic Encephalitis or Herpes Simplex Virus Encephalitis), Schizophrenia, Mania, Stroke, or Sjorgen syndrome. In some patients, the anti-NMDA-NR2A/B antibodies are present in both the serum and the CSF. Some of the anti-NMDA-NR2A/B antibodies cross-react with dsDNA, while others do not. Some of the anti-NMDA-NR2A/B antibodies associate with neuropsychiatric/cognitive/behavior/mood impairments in SLE patients, while others do not. The anti-NMDA-NR2A/B antibodies can undoubtedly be very pathogenic, since they can kill neurons by activating NMDA receptors and inducing 'Excitotoxicity', damage the brain, cause dramatic decrease of membranal NMDA receptors expressed in hippocampal neurons, and also induce behavioral cognitive impairments in animal models. Yet, the concentration of the anti-NMDA-NR2A/B antibodies seems to determine if they have positive or negative effects on the activity of glutamate receptors and on the survival of neurons. Thus, at low concentration, the anti-NMDA-NR2A/B antibodies were found to be positive modulators of receptor function and increase the size of NMDA receptor-mediated excitatory postsynaptic potentials, whereas at high concentration they are pathogenic as they promote 'Excitotoxcity' through enhanced mitochondrial permeability transition. (4) Anti-mGluR1 antibodies were found thus far in very few patients with Paraneoplastic Cerebellar Ataxia, and in these patients they are produced intrathecally and therefore present in much higher levels in the CSF than in the serum. The anti-mGluR1 antibodies can be very pathogenic in the brain since they can reduce the basal neuronal activity, block the induction of long-term depression of Purkinje cells, and altogether cause cerebellar motor coordination deficits by a combination of rapid effects on both the acute and the plastic responses of Purkinje cells, and by chronic degenerative effects. Strikingly, within 30 min after injection of anti-mGluR1 antibodies into the brain of mice, the mice became ataxic. Anti-mGluR1 antibodies derived from patients with Ataxia also caused disturbance of eye movements in animal models. Immunotherapy can be very effective for some Cerebellar Ataxia patients that have anti-mGluR1 antibodies. (5) Anti-mGluR5 antibodies were found thus far in the serum and CSF of very few patients with Hodgkin lymphoma and Limbic Encephalopathy (Ophelia syndrome). The sera of these patients that contained anti-GluR5 antibodies reacted with the neuropil of the hippocampus and cell surface of live rat hippocampal neurons, and immunoprecipitation from cultured neurons and mass spectrometry demonstrated that the antigen was indeed mGluR5. Taken together, all these evidences show that anti-glutamate receptor antibodies are much more frequent among various neurological diseases than ever realized before, and that they are very detrimental to the nervous system. As such, they call for diagnosis, therapeutic removal or silencing and future studies. What we have learned by now about the broad family of anti-glutamate receptor antibodies is so exciting, novel, unique and important, that it makes all future efforts worthy and essential.</AbstractText
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Non-essential heavy metals and protective effects of selenium against mercury toxicity in endangered Australian sea lion (Neophoca cinerea) pups with hookworm disease. The endangered Australian sea lion, Neophoca cinerea, faces ongoing population decline. Identification of key threats to N. cinerea population recovery, including disease and pollutants, is an objective of the species' recovery plan. Previous studies have identified Uncinaria sanguinis, an intestinal nematode, as a significant cause of disease and mortality in N. cinerea pups. Given the impact of heavy metals on the immune response, investigation of these pollutants is critical. To this end, the concentrations of arsenic (As), total mercury (Hg), cadmium (Cd), chromium (Cr), lead (Pb) and selenium (Se) were determined in blood collected from N. cinerea pups sampled during the 2017/18, 2019 and 2020/21 breeding seasons at Seal Bay Conservation Park, South Australia. Significant differences (p < 0.05) in Hg, As, Cr, and Se concentrations and molar ratio of Se:Hg were seen between breeding seasons. Pup age, maternal parity and inter-individual foraging behaviour were considered factors driving these differences. The concentrations of Hg (357, 198 and 241 µg/L) and As (225, 834 and 608 µg/L) were high in 2017/18, 2019 and 2020/21 respectively with Hg concentrations in the blood of N. cinerea pups above toxicological thresholds reported for marine mammals. The concentration of Se (1332, 647, 763 µg/L) and molar ratio of Se:Hg (9.47, 7.98 and 6.82) were low compared to other pinniped pups, indicating potential vulnerability of pups to the toxic effects of Hg. Significant (p < 0.05) negative associations for Pb and Cd with several red blood cell parameters suggest they could be exacerbating the anaemia caused by hookworm disease. Temporal (age-related) changes in element concentrations were also seen, such that pup age needs to be considered when interpreting bioaccumulation patterns. Further investigation of the role of elevated heavy metal concentrations on N. cinerea pup health, disease and development is recommended, particularly with respect to immunological impacts.</AbstractText
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28149391
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21073917
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26960697
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Spatial control of reflexes, posture and movement in normal conditions and after neurological lesions.
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Dynamic task-specific brain network connectivity in children with severe reading difficulties.
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Women with premenstrual dysphoric disorder have altered sensitivity to allopregnanolone over the menstrual cycle compared to controls-a pilot study.
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Control of reflexes is usually associated with central modulation of their sensitivity (gain) or phase-dependent inhibition and facilitation of their influences on motoneurons (reflex gating). Accumulated empirical findings show that the gain modulation and reflex gating are secondary, emergent properties of central control of spatial thresholds at which reflexes become functional. In this way, the system pre-determines, in a feedforward and task-specific way, where, in a spatial domain or a frame of reference, muscles are allowed to work without directly prescribing EMG activity and forces. This control strategy is illustrated by considering reflex adaptation to repeated muscle stretches in healthy subjects, a process associated with implicit learning and generalization. It has also been shown that spasticity, rigidity, weakness and other neurological motor deficits may have a common source - limitations in the range of spatial threshold control elicited by neural lesions.</AbstractText
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We investigated patterns of sensor-level functional connectivity derived from single-trial whole-head magnetoencephalography data during a pseudoword reading and a letter-sound naming task in children with reading difficulties (RD) and children with no reading impairments (NI). The Phase Lag Index (PLI), a linear and nonlinear estimator, computed for each pair of sensors, was used to construct graphs and obtain estimates of local and global network efficiency according to graph theory. In the 8-13 Hz (alpha band) and 20-30 Hz (gamma band) range, RD students showed significantly lower global efficiency than NI children, for the entire MEG recording epoch. RD students also displayed reduced local network efficiency in the alpha band. Correlations between phonological decoding ability and graph metrics were particularly evident during the task that posed significant demands for phonological decoding, and followed distinct time courses depending on signal frequency. Results are consistent with the notion of task-dependent, aberrant long- and short-range functional connectivity in RD children.</AbstractText
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In premenstrual dysphoric disorder (PMDD), a condition that afflicts 3-8 % of women in fertile ages, the cyclic recurrence of debilitating mood symptoms is restricted to the luteal phase of the menstrual cycle. The progesterone metabolite allopregnanolone is produced by the corpus luteum, and circulating levels are reflected in the brain. Allopregnanolone is a modulator of the GABAA receptor, enhancing the effect of γ-aminobutyric acid (GABA). Previous studies have demonstrated different sensitivity to other GABAA receptor agonists, i.e., benzodiazepines, alcohol, and pregnanolone, in PMDD patients compared to controls.</AbstractText This study aimed to investigate the sensitivity to intravenous allopregnanolone over the menstrual cycle in PMDD patients.</AbstractText Allopregnanolone, 0.05 mg/kg, was administered intravenously once in the mid-follicular and once in the luteal phase of the menstrual cycle to 10 PMDD patients and 10 control subjects. The saccadic eye velocity (SEV) was recorded by electrooculography as a measurement of functional GABAA receptor activity, at baseline and repeatedly after the injection. A mixed model was used to analyze data.</AbstractText There was a highly significant group × phase interaction in the SEV response to allopregnanolone (F(1,327.489) = 12.747, p < 0.001). In the PMDD group, the SEV response was decreased in the follicular phase compared to the luteal phase (F(1,168) = 7.776, p = 0.006), whereas in the control group, the difference was opposite during the menstrual cycle (F(1,158.45) = 5.70, p = 0.018).</AbstractText The effect of exogenous allopregnanolone is associated with menstrual cycle phase in PMDD patients and in controls. The results suggest an altered sensitivity to allopregnanolone in PMDD patients.</AbstractText
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Spatial control of reflexes, posture and movement in normal conditions and after neurological lesions. Control of reflexes is usually associated with central modulation of their sensitivity (gain) or phase-dependent inhibition and facilitation of their influences on motoneurons (reflex gating). Accumulated empirical findings show that the gain modulation and reflex gating are secondary, emergent properties of central control of spatial thresholds at which reflexes become functional. In this way, the system pre-determines, in a feedforward and task-specific way, where, in a spatial domain or a frame of reference, muscles are allowed to work without directly prescribing EMG activity and forces. This control strategy is illustrated by considering reflex adaptation to repeated muscle stretches in healthy subjects, a process associated with implicit learning and generalization. It has also been shown that spasticity, rigidity, weakness and other neurological motor deficits may have a common source - limitations in the range of spatial threshold control elicited by neural lesions.</AbstractText
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Dynamic task-specific brain network connectivity in children with severe reading difficulties. We investigated patterns of sensor-level functional connectivity derived from single-trial whole-head magnetoencephalography data during a pseudoword reading and a letter-sound naming task in children with reading difficulties (RD) and children with no reading impairments (NI). The Phase Lag Index (PLI), a linear and nonlinear estimator, computed for each pair of sensors, was used to construct graphs and obtain estimates of local and global network efficiency according to graph theory. In the 8-13 Hz (alpha band) and 20-30 Hz (gamma band) range, RD students showed significantly lower global efficiency than NI children, for the entire MEG recording epoch. RD students also displayed reduced local network efficiency in the alpha band. Correlations between phonological decoding ability and graph metrics were particularly evident during the task that posed significant demands for phonological decoding, and followed distinct time courses depending on signal frequency. Results are consistent with the notion of task-dependent, aberrant long- and short-range functional connectivity in RD children.</AbstractText
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Women with premenstrual dysphoric disorder have altered sensitivity to allopregnanolone over the menstrual cycle compared to controls-a pilot study. In premenstrual dysphoric disorder (PMDD), a condition that afflicts 3-8 % of women in fertile ages, the cyclic recurrence of debilitating mood symptoms is restricted to the luteal phase of the menstrual cycle. The progesterone metabolite allopregnanolone is produced by the corpus luteum, and circulating levels are reflected in the brain. Allopregnanolone is a modulator of the GABAA receptor, enhancing the effect of γ-aminobutyric acid (GABA). Previous studies have demonstrated different sensitivity to other GABAA receptor agonists, i.e., benzodiazepines, alcohol, and pregnanolone, in PMDD patients compared to controls.</AbstractText This study aimed to investigate the sensitivity to intravenous allopregnanolone over the menstrual cycle in PMDD patients.</AbstractText Allopregnanolone, 0.05 mg/kg, was administered intravenously once in the mid-follicular and once in the luteal phase of the menstrual cycle to 10 PMDD patients and 10 control subjects. The saccadic eye velocity (SEV) was recorded by electrooculography as a measurement of functional GABAA receptor activity, at baseline and repeatedly after the injection. A mixed model was used to analyze data.</AbstractText There was a highly significant group × phase interaction in the SEV response to allopregnanolone (F(1,327.489) = 12.747, p < 0.001). In the PMDD group, the SEV response was decreased in the follicular phase compared to the luteal phase (F(1,168) = 7.776, p = 0.006), whereas in the control group, the difference was opposite during the menstrual cycle (F(1,158.45) = 5.70, p = 0.018).</AbstractText The effect of exogenous allopregnanolone is associated with menstrual cycle phase in PMDD patients and in controls. The results suggest an altered sensitivity to allopregnanolone in PMDD patients.</AbstractText
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39102762
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35363534
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39585059
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Manometric Abnormalities in Patients With and Without Chronic Cough.
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Neuroimmune Interactions in Peripheral Organs.
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The Role of Neuropeptide Y in the Pathogenesis of Alzheimer's Disease: Diagnostic Significance and Neuroprotective Functions.
