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Resting-State Connectivity of the Left Frontal Cortex to the Default Mode and Dorsal Attention Network Supports Reserve in Mild Cognitive Impairment.
|
Small-World Propensity and Weighted Brain Networks.
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Simultaneous Time Interleaved MultiSlice (STIMS) for Rapid Susceptibility Weighted acquisition.
|
Reserve refers to the phenomenon of relatively preserved cognition in disproportion to the extent of neuropathology, e.g., in Alzheimer's disease. A putative functional neural substrate underlying reserve is global functional connectivity of the left lateral frontal cortex (LFC, Brodmann Area 6/44). Resting-state fMRI-assessed global LFC-connectivity is associated with protective factors (education) and better maintenance of memory in mild cognitive impairment (MCI). Since the LFC is a hub of the fronto-parietal control network that regulates the activity of other networks, the question arises whether LFC-connectivity to specific networks rather than the whole-brain may underlie reserve. We assessed resting-state fMRI in 24 MCI and 16 healthy controls (HC) and in an independent validation sample (23 MCI/32 HC). Seed-based LFC-connectivity to seven major resting-state networks (i.e., fronto-parietal, limbic, dorsal-attention, somatomotor, default-mode, ventral-attention, visual) was computed, reserve was quantified as residualized memory performance after accounting for age and hippocampal atrophy. In both samples of MCI, LFC-activity was anti-correlated with the default-mode network (DMN), but positively correlated with the dorsal-attention network (DAN). Greater education predicted stronger LFC-DMN-connectivity (anti-correlation) and LFC-DAN-connectivity. Stronger LFC-DMN and LFC-DAN-connectivity each predicted higher reserve, consistently in both MCI samples. No associations were detected for LFC-connectivity to other networks. These novel results extend our previous findings on global functional connectivity of the LFC, showing that LFC-connectivity specifically to the DAN and DMN, two core memory networks, enhances reserve in the memory domain in MCI.</AbstractText
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Quantitative descriptions of network structure can provide fundamental insights into the function of interconnected complex systems. Small-world structure, diagnosed by high local clustering yet short average path length between any two nodes, promotes information flow in coupled systems, a key function that can differ across conditions or between groups. However, current techniques to quantify small-worldness are density dependent and neglect important features such as the strength of network connections, limiting their application in real-world systems. Here, we address both limitations with a novel metric called the Small-World Propensity (SWP). In its binary instantiation, the SWP provides an unbiased assessment of small-world structure in networks of varying densities. We extend this concept to the case of weighted brain networks by developing (i) a standardized procedure for generating weighted small-world networks, (ii) a weighted extension of the SWP, and (iii) a method for mapping observed brain network data onto the theoretical model. In applying these techniques to compare real-world brain networks, we uncover the surprising fact that the canonical biological small-world network, the C. elegans neuronal network, has strikingly low SWP. These metrics, models, and maps form a coherent toolbox for the assessment and comparison of architectural properties in brain networks.</AbstractText
|
T<sub
|
Resting-State Connectivity of the Left Frontal Cortex to the Default Mode and Dorsal Attention Network Supports Reserve in Mild Cognitive Impairment. Reserve refers to the phenomenon of relatively preserved cognition in disproportion to the extent of neuropathology, e.g., in Alzheimer's disease. A putative functional neural substrate underlying reserve is global functional connectivity of the left lateral frontal cortex (LFC, Brodmann Area 6/44). Resting-state fMRI-assessed global LFC-connectivity is associated with protective factors (education) and better maintenance of memory in mild cognitive impairment (MCI). Since the LFC is a hub of the fronto-parietal control network that regulates the activity of other networks, the question arises whether LFC-connectivity to specific networks rather than the whole-brain may underlie reserve. We assessed resting-state fMRI in 24 MCI and 16 healthy controls (HC) and in an independent validation sample (23 MCI/32 HC). Seed-based LFC-connectivity to seven major resting-state networks (i.e., fronto-parietal, limbic, dorsal-attention, somatomotor, default-mode, ventral-attention, visual) was computed, reserve was quantified as residualized memory performance after accounting for age and hippocampal atrophy. In both samples of MCI, LFC-activity was anti-correlated with the default-mode network (DMN), but positively correlated with the dorsal-attention network (DAN). Greater education predicted stronger LFC-DMN-connectivity (anti-correlation) and LFC-DAN-connectivity. Stronger LFC-DMN and LFC-DAN-connectivity each predicted higher reserve, consistently in both MCI samples. No associations were detected for LFC-connectivity to other networks. These novel results extend our previous findings on global functional connectivity of the LFC, showing that LFC-connectivity specifically to the DAN and DMN, two core memory networks, enhances reserve in the memory domain in MCI.</AbstractText
|
Small-World Propensity and Weighted Brain Networks. Quantitative descriptions of network structure can provide fundamental insights into the function of interconnected complex systems. Small-world structure, diagnosed by high local clustering yet short average path length between any two nodes, promotes information flow in coupled systems, a key function that can differ across conditions or between groups. However, current techniques to quantify small-worldness are density dependent and neglect important features such as the strength of network connections, limiting their application in real-world systems. Here, we address both limitations with a novel metric called the Small-World Propensity (SWP). In its binary instantiation, the SWP provides an unbiased assessment of small-world structure in networks of varying densities. We extend this concept to the case of weighted brain networks by developing (i) a standardized procedure for generating weighted small-world networks, (ii) a weighted extension of the SWP, and (iii) a method for mapping observed brain network data onto the theoretical model. In applying these techniques to compare real-world brain networks, we uncover the surprising fact that the canonical biological small-world network, the C. elegans neuronal network, has strikingly low SWP. These metrics, models, and maps form a coherent toolbox for the assessment and comparison of architectural properties in brain networks.</AbstractText
|
Simultaneous Time Interleaved MultiSlice (STIMS) for Rapid Susceptibility Weighted acquisition. T<sub
|
35754143
|
30629330
|
35836410
|
Accelerated dual-venc 4D flow MRI with variable high-venc spatial resolution for neurovascular applications.
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Accuracy of Intraoperative Computed Tomography in Deep Brain Stimulation-A Prospective Noninferiority Study.
|
Design considerations for a cycloidal mass analyzer using a focal plane array detector.
|
Dual-velocity encoded (dual-venc or DV) 4D flow MRI achieves wide velocity dynamic range and velocity-to-noise ratio (VNR), enabling accurate neurovascular flow characterization. To reduce scan time, we present interleaved dual-venc 4D Flow with independently prescribed, prospectively undersampled spatial resolution of the high-venc (HV) acquisition: Variable Spatial Resolution Dual Venc (VSRDV).</AbstractText A prototype VSRDV sequence was developed based on a Cartesian acquisition with eight-point phase encoding, combining PEAK-GRAPPA acceleration with zero-filling in phase and partition directions for HV. The VSRDV approach was optimized by varying z, the zero-filling fraction of HV relative to low-venc, between 0%-80% in vitro (realistic neurovascular model with pulsatile flow) and in vivo (n = 10 volunteers). Antialiasing precision, mean and peak velocity quantification accuracy, and test-retest reproducibility were assessed relative to reference images with equal-resolution HV and low venc (z = 0%).</AbstractText In vitro results for all z demonstrated an antialiasing true positive rate at least 95% for <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" VSRDV allows up to 34.8% scan time reduction compared to PEAK-GRAPPA accelerated DV 4D Flow MRI, enabling large spatial coverage and dynamic range while maintaining VNR and velocity measurement accuracy.</AbstractText
|
Clinical response to deep brain stimulation (DBS) strongly depends on the appropriate placement of the electrode in the targeted structure. Postoperative MRI is recognized as the gold standard to verify the DBS-electrode position in relation to the intended anatomical target. However, intraoperative computed tomography (iCT) might be a feasible alternative to MRI.</AbstractText In this prospective noninferiority study, we compared iCT with postoperative MRI (24-72 hours after surgery) in 29 consecutive patients undergoing placement of 58 DBS electrodes. The primary outcome was defined as the difference in Euclidean distance between lead tip coordinates as determined on both imaging modalities, using the lead tip depicted on MRI as reference. Secondary outcomes were difference in radial error and depth, as well as difference in accuracy relative to target.</AbstractText The mean difference between the lead tips was 0.98 ± 0.49 mm (0.97 ± 0.47 mm for the left-sided electrodes and 1.00 ± 0.53 mm for the right-sided electrodes). The upper confidence interval (95% CI, 0.851 to 1.112) did not exceed the noninferiority margin established. The average radial error between lead tips was 0.74 ± 0.48 mm and the average depth error was determined to be 0.53 ± 0.40 mm. The linear Deming regression indicated a good agreement between both imaging modalities regarding accuracy relative to target.</AbstractText Intraoperative CT is noninferior to MRI for the verification of the DBS-electrode position. CT and MRI have their specific benefits, but both should be considered equally suitable for assessing accuracy.</AbstractText
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With the advent of technologies such as ion array detectors and high energy permanent magnet materials, there is renewed interest in the unique focusing properties of the cycloidal mass analyzer and its ability to enable small, high-resolution, and high-sensitivity instruments. However, most literature dealing with the design of cycloidal mass analyzers assumes a single channel detector because at the time of those publications, compatible multichannel detectors were not available. This manuscript introduces and discusses considerations and a procedure for designing cycloidal mass analyzers coupled with focal plane ion array detectors. To arrive at a set of relevant design considerations, we first review the unique focusing properties of the cycloidal mass analyzer and then present calculations detailing how the dimensions and position of the focal plane array detector relative to the ion source determine the possible mass ranges and resolutions of a cycloidal mass analyzer. We present derivations and calculations used to determine the volume of homogeneous electric and magnetic fields needed to contain the ion trajectories and explore the relationship between electric and magnetic field homogeneity on resolving power using finite element analysis (FEA) simulations. A set of equations relating the electric field homogeneity to the geometry of the electric sector electrodes was developed by fitting homogeneity values from 78 different FEA models. Finally, a sequence of steps is suggested for designing a cycloidal mass analyzer employing an array detector.</AbstractText
|
Accelerated dual-venc 4D flow MRI with variable high-venc spatial resolution for neurovascular applications. Dual-velocity encoded (dual-venc or DV) 4D flow MRI achieves wide velocity dynamic range and velocity-to-noise ratio (VNR), enabling accurate neurovascular flow characterization. To reduce scan time, we present interleaved dual-venc 4D Flow with independently prescribed, prospectively undersampled spatial resolution of the high-venc (HV) acquisition: Variable Spatial Resolution Dual Venc (VSRDV).</AbstractText A prototype VSRDV sequence was developed based on a Cartesian acquisition with eight-point phase encoding, combining PEAK-GRAPPA acceleration with zero-filling in phase and partition directions for HV. The VSRDV approach was optimized by varying z, the zero-filling fraction of HV relative to low-venc, between 0%-80% in vitro (realistic neurovascular model with pulsatile flow) and in vivo (n = 10 volunteers). Antialiasing precision, mean and peak velocity quantification accuracy, and test-retest reproducibility were assessed relative to reference images with equal-resolution HV and low venc (z = 0%).</AbstractText In vitro results for all z demonstrated an antialiasing true positive rate at least 95% for <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" VSRDV allows up to 34.8% scan time reduction compared to PEAK-GRAPPA accelerated DV 4D Flow MRI, enabling large spatial coverage and dynamic range while maintaining VNR and velocity measurement accuracy.</AbstractText
|
Accuracy of Intraoperative Computed Tomography in Deep Brain Stimulation-A Prospective Noninferiority Study. Clinical response to deep brain stimulation (DBS) strongly depends on the appropriate placement of the electrode in the targeted structure. Postoperative MRI is recognized as the gold standard to verify the DBS-electrode position in relation to the intended anatomical target. However, intraoperative computed tomography (iCT) might be a feasible alternative to MRI.</AbstractText In this prospective noninferiority study, we compared iCT with postoperative MRI (24-72 hours after surgery) in 29 consecutive patients undergoing placement of 58 DBS electrodes. The primary outcome was defined as the difference in Euclidean distance between lead tip coordinates as determined on both imaging modalities, using the lead tip depicted on MRI as reference. Secondary outcomes were difference in radial error and depth, as well as difference in accuracy relative to target.</AbstractText The mean difference between the lead tips was 0.98 ± 0.49 mm (0.97 ± 0.47 mm for the left-sided electrodes and 1.00 ± 0.53 mm for the right-sided electrodes). The upper confidence interval (95% CI, 0.851 to 1.112) did not exceed the noninferiority margin established. The average radial error between lead tips was 0.74 ± 0.48 mm and the average depth error was determined to be 0.53 ± 0.40 mm. The linear Deming regression indicated a good agreement between both imaging modalities regarding accuracy relative to target.</AbstractText Intraoperative CT is noninferior to MRI for the verification of the DBS-electrode position. CT and MRI have their specific benefits, but both should be considered equally suitable for assessing accuracy.</AbstractText
|
Design considerations for a cycloidal mass analyzer using a focal plane array detector. With the advent of technologies such as ion array detectors and high energy permanent magnet materials, there is renewed interest in the unique focusing properties of the cycloidal mass analyzer and its ability to enable small, high-resolution, and high-sensitivity instruments. However, most literature dealing with the design of cycloidal mass analyzers assumes a single channel detector because at the time of those publications, compatible multichannel detectors were not available. This manuscript introduces and discusses considerations and a procedure for designing cycloidal mass analyzers coupled with focal plane ion array detectors. To arrive at a set of relevant design considerations, we first review the unique focusing properties of the cycloidal mass analyzer and then present calculations detailing how the dimensions and position of the focal plane array detector relative to the ion source determine the possible mass ranges and resolutions of a cycloidal mass analyzer. We present derivations and calculations used to determine the volume of homogeneous electric and magnetic fields needed to contain the ion trajectories and explore the relationship between electric and magnetic field homogeneity on resolving power using finite element analysis (FEA) simulations. A set of equations relating the electric field homogeneity to the geometry of the electric sector electrodes was developed by fitting homogeneity values from 78 different FEA models. Finally, a sequence of steps is suggested for designing a cycloidal mass analyzer employing an array detector.</AbstractText
|
16795082
|
15065254
|
35081261
|
MR assessment of changes of tumor in response to hyperbaric oxygen treatment.