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This study examines the relationship between chronic cough and vagal hypersensitivity by measuring baseline esophageal motility, with interest in the upper esophageal sphincter (UES).</AbstractText Patients undergoing workup for dysphagia were assigned to a chronic cough or control group based on self-reported symptoms. Differences in demographics, medical comorbidities, and high resolution esophageal manometry findings were obtained retrospectively.</AbstractText 62.5% of our cohort had chronic cough (30/48). There were no significant differences between the two groups with respect to sex, age, and race/ethnicity. Laryngopharyngeal reflux (LPR) was the only statistically significant predictor of CC (OR 74.04, p = 0.010). Cough patients had upper esophageal sphincter relaxation duration (734 ms) significantly longer than the non-cough patients (582 ms; p = 0.03), though both groups had similar upper esophageal mean basal pressure, mean residual pressure, relaxation time-to-nadir, and recovery time. No significant difference was found in the median intrabolus pressure and UES motility mean peak pressure between groups.</AbstractText Subtle differences in high-resolution manometry between patients with and without cough suggest, in line with previous studies, baseline alterations of upper esophageal function may manifest in patients with chronic cough through an undetermined mechanism that may include underlying vagal hypersensitivity. These findings encourage further manometric study examining the relationship between UES dysfunction and chronic cough.</AbstractText
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Interactions between the nervous and immune systems were recognized long ago, but recent studies show that this crosstalk occurs more frequently than was previously appreciated. Moreover, technological advances have enabled the identification of the molecular mediators and receptors that enable the interaction between these two complex systems and provide new insights on the role of neuroimmune crosstalk in organismal physiology. Most neuroimmune interactions occur at discrete anatomical locations in which neurons and immune cells colocalize. Here, we describe the interactions of the different branches of the peripheral nervous system with immune cells in various organs, including the skin, intestine, lung, and adipose tissue. We highlight how neuroimmune crosstalk orchestrates physiological processes such as host defense, tissue repair, metabolism, and thermogenesis. Unraveling these intricate relationships is invaluable to explore the therapeutic potential of neuroimmune interactions.</AbstractText
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<b
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Manometric Abnormalities in Patients With and Without Chronic Cough. This study examines the relationship between chronic cough and vagal hypersensitivity by measuring baseline esophageal motility, with interest in the upper esophageal sphincter (UES).</AbstractText Patients undergoing workup for dysphagia were assigned to a chronic cough or control group based on self-reported symptoms. Differences in demographics, medical comorbidities, and high resolution esophageal manometry findings were obtained retrospectively.</AbstractText 62.5% of our cohort had chronic cough (30/48). There were no significant differences between the two groups with respect to sex, age, and race/ethnicity. Laryngopharyngeal reflux (LPR) was the only statistically significant predictor of CC (OR 74.04, p = 0.010). Cough patients had upper esophageal sphincter relaxation duration (734 ms) significantly longer than the non-cough patients (582 ms; p = 0.03), though both groups had similar upper esophageal mean basal pressure, mean residual pressure, relaxation time-to-nadir, and recovery time. No significant difference was found in the median intrabolus pressure and UES motility mean peak pressure between groups.</AbstractText Subtle differences in high-resolution manometry between patients with and without cough suggest, in line with previous studies, baseline alterations of upper esophageal function may manifest in patients with chronic cough through an undetermined mechanism that may include underlying vagal hypersensitivity. These findings encourage further manometric study examining the relationship between UES dysfunction and chronic cough.</AbstractText
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Neuroimmune Interactions in Peripheral Organs. Interactions between the nervous and immune systems were recognized long ago, but recent studies show that this crosstalk occurs more frequently than was previously appreciated. Moreover, technological advances have enabled the identification of the molecular mediators and receptors that enable the interaction between these two complex systems and provide new insights on the role of neuroimmune crosstalk in organismal physiology. Most neuroimmune interactions occur at discrete anatomical locations in which neurons and immune cells colocalize. Here, we describe the interactions of the different branches of the peripheral nervous system with immune cells in various organs, including the skin, intestine, lung, and adipose tissue. We highlight how neuroimmune crosstalk orchestrates physiological processes such as host defense, tissue repair, metabolism, and thermogenesis. Unraveling these intricate relationships is invaluable to explore the therapeutic potential of neuroimmune interactions.</AbstractText
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The Role of Neuropeptide Y in the Pathogenesis of Alzheimer's Disease: Diagnostic Significance and Neuroprotective Functions. <b
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40480833
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34271020
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39724736
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Novel ADAR2 variants in children with seizures, intellectual disability and motor delay have reduced RNA editing.
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Biology of AMPA receptor interacting proteins - From biogenesis to synaptic plasticity.
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Mechanism of S100A9-mediated astrocyte activation via TLR4/NF-κB in Parkinson's disease.
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The ADARB1 gene encodes the ADAR2 RNA editing enzyme, which edits the GRIA2 transcript Q/R editing site with almost 100% efficiency in the nervous system. The edited GRIA2R transcript encodes the GLUA2 R subunit isoform of tetrameric AMPA receptors, which is essential to prevent seizures associated with aberrantly elevated AMPA receptor cation permeability. Rare biallelic variants in ADARB1 cause severe infant and childhood seizures and developmental delays in seven cases we previously described. Here, we report two new homozygous ADARB1 variants and study ADAR2 variant editing activities at the GRIA2 Q/R site and other editing sites in cell cultures. One new variant in the second dsRNA binding domain (dsRBD II) retains up to 60% editing activity, whereas another, in the deaminase domain, eliminates RNA editing activity. Reduced GRIA2 Q/R site editing increases AMPA receptor permeability by upregulating the expression of the GLUA2 Q isoform and reducing overall GLUA2 subunit levels, resulting in AMPA receptors that lack GLUA2 and are calcium-permeable. Since failure to edit the GRIA2 Q/R site leads to failure of intron 11 splicing, we also examined the effects of ADAR2 variants on the splicing of a mouse Gria2-based reporter and concluded that ADAR2 variants affect splicing only through their effects on RNA editing activity. To expand the number of variants in ADARB1, some variants reported in ClinVar have also been analysed by in silico methods to predict which are likely to be most deleterious and associated with seizures in patients.</AbstractText
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AMPA-type glutamate receptors mediate the majority of excitatory synaptic transmission in the central nervous system. Their signaling properties and abundance at synapses are both crucial determinants of synapse efficacy and plasticity, and are therefore under sophisticated control. Unique to this ionotropic glutamate receptor (iGluR) is the abundance of interacting proteins that contribute to its complex regulation. These include transient interactions with the receptor cytoplasmic tail as well as the N-terminal domain locating to the synaptic cleft, both of which are involved in AMPAR trafficking and receptor stabilization at the synapse. Moreover, an array of transmembrane proteins operate as auxiliary subunits that in addition to receptor trafficking and stabilization also substantially impact AMPAR gating and pharmacology. Here, we provide an overview of the catalogue of AMPAR interacting proteins, and how they contribute to the complex biology of this central glutamate receptor. This article is part of the special Issue on 'Glutamate Receptors - AMPA receptors'.</AbstractText
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Astrocyte-mediated neuroinflammation plays a key role in Parkinson's disease (PD) progression. The proinflammatory protein S100A9 is linked to various neurodegenerative diseases, but its involvement in astrocyte activation in PD remains unclear. Here, we investigate the role of S100A9 in astrocyte-mediated neuroinflammation in PD. C57BL/6J mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 15 mg/kg four times daily) and subsequently treated with Paquinimod, a S100A9 inhibitor (7 mg/kg, once daily for 7 days, totaling 8 doses). We observed an abnormal increase in S100A9 protein expression and a rise in S100A9-positive cells in the striatum of PD mice. Paquinimod treatment significantly improved behavioral deficits (pole test, rotarod test, traction test, and open field tests), prevented the reduction in striatal tyrosine hydroxylase (TH) protein and the loss of dopaminergic neurons (TH<sup
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Novel ADAR2 variants in children with seizures, intellectual disability and motor delay have reduced RNA editing. The ADARB1 gene encodes the ADAR2 RNA editing enzyme, which edits the GRIA2 transcript Q/R editing site with almost 100% efficiency in the nervous system. The edited GRIA2R transcript encodes the GLUA2 R subunit isoform of tetrameric AMPA receptors, which is essential to prevent seizures associated with aberrantly elevated AMPA receptor cation permeability. Rare biallelic variants in ADARB1 cause severe infant and childhood seizures and developmental delays in seven cases we previously described. Here, we report two new homozygous ADARB1 variants and study ADAR2 variant editing activities at the GRIA2 Q/R site and other editing sites in cell cultures. One new variant in the second dsRNA binding domain (dsRBD II) retains up to 60% editing activity, whereas another, in the deaminase domain, eliminates RNA editing activity. Reduced GRIA2 Q/R site editing increases AMPA receptor permeability by upregulating the expression of the GLUA2 Q isoform and reducing overall GLUA2 subunit levels, resulting in AMPA receptors that lack GLUA2 and are calcium-permeable. Since failure to edit the GRIA2 Q/R site leads to failure of intron 11 splicing, we also examined the effects of ADAR2 variants on the splicing of a mouse Gria2-based reporter and concluded that ADAR2 variants affect splicing only through their effects on RNA editing activity. To expand the number of variants in ADARB1, some variants reported in ClinVar have also been analysed by in silico methods to predict which are likely to be most deleterious and associated with seizures in patients.</AbstractText
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Biology of AMPA receptor interacting proteins - From biogenesis to synaptic plasticity. AMPA-type glutamate receptors mediate the majority of excitatory synaptic transmission in the central nervous system. Their signaling properties and abundance at synapses are both crucial determinants of synapse efficacy and plasticity, and are therefore under sophisticated control. Unique to this ionotropic glutamate receptor (iGluR) is the abundance of interacting proteins that contribute to its complex regulation. These include transient interactions with the receptor cytoplasmic tail as well as the N-terminal domain locating to the synaptic cleft, both of which are involved in AMPAR trafficking and receptor stabilization at the synapse. Moreover, an array of transmembrane proteins operate as auxiliary subunits that in addition to receptor trafficking and stabilization also substantially impact AMPAR gating and pharmacology. Here, we provide an overview of the catalogue of AMPAR interacting proteins, and how they contribute to the complex biology of this central glutamate receptor. This article is part of the special Issue on 'Glutamate Receptors - AMPA receptors'.</AbstractText
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Mechanism of S100A9-mediated astrocyte activation via TLR4/NF-κB in Parkinson's disease. Astrocyte-mediated neuroinflammation plays a key role in Parkinson's disease (PD) progression. The proinflammatory protein S100A9 is linked to various neurodegenerative diseases, but its involvement in astrocyte activation in PD remains unclear. Here, we investigate the role of S100A9 in astrocyte-mediated neuroinflammation in PD. C57BL/6J mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 15 mg/kg four times daily) and subsequently treated with Paquinimod, a S100A9 inhibitor (7 mg/kg, once daily for 7 days, totaling 8 doses). We observed an abnormal increase in S100A9 protein expression and a rise in S100A9-positive cells in the striatum of PD mice. Paquinimod treatment significantly improved behavioral deficits (pole test, rotarod test, traction test, and open field tests), prevented the reduction in striatal tyrosine hydroxylase (TH) protein and the loss of dopaminergic neurons (TH<sup
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33033983
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33223582
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34098971
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Peak width of skeletonized mean diffusivity (PSMD) and cognitive functions in relapsing-remitting multiple sclerosis.
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Transfer of Learning in People Who Are Blind: Enhancement of Spatial-Cognitive Abilities Through Drawing.
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Policy options to increase motivation for improving evidence-informed health policy-making in Iran.