|
Cardiac SSFP imaging at 3 Tesla.
|
Jointly estimating parametric maps of multiple diffusion models from undersampled q-space data: A comparison of three deep learning approaches.
|
Enhancement of image intensity, using the T1-weighted spoiled gradient-echo (SPGR) sequence, was measured in SCC tumor implanted in the flank of C3H mice while they were subjected to several types of oxygenation challenges inside a hyperbaric chamber designed and constructed to fit in an MRI resonator. The central portions of the tumor gave a positive enhancement, while the periphery showed signal reduction during both normobaric (NBO) and hyperbaric (HBO) oxygen challenges. In the contralateral normal leg, nearly 70% of the region showed a decrease in intensity, and the rest showed a positive enhancement. The positive signal enhancement was markedly greater under HBO compared to NBO. Calculated R1, R2, and M0 maps from multivariate fitting of images acquired by a multislice multiecho (MSME) sequence with variable TR before, during, and after HBO treatment confirm that the source of SPGR signal enhancement in the tumor is associated with shortening of T1.</AbstractText
|
Balanced steady-state free precession (SSFP) techniques provide excellent contrast between myocardium and blood at a high signal-to-noise ratio (SNR). Hence, SSFP imaging has become the method of choice for assessing cardiac function at 1.5T. The expected improvement in SNR at higher field strength prompted us to implement SSFP at 3.0T. In this work, an optimized sequence protocol for cardiac SSFP imaging at 3.0T is derived, taking into account several partly adverse effects at higher field, such as increased field inhomogeneities, longer T(1), and power deposition limitations. SSFP contrast is established by optimizing the maximum amplitude of the radiofrequency (RF) field strength for shortest TR, as well as by localized linear or second-order shimming and local optimization of the resonance frequency. Given the increased SNR, sensitivity encoding (SENSE) can be employed to shorten breath-hold times. Short-axis, long-axis, and four-chamber cine views obtained in healthy adult subjects are presented, and three different types of artifacts are discussed along with potential methods for reducing them.</AbstractText
|
While advanced diffusion techniques have been found valuable in many studies, their clinical availability has been hampered partly due to their long scan times. Moreover, each diffusion technique can only extract a few relevant microstructural features. Using multiple diffusion methods may help to better understand the brain microstructure, which requires multiple expensive model fittings. In this work, we compare deep learning (DL) approaches to jointly estimate parametric maps of multiple diffusion representations/models from highly undersampled q-space data.</AbstractText We implement three DL approaches to jointly estimate parametric maps of diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI), and multi-compartment spherical mean technique (SMT). A per-voxel q-space deep learning (1D-qDL), a per-slice convolutional neural network (2D-CNN), and a 3D-patch-based microstructure estimation with sparse coding using a separable dictionary (MESC-SD) network are considered.</AbstractText The accuracy of estimated diffusion maps depends on the q-space undersampling, the selected network architecture, and the region and the parameter of interest. The smallest errors are observed for the MESC-SD network architecture (less than 10 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" Our experiments show that DL methods are very efficient tools to simultaneously estimate several diffusion maps from undersampled q-space data. These methods can significantly reduce both the scan ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"
|
MR assessment of changes of tumor in response to hyperbaric oxygen treatment. Enhancement of image intensity, using the T1-weighted spoiled gradient-echo (SPGR) sequence, was measured in SCC tumor implanted in the flank of C3H mice while they were subjected to several types of oxygenation challenges inside a hyperbaric chamber designed and constructed to fit in an MRI resonator. The central portions of the tumor gave a positive enhancement, while the periphery showed signal reduction during both normobaric (NBO) and hyperbaric (HBO) oxygen challenges. In the contralateral normal leg, nearly 70% of the region showed a decrease in intensity, and the rest showed a positive enhancement. The positive signal enhancement was markedly greater under HBO compared to NBO. Calculated R1, R2, and M0 maps from multivariate fitting of images acquired by a multislice multiecho (MSME) sequence with variable TR before, during, and after HBO treatment confirm that the source of SPGR signal enhancement in the tumor is associated with shortening of T1.</AbstractText
|
Cardiac SSFP imaging at 3 Tesla. Balanced steady-state free precession (SSFP) techniques provide excellent contrast between myocardium and blood at a high signal-to-noise ratio (SNR). Hence, SSFP imaging has become the method of choice for assessing cardiac function at 1.5T. The expected improvement in SNR at higher field strength prompted us to implement SSFP at 3.0T. In this work, an optimized sequence protocol for cardiac SSFP imaging at 3.0T is derived, taking into account several partly adverse effects at higher field, such as increased field inhomogeneities, longer T(1), and power deposition limitations. SSFP contrast is established by optimizing the maximum amplitude of the radiofrequency (RF) field strength for shortest TR, as well as by localized linear or second-order shimming and local optimization of the resonance frequency. Given the increased SNR, sensitivity encoding (SENSE) can be employed to shorten breath-hold times. Short-axis, long-axis, and four-chamber cine views obtained in healthy adult subjects are presented, and three different types of artifacts are discussed along with potential methods for reducing them.</AbstractText
|
Jointly estimating parametric maps of multiple diffusion models from undersampled q-space data: A comparison of three deep learning approaches. While advanced diffusion techniques have been found valuable in many studies, their clinical availability has been hampered partly due to their long scan times. Moreover, each diffusion technique can only extract a few relevant microstructural features. Using multiple diffusion methods may help to better understand the brain microstructure, which requires multiple expensive model fittings. In this work, we compare deep learning (DL) approaches to jointly estimate parametric maps of multiple diffusion representations/models from highly undersampled q-space data.</AbstractText We implement three DL approaches to jointly estimate parametric maps of diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI), and multi-compartment spherical mean technique (SMT). A per-voxel q-space deep learning (1D-qDL), a per-slice convolutional neural network (2D-CNN), and a 3D-patch-based microstructure estimation with sparse coding using a separable dictionary (MESC-SD) network are considered.</AbstractText The accuracy of estimated diffusion maps depends on the q-space undersampling, the selected network architecture, and the region and the parameter of interest. The smallest errors are observed for the MESC-SD network architecture (less than 10 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" Our experiments show that DL methods are very efficient tools to simultaneously estimate several diffusion maps from undersampled q-space data. These methods can significantly reduce both the scan ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"
|
18672433
|
18562782
|
17458873
|
Respiratory motion correction in 3-D PET data with advanced optical flow algorithms.
|
Evaluation of the combined effects of target size, respiratory motion and background activity on 3D and 4D PET/CT images.
|
Cognitive outcome in pediatric brain tumor survivors: delayed attention deficit at long-term follow-up.
|
The problem of motion is well known in positron emission tomography (PET) studies. The PET images are formed over an elongated period of time. As the patients cannot hold breath during the PET acquisition, spatial blurring and motion artifacts are the natural result. These may lead to wrong quantification of the radioactive uptake. We present a solution to this problem by respiratory-gating the PET data and correcting the PET images for motion with optical flow algorithms. The algorithm is based on the combined local and global optical flow algorithm with modifications to allow for discontinuity preservation across organ boundaries and for application to 3-D volume sets. The superiority of the algorithm over previous work is demonstrated on software phantom and real patient data.</AbstractText
|
Gated (4D) PET/CT has the potential to greatly improve the accuracy of radiotherapy at treatment sites where internal organ motion is significant. However, the best methodology for applying 4D-PET/CT to target definition is not currently well established. With the goal of better understanding how to best apply 4D information to radiotherapy, initial studies were performed to investigate the effect of target size, respiratory motion and target-to-background activity concentration ratio (TBR) on 3D (ungated) and 4D PET images. Using a PET/CT scanner with 4D or gating capability, a full 3D-PET scan corrected with a 3D attenuation map from 3D-CT scan and a respiratory gated (4D) PET scan corrected with corresponding attenuation maps from 4D-CT were performed by imaging spherical targets (0.5-26.5 mL) filled with (18)F-FDG in a dynamic thorax phantom and NEMA IEC body phantom at different TBRs (infinite, 8 and 4). To simulate respiratory motion, the phantoms were driven sinusoidally in the superior-inferior direction with amplitudes of 0, 1 and 2 cm and a period of 4.5 s. Recovery coefficients were determined on PET images. In addition, gating methods using different numbers of gating bins (1-20 bins) were evaluated with image noise and temporal resolution. For evaluation, volume recovery coefficient, signal-to-noise ratio and contrast-to-noise ratio were calculated as a function of the number of gating bins. Moreover, the optimum thresholds which give accurate moving target volumes were obtained for 3D and 4D images. The partial volume effect and signal loss in the 3D-PET images due to the limited PET resolution and the respiratory motion, respectively were measured. The results show that signal loss depends on both the amplitude and pattern of respiratory motion. However, the 4D-PET successfully recovers most of the loss induced by the respiratory motion. The 5-bin gating method gives the best temporal resolution with acceptable image noise. The results based on the 4D scan protocols can be used to improve the accuracy of determining the gross tumor volume for tumors in the lung and abdomen.</AbstractText
|
Treatment of childhood brain tumors has often been associated with long-term cognitive morbidity in children. Our previous research identified age at diagnosis, polytherapy and brain radiation dose as treatment factors affecting neuropsychological outcome most strongly in children with cancer 1. Our current goal was to measure the change across different cognitive functions.</AbstractText This study examined the cognitive outcome over repeat testing in a heterogeneous sample of 18 children with brain tumors. Tumor types included medulloblastoma and glioma. ANOVA's for repeated measures were used to evaluate the changes in cognitive domains across follow-up evaluations.</AbstractText Consistent with previous findings, the most deleterious effects were seen on IQ indices of non verbal cognitive ability, visual perceptual skills and information processing speed. Analyses reveal that the attentional factor, Freedom from Distractibility, is the only IQ index that declines over subsequent testing. The statistical decline was attributable to a significant decline on the arithmetic subtest, as well as a non-significant trend for the auditory attention span subtest.</AbstractText This study reveals that while most indices remained stable over repeat testing, auditory attention and concentration skills decline. Long-term outcome is discussed in light of the high prevalence of attention and mathematic difficulties reported in these children and the need for preventive and remedial approaches.</AbstractText
|
Respiratory motion correction in 3-D PET data with advanced optical flow algorithms. The problem of motion is well known in positron emission tomography (PET) studies. The PET images are formed over an elongated period of time. As the patients cannot hold breath during the PET acquisition, spatial blurring and motion artifacts are the natural result. These may lead to wrong quantification of the radioactive uptake. We present a solution to this problem by respiratory-gating the PET data and correcting the PET images for motion with optical flow algorithms. The algorithm is based on the combined local and global optical flow algorithm with modifications to allow for discontinuity preservation across organ boundaries and for application to 3-D volume sets. The superiority of the algorithm over previous work is demonstrated on software phantom and real patient data.</AbstractText
|
Evaluation of the combined effects of target size, respiratory motion and background activity on 3D and 4D PET/CT images. Gated (4D) PET/CT has the potential to greatly improve the accuracy of radiotherapy at treatment sites where internal organ motion is significant. However, the best methodology for applying 4D-PET/CT to target definition is not currently well established. With the goal of better understanding how to best apply 4D information to radiotherapy, initial studies were performed to investigate the effect of target size, respiratory motion and target-to-background activity concentration ratio (TBR) on 3D (ungated) and 4D PET images. Using a PET/CT scanner with 4D or gating capability, a full 3D-PET scan corrected with a 3D attenuation map from 3D-CT scan and a respiratory gated (4D) PET scan corrected with corresponding attenuation maps from 4D-CT were performed by imaging spherical targets (0.5-26.5 mL) filled with (18)F-FDG in a dynamic thorax phantom and NEMA IEC body phantom at different TBRs (infinite, 8 and 4). To simulate respiratory motion, the phantoms were driven sinusoidally in the superior-inferior direction with amplitudes of 0, 1 and 2 cm and a period of 4.5 s. Recovery coefficients were determined on PET images. In addition, gating methods using different numbers of gating bins (1-20 bins) were evaluated with image noise and temporal resolution. For evaluation, volume recovery coefficient, signal-to-noise ratio and contrast-to-noise ratio were calculated as a function of the number of gating bins. Moreover, the optimum thresholds which give accurate moving target volumes were obtained for 3D and 4D images. The partial volume effect and signal loss in the 3D-PET images due to the limited PET resolution and the respiratory motion, respectively were measured. The results show that signal loss depends on both the amplitude and pattern of respiratory motion. However, the 4D-PET successfully recovers most of the loss induced by the respiratory motion. The 5-bin gating method gives the best temporal resolution with acceptable image noise. The results based on the 4D scan protocols can be used to improve the accuracy of determining the gross tumor volume for tumors in the lung and abdomen.</AbstractText
|
Cognitive outcome in pediatric brain tumor survivors: delayed attention deficit at long-term follow-up. Treatment of childhood brain tumors has often been associated with long-term cognitive morbidity in children. Our previous research identified age at diagnosis, polytherapy and brain radiation dose as treatment factors affecting neuropsychological outcome most strongly in children with cancer 1. Our current goal was to measure the change across different cognitive functions.</AbstractText This study examined the cognitive outcome over repeat testing in a heterogeneous sample of 18 children with brain tumors. Tumor types included medulloblastoma and glioma. ANOVA's for repeated measures were used to evaluate the changes in cognitive domains across follow-up evaluations.</AbstractText Consistent with previous findings, the most deleterious effects were seen on IQ indices of non verbal cognitive ability, visual perceptual skills and information processing speed. Analyses reveal that the attentional factor, Freedom from Distractibility, is the only IQ index that declines over subsequent testing. The statistical decline was attributable to a significant decline on the arithmetic subtest, as well as a non-significant trend for the auditory attention span subtest.</AbstractText This study reveals that while most indices remained stable over repeat testing, auditory attention and concentration skills decline. Long-term outcome is discussed in light of the high prevalence of attention and mathematic difficulties reported in these children and the need for preventive and remedial approaches.</AbstractText
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36490313
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22190576
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38027814
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Synthesis and Characterization of a Biocompatible Nanoplatform Based on Silica-Embedded SPIONs Functionalized with Polydopamine.
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Cellular MRI as a suitable, sensitive non-invasive modality for correlating in vivo migratory efficiencies of different dendritic cell populations with subsequent immunological outcomes.
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The relationship between cognitive reserve focused on leisure experiences and cognitive functions in bipolar patients.
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Superparamagnetic iron oxide nanoparticles (SPIONs) have gained increasing interest in nanomedicine, but most of those that have entered the clinical trials have been withdrawn due to toxicity concerns. Therefore, there is an urgent need to design low-risk and biocompatible SPION formulations. In this work, we present an original safe-by-design nanoplatform made of silica nanoparticles loaded with SPIONs and decorated with polydopamine (SPIONs@SiO2-PDA) and the study of its biocompatibility performance by an ad hoc thorough in vitro to in vivo nanotoxicological methodology. The results indicate that the SPIONs@SiO<sub
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The clinical application of dendritic cells (DC) as adjuvants in immunotherapies such as the cell-based cancer vaccine continues to gain interest. The overall efficacy of this emerging immunotherapy, however, remains low. Studies suggest the stage of maturation and activation of ex vivo-prepared DC immediately prior to patient administration is critical to subsequent DC migration in vivo, which ultimately affects overall vaccine efficacy. While it is possible to generate mature and activated DC ex vivo using various stimulatory cocktails, in the case of cancer patients, the qualitative and quantitative assessment of which DC stimulatory cocktail works most effectively to enhance subsequent DC migration in vivo is difficult. Thus, a non-invasive imaging modality capable of monitoring the real-time migration of DC in long-term studies is required. In this paper, we address whether cellular magnetic resonance imaging (MRI) is sufficiently sensitive to quantitatively detect differences in the migratory abilities of two different DC preparations: untreated (resting) versus ex vivo matured in a mouse model. In order to distinguish our ex vivo-generated DC of interest from surrounding tissues in magnetic resonance (MR) images, DC were labeled in vitro with the superparamagnetic iron oxide (SPIO) nanoparticle FeREX®. Characterization of DC phenotype and function following addition of a cytokine maturation cocktail and the toll-like receptor ligand CpG, both in the presence and in the absence of SPIO, were also carried out. Conventional histological techniques were used to verify the quantitative data obtained from MR images. This study provides important information relevant to tracking the in vivo migration of ex vivo-prepared and stimulated DC.</AbstractText
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Bipolar disorder (BP) is characterized by cognitive decline. Individual differences exist in maintaining cognitive function due to daily physical activity and sleep. We examined the relationship between leisure experiences as proxies for cognitive reserve (CR) and cognitive function in patients with bipolar disorder after adjusting for daily physical activity and sleep. The CR of patients with BP (n = 24) and healthy study controls (HC) (n = 24) was assessed using premorbid IQ, years of education, and leisure activity history. Performance-based neuropsychological tests were performed to evaluate cognitive function. A self-reported scale was used to assess resilience. Physical activity and sleep were measured using an activity meter. Verbal fluency, story memory, and verbal memory were significantly positively correlated with the kinds of leisure experiences in patients with BP. A hierarchical regression analysis accounting for confounding factors showed that verbal fluency and memory were associated with the kinds of leisure experiences. Neither years of education nor resilience were significantly associated with neuropsychological scores. Various leisure experiences in patients with BP are associated with higher language-related cognitive functioning. Engaging in various leisure experiences may affect higher cognitive functions related to language.</AbstractText
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Synthesis and Characterization of a Biocompatible Nanoplatform Based on Silica-Embedded SPIONs Functionalized with Polydopamine. Superparamagnetic iron oxide nanoparticles (SPIONs) have gained increasing interest in nanomedicine, but most of those that have entered the clinical trials have been withdrawn due to toxicity concerns. Therefore, there is an urgent need to design low-risk and biocompatible SPION formulations. In this work, we present an original safe-by-design nanoplatform made of silica nanoparticles loaded with SPIONs and decorated with polydopamine (SPIONs@SiO2-PDA) and the study of its biocompatibility performance by an ad hoc thorough in vitro to in vivo nanotoxicological methodology. The results indicate that the SPIONs@SiO<sub
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Cellular MRI as a suitable, sensitive non-invasive modality for correlating in vivo migratory efficiencies of different dendritic cell populations with subsequent immunological outcomes. The clinical application of dendritic cells (DC) as adjuvants in immunotherapies such as the cell-based cancer vaccine continues to gain interest. The overall efficacy of this emerging immunotherapy, however, remains low. Studies suggest the stage of maturation and activation of ex vivo-prepared DC immediately prior to patient administration is critical to subsequent DC migration in vivo, which ultimately affects overall vaccine efficacy. While it is possible to generate mature and activated DC ex vivo using various stimulatory cocktails, in the case of cancer patients, the qualitative and quantitative assessment of which DC stimulatory cocktail works most effectively to enhance subsequent DC migration in vivo is difficult. Thus, a non-invasive imaging modality capable of monitoring the real-time migration of DC in long-term studies is required. In this paper, we address whether cellular magnetic resonance imaging (MRI) is sufficiently sensitive to quantitatively detect differences in the migratory abilities of two different DC preparations: untreated (resting) versus ex vivo matured in a mouse model. In order to distinguish our ex vivo-generated DC of interest from surrounding tissues in magnetic resonance (MR) images, DC were labeled in vitro with the superparamagnetic iron oxide (SPIO) nanoparticle FeREX®. Characterization of DC phenotype and function following addition of a cytokine maturation cocktail and the toll-like receptor ligand CpG, both in the presence and in the absence of SPIO, were also carried out. Conventional histological techniques were used to verify the quantitative data obtained from MR images. This study provides important information relevant to tracking the in vivo migration of ex vivo-prepared and stimulated DC.</AbstractText
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The relationship between cognitive reserve focused on leisure experiences and cognitive functions in bipolar patients. Bipolar disorder (BP) is characterized by cognitive decline. Individual differences exist in maintaining cognitive function due to daily physical activity and sleep. We examined the relationship between leisure experiences as proxies for cognitive reserve (CR) and cognitive function in patients with bipolar disorder after adjusting for daily physical activity and sleep. The CR of patients with BP (n = 24) and healthy study controls (HC) (n = 24) was assessed using premorbid IQ, years of education, and leisure activity history. Performance-based neuropsychological tests were performed to evaluate cognitive function. A self-reported scale was used to assess resilience. Physical activity and sleep were measured using an activity meter. Verbal fluency, story memory, and verbal memory were significantly positively correlated with the kinds of leisure experiences in patients with BP. A hierarchical regression analysis accounting for confounding factors showed that verbal fluency and memory were associated with the kinds of leisure experiences. Neither years of education nor resilience were significantly associated with neuropsychological scores. Various leisure experiences in patients with BP are associated with higher language-related cognitive functioning. Engaging in various leisure experiences may affect higher cognitive functions related to language.</AbstractText
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40407177
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34591275
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40155565
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Structure, Mechanics, and Mechanobiology of Fibrocartilage Pericellular Matrix Mediated by Type V Collagen.
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A 1D-3D Hybrid Model of Patient-Specific Coronary Hemodynamics.
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Age-related differences in the relationship between sustained attention and associative memory and Memory-Guided inference.
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The pericellular matrix (PCM) is the immediate microniche surrounding cells in various tissues, regulating matrix turnover, cell-matrix interactions, and disease. This study elucidates the structure-mechanical properties and mechanobiology of the PCM in fibrocartilage, using the murine meniscus as the model. The fibrocartilage PCM is comprised of thin, randomly oriented collagen fibrils that entrap proteoglycans, contrasting with the densely packed, highly aligned collagen fibers in the bulk extracellular matrix (ECM). Compared to the ECM, the PCM exhibits lower modulus and greater isotropy, but has similar relative viscoelastic properties. In Col5a1<sup
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Coronary flow is affected by evolving events such as atherosclerotic plaque formation, rupture, and thrombosis, resulting in myocardial ischemia and infarction. Highly resolved 3D hemodynamic data at the stenosis is essential to model shear-sensitive thrombotic events in coronary artery disease.</AbstractText We developed a hybrid 1D-3D simulation framework to compute patient-specific coronary hemodynamics efficiently. A 1D model of the coronary flow is coupled to an image-based 3D model of the region of interest. This framework affords the advantages of reduced-order modeling, decreasing the global computational cost, without sacrificing the accuracy of the quantities of interest.</AbstractText We validated our 1D-3D model against full 3D coronary simulations in healthy and diseased conditions. Our results showed good agreement between the 3D and the 1D-3D models while reducing the computational cost by 40-fold compared to the 3D simulation. The 1D-3D model predicted left/right coronary flow distribution within 3% and provided an accurate estimation of fractional flow reserve and wall shear stress distribution at the stenosis comparable to the 3D simulation.</AbstractText Savings in computational cost may be significant in situations with changing geometry, such as growing thrombosis. Also, this approach would allow quantifying the time-dependent effect of thrombotic growth and occlusion on the global coronary circulation.</AbstractText
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Episodic memory enables the encoding and retrieval of novel associations, as well as the bridging across learned associations to draw novel inferences. A fundamental goal of memory science is to understand the factors that give rise to individual and age-related differences in memory-dependent cognition. Variability in episodic memory could arise, in part, from both individual differences in sustained attention and diminished attention in aging. We first report that, relative to young adults (N = 23; M = 20.0 years), older adults (N = 26, M = 68.7 years) demonstrated lower associative memory and memory-guided associative inference performance and that this age-related reduction in associative inference occurs even when controlling for associative memory performance. Next, we confirm these age-related memory differences by using a high-powered, online replication study (young adults: N = 143, M = 26.2 years; older adults N = 133, M = 67.7 years), further demonstrating that age-related differences in memory do not reflect group differences in sustained attention (as assayed by the gradual-onset continuous performance task; gradCPT). Finally, we report that individual differences in sustained attention explain between-person variability in associative memory and inference performance in the present, online young adult sample, but not in the older adult sample. These findings extend understanding of the links between attention and memory in young adults, demonstrating that differences in sustained attention was related to differences in memory-guided inference. By contrast, our data suggest that the present age-related differences in memory-dependent behavior and the memory differences between older adults are due to attention-independent mechanisms.</AbstractText
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Structure, Mechanics, and Mechanobiology of Fibrocartilage Pericellular Matrix Mediated by Type V Collagen. The pericellular matrix (PCM) is the immediate microniche surrounding cells in various tissues, regulating matrix turnover, cell-matrix interactions, and disease. This study elucidates the structure-mechanical properties and mechanobiology of the PCM in fibrocartilage, using the murine meniscus as the model. The fibrocartilage PCM is comprised of thin, randomly oriented collagen fibrils that entrap proteoglycans, contrasting with the densely packed, highly aligned collagen fibers in the bulk extracellular matrix (ECM). Compared to the ECM, the PCM exhibits lower modulus and greater isotropy, but has similar relative viscoelastic properties. In Col5a1<sup
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A 1D-3D Hybrid Model of Patient-Specific Coronary Hemodynamics. Coronary flow is affected by evolving events such as atherosclerotic plaque formation, rupture, and thrombosis, resulting in myocardial ischemia and infarction. Highly resolved 3D hemodynamic data at the stenosis is essential to model shear-sensitive thrombotic events in coronary artery disease.</AbstractText We developed a hybrid 1D-3D simulation framework to compute patient-specific coronary hemodynamics efficiently. A 1D model of the coronary flow is coupled to an image-based 3D model of the region of interest. This framework affords the advantages of reduced-order modeling, decreasing the global computational cost, without sacrificing the accuracy of the quantities of interest.</AbstractText We validated our 1D-3D model against full 3D coronary simulations in healthy and diseased conditions. Our results showed good agreement between the 3D and the 1D-3D models while reducing the computational cost by 40-fold compared to the 3D simulation. The 1D-3D model predicted left/right coronary flow distribution within 3% and provided an accurate estimation of fractional flow reserve and wall shear stress distribution at the stenosis comparable to the 3D simulation.</AbstractText Savings in computational cost may be significant in situations with changing geometry, such as growing thrombosis. Also, this approach would allow quantifying the time-dependent effect of thrombotic growth and occlusion on the global coronary circulation.</AbstractText
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Age-related differences in the relationship between sustained attention and associative memory and Memory-Guided inference. Episodic memory enables the encoding and retrieval of novel associations, as well as the bridging across learned associations to draw novel inferences. A fundamental goal of memory science is to understand the factors that give rise to individual and age-related differences in memory-dependent cognition. Variability in episodic memory could arise, in part, from both individual differences in sustained attention and diminished attention in aging. We first report that, relative to young adults (N = 23; M = 20.0 years), older adults (N = 26, M = 68.7 years) demonstrated lower associative memory and memory-guided associative inference performance and that this age-related reduction in associative inference occurs even when controlling for associative memory performance. Next, we confirm these age-related memory differences by using a high-powered, online replication study (young adults: N = 143, M = 26.2 years; older adults N = 133, M = 67.7 years), further demonstrating that age-related differences in memory do not reflect group differences in sustained attention (as assayed by the gradual-onset continuous performance task; gradCPT). Finally, we report that individual differences in sustained attention explain between-person variability in associative memory and inference performance in the present, online young adult sample, but not in the older adult sample. These findings extend understanding of the links between attention and memory in young adults, demonstrating that differences in sustained attention was related to differences in memory-guided inference. By contrast, our data suggest that the present age-related differences in memory-dependent behavior and the memory differences between older adults are due to attention-independent mechanisms.</AbstractText
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39786185
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33717399
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40507497
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Classification of schwannomas and the new naming convention for "neurofibromatosis-2": Genetic updates and international consensus recommendation.
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Malignant transformation in a sciatic plexiform neurofibroma in Neurofibromatosis Type 1 - imaging features that aid diagnosis.
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Enhancing Communication in Minimally Verbal Autistic Children: A Study on NAO-Assisted Therapy.