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Peak width of skeletonized mean diffusivity (PSMD) is a new MRI marker, which has shown clinical relevance in some neurological conditions and, in preliminary data, in multiple sclerosis (MS). We aimed here to investigate, in a group of relapsing-remitting MS (RRMS) patients, the relationship between PSMD and cognitive performances, in comparison with other MRI measures. RRMS patients (n = 60) and normal controls (n = 15) underwent a 3 T MRI examination. MRI-based white matter (WM) lesion volume, microstructural integrity (assessed with Tract-Based Spatial Statistics of diffusion tensor imaging [DTI] images) and brain volumes (i.e., total brain, grey matter [GM] and WM) were computed. In addition, PSMD was calculated through "skeletonization" of WM tracts and diffusion histograms. Cognition was evaluated with Rao's Brief Repeatable Battery (BRB), which incorporated tests of verbal and visual memory, attention, concentration, information processing speed and verbal fluency. PSMD closely correlated with symbol digit modalities test (SDMT) (r = -0.70, p < 0.001) and, to a lesser extent, with verbal and visual memory tests. Multiple regression analysis showed that PSMD explained SDMT variance (R<sup
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This study assessed whether basic spatial-cognitive abilities can be enhanced in people who are blind through transfer of learning from drawing training.</AbstractText Near-body spatial-cognitive performance was assessed through the Cognitive Test for the Blind (CTB), which assesses a wide range of basic spatial-cognitive skills. The CTB was administered to 21 participants who are blind in two behavioral testing sessions separated by five days. For participants in the "trained" group, these intervening days were occupied by the Cognitive-Kinesthetic Drawing Training method, during which participants learned how to draw freehand from memory. The "control" participants were not trained.</AbstractText The results showed significantly increased overall CTB performance in the trained but not in the control group, indicating that the drawing training effectively enhanced spatial-cognitive abilities. A three to six month follow-up session with a subset of trained participants suggested that these training-induced spatial-cognitive improvements might persist over time, at least for some tasks.</AbstractText These findings demonstrate that learning to draw from memory without vision over just five sessions can lead to enhancement of basic spatial-cognitive abilities beyond the drawing task. This study is the first to examine the transfer of learning of cognitive ability in blind individuals.</AbstractText This study sheds light on the Cognitive-Kinesthetic Drawing Training as an effective wide-range rehabilitation technique that could be used to enhance basic spatial-cognitive abilities in those who are blind.</AbstractText
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Current incentive programmes are not sufficient to motivate researchers and policy-makers to use research evidence in policy-making. We conducted a mixed-methods design to identify context-based policy options for strengthening motivations among health researchers and policy-makers to support evidence-informed health policy-making (EIHP) in Iran.</AbstractText This study was conducted in 2019 in two phases. In the first phase, we conducted a scoping review to extract interventions implemented or proposed to strengthen motivations to support EIHP. Additionally, we employed a comparative case study design for reviewing the performance evaluation (PE) processes in Iran and other selected countries to determine the current individual and organizational incentives to encourage EIHP. In the second phase, we developed two policy briefs and then convened two policy dialogues, with 12 and 8 key informants, respectively, where the briefs were discussed. Data were analysed using manifest content analysis in order to propose contextualized policy options.</AbstractText The policy options identified to motivate health researchers and policy-makers to support EIHP in Iran were: revising the criteria of academic PE; designing appropriate incentive programmes for nonacademic researchers; developing an indicator for the evaluation of research impact on policy-making or health outcomes; revising the current policies of scientific journals; revising existing funding mechanisms; presenting the knowledge translation plan when submitting a research proposal, as a mandatory condition; encouraging and supporting mechanisms for increasing interactions between policy-makers and researchers; and revising some administrative processes (e.g. managers and staff PEs; selection, appointment, and changing managers and reward mechanisms).</AbstractText The current individual or organizational incentives are mainly focused on publications, rather than encouraging researchers and policy-makers to support EIHP. Relying more on incentives that consider the other impacts of research (e.g. impacts on health system and policy, or health outcomes) is recommended. These incentives may encourage individuals and organizations to be more involved in conducting research evidence, resulting in promoting EIHP.</AbstractText NA.</AbstractText
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Peak width of skeletonized mean diffusivity (PSMD) and cognitive functions in relapsing-remitting multiple sclerosis. Peak width of skeletonized mean diffusivity (PSMD) is a new MRI marker, which has shown clinical relevance in some neurological conditions and, in preliminary data, in multiple sclerosis (MS). We aimed here to investigate, in a group of relapsing-remitting MS (RRMS) patients, the relationship between PSMD and cognitive performances, in comparison with other MRI measures. RRMS patients (n = 60) and normal controls (n = 15) underwent a 3 T MRI examination. MRI-based white matter (WM) lesion volume, microstructural integrity (assessed with Tract-Based Spatial Statistics of diffusion tensor imaging [DTI] images) and brain volumes (i.e., total brain, grey matter [GM] and WM) were computed. In addition, PSMD was calculated through "skeletonization" of WM tracts and diffusion histograms. Cognition was evaluated with Rao's Brief Repeatable Battery (BRB), which incorporated tests of verbal and visual memory, attention, concentration, information processing speed and verbal fluency. PSMD closely correlated with symbol digit modalities test (SDMT) (r = -0.70, p < 0.001) and, to a lesser extent, with verbal and visual memory tests. Multiple regression analysis showed that PSMD explained SDMT variance (R<sup
|
Transfer of Learning in People Who Are Blind: Enhancement of Spatial-Cognitive Abilities Through Drawing. This study assessed whether basic spatial-cognitive abilities can be enhanced in people who are blind through transfer of learning from drawing training.</AbstractText Near-body spatial-cognitive performance was assessed through the Cognitive Test for the Blind (CTB), which assesses a wide range of basic spatial-cognitive skills. The CTB was administered to 21 participants who are blind in two behavioral testing sessions separated by five days. For participants in the "trained" group, these intervening days were occupied by the Cognitive-Kinesthetic Drawing Training method, during which participants learned how to draw freehand from memory. The "control" participants were not trained.</AbstractText The results showed significantly increased overall CTB performance in the trained but not in the control group, indicating that the drawing training effectively enhanced spatial-cognitive abilities. A three to six month follow-up session with a subset of trained participants suggested that these training-induced spatial-cognitive improvements might persist over time, at least for some tasks.</AbstractText These findings demonstrate that learning to draw from memory without vision over just five sessions can lead to enhancement of basic spatial-cognitive abilities beyond the drawing task. This study is the first to examine the transfer of learning of cognitive ability in blind individuals.</AbstractText This study sheds light on the Cognitive-Kinesthetic Drawing Training as an effective wide-range rehabilitation technique that could be used to enhance basic spatial-cognitive abilities in those who are blind.</AbstractText
|
Policy options to increase motivation for improving evidence-informed health policy-making in Iran. Current incentive programmes are not sufficient to motivate researchers and policy-makers to use research evidence in policy-making. We conducted a mixed-methods design to identify context-based policy options for strengthening motivations among health researchers and policy-makers to support evidence-informed health policy-making (EIHP) in Iran.</AbstractText This study was conducted in 2019 in two phases. In the first phase, we conducted a scoping review to extract interventions implemented or proposed to strengthen motivations to support EIHP. Additionally, we employed a comparative case study design for reviewing the performance evaluation (PE) processes in Iran and other selected countries to determine the current individual and organizational incentives to encourage EIHP. In the second phase, we developed two policy briefs and then convened two policy dialogues, with 12 and 8 key informants, respectively, where the briefs were discussed. Data were analysed using manifest content analysis in order to propose contextualized policy options.</AbstractText The policy options identified to motivate health researchers and policy-makers to support EIHP in Iran were: revising the criteria of academic PE; designing appropriate incentive programmes for nonacademic researchers; developing an indicator for the evaluation of research impact on policy-making or health outcomes; revising the current policies of scientific journals; revising existing funding mechanisms; presenting the knowledge translation plan when submitting a research proposal, as a mandatory condition; encouraging and supporting mechanisms for increasing interactions between policy-makers and researchers; and revising some administrative processes (e.g. managers and staff PEs; selection, appointment, and changing managers and reward mechanisms).</AbstractText The current individual or organizational incentives are mainly focused on publications, rather than encouraging researchers and policy-makers to support EIHP. Relying more on incentives that consider the other impacts of research (e.g. impacts on health system and policy, or health outcomes) is recommended. These incentives may encourage individuals and organizations to be more involved in conducting research evidence, resulting in promoting EIHP.</AbstractText NA.</AbstractText
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31288026
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15930389
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30455322
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Neural architecture of human language: Hierarchical structure building is independent from working memory.
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Shifts of effective connectivity within a language network during rhyming and spelling.
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Blood Pressure Goals in Patients with CKD: A Review of Evidence and Guidelines.
|
Using functional magnetic resonance imaging (fMRI), we show that the neural substrate of language does not overlap with that for verbal working memory when we carefully define verbal working memory in sentence processing. Object-Subject-Verb (OSV) sentences in Japanese were contrasted with canonical Subject-Object-Verb (SOV) sentences, which had less hierarchy in linguistic structure. This contrast revealed the posterior part of Broca's area and the left posterior middle temporal gyrus (pMTG) as the neural bases for hierarchical structure building. Furthermore, we changed verbal working memory load in OSV sentences by adding modifiers to the subject or object noun phrases; this resulted in the activation in the op9, which is situated in the frontal operculum and is adjacent to, but not situated in, Broca's area. The neuroanatomical segregation of language processing from verbal working memory suggests independence of the faculty of language from the verbal working memory system, providing evidence for the domain-specificity of language in human cognition.</AbstractText
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We used functional magnetic resonance imaging to examine task-specific modulations of effective connectivity within a left-hemisphere language network during spelling and rhyming judgments on visually presented words. We identified sites showing task-specific activations for rhyming in the lateral temporal cortex (LTC) and for spelling in the intraparietal sulcus (IPS). The inferior frontal gyrus (IFG) and fusiform gyrus were engaged by both tasks. Dynamic causal modeling showed that each task preferentially strengthened modulatory influences converging on its task-specific site (LTC for rhyming, IPS for spelling). These remarkably selective and symmetrical findings demonstrate that the nature of the behavioral task dynamically shifts the locus of integration (or convergence) to the network component specialized for that task. Furthermore, they suggest that the role of the task-selective areas is to provide a differential synthesis of incoming information rather than providing differential control signals influencing the activity of other network components. Our findings also showed that switching tasks led to changes in the target area influenced by the IFG, suggesting that the IFG may play a pivotal role in setting the cognitive context for each task. We propose that task-dependent shifts in effective connectivity are likely to be mediated through top-down modulations from the IFG to the task-selective regions in a way that differentially enhances their sensitivity to incoming word-form information.</AbstractText
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Hypertension affects the vast majority of patients with CKD and increases the risk of cardiovascular disease, ESKD, and death. Over the past decade, a number of hypertension guidelines have been published with varying recommendations for BP goals in patients with CKD. Most recently, the American College of Cardiology/American Heart Association 2017 hypertension guidelines set a BP goal of <130/80 mm Hg for patients with CKD and others at elevated cardiovascular risk. These guidelines were heavily influenced by the landmark Systolic Blood Pressure Intervention Trial (SPRINT), which documented that an intensive BP goal to a systolic BP <120 mm Hg decreased the risk of cardiovascular disease and mortality in nondiabetic adults at high cardiovascular risk, many of whom had CKD; the intensive BP goal did not retard CKD progression. It is noteworthy that SPRINT measured BP with automated devices (5-minute wait period, average of three readings) often without observers, a technique that potentially results in BP values that are lower than what is typically measured in the office. Still, results from SPRINT along with long-term follow-up data from the Modification of Diet in Renal Disease and the African American Study of Kidney Disease and Hypertension suggest that a BP goal <130/80 mm Hg will reduce mortality in patients with CKD. Unfortunately, data are more limited in patients with diabetes or stage 4-5 CKD. Increased adverse events, including electrolyte abnormalities and decreased eGFR, necessitate careful laboratory monitoring. In conclusion, a BP goal of <130/80 is a reasonable, evidence-based BP goal in patients with CKD. Implementation of this intensive BP target will require increased attention to measuring BP accurately, assessing patient preferences and concurrent medical conditions, and monitoring for adverse effects of therapy.</AbstractText
|
Neural architecture of human language: Hierarchical structure building is independent from working memory. Using functional magnetic resonance imaging (fMRI), we show that the neural substrate of language does not overlap with that for verbal working memory when we carefully define verbal working memory in sentence processing. Object-Subject-Verb (OSV) sentences in Japanese were contrasted with canonical Subject-Object-Verb (SOV) sentences, which had less hierarchy in linguistic structure. This contrast revealed the posterior part of Broca's area and the left posterior middle temporal gyrus (pMTG) as the neural bases for hierarchical structure building. Furthermore, we changed verbal working memory load in OSV sentences by adding modifiers to the subject or object noun phrases; this resulted in the activation in the op9, which is situated in the frontal operculum and is adjacent to, but not situated in, Broca's area. The neuroanatomical segregation of language processing from verbal working memory suggests independence of the faculty of language from the verbal working memory system, providing evidence for the domain-specificity of language in human cognition.</AbstractText
|
Shifts of effective connectivity within a language network during rhyming and spelling. We used functional magnetic resonance imaging to examine task-specific modulations of effective connectivity within a left-hemisphere language network during spelling and rhyming judgments on visually presented words. We identified sites showing task-specific activations for rhyming in the lateral temporal cortex (LTC) and for spelling in the intraparietal sulcus (IPS). The inferior frontal gyrus (IFG) and fusiform gyrus were engaged by both tasks. Dynamic causal modeling showed that each task preferentially strengthened modulatory influences converging on its task-specific site (LTC for rhyming, IPS for spelling). These remarkably selective and symmetrical findings demonstrate that the nature of the behavioral task dynamically shifts the locus of integration (or convergence) to the network component specialized for that task. Furthermore, they suggest that the role of the task-selective areas is to provide a differential synthesis of incoming information rather than providing differential control signals influencing the activity of other network components. Our findings also showed that switching tasks led to changes in the target area influenced by the IFG, suggesting that the IFG may play a pivotal role in setting the cognitive context for each task. We propose that task-dependent shifts in effective connectivity are likely to be mediated through top-down modulations from the IFG to the task-selective regions in a way that differentially enhances their sensitivity to incoming word-form information.</AbstractText
|
Blood Pressure Goals in Patients with CKD: A Review of Evidence and Guidelines. Hypertension affects the vast majority of patients with CKD and increases the risk of cardiovascular disease, ESKD, and death. Over the past decade, a number of hypertension guidelines have been published with varying recommendations for BP goals in patients with CKD. Most recently, the American College of Cardiology/American Heart Association 2017 hypertension guidelines set a BP goal of <130/80 mm Hg for patients with CKD and others at elevated cardiovascular risk. These guidelines were heavily influenced by the landmark Systolic Blood Pressure Intervention Trial (SPRINT), which documented that an intensive BP goal to a systolic BP <120 mm Hg decreased the risk of cardiovascular disease and mortality in nondiabetic adults at high cardiovascular risk, many of whom had CKD; the intensive BP goal did not retard CKD progression. It is noteworthy that SPRINT measured BP with automated devices (5-minute wait period, average of three readings) often without observers, a technique that potentially results in BP values that are lower than what is typically measured in the office. Still, results from SPRINT along with long-term follow-up data from the Modification of Diet in Renal Disease and the African American Study of Kidney Disease and Hypertension suggest that a BP goal <130/80 mm Hg will reduce mortality in patients with CKD. Unfortunately, data are more limited in patients with diabetes or stage 4-5 CKD. Increased adverse events, including electrolyte abnormalities and decreased eGFR, necessitate careful laboratory monitoring. In conclusion, a BP goal of <130/80 is a reasonable, evidence-based BP goal in patients with CKD. Implementation of this intensive BP target will require increased attention to measuring BP accurately, assessing patient preferences and concurrent medical conditions, and monitoring for adverse effects of therapy.</AbstractText
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38360144
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27251213
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39023368
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Continuous electrical stimulation of superior laryngeal nerve inhibits initiation of swallowing in anesthetized rats.
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Vagal neurocircuitry and its influence on gastric motility.
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Speaker Demographics Modulate Listeners' Neural Correlates of Spoken Word Processing.
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Pharyngeal electrical stimulation (PES) applies electrical stimulation to pharyngeal mucosa (PhM) and represents a useful approach to improve swallowing function in patients with dysphagia. To determine the optimal PES modality to treat dysphagia, the mechanism underlying the effects of PES on swallowing function must be elucidated. In this study, we evaluated how PES and electrical stimulation of the superior laryngeal nerve (SLN) modulate the initiation of swallowing in anesthetized rats. A swallow was evoked by electrical stimulation of the PhM, SLN, and nucleus of the solitary tract (nTS) and pharyngeal mechanical stimulation using a von Frey filament. A swallow was identified by electromyographic bursts in mylohyoid and thyrohyoid muscles. Bilateral SLN transection abolished the swallows evoked by PhM electrical stimulation. PhM and SLN electrical stimulation decreased swallowing frequency in a similar time-dependent manner. Intravenous administration of the GABA<sub
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A large body of research has been dedicated to the effects of gastrointestinal peptides on vagal afferent fibres, yet multiple lines of evidence indicate that gastrointestinal peptides also modulate brainstem vagal neurocircuitry, and that this modulation has a fundamental role in the physiology and pathophysiology of the upper gastrointestinal tract. In fact, brainstem vagovagal neurocircuits comprise highly plastic neurons and synapses connecting afferent vagal fibres, second order neurons of the nucleus tractus solitarius (NTS), and efferent fibres originating in the dorsal motor nucleus of the vagus (DMV). Neuronal communication between the NTS and DMV is regulated by the presence of a variety of inputs, both from within the brainstem itself as well as from higher centres, which utilize an array of neurotransmitters and neuromodulators. Because of the circumventricular nature of these brainstem areas, circulating hormones can also modulate the vagal output to the upper gastrointestinal tract. This Review summarizes the organization and function of vagovagal reflex control of the upper gastrointestinal tract, presents data on the plasticity within these neurocircuits after stress, and discusses the gastrointestinal dysfunctions observed in Parkinson disease as examples of physiological adjustment and maladaptation of these reflexes.</AbstractText
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In language comprehension, listeners expect a speaker to be consistent in their word choice for labeling the same object. For instance, if a speaker previously refers to a piece of furniture as a "couch," in subsequent references, listeners would expect the speaker to repeat this label instead of switching to an alternative label such as "sofa." Moreover, it has been found that speakers' demographic backgrounds, often inferred from their voice, influence how listeners process their language. The question in focus, therefore, is whether speaker demographics influence how listeners expect the speaker to repeat or switch labels. In this study, we used ERPs to investigate whether listeners expect a child speaker to be less likely to switch labels compared to an adult speaker, given the common belief that children are less flexible in language use. In the experiment, we used 80 pictures with alternative labels in Mandarin Chinese (e.g., yi1sheng1 vs. dai4fu, "doctor"). Each picture was presented twice over two experimental phases: In the establishment phase, participants listened to an adult or a child naming a picture with one of the labels and decided whether the label matched the picture they saw; in the test phase, participants listened to the same speaker naming the same picture by either repeating the original label or switching to an alternative label and, again, decided whether the label matched the picture they saw. ERP results in the test phase revealed that, compared to repeated labels, switched labels elicited an N400 effect (300-600 msec after label onset) and a P600 effect (600-1000 msec after label onset). Critically, the N400 effect was larger when listeners were exposed to the child speaker than to the adult speaker, suggesting that listeners found a switched label harder to comprehend when it was produced by a child speaker than an adult speaker. Our study shows that the perceived speaker demographic backgrounds influence listeners' neural responses to spoken words, particularly in relation to their expectations regarding the speaker's label switching behavior. This finding contributes to a broader understanding of the relationship between social cognition and language processing.</AbstractText
|
Continuous electrical stimulation of superior laryngeal nerve inhibits initiation of swallowing in anesthetized rats. Pharyngeal electrical stimulation (PES) applies electrical stimulation to pharyngeal mucosa (PhM) and represents a useful approach to improve swallowing function in patients with dysphagia. To determine the optimal PES modality to treat dysphagia, the mechanism underlying the effects of PES on swallowing function must be elucidated. In this study, we evaluated how PES and electrical stimulation of the superior laryngeal nerve (SLN) modulate the initiation of swallowing in anesthetized rats. A swallow was evoked by electrical stimulation of the PhM, SLN, and nucleus of the solitary tract (nTS) and pharyngeal mechanical stimulation using a von Frey filament. A swallow was identified by electromyographic bursts in mylohyoid and thyrohyoid muscles. Bilateral SLN transection abolished the swallows evoked by PhM electrical stimulation. PhM and SLN electrical stimulation decreased swallowing frequency in a similar time-dependent manner. Intravenous administration of the GABA<sub
|
Vagal neurocircuitry and its influence on gastric motility. A large body of research has been dedicated to the effects of gastrointestinal peptides on vagal afferent fibres, yet multiple lines of evidence indicate that gastrointestinal peptides also modulate brainstem vagal neurocircuitry, and that this modulation has a fundamental role in the physiology and pathophysiology of the upper gastrointestinal tract. In fact, brainstem vagovagal neurocircuits comprise highly plastic neurons and synapses connecting afferent vagal fibres, second order neurons of the nucleus tractus solitarius (NTS), and efferent fibres originating in the dorsal motor nucleus of the vagus (DMV). Neuronal communication between the NTS and DMV is regulated by the presence of a variety of inputs, both from within the brainstem itself as well as from higher centres, which utilize an array of neurotransmitters and neuromodulators. Because of the circumventricular nature of these brainstem areas, circulating hormones can also modulate the vagal output to the upper gastrointestinal tract. This Review summarizes the organization and function of vagovagal reflex control of the upper gastrointestinal tract, presents data on the plasticity within these neurocircuits after stress, and discusses the gastrointestinal dysfunctions observed in Parkinson disease as examples of physiological adjustment and maladaptation of these reflexes.</AbstractText
|
Speaker Demographics Modulate Listeners' Neural Correlates of Spoken Word Processing. In language comprehension, listeners expect a speaker to be consistent in their word choice for labeling the same object. For instance, if a speaker previously refers to a piece of furniture as a "couch," in subsequent references, listeners would expect the speaker to repeat this label instead of switching to an alternative label such as "sofa." Moreover, it has been found that speakers' demographic backgrounds, often inferred from their voice, influence how listeners process their language. The question in focus, therefore, is whether speaker demographics influence how listeners expect the speaker to repeat or switch labels. In this study, we used ERPs to investigate whether listeners expect a child speaker to be less likely to switch labels compared to an adult speaker, given the common belief that children are less flexible in language use. In the experiment, we used 80 pictures with alternative labels in Mandarin Chinese (e.g., yi1sheng1 vs. dai4fu, "doctor"). Each picture was presented twice over two experimental phases: In the establishment phase, participants listened to an adult or a child naming a picture with one of the labels and decided whether the label matched the picture they saw; in the test phase, participants listened to the same speaker naming the same picture by either repeating the original label or switching to an alternative label and, again, decided whether the label matched the picture they saw. ERP results in the test phase revealed that, compared to repeated labels, switched labels elicited an N400 effect (300-600 msec after label onset) and a P600 effect (600-1000 msec after label onset). Critically, the N400 effect was larger when listeners were exposed to the child speaker than to the adult speaker, suggesting that listeners found a switched label harder to comprehend when it was produced by a child speaker than an adult speaker. Our study shows that the perceived speaker demographic backgrounds influence listeners' neural responses to spoken words, particularly in relation to their expectations regarding the speaker's label switching behavior. This finding contributes to a broader understanding of the relationship between social cognition and language processing.</AbstractText
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36796237
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32900658
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37779723
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A comparison of how deep brain stimulation in two targets with anti-compulsive efficacy modulates brain activity using fMRI in awake rats.
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Temporal Dynamics of Large-Scale Networks Predict Neural Cue Reactivity and Cue-Induced Craving.
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Molecular surveillance of dengue virus in field-collected Aedes mosquitoes from Bhopal, central India: evidence of circulation of a new lineage of serotype 2.
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Deep brain stimulation (DBS) is an established neuromodulatory intervention against otherwise treatment-refractory obsessive-compulsive disorder (OCD). Several DBS targets, all of which are part of brain networks connecting basal ganglia and prefrontal cortex, alleviate OCD symptoms. Stimulation of these targets is thought to unfold its therapeutic effect by modulation of network activity through internal capsule (IC) connections. Research into DBS-induced network changes and the nature of IC-related effects of DBS in OCD is needed to further improve DBS. Here, we studied the effects of DBS at the ventral medial striatum (VMS) and IC on blood-oxygen level dependent (BOLD) responses in awake rats using functional magnetic resonance imaging (fMRI). BOLD-signal intensity was measured in five regions of interest (ROIs): medial and orbital prefrontal cortex, nucleus accumbens (NAc), IC area, and mediodorsal thalamus. In previous rodent studies, stimulation at both target locations resulted in a reduction of OCD-like behavior and activation of prefrontal cortical areas. Therefore, we hypothesized that stimulation at both targets would result in partially overlapping BOLD responses. Both differential and overlapping activity between VMS and IC stimulation was found. Stimulating the caudal part of the IC resulted in activation around the electrode, while stimulating the rostral part of the IC resulted in increased cross-correlations between the IC area, orbitofrontal cortex, and NAc. Stimulation of the dorsal part of the VMS resulted in increased activity in the IC area, suggesting this area is activated during both VMS and IC stimulation. This activation is also indicative of VMS-DBS impacting corticofugal fibers running through the medial caudate into the anterior IC, and both VMS and IC DBS might act on these fibers to induce OCD-reducing effects. These results show that rodent fMRI with simultaneous electrode stimulation is a promising approach to study the neural mechanisms of DBS. Comparing the effects of DBS in different target areas has the potential to improve our understanding of the neuromodulatory changes that take place across various networks and connections in the brain. Performing this research in animal disease models will lead to translational insights in the mechanisms underlying DBS, and can aid improvement and optimization of DBS in patient populations.</AbstractText
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Cue reactivity, a core characteristic of substance use disorders, commonly recruits brain regions that are key nodes in neurocognitive networks, including the default mode network (DMN) and salience network (SN). Whether resting-state temporal dynamic properties of these networks relate to subsequent cue reactivity and cue-induced craving is unknown.</AbstractText The resting-state data of 46 nicotine-dependent participants were assessed to define temporal dynamic properties of DMN and SN states. Temporal dynamics focused on the total time across the scan session that brain activity resides in these specific states. Using regression models, we examined how the total time in each state related to neural reactivity to smoking cues within key DMN (posterior cingulate cortex, medial prefrontal cortex) or SN (anterior insula, dorsal anterior cingulate cortex) nodes. Mediation analyses were subsequently conducted to study how neural cue reactivity mediates the relationship between total time in state at rest and subjective cue-induced craving.</AbstractText Increased time spent in the DMN state and decreased time spent in the SN state predicted subsequent cue-induced increases in the anterior insula and dorsal anterior cingulate cortex, respectively. Cue-induced anterior insula and dorsal anterior cingulate cortex activity significantly mediated the relationship between time spent in DMN/SN and cue-induced subjective craving.</AbstractText Our findings showed a significant relationship between resting-state dynamics of the DMN/SN and task-activated SN nodes that together predicted cue-induced craving changes in nicotine-dependent individuals. These findings propose a neurobiological pathway for cue-induced craving that begins with resting-state temporal dynamics, suggesting that brain responding to external stimuli is driven by resting temporal dynamics.</AbstractText
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Dengue fever is hyperendemic in several Southeast and South Asian countries, including India, with all four serotypes (DENV 1-4) circulating at different periods and in different locations. Sustainable and improved virological and entomological surveillance is the only tool to prevent dengue and other vector-borne diseases.</AbstractText The present study has been carried out to detect and characterize the circulating dengue virus (DENV) in field-collected <i <i DENV RNA was detected in 7 <i The observed emergence of the non-Indian lineage of DENV-2 in Bhopal, which again is a first report from the area, coincides with the gradual increase in DENV cases in Bhopal since 2014. This study emphasizes the importance of DENV surveillance and risk assessment in this strategically important part of the country to decipher its outbreak and severe disease-causing potential.</AbstractText
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A comparison of how deep brain stimulation in two targets with anti-compulsive efficacy modulates brain activity using fMRI in awake rats. Deep brain stimulation (DBS) is an established neuromodulatory intervention against otherwise treatment-refractory obsessive-compulsive disorder (OCD). Several DBS targets, all of which are part of brain networks connecting basal ganglia and prefrontal cortex, alleviate OCD symptoms. Stimulation of these targets is thought to unfold its therapeutic effect by modulation of network activity through internal capsule (IC) connections. Research into DBS-induced network changes and the nature of IC-related effects of DBS in OCD is needed to further improve DBS. Here, we studied the effects of DBS at the ventral medial striatum (VMS) and IC on blood-oxygen level dependent (BOLD) responses in awake rats using functional magnetic resonance imaging (fMRI). BOLD-signal intensity was measured in five regions of interest (ROIs): medial and orbital prefrontal cortex, nucleus accumbens (NAc), IC area, and mediodorsal thalamus. In previous rodent studies, stimulation at both target locations resulted in a reduction of OCD-like behavior and activation of prefrontal cortical areas. Therefore, we hypothesized that stimulation at both targets would result in partially overlapping BOLD responses. Both differential and overlapping activity between VMS and IC stimulation was found. Stimulating the caudal part of the IC resulted in activation around the electrode, while stimulating the rostral part of the IC resulted in increased cross-correlations between the IC area, orbitofrontal cortex, and NAc. Stimulation of the dorsal part of the VMS resulted in increased activity in the IC area, suggesting this area is activated during both VMS and IC stimulation. This activation is also indicative of VMS-DBS impacting corticofugal fibers running through the medial caudate into the anterior IC, and both VMS and IC DBS might act on these fibers to induce OCD-reducing effects. These results show that rodent fMRI with simultaneous electrode stimulation is a promising approach to study the neural mechanisms of DBS. Comparing the effects of DBS in different target areas has the potential to improve our understanding of the neuromodulatory changes that take place across various networks and connections in the brain. Performing this research in animal disease models will lead to translational insights in the mechanisms underlying DBS, and can aid improvement and optimization of DBS in patient populations.</AbstractText
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Temporal Dynamics of Large-Scale Networks Predict Neural Cue Reactivity and Cue-Induced Craving. Cue reactivity, a core characteristic of substance use disorders, commonly recruits brain regions that are key nodes in neurocognitive networks, including the default mode network (DMN) and salience network (SN). Whether resting-state temporal dynamic properties of these networks relate to subsequent cue reactivity and cue-induced craving is unknown.</AbstractText The resting-state data of 46 nicotine-dependent participants were assessed to define temporal dynamic properties of DMN and SN states. Temporal dynamics focused on the total time across the scan session that brain activity resides in these specific states. Using regression models, we examined how the total time in each state related to neural reactivity to smoking cues within key DMN (posterior cingulate cortex, medial prefrontal cortex) or SN (anterior insula, dorsal anterior cingulate cortex) nodes. Mediation analyses were subsequently conducted to study how neural cue reactivity mediates the relationship between total time in state at rest and subjective cue-induced craving.</AbstractText Increased time spent in the DMN state and decreased time spent in the SN state predicted subsequent cue-induced increases in the anterior insula and dorsal anterior cingulate cortex, respectively. Cue-induced anterior insula and dorsal anterior cingulate cortex activity significantly mediated the relationship between time spent in DMN/SN and cue-induced subjective craving.</AbstractText Our findings showed a significant relationship between resting-state dynamics of the DMN/SN and task-activated SN nodes that together predicted cue-induced craving changes in nicotine-dependent individuals. These findings propose a neurobiological pathway for cue-induced craving that begins with resting-state temporal dynamics, suggesting that brain responding to external stimuli is driven by resting temporal dynamics.</AbstractText
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Molecular surveillance of dengue virus in field-collected Aedes mosquitoes from Bhopal, central India: evidence of circulation of a new lineage of serotype 2. Dengue fever is hyperendemic in several Southeast and South Asian countries, including India, with all four serotypes (DENV 1-4) circulating at different periods and in different locations. Sustainable and improved virological and entomological surveillance is the only tool to prevent dengue and other vector-borne diseases.</AbstractText The present study has been carried out to detect and characterize the circulating dengue virus (DENV) in field-collected <i <i DENV RNA was detected in 7 <i The observed emergence of the non-Indian lineage of DENV-2 in Bhopal, which again is a first report from the area, coincides with the gradual increase in DENV cases in Bhopal since 2014. This study emphasizes the importance of DENV surveillance and risk assessment in this strategically important part of the country to decipher its outbreak and severe disease-causing potential.</AbstractText
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35047400
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24214526
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34393924
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Amide Proton Transfer Weighted and Intravoxel Incoherent Motion Imaging in Evaluation of Prognostic Factors for Rectal Adenocarcinoma.