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Despite their similar nomenclature, Neurofibromatosis type 1 (NF1) and "Neurofibromatosis type 2" are discrete and clinically distinguishable entities. The name of "neurofibromatosis type 2" has been changed to NF2-related schwannomatosis, to reflect the fact that neurofibromas do not occur in this syndrome and therefore the name "Neurofibromatosis" is factually incorrect. Furthermore, multiple schwannomas, a hallmark feature of NF2, can also occur in patients with mutations in genes including SMARCB1 and LZTR1, all exhibiting overlapping clinical features. Current understanding suggests that schwannomatosis (SWN) encompasses a range of clinical presentations consisting of clearly defined, separate subtypes which share a common phenotype of schwannomas. Recognizing these newly emerging subtypes, the International Consensus Group on Neurofibromatosis Diagnostic Criteria (I-NF-DC) proposed a revised nomenclature for NF2 and related disorders in 2022. This review article focuses on this critical update in diagnostic terminology, highlighting the key gene-related SWN subtypes relevant to neuroradiologists. By emphasizing molecular testing alongside clinical features, the revised system facilitates a more precise diagnosis, potentially paving the way for personalized treatment strategies. Additionally, the flexible structure accommodates future discoveries of genes associated with SWN.</AbstractText
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A 41-year-old Asian male with NF1 and bilateral sciatic plexiform neurofibromas, presented with unintentional weight loss, increasing size of a left thigh mass associated with increasing pain and radiculopathy. MRI of the left thigh demonstrated imaging features suspicious of malignant transformation. The patient had a new left lung mass, demonstrating avid FDG uptake, raising suspicion for metastasis. Surgical resection of the left thigh mass confirms malignant transformation in a preexisting sciatic plexiform neurofibroma. Diagnosis of malignant transformation in a nerve sheath tumour can be challenging. MRI remains the main preferred imaging modality in the evaluation of these tumours. Imaging features that raise suspicion for malignant transformation are discussed. Although none of these are specific for malignant transformation, studies suggest that the presence of two to four of these features should prompt further investigations.</AbstractText
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<b
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Classification of schwannomas and the new naming convention for "neurofibromatosis-2": Genetic updates and international consensus recommendation. Despite their similar nomenclature, Neurofibromatosis type 1 (NF1) and "Neurofibromatosis type 2" are discrete and clinically distinguishable entities. The name of "neurofibromatosis type 2" has been changed to NF2-related schwannomatosis, to reflect the fact that neurofibromas do not occur in this syndrome and therefore the name "Neurofibromatosis" is factually incorrect. Furthermore, multiple schwannomas, a hallmark feature of NF2, can also occur in patients with mutations in genes including SMARCB1 and LZTR1, all exhibiting overlapping clinical features. Current understanding suggests that schwannomatosis (SWN) encompasses a range of clinical presentations consisting of clearly defined, separate subtypes which share a common phenotype of schwannomas. Recognizing these newly emerging subtypes, the International Consensus Group on Neurofibromatosis Diagnostic Criteria (I-NF-DC) proposed a revised nomenclature for NF2 and related disorders in 2022. This review article focuses on this critical update in diagnostic terminology, highlighting the key gene-related SWN subtypes relevant to neuroradiologists. By emphasizing molecular testing alongside clinical features, the revised system facilitates a more precise diagnosis, potentially paving the way for personalized treatment strategies. Additionally, the flexible structure accommodates future discoveries of genes associated with SWN.</AbstractText
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Malignant transformation in a sciatic plexiform neurofibroma in Neurofibromatosis Type 1 - imaging features that aid diagnosis. A 41-year-old Asian male with NF1 and bilateral sciatic plexiform neurofibromas, presented with unintentional weight loss, increasing size of a left thigh mass associated with increasing pain and radiculopathy. MRI of the left thigh demonstrated imaging features suspicious of malignant transformation. The patient had a new left lung mass, demonstrating avid FDG uptake, raising suspicion for metastasis. Surgical resection of the left thigh mass confirms malignant transformation in a preexisting sciatic plexiform neurofibroma. Diagnosis of malignant transformation in a nerve sheath tumour can be challenging. MRI remains the main preferred imaging modality in the evaluation of these tumours. Imaging features that raise suspicion for malignant transformation are discussed. Although none of these are specific for malignant transformation, studies suggest that the presence of two to four of these features should prompt further investigations.</AbstractText
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Enhancing Communication in Minimally Verbal Autistic Children: A Study on NAO-Assisted Therapy. <b
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39950545
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34036710
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40463770
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Sleep need driven oscillation of glutamate synaptic phenotype.
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Potentiation of glutamatergic synaptic transmission onto lateral habenula neurons following early life stress and intravenous morphine self-administration in rats.
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Association Between Physical, Social, and Attitudinal Environments and Quality of Life in Adolescents With Cerebral Palsy: Insights From the SPARCLE Cross-Sectional Study.
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Sleep loss increases AMPA-synaptic strength and number in the neocortex. However, this is only part of the synaptic sleep loss response. We report an increased AMPA/NMDA EPSC ratio in frontal-cortical pyramidal neurons of layers 2-3. Silent synapses are absent, decreasing the plastic potential to convert silent NMDA to active AMPA synapses. These sleep loss changes are recovered by sleep. Sleep genes are enriched for synaptic shaping cellular components controlling glutamate synapse phenotype, overlap with autism risk genes, and are primarily observed in excitatory pyramidal neurons projecting intra-telencephalically. These genes are enriched with genes controlled by the transcription factor, MEF2c, and its repressor, HDAC4. Sleep genes can thus provide a framework within which motor learning and training occur mediated by the sleep-dependent oscillation of glutamate-synaptic phenotypes.</AbstractText
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Early life stress presents an important risk factor for drug addiction and comorbid depression and anxiety through persistent effects on the mesolimbic dopamine pathways. Using an early life stress model for child neglect (a single 24 h episode of maternal deprivation, MD) in rats, recent published works from our lab show that MD induces dysfunction in the ventral tegmental area and its negative controller, the lateral habenula (LHb). MD-induced potentiation of glutamatergic synaptic transmission onto LHb neurons shifts the coordination of excitation/inhibition (E/I) balance towards excitation, resulting in an increase in the overall spontaneous neuronal activity with elevation in bursting and tonic firing, and in the intrinsic excitability of LHb neurons in early adolescent male rats. Here, we explored how MD affects intravenous morphine self-administration (MSA) acquisition and sucrose preference as well as glutamatergic synaptic function in LHb neurons of adult male rats self-administering morphine. We found that MD-induced increases in LHb neuronal and glutamatergic synaptic activity and E/I ratio persisted into adulthood. Moreover, MD significantly reduced morphine intake, triggered anhedonia-like behaviour in the sucrose preference test and was associated with persistent glutamatergic potentiation 24 h after the last MSA session. MSA also altered the decay time kinetics of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR) currents in LHb neurons of control rats during this time period. Our data highlight that early life stress-induced glutamatergic plasticity in LHb may dampen the positive reinforcing and motivational properties of both natural rewards and opioids, and may contribute to the development of anhedonia and dysphoric states associated with opioids.</AbstractText
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To assess the correlation between the adequacy of the environment (the quantity of met individual environmental needs) and quality of life (QoL) in adolescents with cerebral palsy (CP) and to examine the magnitude of effects against personal and family factors.</AbstractText Cross-sectional study.</AbstractText Nine administrative regions in Denmark, France, Germany, Ireland, Italy, Sweden, and the United Kingdom.</AbstractText Adolescents with confirmed diagnosis of CP, born 1991-1997, aged 13-17 years at the time of data collection. Nonwalkers (GMFCS IV-V) were overrepresented.</AbstractText Not applicable.</AbstractText Parent reports of the adequacy of the environment (using the European Child Environment Questionnaire) and their adolescent's QoL (using the Kidscreen-52 generic instrument, focusing on 4 domains: physical well-being, psychological well-being, autonomy, and school environment).</AbstractText Six hundred sixty-four adolescents with CP participated in the study: 57.2% boys, mean age 15.1 years, 45.1% with GMFCS IV-V, and 45.7% attending mainstream schools. The adequacy of the environment was positively associated with QoL. More specifically, once adjusted for personal and family factors, positive correlations were observed between the adequacy of social support in the community and physical well-being, a supportive attitudinal environment from peers and psychological well-being, a supportive attitudinal environment from peers and teachers and satisfaction with school life, and the adequacy of physical environment at home and QoL in the autonomy domain, the latter only in the subgroup of those with GMFCS IV-V<i The adequacy of the environment relates to adolescent QoL. Personal and family factors correlated slightly higher with QoL than with environmental factors.</AbstractText
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Sleep need driven oscillation of glutamate synaptic phenotype. Sleep loss increases AMPA-synaptic strength and number in the neocortex. However, this is only part of the synaptic sleep loss response. We report an increased AMPA/NMDA EPSC ratio in frontal-cortical pyramidal neurons of layers 2-3. Silent synapses are absent, decreasing the plastic potential to convert silent NMDA to active AMPA synapses. These sleep loss changes are recovered by sleep. Sleep genes are enriched for synaptic shaping cellular components controlling glutamate synapse phenotype, overlap with autism risk genes, and are primarily observed in excitatory pyramidal neurons projecting intra-telencephalically. These genes are enriched with genes controlled by the transcription factor, MEF2c, and its repressor, HDAC4. Sleep genes can thus provide a framework within which motor learning and training occur mediated by the sleep-dependent oscillation of glutamate-synaptic phenotypes.</AbstractText
|
Potentiation of glutamatergic synaptic transmission onto lateral habenula neurons following early life stress and intravenous morphine self-administration in rats. Early life stress presents an important risk factor for drug addiction and comorbid depression and anxiety through persistent effects on the mesolimbic dopamine pathways. Using an early life stress model for child neglect (a single 24 h episode of maternal deprivation, MD) in rats, recent published works from our lab show that MD induces dysfunction in the ventral tegmental area and its negative controller, the lateral habenula (LHb). MD-induced potentiation of glutamatergic synaptic transmission onto LHb neurons shifts the coordination of excitation/inhibition (E/I) balance towards excitation, resulting in an increase in the overall spontaneous neuronal activity with elevation in bursting and tonic firing, and in the intrinsic excitability of LHb neurons in early adolescent male rats. Here, we explored how MD affects intravenous morphine self-administration (MSA) acquisition and sucrose preference as well as glutamatergic synaptic function in LHb neurons of adult male rats self-administering morphine. We found that MD-induced increases in LHb neuronal and glutamatergic synaptic activity and E/I ratio persisted into adulthood. Moreover, MD significantly reduced morphine intake, triggered anhedonia-like behaviour in the sucrose preference test and was associated with persistent glutamatergic potentiation 24 h after the last MSA session. MSA also altered the decay time kinetics of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR) currents in LHb neurons of control rats during this time period. Our data highlight that early life stress-induced glutamatergic plasticity in LHb may dampen the positive reinforcing and motivational properties of both natural rewards and opioids, and may contribute to the development of anhedonia and dysphoric states associated with opioids.</AbstractText
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Association Between Physical, Social, and Attitudinal Environments and Quality of Life in Adolescents With Cerebral Palsy: Insights From the SPARCLE Cross-Sectional Study. To assess the correlation between the adequacy of the environment (the quantity of met individual environmental needs) and quality of life (QoL) in adolescents with cerebral palsy (CP) and to examine the magnitude of effects against personal and family factors.</AbstractText Cross-sectional study.</AbstractText Nine administrative regions in Denmark, France, Germany, Ireland, Italy, Sweden, and the United Kingdom.</AbstractText Adolescents with confirmed diagnosis of CP, born 1991-1997, aged 13-17 years at the time of data collection. Nonwalkers (GMFCS IV-V) were overrepresented.</AbstractText Not applicable.</AbstractText Parent reports of the adequacy of the environment (using the European Child Environment Questionnaire) and their adolescent's QoL (using the Kidscreen-52 generic instrument, focusing on 4 domains: physical well-being, psychological well-being, autonomy, and school environment).</AbstractText Six hundred sixty-four adolescents with CP participated in the study: 57.2% boys, mean age 15.1 years, 45.1% with GMFCS IV-V, and 45.7% attending mainstream schools. The adequacy of the environment was positively associated with QoL. More specifically, once adjusted for personal and family factors, positive correlations were observed between the adequacy of social support in the community and physical well-being, a supportive attitudinal environment from peers and psychological well-being, a supportive attitudinal environment from peers and teachers and satisfaction with school life, and the adequacy of physical environment at home and QoL in the autonomy domain, the latter only in the subgroup of those with GMFCS IV-V<i The adequacy of the environment relates to adolescent QoL. Personal and family factors correlated slightly higher with QoL than with environmental factors.</AbstractText
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39237467
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35377407
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40349633
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Post-traumatic cauda equina concussion: Definition and description of the injury mechanism.
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Post-acute blood biomarkers and disease progression in traumatic brain injury.
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Exploring the mechanisms of neurotoxic effects from combined exposure to polystyrene and microcystin-LR in Caenorhabditis elegans.