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Quantification of amide proton transfer effect pre- and post-gadolinium contrast agent administration.
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Neuroscience, Empathy, and Violent Crime in an Incarcerated Population: A Narrative Review.
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To analyze the value of amide proton transfer (APT) weighted and intravoxel incoherent motion (IVIM) imaging in evaluation of prognostic factors for rectal adenocarcinoma, compared with diffusion weighted imaging (DWI).</AbstractText Preoperative pelvic MRI data of 110 patients with surgical pathologically confirmed diagnosis of rectal adenocarcinoma were retrospectively evaluated. All patients underwent high-resolution T<sub APT SI, D and ADC values of rectal mucinous adenocarcinoma (MC) were significantly higher than those of rectal common adenocarcinoma (AC) ([3.192 ± 0.661%] <i APT and IVIM were helpful to assess the prognostic factors related to rectal adenocarcinoma, including histopathological type, tumor grade and the EMVI status.</AbstractText
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To compare quantification of the amide proton transfer (APT) effect pre- and post-gadolinium contrast agent (Gd) administration in order to establish to what extent Gd alters quantification of the APT effect.</AbstractText Four patients with internal carotid stenosis were recruited. APT imaging was acquired pre- and post-contrast in two sessions (before and after surgery) to assess the extent of relaxation time, T1 , change on APT effect calculated using magnetization transfer ratio asymmetry analysis at offsets of ±3.5 ppm relative to water resonance. Statistical and modeling evaluations were performed on the pre- and post-contrast APT effect to study the sensitivity to contrast administration.</AbstractText Before surgery, the post-contrast T1 was estimated to drop <10% of the pre-value for the majority of the patients. After surgery, higher post-contrast T1 reductions were observed in all the patients (maximum decrease was about 20% of the pre-value). Consistent differences between pre- and post-contrast were seen in the APT effect quantified using the asymmetry measure in most regions of the brain, with significant differences found in the white matter at the group level and in 25% of the individual patient results.</AbstractText APT imaging should be performed prior to Gd administration to avoid potential misinterpretation of the APT effect.</AbstractText
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Empathy is a fundamental construct that allows individuals to perceive and understand the cognitive and emotional state of others. Empathy is not only a psychological and sociological concept; it also heavily impacts our daily lives by affecting our decisions and actions. Empathy is connected to and involves specific parts of the brain which, if damaged or of reduced volume, can lead to actions that are morally unjust, aggressive, or simply denoting a lack of understanding and sensitivity. The literature affirms that the low level of empathy, guilt, embarrassment, and moral reasoning displayed by violent and psychopathic criminals is strongly associated with empathy-linked brain regions that are smaller in size or less developed. The aim of this review is to show empirical data over the last 5 years on the connection between empathy and neuroscience among violent and psychopathic offenders, reflecting on future research on the topic.</AbstractText
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Amide Proton Transfer Weighted and Intravoxel Incoherent Motion Imaging in Evaluation of Prognostic Factors for Rectal Adenocarcinoma. To analyze the value of amide proton transfer (APT) weighted and intravoxel incoherent motion (IVIM) imaging in evaluation of prognostic factors for rectal adenocarcinoma, compared with diffusion weighted imaging (DWI).</AbstractText Preoperative pelvic MRI data of 110 patients with surgical pathologically confirmed diagnosis of rectal adenocarcinoma were retrospectively evaluated. All patients underwent high-resolution T<sub APT SI, D and ADC values of rectal mucinous adenocarcinoma (MC) were significantly higher than those of rectal common adenocarcinoma (AC) ([3.192 ± 0.661%] <i APT and IVIM were helpful to assess the prognostic factors related to rectal adenocarcinoma, including histopathological type, tumor grade and the EMVI status.</AbstractText
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Quantification of amide proton transfer effect pre- and post-gadolinium contrast agent administration. To compare quantification of the amide proton transfer (APT) effect pre- and post-gadolinium contrast agent (Gd) administration in order to establish to what extent Gd alters quantification of the APT effect.</AbstractText Four patients with internal carotid stenosis were recruited. APT imaging was acquired pre- and post-contrast in two sessions (before and after surgery) to assess the extent of relaxation time, T1 , change on APT effect calculated using magnetization transfer ratio asymmetry analysis at offsets of ±3.5 ppm relative to water resonance. Statistical and modeling evaluations were performed on the pre- and post-contrast APT effect to study the sensitivity to contrast administration.</AbstractText Before surgery, the post-contrast T1 was estimated to drop <10% of the pre-value for the majority of the patients. After surgery, higher post-contrast T1 reductions were observed in all the patients (maximum decrease was about 20% of the pre-value). Consistent differences between pre- and post-contrast were seen in the APT effect quantified using the asymmetry measure in most regions of the brain, with significant differences found in the white matter at the group level and in 25% of the individual patient results.</AbstractText APT imaging should be performed prior to Gd administration to avoid potential misinterpretation of the APT effect.</AbstractText
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Neuroscience, Empathy, and Violent Crime in an Incarcerated Population: A Narrative Review. Empathy is a fundamental construct that allows individuals to perceive and understand the cognitive and emotional state of others. Empathy is not only a psychological and sociological concept; it also heavily impacts our daily lives by affecting our decisions and actions. Empathy is connected to and involves specific parts of the brain which, if damaged or of reduced volume, can lead to actions that are morally unjust, aggressive, or simply denoting a lack of understanding and sensitivity. The literature affirms that the low level of empathy, guilt, embarrassment, and moral reasoning displayed by violent and psychopathic criminals is strongly associated with empathy-linked brain regions that are smaller in size or less developed. The aim of this review is to show empirical data over the last 5 years on the connection between empathy and neuroscience among violent and psychopathic offenders, reflecting on future research on the topic.</AbstractText
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37851553
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35070225
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38214229
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Deep Representation Learning With Sample Generation and Augmented Attention Module for Imbalanced ECG Classification.
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A Novel Diabetes Healthcare Disease Prediction Framework Using Machine Learning Techniques.
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A super minigene with a short promoter and truncated introns recapitulates essential features of transcription and splicing regulation of the SMN1 and SMN2 genes.
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Developing an efficient heartbeat monitoring system has become a focal point in numerous healthcare applications. Specifically, in the last few years, heartbeat classification for arrhythmia detection has gained considerable interest from researchers. This paper presents a novel deep representation learning method for the efficient detection of arrhythmic beats. To mitigate the issues associated with the imbalanced data distribution, a novel re-sampling strategy is introduced. Unlike the existing oversampling methods, the proposed technique transforms majority-class samples into minority-class samples with a novel translation loss function. This approach assists the model in learning a more generalized representation of crucially important minority class samples. Moreover, by exploiting an auxiliary feature, an augmented attention module is designed that focuses on the most relevant and target-specific information. We adopted an inter-patient classification paradigm to evaluate the proposed method. The experimental results of this study on the MIT-BIH arrhythmia database clearly indicate that the proposed model with augmented attention mechanism and over-sampling strategy significantly learns a balanced deep representation and improves the classification performance of vital heartbeats.</AbstractText
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Diabetes is a chronic disease that continues to be a significant and global concern since it affects the entire population's health. It is a metabolic disorder that leads to high blood sugar levels and many other problems such as stroke, kidney failure, and heart and nerve problems. Several researchers have attempted to construct an accurate diabetes prediction model over the years. However, this subject still faces significant open research issues due to a lack of appropriate data sets and prediction approaches, which pushes researchers to use big data analytics and machine learning (ML)-based methods. Applying four different machine learning methods, the research tries to overcome the problems and investigate healthcare predictive analytics. The study's primary goal was to see how big data analytics and machine learning-based techniques may be used in diabetes. The examination of the results shows that the suggested ML-based framework may achieve a score of 86. Health experts and other stakeholders are working to develop categorization models that will aid in the prediction of diabetes and the formulation of preventative initiatives. The authors perform a review of the literature on machine models and suggest an intelligent framework for diabetes prediction based on their findings. Machine learning models are critically examined, and an intelligent machine learning-based architecture for diabetes prediction is proposed and evaluated by the authors. In this study, the authors utilize our framework to develop and assess decision tree (DT)-based random forest (RF) and support vector machine (SVM) learning models for diabetes prediction, which are the most widely used techniques in the literature at the time of writing. It is proposed in this study that a unique intelligent diabetes mellitus prediction framework (IDMPF) is developed using machine learning. According to the framework, it was developed after conducting a rigorous review of existing prediction models in the literature and examining their applicability to diabetes. Using the framework, the authors describe the training procedures, model assessment strategies, and issues associated with diabetes prediction, as well as solutions they provide. The findings of this study may be utilized by health professionals, stakeholders, students, and researchers who are involved in diabetes prediction research and development. The proposed work gives 83% accuracy with the minimum error rate.</AbstractText
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Here we report a Survival Motor Neuron 2 (SMN2) super minigene, SMN2Sup, encompassing its own promoter, all exons, their flanking intronic sequences and the entire 3'-untranslated region. We confirm that the pre-mRNA generated from SMN2Sup undergoes splicing to produce a translation-competent mRNA. We demonstrate that mRNA generated from SMN2Sup produces more SMN than an identical mRNA generated from a cDNA clone. We uncover that overexpression of SMN triggers skipping of exon 3 of SMN1/SMN2. We define the minimal promoter and regulatory elements associated with the initiation and elongation of transcription of SMN2. The shortened introns within SMN2Sup preserved the ability of camptothecin, a transcription elongation inhibitor, to induce skipping of exons 3 and 7 of SMN2. We show that intron 1-retained transcripts undergo nonsense-mediated decay. We demonstrate that splicing factor SRSF3 and DNA/RNA helicase DHX9 regulate splicing of multiple exons in the context of both SMN2Sup and endogenous SMN1/SMN2. Prevention of SMN2 exon 7 skipping has implications for the treatment of spinal muscular atrophy (SMA). We validate the utility of the super minigene in monitoring SMN levels upon splicing correction. Finally, we demonstrate how the super minigene could be employed to capture the cell type-specific effects of a pathogenic SMN1 mutation.</AbstractText
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Deep Representation Learning With Sample Generation and Augmented Attention Module for Imbalanced ECG Classification. Developing an efficient heartbeat monitoring system has become a focal point in numerous healthcare applications. Specifically, in the last few years, heartbeat classification for arrhythmia detection has gained considerable interest from researchers. This paper presents a novel deep representation learning method for the efficient detection of arrhythmic beats. To mitigate the issues associated with the imbalanced data distribution, a novel re-sampling strategy is introduced. Unlike the existing oversampling methods, the proposed technique transforms majority-class samples into minority-class samples with a novel translation loss function. This approach assists the model in learning a more generalized representation of crucially important minority class samples. Moreover, by exploiting an auxiliary feature, an augmented attention module is designed that focuses on the most relevant and target-specific information. We adopted an inter-patient classification paradigm to evaluate the proposed method. The experimental results of this study on the MIT-BIH arrhythmia database clearly indicate that the proposed model with augmented attention mechanism and over-sampling strategy significantly learns a balanced deep representation and improves the classification performance of vital heartbeats.</AbstractText
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A Novel Diabetes Healthcare Disease Prediction Framework Using Machine Learning Techniques. Diabetes is a chronic disease that continues to be a significant and global concern since it affects the entire population's health. It is a metabolic disorder that leads to high blood sugar levels and many other problems such as stroke, kidney failure, and heart and nerve problems. Several researchers have attempted to construct an accurate diabetes prediction model over the years. However, this subject still faces significant open research issues due to a lack of appropriate data sets and prediction approaches, which pushes researchers to use big data analytics and machine learning (ML)-based methods. Applying four different machine learning methods, the research tries to overcome the problems and investigate healthcare predictive analytics. The study's primary goal was to see how big data analytics and machine learning-based techniques may be used in diabetes. The examination of the results shows that the suggested ML-based framework may achieve a score of 86. Health experts and other stakeholders are working to develop categorization models that will aid in the prediction of diabetes and the formulation of preventative initiatives. The authors perform a review of the literature on machine models and suggest an intelligent framework for diabetes prediction based on their findings. Machine learning models are critically examined, and an intelligent machine learning-based architecture for diabetes prediction is proposed and evaluated by the authors. In this study, the authors utilize our framework to develop and assess decision tree (DT)-based random forest (RF) and support vector machine (SVM) learning models for diabetes prediction, which are the most widely used techniques in the literature at the time of writing. It is proposed in this study that a unique intelligent diabetes mellitus prediction framework (IDMPF) is developed using machine learning. According to the framework, it was developed after conducting a rigorous review of existing prediction models in the literature and examining their applicability to diabetes. Using the framework, the authors describe the training procedures, model assessment strategies, and issues associated with diabetes prediction, as well as solutions they provide. The findings of this study may be utilized by health professionals, stakeholders, students, and researchers who are involved in diabetes prediction research and development. The proposed work gives 83% accuracy with the minimum error rate.</AbstractText
|
A super minigene with a short promoter and truncated introns recapitulates essential features of transcription and splicing regulation of the SMN1 and SMN2 genes. Here we report a Survival Motor Neuron 2 (SMN2) super minigene, SMN2Sup, encompassing its own promoter, all exons, their flanking intronic sequences and the entire 3'-untranslated region. We confirm that the pre-mRNA generated from SMN2Sup undergoes splicing to produce a translation-competent mRNA. We demonstrate that mRNA generated from SMN2Sup produces more SMN than an identical mRNA generated from a cDNA clone. We uncover that overexpression of SMN triggers skipping of exon 3 of SMN1/SMN2. We define the minimal promoter and regulatory elements associated with the initiation and elongation of transcription of SMN2. The shortened introns within SMN2Sup preserved the ability of camptothecin, a transcription elongation inhibitor, to induce skipping of exons 3 and 7 of SMN2. We show that intron 1-retained transcripts undergo nonsense-mediated decay. We demonstrate that splicing factor SRSF3 and DNA/RNA helicase DHX9 regulate splicing of multiple exons in the context of both SMN2Sup and endogenous SMN1/SMN2. Prevention of SMN2 exon 7 skipping has implications for the treatment of spinal muscular atrophy (SMA). We validate the utility of the super minigene in monitoring SMN levels upon splicing correction. Finally, we demonstrate how the super minigene could be employed to capture the cell type-specific effects of a pathogenic SMN1 mutation.</AbstractText
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18404869
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27374335
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19049709
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Optimal control of psychological processes: a new computational paradigm.