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Despite being a prevalent clinical condition, cauda equina concussion has not been thoroughly elucidated in the literature. The aim of this study is to delineate the etiology and pathogenesis of cauda equina concussion and its associated clinical manifestations. Patients exhibiting clinical manifestations indicative of spinal cord injury and transient neurological deficits after spinal trauma were evaluated retrospectively. The pathogenesis was elucidated through correlating clinical presentations with radiological findings. Neurological deficits were categorized into two principal groups, symmetrical and asymmetrical. Non-penetrating fractures were classified to ascertain the relationship between the type of trauma and the ensuing neurological deficits. A cohort of 82 patients was diagnosed with cauda equina concussion. Among these, 58 had experienced vertical trauma resulting from falls, while 24 had encountered axial trauma in vehicular accidents. Stable spinal fractures were identified in 52 patients across multiple levels, whereas single-level fractures were observed in 30. Asymmetrical neurological deficits were detected in 51 (62.19%) patients, with a notably higher incidence among those subjected to vertical trauma (p < 0.014). The mean recovery time was 14.25 ± 15.16 h for sensory deficits and 11.25 ± 13.36 h for motor deficits in those patients. Notably, motor deficits resolved more expeditiously than sensory deficits in all cases presenting with both. Cauda equina concussion emerges as a frequently encountered clinical phenomenon attributable to the impact of high-energy vertical forces. Neurological deficits commonly manifest asymmetrically. The rapid resolution of neurological deficits presents challenges for the diagnostic process.</AbstractText
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There is substantial interest in the potential for traumatic brain injury to result in progressive neurological deterioration. While blood biomarkers such as glial fibrillary acid protein (GFAP) and neurofilament light have been widely explored in characterizing acute traumatic brain injury (TBI), their use in the chronic phase is limited. Given increasing evidence that these proteins may be markers of ongoing neurodegeneration in a range of diseases, we examined their relationship to imaging changes and functional outcome in the months to years following TBI. Two-hundred and three patients were recruited in two separate cohorts; 6 months post-injury (n = 165); and >5 years post-injury (n = 38; 12 of whom also provided data ∼8 months post-TBI). Subjects underwent blood biomarker sampling (n = 199) and MRI (n = 172; including diffusion tensor imaging). Data from patient cohorts were compared to 59 healthy volunteers and 21 non-brain injury trauma controls. Mean diffusivity and fractional anisotropy were calculated in cortical grey matter, deep grey matter and whole brain white matter. Accelerated brain ageing was calculated at a whole brain level as the predicted age difference defined using T1-weighted images, and at a voxel-based level as the annualized Jacobian determinants in white matter and grey matter, referenced to a population of 652 healthy control subjects. Serum neurofilament light concentrations were elevated in the early chronic phase. While GFAP values were within the normal range at ∼8 months, many patients showed a secondary and temporally distinct elevations up to >5 years after injury. Biomarker elevation at 6 months was significantly related to metrics of microstructural injury on diffusion tensor imaging. Biomarker levels at ∼8 months predicted white matter volume loss at >5 years, and annualized brain volume loss between ∼8 months and 5 years. Patients who worsened functionally between ∼8 months and >5 years showed higher than predicted brain age and elevated neurofilament light levels. GFAP and neurofilament light levels can remain elevated months to years after TBI, and show distinct temporal profiles. These elevations correlate closely with microstructural injury in both grey and white matter on contemporaneous quantitative diffusion tensor imaging. Neurofilament light elevations at ∼8 months may predict ongoing white matter and brain volume loss over >5 years of follow-up. If confirmed, these findings suggest that blood biomarker levels at late time points could be used to identify TBI survivors who are at high risk of progressive neurological damage.</AbstractText
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Microplastics (MPs) are newly emerged pollutants found in water and soil, while microcystin-leucine arginine (MC-LR) is often detected in drinking water and water products, both posing serious threats to aquatic environment and food safety. MPs can serve as carriers of MC-LR. These pollutants are often found together, rather than separately. This study focused on assessing the neurotoxicity of co-exposure to MC-LR and PS in Caenorhabditis elegans (C. elegans) after combined exposure to these two pollutants. Exposure to varying concentrations of polystyrene (PS) and MC-LR individually caused a dose-dependent decrease in the locomotion behaviors of C. elegans. Exposure to either of these substances alone caused damage to the phenotypic indicators of the C. elegans. To further explore the additional damage caused by the combined exposure of PS and MC-LR, the low, medium, and high combined dose groups were selected based on the locomotion behaviors and survival results. Combined exposure increased the level of oxidative stress indicators and resulted in neuronal loss. It also reduced serotonin, glutamate, GABA, and dopamine neurotransmitters levels, without affecting cholinergic neurons. The expression of neurotransmitter-related genes also decreased. The high-dose group showed the most significant effects. This article is the first to study the combined effect of PS and MC-LR on C. elegans nervous systems, offering novel insights into the risks posed by co-occurring contaminants and their implications for aquatic ecosystems and food safety.</AbstractText
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Post-traumatic cauda equina concussion: Definition and description of the injury mechanism. Despite being a prevalent clinical condition, cauda equina concussion has not been thoroughly elucidated in the literature. The aim of this study is to delineate the etiology and pathogenesis of cauda equina concussion and its associated clinical manifestations. Patients exhibiting clinical manifestations indicative of spinal cord injury and transient neurological deficits after spinal trauma were evaluated retrospectively. The pathogenesis was elucidated through correlating clinical presentations with radiological findings. Neurological deficits were categorized into two principal groups, symmetrical and asymmetrical. Non-penetrating fractures were classified to ascertain the relationship between the type of trauma and the ensuing neurological deficits. A cohort of 82 patients was diagnosed with cauda equina concussion. Among these, 58 had experienced vertical trauma resulting from falls, while 24 had encountered axial trauma in vehicular accidents. Stable spinal fractures were identified in 52 patients across multiple levels, whereas single-level fractures were observed in 30. Asymmetrical neurological deficits were detected in 51 (62.19%) patients, with a notably higher incidence among those subjected to vertical trauma (p < 0.014). The mean recovery time was 14.25 ± 15.16 h for sensory deficits and 11.25 ± 13.36 h for motor deficits in those patients. Notably, motor deficits resolved more expeditiously than sensory deficits in all cases presenting with both. Cauda equina concussion emerges as a frequently encountered clinical phenomenon attributable to the impact of high-energy vertical forces. Neurological deficits commonly manifest asymmetrically. The rapid resolution of neurological deficits presents challenges for the diagnostic process.</AbstractText
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Post-acute blood biomarkers and disease progression in traumatic brain injury. There is substantial interest in the potential for traumatic brain injury to result in progressive neurological deterioration. While blood biomarkers such as glial fibrillary acid protein (GFAP) and neurofilament light have been widely explored in characterizing acute traumatic brain injury (TBI), their use in the chronic phase is limited. Given increasing evidence that these proteins may be markers of ongoing neurodegeneration in a range of diseases, we examined their relationship to imaging changes and functional outcome in the months to years following TBI. Two-hundred and three patients were recruited in two separate cohorts; 6 months post-injury (n = 165); and >5 years post-injury (n = 38; 12 of whom also provided data ∼8 months post-TBI). Subjects underwent blood biomarker sampling (n = 199) and MRI (n = 172; including diffusion tensor imaging). Data from patient cohorts were compared to 59 healthy volunteers and 21 non-brain injury trauma controls. Mean diffusivity and fractional anisotropy were calculated in cortical grey matter, deep grey matter and whole brain white matter. Accelerated brain ageing was calculated at a whole brain level as the predicted age difference defined using T1-weighted images, and at a voxel-based level as the annualized Jacobian determinants in white matter and grey matter, referenced to a population of 652 healthy control subjects. Serum neurofilament light concentrations were elevated in the early chronic phase. While GFAP values were within the normal range at ∼8 months, many patients showed a secondary and temporally distinct elevations up to >5 years after injury. Biomarker elevation at 6 months was significantly related to metrics of microstructural injury on diffusion tensor imaging. Biomarker levels at ∼8 months predicted white matter volume loss at >5 years, and annualized brain volume loss between ∼8 months and 5 years. Patients who worsened functionally between ∼8 months and >5 years showed higher than predicted brain age and elevated neurofilament light levels. GFAP and neurofilament light levels can remain elevated months to years after TBI, and show distinct temporal profiles. These elevations correlate closely with microstructural injury in both grey and white matter on contemporaneous quantitative diffusion tensor imaging. Neurofilament light elevations at ∼8 months may predict ongoing white matter and brain volume loss over >5 years of follow-up. If confirmed, these findings suggest that blood biomarker levels at late time points could be used to identify TBI survivors who are at high risk of progressive neurological damage.</AbstractText
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Exploring the mechanisms of neurotoxic effects from combined exposure to polystyrene and microcystin-LR in Caenorhabditis elegans. Microplastics (MPs) are newly emerged pollutants found in water and soil, while microcystin-leucine arginine (MC-LR) is often detected in drinking water and water products, both posing serious threats to aquatic environment and food safety. MPs can serve as carriers of MC-LR. These pollutants are often found together, rather than separately. This study focused on assessing the neurotoxicity of co-exposure to MC-LR and PS in Caenorhabditis elegans (C. elegans) after combined exposure to these two pollutants. Exposure to varying concentrations of polystyrene (PS) and MC-LR individually caused a dose-dependent decrease in the locomotion behaviors of C. elegans. Exposure to either of these substances alone caused damage to the phenotypic indicators of the C. elegans. To further explore the additional damage caused by the combined exposure of PS and MC-LR, the low, medium, and high combined dose groups were selected based on the locomotion behaviors and survival results. Combined exposure increased the level of oxidative stress indicators and resulted in neuronal loss. It also reduced serotonin, glutamate, GABA, and dopamine neurotransmitters levels, without affecting cholinergic neurons. The expression of neurotransmitter-related genes also decreased. The high-dose group showed the most significant effects. This article is the first to study the combined effect of PS and MC-LR on C. elegans nervous systems, offering novel insights into the risks posed by co-occurring contaminants and their implications for aquatic ecosystems and food safety.</AbstractText
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39674319
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38340971
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40675596
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Multinodular and Vacuolating Neuronal Tumors of the Cerebrum: A Systematic Review of the Literature.
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Improved image quality in contrast-enhanced 3D-T1 weighted sequence by compressed sensing-based deep-learning reconstruction for the evaluation of head and neck.
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IMPROVED SURVEILLANCE OF AEDES TRISERIATUS USING THE BG-PRO TRAP: IMPLICATIONS FOR SAMPLING HOST-SEEKING LA CROSSE VIRUS VECTORS.
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Multinodular and vacuolating neuronal tumors (MVNTs) of the cerebrum are rare, seizure-related, low-grade tumors of the central nervous system that usually affect young adults. First described by Huse et al. in 2013, these neoplasms are usually located within the deep cortical ribbon and the superficial white matter and have a characteristic cytoarchitecture of cells with neuronal and glial differentiation that form multiple nodules with conspicuous vacuolation. Because of their benign nature and indolent clinical course, radiologically based differentiation from other entities is of paramount importance to avoid unnecessary surgical intervention. To the best of our knowledge, our study represents the first systematic review in the literature aiming to delineate the characteristics of MVNTs regarding epidemiology, clinical manifestation, histopathology, imaging, and management. PubMed/MEDLINE and SCOPUS databases were systematically investigated for MVNT cases until November 2023. The search yielded 29 case reports comprising 41 patients with a mean age of 32.6 years and 7 case series with 164 patients. MVNTs were most commonly located in the supratentorial compartment, affecting the temporal, frontal, or parietal lobes. Their most frequent initial clinical manifestation was either seizures or headaches. On conventional magnetic resonance imaging techniques, they usually appear hypointense in T1-weighted images and hyperintense in T2-weighted and fluid-attenuated inversion recovery images and lack perilesional edema or postcontrast enhancement. MVNTs do not seem to change size or recur, even after partial resection of the tumor, indicating their indolent course, and, thus, surveillance with serial magnetic resonance imaging is the most appropriate management technique for these lesions.</AbstractText
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To assess the utility of deep learning (DL)-based image reconstruction with the combination of compressed sensing (CS) denoising cycle by comparing images reconstructed by conventional CS-based method without DL in fat-suppressed (Fs)-contrast enhanced (CE) three-dimensional (3D) T1-weighted images (T1WIs) of the head and neck.</AbstractText We retrospectively analyzed the cases of 39 patients who had undergone head and neck Fs-CE 3D T1WI applying reconstructions based on conventional CS and CS augmented by DL, respectively. In the qualitative assessment, we evaluated overall image quality, visualization of anatomical structures, degree of artifacts, lesion conspicuity, and lesion edge sharpness based on a five-point system. In the quantitative assessment, we calculated the signal-to-noise ratios (SNRs) of the lesion and the posterior neck muscle and the contrast-to-noise ratio (CNR) between the lesion and the adjacent muscle.</AbstractText For all items of the qualitative analysis, significantly higher scores were awarded to images with DL-based reconstruction (p < 0.001). In the quantitative analysis, DL-based reconstruction resulted in significantly higher values for both the SNR of lesions (p < 0.001) and posterior neck muscles (p < 0.001). Significantly higher CNRs were also observed in images with DL-based reconstruction (p < 0.001).</AbstractText DL-based image reconstruction integrating into the CS-based denoising cycle offered superior image quality compared to the conventional CS method. This technique will be useful for the assessment of patients with head and neck disease.</AbstractText
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La Crosse virus (LACV) is responsible for the majority of pediatric arboviral encephalitis in the United States. At present there are limited options for host-seeking surveillance for the primary vector (Aedes triseriatus) and, to a lesser extent, two invasive species (Ae. albopictus and Ae. japonicus) capable of transmitting LACV. We evaluated four host-seeking trap configurations (Centers for Disease Control and Prevention [CDC] Light trap, BG-Pro with BG lure, and BG-Sentinel 2 with and without BG lure) via two 4 × 4 Latin square field studies. Over the course of 128 trap-days, 436 mosquitoes were collected with the two most common species being Aedes triseriatus (n = 156, 35.8% of total) and Ae. albopictus (n = 182, 41.7% of total). The BG-Pro, on average, collected approximately 3 times more female Ae. triseriatus than the CDC light trap or the BG-Sentinel with BG lure. Similarly, the odds of collecting Ae. triseriatus with the BG-Pro trap were 3.02 times (95% CI: 1.96-4.67) than the CDC light trap; statistically greater than any other trap. There was no statistical difference in the odds of collecting Ae. triseriatus by the BG-Sentinel 2 (irrespective of lure presence) when compared to the CDC light trap as the reference. There was no difference in the odds of collecting Ae. albopictus using the BG-Sentinel 2 (OR: 4.62, 95% CI: 2.76-7.74) or the BG-Pro (3.06, 95% CI: 1.78-5.24) when compared to the CDC light trap as the reference. The limited collection of Ae. japonicus precluded any meaningful comparisons. Taken together, the BG-Pro trap should be considered for the surveillance or collection of the primary LACV vector, Ae. triseriatus.</AbstractText
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Multinodular and Vacuolating Neuronal Tumors of the Cerebrum: A Systematic Review of the Literature. Multinodular and vacuolating neuronal tumors (MVNTs) of the cerebrum are rare, seizure-related, low-grade tumors of the central nervous system that usually affect young adults. First described by Huse et al. in 2013, these neoplasms are usually located within the deep cortical ribbon and the superficial white matter and have a characteristic cytoarchitecture of cells with neuronal and glial differentiation that form multiple nodules with conspicuous vacuolation. Because of their benign nature and indolent clinical course, radiologically based differentiation from other entities is of paramount importance to avoid unnecessary surgical intervention. To the best of our knowledge, our study represents the first systematic review in the literature aiming to delineate the characteristics of MVNTs regarding epidemiology, clinical manifestation, histopathology, imaging, and management. PubMed/MEDLINE and SCOPUS databases were systematically investigated for MVNT cases until November 2023. The search yielded 29 case reports comprising 41 patients with a mean age of 32.6 years and 7 case series with 164 patients. MVNTs were most commonly located in the supratentorial compartment, affecting the temporal, frontal, or parietal lobes. Their most frequent initial clinical manifestation was either seizures or headaches. On conventional magnetic resonance imaging techniques, they usually appear hypointense in T1-weighted images and hyperintense in T2-weighted and fluid-attenuated inversion recovery images and lack perilesional edema or postcontrast enhancement. MVNTs do not seem to change size or recur, even after partial resection of the tumor, indicating their indolent course, and, thus, surveillance with serial magnetic resonance imaging is the most appropriate management technique for these lesions.</AbstractText
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Improved image quality in contrast-enhanced 3D-T1 weighted sequence by compressed sensing-based deep-learning reconstruction for the evaluation of head and neck. To assess the utility of deep learning (DL)-based image reconstruction with the combination of compressed sensing (CS) denoising cycle by comparing images reconstructed by conventional CS-based method without DL in fat-suppressed (Fs)-contrast enhanced (CE) three-dimensional (3D) T1-weighted images (T1WIs) of the head and neck.</AbstractText We retrospectively analyzed the cases of 39 patients who had undergone head and neck Fs-CE 3D T1WI applying reconstructions based on conventional CS and CS augmented by DL, respectively. In the qualitative assessment, we evaluated overall image quality, visualization of anatomical structures, degree of artifacts, lesion conspicuity, and lesion edge sharpness based on a five-point system. In the quantitative assessment, we calculated the signal-to-noise ratios (SNRs) of the lesion and the posterior neck muscle and the contrast-to-noise ratio (CNR) between the lesion and the adjacent muscle.</AbstractText For all items of the qualitative analysis, significantly higher scores were awarded to images with DL-based reconstruction (p < 0.001). In the quantitative analysis, DL-based reconstruction resulted in significantly higher values for both the SNR of lesions (p < 0.001) and posterior neck muscles (p < 0.001). Significantly higher CNRs were also observed in images with DL-based reconstruction (p < 0.001).</AbstractText DL-based image reconstruction integrating into the CS-based denoising cycle offered superior image quality compared to the conventional CS method. This technique will be useful for the assessment of patients with head and neck disease.</AbstractText
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IMPROVED SURVEILLANCE OF AEDES TRISERIATUS USING THE BG-PRO TRAP: IMPLICATIONS FOR SAMPLING HOST-SEEKING LA CROSSE VIRUS VECTORS. La Crosse virus (LACV) is responsible for the majority of pediatric arboviral encephalitis in the United States. At present there are limited options for host-seeking surveillance for the primary vector (Aedes triseriatus) and, to a lesser extent, two invasive species (Ae. albopictus and Ae. japonicus) capable of transmitting LACV. We evaluated four host-seeking trap configurations (Centers for Disease Control and Prevention [CDC] Light trap, BG-Pro with BG lure, and BG-Sentinel 2 with and without BG lure) via two 4 × 4 Latin square field studies. Over the course of 128 trap-days, 436 mosquitoes were collected with the two most common species being Aedes triseriatus (n = 156, 35.8% of total) and Ae. albopictus (n = 182, 41.7% of total). The BG-Pro, on average, collected approximately 3 times more female Ae. triseriatus than the CDC light trap or the BG-Sentinel with BG lure. Similarly, the odds of collecting Ae. triseriatus with the BG-Pro trap were 3.02 times (95% CI: 1.96-4.67) than the CDC light trap; statistically greater than any other trap. There was no statistical difference in the odds of collecting Ae. triseriatus by the BG-Sentinel 2 (irrespective of lure presence) when compared to the CDC light trap as the reference. There was no difference in the odds of collecting Ae. albopictus using the BG-Sentinel 2 (OR: 4.62, 95% CI: 2.76-7.74) or the BG-Pro (3.06, 95% CI: 1.78-5.24) when compared to the CDC light trap as the reference. The limited collection of Ae. japonicus precluded any meaningful comparisons. Taken together, the BG-Pro trap should be considered for the surveillance or collection of the primary LACV vector, Ae. triseriatus.</AbstractText
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36833258
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32973043
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36905775
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Novel Variants in MPV17, PRX, GJB1, and SACS Cause Charcot-Marie-Tooth and Spastic Ataxia of Charlevoix-Saguenay Type Diseases.
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Phosphorylation of eIF2α Promotes Schwann Cell Differentiation and Myelination in CMT1B Mice with Activated UPR.
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Brain image quality according to beam collimation width and image reconstruction algorithm: A phantom study.
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Charcot-Marie-Tooth disease (CMT) and autosomal recessive spastic ataxia of Charlevoix-Saguenay type (ARSACS) are large heterogeneous groups of sensory, neurological genetic disorders characterized by sensory neuropathies, muscular atrophies, abnormal sensory conduction velocities, and ataxia. CMT2EE (OMIM: 618400) is caused by mutations in <i
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Myelin Protein Zero (MPZ/P0) is the most abundant glycoprotein of peripheral nerve myelin. P0 is synthesized by myelinating Schwann cells, processed in the endoplasmic reticulum (ER) and delivered to myelin via the secretory pathway. The mutant P0S63del (deletion of serine 63 in the extracellular domain of P0), that causes Charcot-Marie-Tooth type 1B (CMT1B) neuropathy in humans and a similar demyelinating neuropathy in transgenic mice, is instead retained the ER where it activates an unfolded protein response. Under ER-stress conditions, protein kinase R-like endoplasmic reticulum kinase (PERK) phosphorylates eukaryotic initiation factor 2α (eIF2α) to attenuate global translation, thus reducing the misfolded protein overload in the ER. Genetic and pharmacological inactivation of Gadd34 (damage-inducible protein 34), a subunit of the PP1 phosphatase complex that promotes the dephosphorylation of eIF2α, prolonged eIF2α phosphorylation and improved motor, neurophysiological, and morphologic deficits in S63del mice. However, PERK ablation in S63del Schwann cells ameliorated, rather than worsened, S63del neuropathy despite reduced levels of phosphorylated eIF2α. These contradictory findings prompted us to genetically explore the role of eIF2α phosphorylation in P0S63del-CMT1B neuropathy through the generation of mice in which eIF2α cannot be phosphorylated specifically in Schwann cells. Morphologic and electrophysiological analysis of male and female S63del mice showed a worsening of the neuropathy in the absence of eIF2α phosphorylation. However, we did not detect significant changes in ER stress levels, but rather a dramatic increase of the MEK/ERK/c-Jun pathway accompanied by a reduction in expression of myelin genes and a delay in Schwann cell differentiation. Our results support the hypothesis that eIF2α phosphorylation is protective in CMT1B and unveil a possible cross talk between eIF2α and the MEK/ERK pathway in neuropathic nerves.<b
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To compare quantitatively and qualitatively brain image quality acquired in helical and axial modes on two wide collimation CT systems according to the dose level and algorithm used.</AbstractText Acquisitions were performed on an image quality and an anthropomorphic phantoms at three dose levels (CTDI<sub For the GE system, noise magnitude and noise texture (average NPS spatial frequency) were lower with DLR than with IR. For the Canon system, noise magnitude values were lower with DLR than with IR for similar noise texture but the opposite was true for spatial resolution. For both CT systems, noise magnitude was lower with the axial mode than with the helical mode for similar noise texture and spatial resolution. Radiologists rated the overall quality of all brain images as "satisfactory for clinical use", whatever the dose level, algorithm or acquisition mode.</AbstractText Using 16-cm axial acquisition reduces image noise without changing the spatial resolution and image texture compared to helical acquisitions. Axial acquisition can be used in clinical routine for brain CT examinations with an explored length of less than 16 cm.</AbstractText
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Novel Variants in MPV17, PRX, GJB1, and SACS Cause Charcot-Marie-Tooth and Spastic Ataxia of Charlevoix-Saguenay Type Diseases. Charcot-Marie-Tooth disease (CMT) and autosomal recessive spastic ataxia of Charlevoix-Saguenay type (ARSACS) are large heterogeneous groups of sensory, neurological genetic disorders characterized by sensory neuropathies, muscular atrophies, abnormal sensory conduction velocities, and ataxia. CMT2EE (OMIM: 618400) is caused by mutations in <i
|
Phosphorylation of eIF2α Promotes Schwann Cell Differentiation and Myelination in CMT1B Mice with Activated UPR. Myelin Protein Zero (MPZ/P0) is the most abundant glycoprotein of peripheral nerve myelin. P0 is synthesized by myelinating Schwann cells, processed in the endoplasmic reticulum (ER) and delivered to myelin via the secretory pathway. The mutant P0S63del (deletion of serine 63 in the extracellular domain of P0), that causes Charcot-Marie-Tooth type 1B (CMT1B) neuropathy in humans and a similar demyelinating neuropathy in transgenic mice, is instead retained the ER where it activates an unfolded protein response. Under ER-stress conditions, protein kinase R-like endoplasmic reticulum kinase (PERK) phosphorylates eukaryotic initiation factor 2α (eIF2α) to attenuate global translation, thus reducing the misfolded protein overload in the ER. Genetic and pharmacological inactivation of Gadd34 (damage-inducible protein 34), a subunit of the PP1 phosphatase complex that promotes the dephosphorylation of eIF2α, prolonged eIF2α phosphorylation and improved motor, neurophysiological, and morphologic deficits in S63del mice. However, PERK ablation in S63del Schwann cells ameliorated, rather than worsened, S63del neuropathy despite reduced levels of phosphorylated eIF2α. These contradictory findings prompted us to genetically explore the role of eIF2α phosphorylation in P0S63del-CMT1B neuropathy through the generation of mice in which eIF2α cannot be phosphorylated specifically in Schwann cells. Morphologic and electrophysiological analysis of male and female S63del mice showed a worsening of the neuropathy in the absence of eIF2α phosphorylation. However, we did not detect significant changes in ER stress levels, but rather a dramatic increase of the MEK/ERK/c-Jun pathway accompanied by a reduction in expression of myelin genes and a delay in Schwann cell differentiation. Our results support the hypothesis that eIF2α phosphorylation is protective in CMT1B and unveil a possible cross talk between eIF2α and the MEK/ERK pathway in neuropathic nerves.<b
|
Brain image quality according to beam collimation width and image reconstruction algorithm: A phantom study. To compare quantitatively and qualitatively brain image quality acquired in helical and axial modes on two wide collimation CT systems according to the dose level and algorithm used.</AbstractText Acquisitions were performed on an image quality and an anthropomorphic phantoms at three dose levels (CTDI<sub For the GE system, noise magnitude and noise texture (average NPS spatial frequency) were lower with DLR than with IR. For the Canon system, noise magnitude values were lower with DLR than with IR for similar noise texture but the opposite was true for spatial resolution. For both CT systems, noise magnitude was lower with the axial mode than with the helical mode for similar noise texture and spatial resolution. Radiologists rated the overall quality of all brain images as "satisfactory for clinical use", whatever the dose level, algorithm or acquisition mode.</AbstractText Using 16-cm axial acquisition reduces image noise without changing the spatial resolution and image texture compared to helical acquisitions. Axial acquisition can be used in clinical routine for brain CT examinations with an explored length of less than 16 cm.</AbstractText
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40286220
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21677183
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40765283
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Astaxanthin Mitigates ADHD Symptoms in Spontaneously Hypertensive Rats via Dopaminergic Modulation and Brain-Gut Axis Regulation.
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Essential roles of enteric neuronal serotonin in gastrointestinal motility and the development/survival of enteric dopaminergic neurons.
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Revisiting Cyanobacteria-Temperature Dynamics: Intraspecific Competition and Trait Diversity as Keys to Predicting Harmful Algal Blooms under Climate Change.