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Learning to Associate Orientation with Color in Early Visual Areas by Associative Decoded fMRI Neurofeedback.
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Nephrogenic systemic fibrosis: the first Italian gadolinium-proven case.
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In this paper, we use general mathematical-statistical theorems to prove that developmental processes must be studied at the intra-individual level. We demonstrate how to model intra-individual variation using single-participant time series analysis with time-varying parameters. We use advanced signal analysis techniques based on nonlinear state-space modeling to present simulation results obtained with a new Maximum Likelihood technique based on Extended Kalman Filtering with Iteration and Smoothing (EKFIS) embedded in an Expectation Maximization (EM) loop. After showing how EKFIS results yield state-space models with time-varying parameters, we then couple EKFIS to recursive optimal control techniques to produce a receding horizon feedback-feedforward controller. In this way, we obtain a flexible on-line computational paradigm with which we can optimally control observed behavioral processes for an individual person in real time. We will present optimal control techniques using simulated data and outline preliminary applications to real time patient-specific treatment of type I diabetic patients and asthma patients.</AbstractText
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Associative learning is an essential brain process where the contingency of different items increases after training. Associative learning has been found to occur in many brain regions [1-4]. However, there is no clear evidence that associative learning of visual features occurs in early visual areas, although a number of studies have indicated that learning of a single visual feature (perceptual learning) involves early visual areas [5-8]. Here, via decoded fMRI neurofeedback termed "DecNef" [9], we tested whether associative learning of orientation and color can be created in early visual areas. During 3 days of training, DecNef induced fMRI signal patterns that corresponded to a specific target color (red) mostly in early visual areas while a vertical achromatic grating was physically presented to participants. As a result, participants came to perceive "red" significantly more frequently than "green" in an achromatic vertical grating. This effect was also observed 3-5 months after the training. These results suggest that long-term associative learning of two different visual features such as orientation and color was created, most likely in early visual areas. This newly extended technique that induces associative learning is called "A-DecNef," and it may be used as an important tool for understanding and modifying brain functions because associations are fundamental and ubiquitous functions in the brain.</AbstractText
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Nephrogenic systemic fibrosis (NSF) is a systemic disease, recently described in patients with advanced chronic kidney disease (CKD), characterized by progressive scleromyxedema-like fibrotic involvement mainly of the skin. We describe the case of a 66-year-old woman on chronic hemodialysis for end-stage renal failure, also affected by hypothyroidism, secondary hyperparathyroidism and occluding arteriopathy, for which she underwent a contrast-enhanced magnetic resonance angiography of the lower limbs in February 2007. One month later, she began complaining of progressive, painful distal lower limb stiffness, which subsequently spread to all four limbs and to the whole trunk. A deep-skin biopsy, taken from an affected area, showed gadolinium deposits. The case reported is, to best of our knowledge, the first Italian case of NSF. This diagnosis should be considered with care in CKD patients with a recent exposure to a gadolinium-based contrast agent, complaining of limb stiffness, especially in the presence of risk factors.</AbstractText
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Optimal control of psychological processes: a new computational paradigm. In this paper, we use general mathematical-statistical theorems to prove that developmental processes must be studied at the intra-individual level. We demonstrate how to model intra-individual variation using single-participant time series analysis with time-varying parameters. We use advanced signal analysis techniques based on nonlinear state-space modeling to present simulation results obtained with a new Maximum Likelihood technique based on Extended Kalman Filtering with Iteration and Smoothing (EKFIS) embedded in an Expectation Maximization (EM) loop. After showing how EKFIS results yield state-space models with time-varying parameters, we then couple EKFIS to recursive optimal control techniques to produce a receding horizon feedback-feedforward controller. In this way, we obtain a flexible on-line computational paradigm with which we can optimally control observed behavioral processes for an individual person in real time. We will present optimal control techniques using simulated data and outline preliminary applications to real time patient-specific treatment of type I diabetic patients and asthma patients.</AbstractText
|
Learning to Associate Orientation with Color in Early Visual Areas by Associative Decoded fMRI Neurofeedback. Associative learning is an essential brain process where the contingency of different items increases after training. Associative learning has been found to occur in many brain regions [1-4]. However, there is no clear evidence that associative learning of visual features occurs in early visual areas, although a number of studies have indicated that learning of a single visual feature (perceptual learning) involves early visual areas [5-8]. Here, via decoded fMRI neurofeedback termed "DecNef" [9], we tested whether associative learning of orientation and color can be created in early visual areas. During 3 days of training, DecNef induced fMRI signal patterns that corresponded to a specific target color (red) mostly in early visual areas while a vertical achromatic grating was physically presented to participants. As a result, participants came to perceive "red" significantly more frequently than "green" in an achromatic vertical grating. This effect was also observed 3-5 months after the training. These results suggest that long-term associative learning of two different visual features such as orientation and color was created, most likely in early visual areas. This newly extended technique that induces associative learning is called "A-DecNef," and it may be used as an important tool for understanding and modifying brain functions because associations are fundamental and ubiquitous functions in the brain.</AbstractText
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Nephrogenic systemic fibrosis: the first Italian gadolinium-proven case. Nephrogenic systemic fibrosis (NSF) is a systemic disease, recently described in patients with advanced chronic kidney disease (CKD), characterized by progressive scleromyxedema-like fibrotic involvement mainly of the skin. We describe the case of a 66-year-old woman on chronic hemodialysis for end-stage renal failure, also affected by hypothyroidism, secondary hyperparathyroidism and occluding arteriopathy, for which she underwent a contrast-enhanced magnetic resonance angiography of the lower limbs in February 2007. One month later, she began complaining of progressive, painful distal lower limb stiffness, which subsequently spread to all four limbs and to the whole trunk. A deep-skin biopsy, taken from an affected area, showed gadolinium deposits. The case reported is, to best of our knowledge, the first Italian case of NSF. This diagnosis should be considered with care in CKD patients with a recent exposure to a gadolinium-based contrast agent, complaining of limb stiffness, especially in the presence of risk factors.</AbstractText
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26769224
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21199535
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27145112
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Involvement of GABAB Receptor Signaling in Antipsychotic-like Action of the Novel Orthosteric Agonist of the mGlu4 Receptor, LSP4-2022.
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The analgesic effects of the GABAB receptor agonist, baclofen, in a rodent model of functional dyspepsia.
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Multielectrode Array (MEA) Assay for Profiling Electrophysiological Drug Effects in Human Stem Cell-Derived Cardiomyocytes.
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Considering that ligands of metabotropic glutamate and GABA receptors may exert beneficial effects on schizophrenia, we assessed the actions of the first mGlu>4-selective orthosteric agonist, LSP4-2022, in several tests reflecting positive, negative, and cognitive symptoms of schizophrenia. Moreover, we investigated the possible involvement of GABAB receptors in LSP4-2022-induced actions. Hyperactivity induced by MK-801 or amphetamine and DOI-induced head twitches in mice were used as the models of positive symptoms. The social interaction test, modified forced swim test (FST), and novel object recognition (NOR) test were used as the models of negative and cognitive symptoms of schizophrenia. LSP4-2022 inhibited hyperactivity (in a dose-dependent manner, 0.5-2 mg/kg) induced by MK-801 or amphetamine and DOI-induced head twitches. In mGlu4 receptor knockout mice, LSP4-2022 was not effective. However, it reversed MK-801-induced impairment in the social interaction test and the MK-801-induced increase of immobility in the modified FST. In the NOR test, LSP4-2022 was active at a dose of 2 mg/kg. GABAB receptor antagonist, CGP55845 (10 mg/kg), reversed LSP4-2022-induced effects in hyperactivity and head twitch tests. At the same time, the simultaneous administration of subeffective doses of LSP4-2022 (0.1 mg/kg) and a positive allosteric modulator of GABAB receptor PAM, GS39783 (0.1 mg/kg), induced clear antipsychotic-like effects in those two tests. Such an interaction between mGlu4 and GABAB receptors was not observed in the social interaction and NOR tests. Therefore, we suggest that the activation of the mGlu<sub
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The amino acid γ-aminobutyric acid (GABA) is an important modulator of pain but its role in visceral pain syndromes is just beginning to be studied. Our aims were to investigate the effect and mechanism of action of the GABA(B) receptor agonist, baclofen, on gastric hypersensitivity in a validated rat model of functional dyspepsia (FD).</AbstractText 10-day-old male rats received 0.2 mL of 0.1% iodoacetamide in 2% sucrose daily by oral gavages for 6 days. Control group received 2% sucrose. At 8-10 weeks rats treated with baclofen (0.3, 1, and 3 mg kg(-1) bw) or saline were tested for behavioral and electromyographic (EMG) visceromotor responses; gastric spinal afferent nerve activity to graded gastric distention and Fos protein expression in dorsal horn of spinal cord segments T8-T10 to noxious gastric distention.</AbstractText Baclofen administration was associated with a significant attenuation of the behavioral and EMG responses (at 1 and 3 mg kg(-1)) and expression of Fos in T8 and T9 segments in neonatal iodoacetamide sensitized rats. However, baclofen administration did not significantly affect splanchnic nerve activity to gastric distention. Baclofen (3 mg kg(-1)) also significantly reduced the expression of spinal Fos in response to gastric distention in control rats to a lesser extent than sensitized rats.</AbstractText Baclofen is effective in attenuating pain associated responses in an experimental model of FD and appears to act by central mechanisms. These results provide a basis for clinical trials of this drug in FD patients.</AbstractText
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More relevant and reliable preclinical cardiotoxicity tests are required to improve drug safety and reduce the cost of drug development. Human stem cell-derived cardiomyocytes (hSC-CMs) provide a potential model for the development of superior assays for preclinical drug safety screening. One such hSC-CM assay that has shown significant potential for enabling more predictive drug cardiac risk assessment is the MEA assay. The Multi-electrode Array (MEA) assay is an electrophysiology-based technique that uses microelectrodes embedded in the culture surface of each well to measure fluctuations in extracellular field potential (FP) generated from spontaneously beating hSC-CMs. Perturbations to the recorded FP waveform can be used as an unbiased method of predicting the identity of ion channel(s) impacted on drug exposure. Here, a higher throughput MEA assay using hSC-CMs in 48-well MEA plates is described for profiling compound-induced effects on cardiomyocyte electrophysiology. Techniques for preparing hSC-CM monolayers in MEA plates and methods to contextualize MEA assay experimental results are also covered. © 2016 by John Wiley & Sons, Inc.</AbstractText
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Involvement of GABAB Receptor Signaling in Antipsychotic-like Action of the Novel Orthosteric Agonist of the mGlu4 Receptor, LSP4-2022. Considering that ligands of metabotropic glutamate and GABA receptors may exert beneficial effects on schizophrenia, we assessed the actions of the first mGlu>4-selective orthosteric agonist, LSP4-2022, in several tests reflecting positive, negative, and cognitive symptoms of schizophrenia. Moreover, we investigated the possible involvement of GABAB receptors in LSP4-2022-induced actions. Hyperactivity induced by MK-801 or amphetamine and DOI-induced head twitches in mice were used as the models of positive symptoms. The social interaction test, modified forced swim test (FST), and novel object recognition (NOR) test were used as the models of negative and cognitive symptoms of schizophrenia. LSP4-2022 inhibited hyperactivity (in a dose-dependent manner, 0.5-2 mg/kg) induced by MK-801 or amphetamine and DOI-induced head twitches. In mGlu4 receptor knockout mice, LSP4-2022 was not effective. However, it reversed MK-801-induced impairment in the social interaction test and the MK-801-induced increase of immobility in the modified FST. In the NOR test, LSP4-2022 was active at a dose of 2 mg/kg. GABAB receptor antagonist, CGP55845 (10 mg/kg), reversed LSP4-2022-induced effects in hyperactivity and head twitch tests. At the same time, the simultaneous administration of subeffective doses of LSP4-2022 (0.1 mg/kg) and a positive allosteric modulator of GABAB receptor PAM, GS39783 (0.1 mg/kg), induced clear antipsychotic-like effects in those two tests. Such an interaction between mGlu4 and GABAB receptors was not observed in the social interaction and NOR tests. Therefore, we suggest that the activation of the mGlu<sub
|
The analgesic effects of the GABAB receptor agonist, baclofen, in a rodent model of functional dyspepsia. The amino acid γ-aminobutyric acid (GABA) is an important modulator of pain but its role in visceral pain syndromes is just beginning to be studied. Our aims were to investigate the effect and mechanism of action of the GABA(B) receptor agonist, baclofen, on gastric hypersensitivity in a validated rat model of functional dyspepsia (FD).</AbstractText 10-day-old male rats received 0.2 mL of 0.1% iodoacetamide in 2% sucrose daily by oral gavages for 6 days. Control group received 2% sucrose. At 8-10 weeks rats treated with baclofen (0.3, 1, and 3 mg kg(-1) bw) or saline were tested for behavioral and electromyographic (EMG) visceromotor responses; gastric spinal afferent nerve activity to graded gastric distention and Fos protein expression in dorsal horn of spinal cord segments T8-T10 to noxious gastric distention.</AbstractText Baclofen administration was associated with a significant attenuation of the behavioral and EMG responses (at 1 and 3 mg kg(-1)) and expression of Fos in T8 and T9 segments in neonatal iodoacetamide sensitized rats. However, baclofen administration did not significantly affect splanchnic nerve activity to gastric distention. Baclofen (3 mg kg(-1)) also significantly reduced the expression of spinal Fos in response to gastric distention in control rats to a lesser extent than sensitized rats.</AbstractText Baclofen is effective in attenuating pain associated responses in an experimental model of FD and appears to act by central mechanisms. These results provide a basis for clinical trials of this drug in FD patients.</AbstractText
|
Multielectrode Array (MEA) Assay for Profiling Electrophysiological Drug Effects in Human Stem Cell-Derived Cardiomyocytes. More relevant and reliable preclinical cardiotoxicity tests are required to improve drug safety and reduce the cost of drug development. Human stem cell-derived cardiomyocytes (hSC-CMs) provide a potential model for the development of superior assays for preclinical drug safety screening. One such hSC-CM assay that has shown significant potential for enabling more predictive drug cardiac risk assessment is the MEA assay. The Multi-electrode Array (MEA) assay is an electrophysiology-based technique that uses microelectrodes embedded in the culture surface of each well to measure fluctuations in extracellular field potential (FP) generated from spontaneously beating hSC-CMs. Perturbations to the recorded FP waveform can be used as an unbiased method of predicting the identity of ion channel(s) impacted on drug exposure. Here, a higher throughput MEA assay using hSC-CMs in 48-well MEA plates is described for profiling compound-induced effects on cardiomyocyte electrophysiology. Techniques for preparing hSC-CM monolayers in MEA plates and methods to contextualize MEA assay experimental results are also covered. © 2016 by John Wiley & Sons, Inc.</AbstractText
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31617444
|
25310420
|
31941660
|
Focused ultrasound thalamotomy for multiple sclerosis-associated tremor.