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Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder that significantly impacts learning, daily functioning, and personal development. Astaxanthin (ASTA), a naturally occurring antioxidant, has garnered interest as a potential therapeutic agent for various diseases, particularly in mitigating oxidative stress. This study explores a novel application of ASTA in the context of ADHD, aiming to investigate its therapeutic effects and underlying mechanisms. Spontaneously hypertensive rats (SHRs), widely used ADHD model animals, were treated with ASTA (50/100 mg/kg/day) for three weeks, 5 mg/kg/day atomoxetine (ATO) as the positive, and Wistar Kyoto (WKY) rats as control. Behavioral improvements were assessed using the open field test (OFT) and the Morris water maze (MWM). Biochemical analyses were conducted to evaluate changes in the levels of various neurotrophic factors, while histological examinations were performed to assess neuroprotective effects. Additionally, the role of ASTA in the brain-gut axis was investigated. The behavioral symptoms of hyperactivity, anxiety, and impaired spatial memory in ADHD animals were mitigated by ASTA. This improvement is primarily attributed to the restoration of neurotransmitter levels, particularly dopamine (DA), achieved through the modulation of several critical components within the dopamine system, including dopamine receptor 1 (DR1), dopamine transporter (DAT), tyrosine hydroxylase (TH), and synaptic-associated protein 25 (SNAP-25). Additionally, regulating the serotonin transporter (SERT) and glial cell-derived neurotrophic factor (GDNF) supports the recovery of serotonin levels and facilitates optimal brain development. Furthermore, cerebellar cells were protected, and the structure of the intestinal microbiota was regulated. ASTA can mitigate ADHD symptoms in SHR through the modulation of the dopaminergic system, multiple neurotransmitters, neurotrophic factors, and the neuro-intestinal environment, which establishes ASTA as a promising nutraceutical candidate for adjunctive therapy in pediatric ADHD.</AbstractText
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The gut contains a large 5-HT pool in enterochromaffin (EC) cells and a smaller 5-HT pool in the enteric nervous system (ENS). During development, enteric neurons are generated asynchronously. We tested hypotheses that serotonergic neurons, which arise early, affect development/survival of later-born dopaminergic, GABAergic, nitrergic, and calcitonin gene-related peptide-expressing neurons and are essential for gastrointestinal motility. 5-HT biosynthesis depends on tryptophan hydroxylase 1 (TPH1) in EC cells and on TPH2 in neurons; therefore, mice lacking TPH1 and/or TPH2 distinguish EC-derived from neuronal 5-HT. Deletion of TPH2, but not TPH1, decreased myenteric neuronal density and proportions of dopaminergic and GABAergic neurons but did not affect the extrinsic sympathetic innervation of the gut; intestinal transit slowed in mice lacking TPH2 mice, but gastric emptying accelerated. Isolated enteric crest-derived cells (ENCDCs) expressed the serotonin reuptake transporter (SERT) and 15 subtypes of 5-HT receptor. Addition of 5-HT to cultures of isolated ENCDCs promoted total and dopaminergic neuronal development. Rings of SERT-immunoreactive terminal axons surrounded myenteric dopaminergic neurons and SERT knock-out increased intestinal levels of dopamine metabolites, implying that enteric dopaminergic neurons receive a serotonergic innervation. Observations suggest that constitutive gastrointestinal motility depends more on neuronal than EC cell serotonin; moreover, serotonergic neurons promote development/survival of some classes of late-born enteric neurons, including dopaminergic neurons, which appear to innervate and activate in the adult ENS.</AbstractText
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Cyanobacterial harmful algal blooms are expanding spatiotemporally, with an increasing occurrence of cold-water cyanobacterial blooms (CWCBs), intensifying ecological and water quality challenges. While abiotic drivers have been identified as contributors to CWCBs, the role of biotic factors─particularly the adaptation induced by the shifts in intraspecific trait distributions─in this process remains largely unexplored. Here, we tested the hypothesis that the thermal history of cyanobacteria affects their thermal adaptations by reshaping the distribution of optimum growth temperature (<i
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Astaxanthin Mitigates ADHD Symptoms in Spontaneously Hypertensive Rats via Dopaminergic Modulation and Brain-Gut Axis Regulation. Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder that significantly impacts learning, daily functioning, and personal development. Astaxanthin (ASTA), a naturally occurring antioxidant, has garnered interest as a potential therapeutic agent for various diseases, particularly in mitigating oxidative stress. This study explores a novel application of ASTA in the context of ADHD, aiming to investigate its therapeutic effects and underlying mechanisms. Spontaneously hypertensive rats (SHRs), widely used ADHD model animals, were treated with ASTA (50/100 mg/kg/day) for three weeks, 5 mg/kg/day atomoxetine (ATO) as the positive, and Wistar Kyoto (WKY) rats as control. Behavioral improvements were assessed using the open field test (OFT) and the Morris water maze (MWM). Biochemical analyses were conducted to evaluate changes in the levels of various neurotrophic factors, while histological examinations were performed to assess neuroprotective effects. Additionally, the role of ASTA in the brain-gut axis was investigated. The behavioral symptoms of hyperactivity, anxiety, and impaired spatial memory in ADHD animals were mitigated by ASTA. This improvement is primarily attributed to the restoration of neurotransmitter levels, particularly dopamine (DA), achieved through the modulation of several critical components within the dopamine system, including dopamine receptor 1 (DR1), dopamine transporter (DAT), tyrosine hydroxylase (TH), and synaptic-associated protein 25 (SNAP-25). Additionally, regulating the serotonin transporter (SERT) and glial cell-derived neurotrophic factor (GDNF) supports the recovery of serotonin levels and facilitates optimal brain development. Furthermore, cerebellar cells were protected, and the structure of the intestinal microbiota was regulated. ASTA can mitigate ADHD symptoms in SHR through the modulation of the dopaminergic system, multiple neurotransmitters, neurotrophic factors, and the neuro-intestinal environment, which establishes ASTA as a promising nutraceutical candidate for adjunctive therapy in pediatric ADHD.</AbstractText
|
Essential roles of enteric neuronal serotonin in gastrointestinal motility and the development/survival of enteric dopaminergic neurons. The gut contains a large 5-HT pool in enterochromaffin (EC) cells and a smaller 5-HT pool in the enteric nervous system (ENS). During development, enteric neurons are generated asynchronously. We tested hypotheses that serotonergic neurons, which arise early, affect development/survival of later-born dopaminergic, GABAergic, nitrergic, and calcitonin gene-related peptide-expressing neurons and are essential for gastrointestinal motility. 5-HT biosynthesis depends on tryptophan hydroxylase 1 (TPH1) in EC cells and on TPH2 in neurons; therefore, mice lacking TPH1 and/or TPH2 distinguish EC-derived from neuronal 5-HT. Deletion of TPH2, but not TPH1, decreased myenteric neuronal density and proportions of dopaminergic and GABAergic neurons but did not affect the extrinsic sympathetic innervation of the gut; intestinal transit slowed in mice lacking TPH2 mice, but gastric emptying accelerated. Isolated enteric crest-derived cells (ENCDCs) expressed the serotonin reuptake transporter (SERT) and 15 subtypes of 5-HT receptor. Addition of 5-HT to cultures of isolated ENCDCs promoted total and dopaminergic neuronal development. Rings of SERT-immunoreactive terminal axons surrounded myenteric dopaminergic neurons and SERT knock-out increased intestinal levels of dopamine metabolites, implying that enteric dopaminergic neurons receive a serotonergic innervation. Observations suggest that constitutive gastrointestinal motility depends more on neuronal than EC cell serotonin; moreover, serotonergic neurons promote development/survival of some classes of late-born enteric neurons, including dopaminergic neurons, which appear to innervate and activate in the adult ENS.</AbstractText
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Revisiting Cyanobacteria-Temperature Dynamics: Intraspecific Competition and Trait Diversity as Keys to Predicting Harmful Algal Blooms under Climate Change. Cyanobacterial harmful algal blooms are expanding spatiotemporally, with an increasing occurrence of cold-water cyanobacterial blooms (CWCBs), intensifying ecological and water quality challenges. While abiotic drivers have been identified as contributors to CWCBs, the role of biotic factors─particularly the adaptation induced by the shifts in intraspecific trait distributions─in this process remains largely unexplored. Here, we tested the hypothesis that the thermal history of cyanobacteria affects their thermal adaptations by reshaping the distribution of optimum growth temperature (<i
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37778105
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36263188
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37328296
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Determining the risk of spinal pathology progression in neurofibromatosis type 1 patients - a national tertiary neurofibromatosis type 1 centre study.
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Diagnosis and Treatment Strategies for Arachnoiditis Ossificans Following Subarachnoid Hemorrhage: A Case Report.
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Neural Signatures of Hierarchical Linguistic Structures in Second Language Listening Comprehension.
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Neurofibromatosis type 1 (NF1) gives rise to a variety of spinal pathologies that include dural ectasia (DE), vertebral malalignments (VMA), spinal deformities (SD), syrinx, meningoceles, spinal nerve root tumours (SNRT), and spinal plexiform tumours (SPT). The relationship between these and the progression of these pathologies has not been explored before in detail and this paper aims to address this.</AbstractText Data was retrospectively collected from adult NF1 multi-disciplinary team meetings from 2016 to 2022 involving a total of 593 patients with 20 distinct predictor variables. Data were analyzed utilizing; Chi-Square tests, binary logistic regression, and Kaplan-Meier analysis.</AbstractText SNRT (19.9%), SD (18.6%), and (17.7%) of VMA had the highest rates of progression. SD was significantly associated (p < 0.02) with the presence and progression of all spinal pathologies except for SPT. Statistically significant predictors of SD progression included the presence of DVA, VMA, syrinx, meningocele, and SNRT. Kaplan-Meier analysis revealed no statistically significant difference between the times to progression for SD (85 days), SNRT (1196 days), and VMA (2243 days).</AbstractText This paper explores for the first time in detail, the progression of various spinal pathologies in NF1. The presence and progression of SD is a key factor that correlated with the progression of different spinal pathologies. Early identification of SD may help support clinical decision-making and guide radiological follow-up protocols and treatment.</AbstractText
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Arachnoiditis ossificans (AO) is a rare disease, wherein ossified lesions in the subarachnoid space obstruct the flow of spinal fluid or compress the spinal cord, thereby causing myelopathy. Here we describe a rare case of AO and discuss the diagnosis and treatment strategies for this disease. A 66-year-old man with a history of subarachnoid hemorrhage presented with gait disturbance and dysuria for 7 months. Spinal magnetic resonance imaging and computed tomography (CT) myelography showed syringomyelia at the T5-T8 level and dorsally tethered spinal cord at the T8-T10 level. Preoperative noncontrast CT was not performed. The patient was diagnosed with adhesive arachnoiditis and underwent arachnoidolysis. However, intraoperative findings showed the presence of ossification lesions on the dorsal surface of the spinal cord, and intraoperative ultrasound (IOU) showed a hyperintense lesion with acoustic shadowing on the dorsal surface of the spinal cord, with limited visibility of the spinal cord. After removal of the lesions, IOU showed untethered and well-decompressed spinal cord and restoration of cerebrospinal fluid pulsation. Based on these findings, the patient was finally diagnosed with AO, which is an extremely rare disease, with an unknown frequency of occurrence. Therefore, all patients with adhesive spinal arachnoiditis require a preoperative noncontrast CT scan to evaluate for ossification lesions. In this case, we were fortunate to be able to treat AO with IOU, which demonstrated specific findings.</AbstractText
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Native speakers excel at parsing continuous speech into smaller elements and entraining their neural activities to the linguistic hierarchy at different levels (e.g., syllables, phrases, and sentences) to achieve speech comprehension. However, how a nonnative brain tracks hierarchical linguistic structures in second language (L2) speech comprehension and whether it relates to top-down attention and language proficiency remains elusive. Here, we applied a frequency-tagging paradigm in human adults and investigated the neural tracking responses to hierarchically organized linguistic structures (i.e., the syllabic rate of 4 Hz, the phrasal rate of 2 Hz, and the sentential rate of 1 Hz) in both first language (L1) and L2 listeners when they attended to a speech stream or ignored it. We revealed disrupted neural responses to higher-order linguistic structures (i.e., phrases and sentences) for L2 listeners in which the phrasal-level tracking was functionally related to an L2 subject's language proficiency. We also observed less efficient top-down modulation of attention in L2 speech comprehension than in L1 speech comprehension. Our results indicate that the reduced δ-band neuronal oscillations that subserve the internal construction of higher-order linguistic structures may compromise listening comprehension in a nonnative language.</AbstractText
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Determining the risk of spinal pathology progression in neurofibromatosis type 1 patients - a national tertiary neurofibromatosis type 1 centre study. Neurofibromatosis type 1 (NF1) gives rise to a variety of spinal pathologies that include dural ectasia (DE), vertebral malalignments (VMA), spinal deformities (SD), syrinx, meningoceles, spinal nerve root tumours (SNRT), and spinal plexiform tumours (SPT). The relationship between these and the progression of these pathologies has not been explored before in detail and this paper aims to address this.</AbstractText Data was retrospectively collected from adult NF1 multi-disciplinary team meetings from 2016 to 2022 involving a total of 593 patients with 20 distinct predictor variables. Data were analyzed utilizing; Chi-Square tests, binary logistic regression, and Kaplan-Meier analysis.</AbstractText SNRT (19.9%), SD (18.6%), and (17.7%) of VMA had the highest rates of progression. SD was significantly associated (p < 0.02) with the presence and progression of all spinal pathologies except for SPT. Statistically significant predictors of SD progression included the presence of DVA, VMA, syrinx, meningocele, and SNRT. Kaplan-Meier analysis revealed no statistically significant difference between the times to progression for SD (85 days), SNRT (1196 days), and VMA (2243 days).</AbstractText This paper explores for the first time in detail, the progression of various spinal pathologies in NF1. The presence and progression of SD is a key factor that correlated with the progression of different spinal pathologies. Early identification of SD may help support clinical decision-making and guide radiological follow-up protocols and treatment.</AbstractText
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Diagnosis and Treatment Strategies for Arachnoiditis Ossificans Following Subarachnoid Hemorrhage: A Case Report. Arachnoiditis ossificans (AO) is a rare disease, wherein ossified lesions in the subarachnoid space obstruct the flow of spinal fluid or compress the spinal cord, thereby causing myelopathy. Here we describe a rare case of AO and discuss the diagnosis and treatment strategies for this disease. A 66-year-old man with a history of subarachnoid hemorrhage presented with gait disturbance and dysuria for 7 months. Spinal magnetic resonance imaging and computed tomography (CT) myelography showed syringomyelia at the T5-T8 level and dorsally tethered spinal cord at the T8-T10 level. Preoperative noncontrast CT was not performed. The patient was diagnosed with adhesive arachnoiditis and underwent arachnoidolysis. However, intraoperative findings showed the presence of ossification lesions on the dorsal surface of the spinal cord, and intraoperative ultrasound (IOU) showed a hyperintense lesion with acoustic shadowing on the dorsal surface of the spinal cord, with limited visibility of the spinal cord. After removal of the lesions, IOU showed untethered and well-decompressed spinal cord and restoration of cerebrospinal fluid pulsation. Based on these findings, the patient was finally diagnosed with AO, which is an extremely rare disease, with an unknown frequency of occurrence. Therefore, all patients with adhesive spinal arachnoiditis require a preoperative noncontrast CT scan to evaluate for ossification lesions. In this case, we were fortunate to be able to treat AO with IOU, which demonstrated specific findings.</AbstractText
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Neural Signatures of Hierarchical Linguistic Structures in Second Language Listening Comprehension. Native speakers excel at parsing continuous speech into smaller elements and entraining their neural activities to the linguistic hierarchy at different levels (e.g., syllables, phrases, and sentences) to achieve speech comprehension. However, how a nonnative brain tracks hierarchical linguistic structures in second language (L2) speech comprehension and whether it relates to top-down attention and language proficiency remains elusive. Here, we applied a frequency-tagging paradigm in human adults and investigated the neural tracking responses to hierarchically organized linguistic structures (i.e., the syllabic rate of 4 Hz, the phrasal rate of 2 Hz, and the sentential rate of 1 Hz) in both first language (L1) and L2 listeners when they attended to a speech stream or ignored it. We revealed disrupted neural responses to higher-order linguistic structures (i.e., phrases and sentences) for L2 listeners in which the phrasal-level tracking was functionally related to an L2 subject's language proficiency. We also observed less efficient top-down modulation of attention in L2 speech comprehension than in L1 speech comprehension. Our results indicate that the reduced δ-band neuronal oscillations that subserve the internal construction of higher-order linguistic structures may compromise listening comprehension in a nonnative language.</AbstractText
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37137528
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30965199
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35904594
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Restless leg syndrome in rheumatic conditions: Its prevalence and risk factors, a meta-analysis.