|
Cardiovascular MR imaging at 3 T: opportunities, challenges, and solutions.
|
Optogenetic Activation of β-Endorphin Terminals in the Medial Preoptic Nucleus Regulates Female Sexual Receptivity.
|
Multiple sclerosis (MS)-related tremor is frequent and can often be refractory to medical treatment, which makes it a potential source of major disability. Functional neurosurgery approaches such as thalamic deep brain stimulation (DBS) or radiofrequency thalamotomy are proven to be effective, but the application of invasive techniques in MS tremor has so far been limited. Magnetic resonance (MR)-guided focused ultrasound thalamotomy, which has already been approved for treating essential and parkinsonian tremor, provides a minimally invasive approach that could be useful in the management of MS tremor. We report for the first time a patient with medically refractory MS-associated tremor successfully treated by focused ultrasound thalamotomy.</AbstractText
|
Although 3-T magnetic resonance (MR) imaging is well established in neuroradiology and musculoskeletal imaging, it is in the nascent stages in cardiovascular imaging applications, and there is limited literature on this topic. The primary advantage of 3 T over 1.5 T is a higher signal-to-noise ratio (SNR), which can be used as such or traded off to improve spatial or temporal resolution and decrease acquisition time. However, the actual gain in SNR is limited by other factors and modifications in sequences adapted for use at 3 T. Higher resonance frequencies result in improved spectral resolution, which is beneficial for fat suppression and spectroscopy. The higher T1 values of tissues at 3 T aid in myocardial tagging, angiography, and perfusion and delayed-enhancement sequences. However, there are substantial challenges with 3-T cardiac MR imaging, including higher magnetic field and radiofrequency inhomogeneities and susceptibility effects, which diminish image quality. Off-resonance artifacts are particularly challenging, especially with steady-state free precession sequences. These artifacts can be managed by using higher-order shimming, frequency scouts, or low repetition times. B1 inhomogeneities can be managed by using radiofrequency shimming, multitransmit coils, or adiabatic pulses. Chemical shifts are also increased at 3 T. The higher radiofrequency results in higher radiofrequency deposition power and a higher specific absorption rate. MR angiography, dynamic first-pass perfusion sequences, myocardial tagging, and MR spectroscopy are more effective at 3 T, whereas delayed-enhancement, flow quantification, and black-blood sequences are comparable at 1.5 T and 3 T. Knowledge of the relevant physics helps in identifying artifacts and modifying sequences to optimize image quality. Online supplemental material is available for this article.</AbstractText
|
Estrogen and progesterone (P4) act in neural circuits to elicit lordosis, the stereotypical female sexual receptivity behavior. Estradiol acts through membrane receptors to rapidly activate a limbic-hypothalamic circuit consisting of the arcuate (ARH), medial preoptic (MPN), and ventromedial (VMH) nuclei of the hypothalamus. This initial activation results in a transient but necessary inhibition of lordosis, which appears to be a result of the release of β-endorphin (β-End) from proopiomelanocortin (POMC) terminals onto cells containing the µ-opioid receptor (MOR) in the MPN. To functionally examine the role of the MOR in the hypothalamic lordosis circuit, we transfected a channelrhodopsin (ChR2) adeno-associated virus into POMC cell bodies in the ARH and photostimulated POMC/β-End axon terminals in the MPN in sexually receptive female Pomc-cre mice. Following estrogen and P4 priming, sexual receptivity was assessed by measuring the lordosis quotient (LQ). Following an initial trial for sexual receptivity, mice were photostimulated during behavioral testing, and brains were processed for MOR immunohistochemistry (IHC). Photostimulation decreased the LQ only in ChR2-expressing Pomc-cre mice. Furthermore, photostimulation of ChR2 in POMC/β-End axon terminals in the MPN resulted in the internalization of MOR, indicating activation of the receptor. Our results suggest that the activation of the MOR in the MPN is sufficient to attenuate lordosis behavior in a hormone-primed, sexually receptive female mouse. These data support a central role of MOR in female sexual behavior, and provide further insight into the hypothalamus control of sexual receptivity.</AbstractText
|
Focused ultrasound thalamotomy for multiple sclerosis-associated tremor. Multiple sclerosis (MS)-related tremor is frequent and can often be refractory to medical treatment, which makes it a potential source of major disability. Functional neurosurgery approaches such as thalamic deep brain stimulation (DBS) or radiofrequency thalamotomy are proven to be effective, but the application of invasive techniques in MS tremor has so far been limited. Magnetic resonance (MR)-guided focused ultrasound thalamotomy, which has already been approved for treating essential and parkinsonian tremor, provides a minimally invasive approach that could be useful in the management of MS tremor. We report for the first time a patient with medically refractory MS-associated tremor successfully treated by focused ultrasound thalamotomy.</AbstractText
|
Cardiovascular MR imaging at 3 T: opportunities, challenges, and solutions. Although 3-T magnetic resonance (MR) imaging is well established in neuroradiology and musculoskeletal imaging, it is in the nascent stages in cardiovascular imaging applications, and there is limited literature on this topic. The primary advantage of 3 T over 1.5 T is a higher signal-to-noise ratio (SNR), which can be used as such or traded off to improve spatial or temporal resolution and decrease acquisition time. However, the actual gain in SNR is limited by other factors and modifications in sequences adapted for use at 3 T. Higher resonance frequencies result in improved spectral resolution, which is beneficial for fat suppression and spectroscopy. The higher T1 values of tissues at 3 T aid in myocardial tagging, angiography, and perfusion and delayed-enhancement sequences. However, there are substantial challenges with 3-T cardiac MR imaging, including higher magnetic field and radiofrequency inhomogeneities and susceptibility effects, which diminish image quality. Off-resonance artifacts are particularly challenging, especially with steady-state free precession sequences. These artifacts can be managed by using higher-order shimming, frequency scouts, or low repetition times. B1 inhomogeneities can be managed by using radiofrequency shimming, multitransmit coils, or adiabatic pulses. Chemical shifts are also increased at 3 T. The higher radiofrequency results in higher radiofrequency deposition power and a higher specific absorption rate. MR angiography, dynamic first-pass perfusion sequences, myocardial tagging, and MR spectroscopy are more effective at 3 T, whereas delayed-enhancement, flow quantification, and black-blood sequences are comparable at 1.5 T and 3 T. Knowledge of the relevant physics helps in identifying artifacts and modifying sequences to optimize image quality. Online supplemental material is available for this article.</AbstractText
|
Optogenetic Activation of β-Endorphin Terminals in the Medial Preoptic Nucleus Regulates Female Sexual Receptivity. Estrogen and progesterone (P4) act in neural circuits to elicit lordosis, the stereotypical female sexual receptivity behavior. Estradiol acts through membrane receptors to rapidly activate a limbic-hypothalamic circuit consisting of the arcuate (ARH), medial preoptic (MPN), and ventromedial (VMH) nuclei of the hypothalamus. This initial activation results in a transient but necessary inhibition of lordosis, which appears to be a result of the release of β-endorphin (β-End) from proopiomelanocortin (POMC) terminals onto cells containing the µ-opioid receptor (MOR) in the MPN. To functionally examine the role of the MOR in the hypothalamic lordosis circuit, we transfected a channelrhodopsin (ChR2) adeno-associated virus into POMC cell bodies in the ARH and photostimulated POMC/β-End axon terminals in the MPN in sexually receptive female Pomc-cre mice. Following estrogen and P4 priming, sexual receptivity was assessed by measuring the lordosis quotient (LQ). Following an initial trial for sexual receptivity, mice were photostimulated during behavioral testing, and brains were processed for MOR immunohistochemistry (IHC). Photostimulation decreased the LQ only in ChR2-expressing Pomc-cre mice. Furthermore, photostimulation of ChR2 in POMC/β-End axon terminals in the MPN resulted in the internalization of MOR, indicating activation of the receptor. Our results suggest that the activation of the MOR in the MPN is sufficient to attenuate lordosis behavior in a hormone-primed, sexually receptive female mouse. These data support a central role of MOR in female sexual behavior, and provide further insight into the hypothalamus control of sexual receptivity.</AbstractText
|
40751218
|
26404723
|
40710493
|
Monosodium glutamate exacerbated the lipopolysaccharide-induced reproductive toxicity of male Wistar rats.
|
(31)P-MRS of healthy human brain: ATP synthesis, metabolite concentrations, pH, and T1 relaxation times.
|
Selective Antiproliferative Effects of Marine Oils on Neuroblastoma Cells in 3D Cultures.
|
Monosodium glutamate (MSG) is a common food additive that has been linked to oxidative stress and reproductive dysfunction. Lipopolysaccharide (LPS), a bacterial endotoxin, is known to induce systemic inflammation, leading to oxidative damage and hormonal disruption. This study investigated whether MSG exacerbates LPS-induced testicular toxicity in male Wistar rats via oxidative stress and endocrine dysfunction.</AbstractText Twenty-eight male Wistar rats were divided into four groups (n = 7): control (distilled water), MSG (1500 mg/kg), LPS (250 µL/kg), and a combination of MSG + LPS. MSG was used in the background of LPS to model a real-life "double-hit" exposure where dietary and microbial toxins co-exist. We hypothesised that MSG would amplify LPS-induced reproductive damage through converging mechanisms such as ROS generation, antioxidant depletion, and hormonal dysregulation.</AbstractText Compared to control, MSG and LPS significantly reduced sperm count (MSG: p = 0.0001; LPS: p = 0.0001), motility (p = 0.0001; p = 0.0001), and viability (p = 0.0001; p = 0.0001), with more pronounced effects in the MSG + LPS group (p = 0.0001). The number of abnormal sperm cells was, however, increased significantly (p = 0.0001 for MSG; p = 0.0001 for LPS; p = 0.0009 for MSG + LPS). Serum testosterone (p = 0.0001 for MSG; p = 0.0001 for LPS; p = 0.0001 for MSG + LPS), FSH (p = 0.0001, 0.0001, 0.0001), and LH (p = 0.0001, 0.0001, 0.0001) were significantly decreased. Antioxidant enzymes/parameter SOD (p = 0.0001, 0.0001, 0.0001), CAT (p = 0.0001, 0.0001, 0.0001), GST (p = 0.0001, 0.0001, 0.0001), and GSH (p = 0.0001, 0.0001, 0.0001) were depleted, while TBARS levels increased significantly (p = 0.0001, 0.0001, 0.0001). Histological analysis revealed extensive structural damage in the MSG + LPS group.</AbstractText These findings suggest that MSG potentiated LPS-induced testicular toxicity through oxidative stress and endocrine suppression, underscoring potential reproductive risks associated with combined dietary and inflammatory exposures.</AbstractText
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The conventional method for measuring brain ATP synthesis is (31)P saturation transfer (ST), a technique typically dependent on prolonged pre-saturation with γ-ATP. In this study, ATP synthesis rate in resting human brain is evaluated using EBIT (exchange kinetics by band inversion transfer), a technique based on slow recovery of γ-ATP magnetization in the absence of B1 field following co-inversion of PCr and ATP resonances with a short adiabatic pulse. The unidirectional rate constant for the Pi → γ-ATP reaction is 0.21 ± 0.04 s(-1) and the ATP synthesis rate is 9.9 ± 2.1 mmol min(-1)  kg(-1) in human brain (n = 12 subjects), consistent with the results by ST. Therefore, EBIT could be a useful alternative to ST in studying brain energy metabolism in normal physiology and under pathological conditions. In addition to ATP synthesis, all detectable (31)P signals are analyzed to determine the brain concentration of phosphorus metabolites, including UDPG at around 10 ppm, a previously reported resonance in liver tissues and now confirmed in human brain. Inversion recovery measurements indicate that UDPG, like its diphosphate analogue NAD, has apparent T1 shorter than that of monophosphates (Pi, PMEs, and PDEs) but longer than that of triphosphate ATP, highlighting the significance of the (31)P-(31)P dipolar mechanism in T1 relaxation of polyphosphates. Another interesting finding is the observation of approximately 40% shorter T1 for intracellular Pi relative to extracellular Pi, attributed to the modulation by the intracellular phosphoryl exchange reaction Pi ↔ γ-ATP. The sufficiently separated intra- and extracellular Pi signals also permit the distinction of pH between intra- and extracellular environments (pH 7.0 versus pH 7.4). In summary, quantitative (31)P MRS in combination with ATP synthesis, pH, and T1 relaxation measurements may offer a promising tool to detect biochemical alterations at early stages of brain dysfunctions and diseases.</AbstractText
|
Dietary marine lipids enriched in <i
|
Monosodium glutamate exacerbated the lipopolysaccharide-induced reproductive toxicity of male Wistar rats. Monosodium glutamate (MSG) is a common food additive that has been linked to oxidative stress and reproductive dysfunction. Lipopolysaccharide (LPS), a bacterial endotoxin, is known to induce systemic inflammation, leading to oxidative damage and hormonal disruption. This study investigated whether MSG exacerbates LPS-induced testicular toxicity in male Wistar rats via oxidative stress and endocrine dysfunction.</AbstractText Twenty-eight male Wistar rats were divided into four groups (n = 7): control (distilled water), MSG (1500 mg/kg), LPS (250 µL/kg), and a combination of MSG + LPS. MSG was used in the background of LPS to model a real-life "double-hit" exposure where dietary and microbial toxins co-exist. We hypothesised that MSG would amplify LPS-induced reproductive damage through converging mechanisms such as ROS generation, antioxidant depletion, and hormonal dysregulation.</AbstractText Compared to control, MSG and LPS significantly reduced sperm count (MSG: p = 0.0001; LPS: p = 0.0001), motility (p = 0.0001; p = 0.0001), and viability (p = 0.0001; p = 0.0001), with more pronounced effects in the MSG + LPS group (p = 0.0001). The number of abnormal sperm cells was, however, increased significantly (p = 0.0001 for MSG; p = 0.0001 for LPS; p = 0.0009 for MSG + LPS). Serum testosterone (p = 0.0001 for MSG; p = 0.0001 for LPS; p = 0.0001 for MSG + LPS), FSH (p = 0.0001, 0.0001, 0.0001), and LH (p = 0.0001, 0.0001, 0.0001) were significantly decreased. Antioxidant enzymes/parameter SOD (p = 0.0001, 0.0001, 0.0001), CAT (p = 0.0001, 0.0001, 0.0001), GST (p = 0.0001, 0.0001, 0.0001), and GSH (p = 0.0001, 0.0001, 0.0001) were depleted, while TBARS levels increased significantly (p = 0.0001, 0.0001, 0.0001). Histological analysis revealed extensive structural damage in the MSG + LPS group.</AbstractText These findings suggest that MSG potentiated LPS-induced testicular toxicity through oxidative stress and endocrine suppression, underscoring potential reproductive risks associated with combined dietary and inflammatory exposures.</AbstractText
|
(31)P-MRS of healthy human brain: ATP synthesis, metabolite concentrations, pH, and T1 relaxation times. The conventional method for measuring brain ATP synthesis is (31)P saturation transfer (ST), a technique typically dependent on prolonged pre-saturation with γ-ATP. In this study, ATP synthesis rate in resting human brain is evaluated using EBIT (exchange kinetics by band inversion transfer), a technique based on slow recovery of γ-ATP magnetization in the absence of B1 field following co-inversion of PCr and ATP resonances with a short adiabatic pulse. The unidirectional rate constant for the Pi → γ-ATP reaction is 0.21 ± 0.04 s(-1) and the ATP synthesis rate is 9.9 ± 2.1 mmol min(-1)  kg(-1) in human brain (n = 12 subjects), consistent with the results by ST. Therefore, EBIT could be a useful alternative to ST in studying brain energy metabolism in normal physiology and under pathological conditions. In addition to ATP synthesis, all detectable (31)P signals are analyzed to determine the brain concentration of phosphorus metabolites, including UDPG at around 10 ppm, a previously reported resonance in liver tissues and now confirmed in human brain. Inversion recovery measurements indicate that UDPG, like its diphosphate analogue NAD, has apparent T1 shorter than that of monophosphates (Pi, PMEs, and PDEs) but longer than that of triphosphate ATP, highlighting the significance of the (31)P-(31)P dipolar mechanism in T1 relaxation of polyphosphates. Another interesting finding is the observation of approximately 40% shorter T1 for intracellular Pi relative to extracellular Pi, attributed to the modulation by the intracellular phosphoryl exchange reaction Pi ↔ γ-ATP. The sufficiently separated intra- and extracellular Pi signals also permit the distinction of pH between intra- and extracellular environments (pH 7.0 versus pH 7.4). In summary, quantitative (31)P MRS in combination with ATP synthesis, pH, and T1 relaxation measurements may offer a promising tool to detect biochemical alterations at early stages of brain dysfunctions and diseases.</AbstractText
|
Selective Antiproliferative Effects of Marine Oils on Neuroblastoma Cells in 3D Cultures. Dietary marine lipids enriched in <i
|
30239439
|
28168521
|
30150657
|
Microstructural Alterations in the Brains of Adults With Prelingual Sensorineural Hearing Loss: a Diffusion Kurtosis Imaging Study.
|
Does apolipoprotein A1 predict microstructural changes in subgenual cingulum in early Parkinson?
|
Deciding for others as a neutral party recruits risk-neutral perspective-taking: Model-based behavioral and fMRI experiments.
|
To investigate the alterations in microstructural gray matter (GM) and white matter (WM) in adults with prelingual sensorineural hearing loss (SNHL) using diffusion kurtosis imaging (DKI) and explore whether the clinical data are associated with the whole brain structure changes in SNHL subjects.</AbstractText Prospective case study.</AbstractText Tertiary class A teaching hospital.</AbstractText Eighty adults with prelingual SNHL.</AbstractText Diagnostic.</AbstractText DKI-derived metrics, including mean kurtosis, radial kurtosis, axial kurtosis, fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity were applied to explore the differences in GM and WM between the groups across the whole brain with voxel-based analysis.</AbstractText Compared with the control group, adults with prelingual SNHL exhibited significantly decreased fractional anisotropy, mean kurtosis, radial kurtosis, and axial kurtosis in the bilateral superior temporal gyrus in both the GM and WM. No correlations were detected between these alterations and clinical data.</AbstractText These findings suggest that DKI can provide comprehensive characteristics to demonstrate reductions in the auditory cortical GM and hypomyelination of WM fibers in the auditory pathway caused by auditory deprivation early in life.</AbstractText
|
Higher plasma cholesterol levels are associated with lower Parkinson's disease (PD) risk. Apolipoprotein A-1 (ApoA-1) is a surface marker of brain HDL-like particles associated with the time of PD onset. Clinical correlates of serum Apolipoprotein A1 levels with structural brain connectivity in PD-related disorders remains unclear. Here, we applied a novel diffusion-weighted imaging approach [Diffusion Magnetic Resonance Imaging (MRI) Connectometry] to explore the association between ApoA-1 and structural brain connectivity in PD. Participants involved in this research were recruited from Parkinson's Progression Markers Initiative (PPMI). Diffusion MRI connectometry was conducted using a multiple regression against apoA-1 for 36 patients with DTI measurements available in the baseline visit. Fiber results of the connectometry were then reconstructed for each patient, and diffusion parameters were extracted and regressed against apoA-1 levels. Connectometry results revealed the subgenual cingulum to be associated with ApoA-1, with different FDR yields. This result was further supported by significant negative correlation of Quantitative Anisotropic (QA) of left subgenual cingulum (Pearson's coefficient = -0.398, p = 0.020) and Generalized Fractional Anisotropic (GFA) of right subgenual cingulum (Pearson's coefficient -0.457, p = 0.007) with plasma apoA-1 levels, in a multiple regression model with age and sex. The subgenual cingulum encompasses fibers from the anterior cingulate cortex and anterior thalamus. These structures are involved in PD-associated psychosis and executive cognitive decline. We demonstrated for the first time that apoA-1, as a blood marker, can predict microstructural changes in white matter regions in PD patients with undisturbed cognition and mild motor disability.</AbstractText
|
Risky decision making for others is ubiquitous in our societies. Whereas financial decision making for oneself induces strong concern about the worst outcome (maximin concern) as well as the expected value, behavioral and neural characteristics of decision making for others are less well understood. We conducted behavioral and functional magnetic resonance imaging (fMRI) experiments to examine the neurocognitive underpinnings of risky decisions for an anonymous other, using decisions for self as a benchmark. We show that, although the maximin concern affected both types of decisions equally strongly, decision making for others recruited a more risk-neutral computational mechanism than decision making for self. Specifically, participants exhibited more balanced information search when choosing a risky option for others. Activity of right temporoparietal junction (rTPJ, associated with cognitive perspective taking) was parametrically modulated by options' expected values in decisions for others, and by the minimum amounts in decisions for self. Furthermore, individual differences in self-reported empathic concern modified these attentional and neural processes. Overall, these results indicate that the typical maximin concern is attenuated in a risk-neutral direction in decisions for others as compared to self. We conjecture that, given others' diverse preferences, deciding as a neutral party may cognitively recruit such risk-neutrality.</AbstractText
|
Microstructural Alterations in the Brains of Adults With Prelingual Sensorineural Hearing Loss: a Diffusion Kurtosis Imaging Study. To investigate the alterations in microstructural gray matter (GM) and white matter (WM) in adults with prelingual sensorineural hearing loss (SNHL) using diffusion kurtosis imaging (DKI) and explore whether the clinical data are associated with the whole brain structure changes in SNHL subjects.</AbstractText Prospective case study.</AbstractText Tertiary class A teaching hospital.</AbstractText Eighty adults with prelingual SNHL.</AbstractText Diagnostic.</AbstractText DKI-derived metrics, including mean kurtosis, radial kurtosis, axial kurtosis, fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity were applied to explore the differences in GM and WM between the groups across the whole brain with voxel-based analysis.</AbstractText Compared with the control group, adults with prelingual SNHL exhibited significantly decreased fractional anisotropy, mean kurtosis, radial kurtosis, and axial kurtosis in the bilateral superior temporal gyrus in both the GM and WM. No correlations were detected between these alterations and clinical data.</AbstractText These findings suggest that DKI can provide comprehensive characteristics to demonstrate reductions in the auditory cortical GM and hypomyelination of WM fibers in the auditory pathway caused by auditory deprivation early in life.</AbstractText
|
Does apolipoprotein A1 predict microstructural changes in subgenual cingulum in early Parkinson? Higher plasma cholesterol levels are associated with lower Parkinson's disease (PD) risk. Apolipoprotein A-1 (ApoA-1) is a surface marker of brain HDL-like particles associated with the time of PD onset. Clinical correlates of serum Apolipoprotein A1 levels with structural brain connectivity in PD-related disorders remains unclear. Here, we applied a novel diffusion-weighted imaging approach [Diffusion Magnetic Resonance Imaging (MRI) Connectometry] to explore the association between ApoA-1 and structural brain connectivity in PD. Participants involved in this research were recruited from Parkinson's Progression Markers Initiative (PPMI). Diffusion MRI connectometry was conducted using a multiple regression against apoA-1 for 36 patients with DTI measurements available in the baseline visit. Fiber results of the connectometry were then reconstructed for each patient, and diffusion parameters were extracted and regressed against apoA-1 levels. Connectometry results revealed the subgenual cingulum to be associated with ApoA-1, with different FDR yields. This result was further supported by significant negative correlation of Quantitative Anisotropic (QA) of left subgenual cingulum (Pearson's coefficient = -0.398, p = 0.020) and Generalized Fractional Anisotropic (GFA) of right subgenual cingulum (Pearson's coefficient -0.457, p = 0.007) with plasma apoA-1 levels, in a multiple regression model with age and sex. The subgenual cingulum encompasses fibers from the anterior cingulate cortex and anterior thalamus. These structures are involved in PD-associated psychosis and executive cognitive decline. We demonstrated for the first time that apoA-1, as a blood marker, can predict microstructural changes in white matter regions in PD patients with undisturbed cognition and mild motor disability.</AbstractText
|
Deciding for others as a neutral party recruits risk-neutral perspective-taking: Model-based behavioral and fMRI experiments. Risky decision making for others is ubiquitous in our societies. Whereas financial decision making for oneself induces strong concern about the worst outcome (maximin concern) as well as the expected value, behavioral and neural characteristics of decision making for others are less well understood. We conducted behavioral and functional magnetic resonance imaging (fMRI) experiments to examine the neurocognitive underpinnings of risky decisions for an anonymous other, using decisions for self as a benchmark. We show that, although the maximin concern affected both types of decisions equally strongly, decision making for others recruited a more risk-neutral computational mechanism than decision making for self. Specifically, participants exhibited more balanced information search when choosing a risky option for others. Activity of right temporoparietal junction (rTPJ, associated with cognitive perspective taking) was parametrically modulated by options' expected values in decisions for others, and by the minimum amounts in decisions for self. Furthermore, individual differences in self-reported empathic concern modified these attentional and neural processes. Overall, these results indicate that the typical maximin concern is attenuated in a risk-neutral direction in decisions for others as compared to self. We conjecture that, given others' diverse preferences, deciding as a neutral party may cognitively recruit such risk-neutrality.</AbstractText
|
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