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Neurochemical features of idiopathic restless legs syndrome.
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Characterization of the angular gyrus in an older adult population: a multimodal multilevel approach.
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Restless leg syndrome (RLS) is a neurological disorder characterized by an uncontrollable desire to move legs along with abnormal sensations, particularly at night, which can lead to sleep disturbance. RLS may mimic rheumatic diseases or can be associated with them, hence their identification and treatment are important to improve sleep quality and overall quality of life in rheumatic diseases.</AbstractText We conducted a search of the PubMed, SCOPUS, and EMBASE databases to identify studies reporting a prevalence of RLS in patients with rheumatic disease. Two authors independently screened, selected, and extracted the data. Heterogeneity was assessed using I<sup Out of 273 unique records, 17 eligible studies including 2406 rheumatic patients were identified. RLS prevalence (95% CI) among patients of rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, fibromyalgia and ankylosing spondylitis are found to be 26.6% (18.6 34.6); 32.5% (23.1-41.9), 4.4% (2.0-6.8), 38.1% (31.3-45.0) and 30.8% (23.48-39.16) respectively. RLS prevalence was similar for males and females.</AbstractText Our study indicates a high prevalence of RLS in patients with rheumatic diseases. Early detection and treatment of RLS in patients with rheumatic conditions could be beneficial in improving their overall health and quality of life.</AbstractText
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The most important traditional hypotheses of the pathogenesis of idiopathic restless legs syndrome (iRLS) involve dopaminergic dysfunction and iron deficiency. However, a possible role of other neurotransmitter or neuromodulators, mainly glutamate, gamma-hydroxybutyric acid (GABA), and adenosine have been suggested in recent reports. Moreover, iron deficiency in experimental models (which causes sensorimotor symptoms resembling those of RLS) is able to induce changes in dopaminergic, glutamatergic and adenosinergic neurotransmission, thus suggesting its crucial role in the pathogenesis of this disease. Relationship between iRLS and opiates, oxidative stress and nitric oxide, and with vitamin D deficiency has also been reported, although data regarding these variables should be considered as preliminary. In this review, we focus on studies relating to neurochemical findings in iRLS.</AbstractText
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The angular gyrus (AG) has been associated with multiple cognitive functions, such as language, spatial and memory functions. Since the AG is thought to be a cross-modal hub region suffering from significant age-related structural atrophy, it may also play a key role in age-related cognitive decline. However, the exact relation between structural atrophy of the AG and cognitive decline in older adults is not fully understood, which may be related to two aspects: First, the AG is cytoarchitectonically divided into two areas, PGa and PGp, potentially sub-serving different cognitive functions. Second, the older adult population is characterized by high between-subjects variability which requires targeting individual phenomena during the aging process. We therefore performed a multimodal (gray matter volume [GMV], resting-state functional connectivity [RSFC] and structural connectivity [SC]) characterization of AG subdivisions PGa and PGp in a large older adult population, together with relations to age, cognition and lifestyle on the group level. Afterwards, we switched the perspective to the individual, which is especially important when it comes to the assessment of individual patients. The AG can be considered a heterogeneous structure in of the older brain: we found the different AG parts to be associated with different patterns of whole-brain GMV associations as well as their associations with RSFC, and SC patterns. Similarly, differential effects of age, cognition and lifestyle on the GMV of AG subdivisions were observed. This suggests each region to be structurally and functionally differentially involved in the older adult's brain network architecture, which was supported by differential molecular and genetic patterns, derived from the EBRAINS multilevel atlas framework. Importantly, individual profiles deviated considerably from the global conclusion drawn from the group study. Hence, general observations within the older adult population need to be carefully considered, when addressing individual conditions in clinical practice.</AbstractText
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Restless leg syndrome in rheumatic conditions: Its prevalence and risk factors, a meta-analysis. Restless leg syndrome (RLS) is a neurological disorder characterized by an uncontrollable desire to move legs along with abnormal sensations, particularly at night, which can lead to sleep disturbance. RLS may mimic rheumatic diseases or can be associated with them, hence their identification and treatment are important to improve sleep quality and overall quality of life in rheumatic diseases.</AbstractText We conducted a search of the PubMed, SCOPUS, and EMBASE databases to identify studies reporting a prevalence of RLS in patients with rheumatic disease. Two authors independently screened, selected, and extracted the data. Heterogeneity was assessed using I<sup Out of 273 unique records, 17 eligible studies including 2406 rheumatic patients were identified. RLS prevalence (95% CI) among patients of rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, fibromyalgia and ankylosing spondylitis are found to be 26.6% (18.6 34.6); 32.5% (23.1-41.9), 4.4% (2.0-6.8), 38.1% (31.3-45.0) and 30.8% (23.48-39.16) respectively. RLS prevalence was similar for males and females.</AbstractText Our study indicates a high prevalence of RLS in patients with rheumatic diseases. Early detection and treatment of RLS in patients with rheumatic conditions could be beneficial in improving their overall health and quality of life.</AbstractText
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Neurochemical features of idiopathic restless legs syndrome. The most important traditional hypotheses of the pathogenesis of idiopathic restless legs syndrome (iRLS) involve dopaminergic dysfunction and iron deficiency. However, a possible role of other neurotransmitter or neuromodulators, mainly glutamate, gamma-hydroxybutyric acid (GABA), and adenosine have been suggested in recent reports. Moreover, iron deficiency in experimental models (which causes sensorimotor symptoms resembling those of RLS) is able to induce changes in dopaminergic, glutamatergic and adenosinergic neurotransmission, thus suggesting its crucial role in the pathogenesis of this disease. Relationship between iRLS and opiates, oxidative stress and nitric oxide, and with vitamin D deficiency has also been reported, although data regarding these variables should be considered as preliminary. In this review, we focus on studies relating to neurochemical findings in iRLS.</AbstractText
|
Characterization of the angular gyrus in an older adult population: a multimodal multilevel approach. The angular gyrus (AG) has been associated with multiple cognitive functions, such as language, spatial and memory functions. Since the AG is thought to be a cross-modal hub region suffering from significant age-related structural atrophy, it may also play a key role in age-related cognitive decline. However, the exact relation between structural atrophy of the AG and cognitive decline in older adults is not fully understood, which may be related to two aspects: First, the AG is cytoarchitectonically divided into two areas, PGa and PGp, potentially sub-serving different cognitive functions. Second, the older adult population is characterized by high between-subjects variability which requires targeting individual phenomena during the aging process. We therefore performed a multimodal (gray matter volume [GMV], resting-state functional connectivity [RSFC] and structural connectivity [SC]) characterization of AG subdivisions PGa and PGp in a large older adult population, together with relations to age, cognition and lifestyle on the group level. Afterwards, we switched the perspective to the individual, which is especially important when it comes to the assessment of individual patients. The AG can be considered a heterogeneous structure in of the older brain: we found the different AG parts to be associated with different patterns of whole-brain GMV associations as well as their associations with RSFC, and SC patterns. Similarly, differential effects of age, cognition and lifestyle on the GMV of AG subdivisions were observed. This suggests each region to be structurally and functionally differentially involved in the older adult's brain network architecture, which was supported by differential molecular and genetic patterns, derived from the EBRAINS multilevel atlas framework. Importantly, individual profiles deviated considerably from the global conclusion drawn from the group study. Hence, general observations within the older adult population need to be carefully considered, when addressing individual conditions in clinical practice.</AbstractText
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40442895
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31215107
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40672157
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Mathematical Model Analysis in Dynamic Contrast-Enhanced Magnetic Resonance Imaging: A Predictive Approach for Joint Deformity Progression in Rheumatoid Arthritis.
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New parameters of ultrafast dynamic contrast-enhanced breast MRI using compressed sensing.
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Modeling Laryngeal Dystonia through Spectral Analyses of Vocalizations in a Dystonia Mouse Model.
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Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) offers quantitative insights into synovitis by evaluating vascular changes. However, its potential to predict progressive bone destruction in rheumatoid arthritis (RA) remains unclear. This study aimed to identify DCE-MRI parameters that predict joint deformity progression and establish their clinical relevance.</AbstractText This prospective cohort study included 24 RA patients undergoing DCE-MRI at baseline and after treatment initiation. Radiographic progression was assessed using the modified total Sharp score 1 year after the second DCE-MRI. Histogram analysis of the enhanced synovium was performed using a mathematical model to derive parameters, including β (washout rate) and signal enhancement ratio (SER). The differences in mathematical parameters between the groups were statistically evaluated using the Mann-Whitney U test.</AbstractText Clinical factors, including 28-joint disease activity score (DAS28)-erythrocyte sedimentation rate and visual analog scale scores, were elevated in the progression group (p = 0.001 and p = 0.02, respectively). Patients with progressive bone destruction exhibited significantly higher posttreatment β and SER values (p = 0.023 and p = 0.03, respectively), reflecting delayed-phase curve patterns associated with angiogenesis and increased vascular permeability. No significant differences in the volume of enhanced synovium or Rheumatoid Arthritis Magnetic Resonance Imaging Score synovitis scores were observed. There was no difference between the groups in the change in clinical parameters.</AbstractText Posttreatment β and SER values derived from DCE-MRI may serve as predictive markers of future bone destruction in RA. These findings highlight the potential of DCE-MRI in guiding therapeutic decisions. Future studies with larger cohorts and automated analysis methods are warranted to validate these results and enhance clinical feasibility.</AbstractText
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Ultrafast dynamic contrast-enhanced (UF-DCE) breast MRI is considered a promising method of accelerated breast MRI. However, the value of new kinetic parameters derived from UF-DCE need clinical evaluation.</AbstractText To evaluate the diagnostic performance of the maximum slope (MS), time to enhancement (TTE), and time interval between arterial and venous visualization (AVI) derived from UF-DCE MRI using compressed sensing (CS).</AbstractText Retrospective.</AbstractText Seventy-five patients with histologically proven breast lesions. The total number of analyzed lesions was 90 (61 malignant and 29 benign).</AbstractText 3T MRI with UF-DCE MRI based on the 3D gradient-echo volumetric interpolated breath-hold examination (VIBE) sequence using incoherent k-space sampling combined with a CS reconstruction followed by conventional DCE MRI.</AbstractText The diagnostic performance of the MS, TTE, AVI, and conventional kinetic analysis was analyzed and compared with histology.</AbstractText Wilcoxon rank sum test, receiver operating characteristic analysis.</AbstractText The MS was larger and the TTE and AVI were smaller for malignant lesions compared with benign lesions: MS: 29.3%/s and 18.4%/s (P < 0.001), TTE: 7.0 and 12.0 seconds (P < 0.001), AVI: 2.7 and 4.4 frames (P = 0.006) for malignant and benign lesions. The discriminating power of the MS (area under the curve [AUC], 0.76) was slightly better than that of conventional kinetic analysis (AUC, 0.69) and comparable to that of the TTE and AVI (AUC, 0.78 and 0.76 for TTE and AVI, respectively). Invasive lobular carcinoma had smaller MS (21.8%/s) among malignant lesions (29.3%/s).</AbstractText The MS, TTE, and AVI can be used to evaluate breast lesions with clinical performance equivalent to that of conventional kinetic analysis. These parameters vary among histologies.</AbstractText 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:164-174.</AbstractText
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Laryngeal dystonia is a task-specific, focal dystonia that disrupts vocal-motor control and significantly alters quality of life through impaired communication. Despite its early onset in many hereditary dystonias, effective treatments remain limited, in part due to the lack of a preclinical model that captures its circuit-level pathophysiology. Our experiment evaluates ultrasonic vocalizations (USVs) in <i
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Mathematical Model Analysis in Dynamic Contrast-Enhanced Magnetic Resonance Imaging: A Predictive Approach for Joint Deformity Progression in Rheumatoid Arthritis. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) offers quantitative insights into synovitis by evaluating vascular changes. However, its potential to predict progressive bone destruction in rheumatoid arthritis (RA) remains unclear. This study aimed to identify DCE-MRI parameters that predict joint deformity progression and establish their clinical relevance.</AbstractText This prospective cohort study included 24 RA patients undergoing DCE-MRI at baseline and after treatment initiation. Radiographic progression was assessed using the modified total Sharp score 1 year after the second DCE-MRI. Histogram analysis of the enhanced synovium was performed using a mathematical model to derive parameters, including β (washout rate) and signal enhancement ratio (SER). The differences in mathematical parameters between the groups were statistically evaluated using the Mann-Whitney U test.</AbstractText Clinical factors, including 28-joint disease activity score (DAS28)-erythrocyte sedimentation rate and visual analog scale scores, were elevated in the progression group (p = 0.001 and p = 0.02, respectively). Patients with progressive bone destruction exhibited significantly higher posttreatment β and SER values (p = 0.023 and p = 0.03, respectively), reflecting delayed-phase curve patterns associated with angiogenesis and increased vascular permeability. No significant differences in the volume of enhanced synovium or Rheumatoid Arthritis Magnetic Resonance Imaging Score synovitis scores were observed. There was no difference between the groups in the change in clinical parameters.</AbstractText Posttreatment β and SER values derived from DCE-MRI may serve as predictive markers of future bone destruction in RA. These findings highlight the potential of DCE-MRI in guiding therapeutic decisions. Future studies with larger cohorts and automated analysis methods are warranted to validate these results and enhance clinical feasibility.</AbstractText
|
New parameters of ultrafast dynamic contrast-enhanced breast MRI using compressed sensing. Ultrafast dynamic contrast-enhanced (UF-DCE) breast MRI is considered a promising method of accelerated breast MRI. However, the value of new kinetic parameters derived from UF-DCE need clinical evaluation.</AbstractText To evaluate the diagnostic performance of the maximum slope (MS), time to enhancement (TTE), and time interval between arterial and venous visualization (AVI) derived from UF-DCE MRI using compressed sensing (CS).</AbstractText Retrospective.</AbstractText Seventy-five patients with histologically proven breast lesions. The total number of analyzed lesions was 90 (61 malignant and 29 benign).</AbstractText 3T MRI with UF-DCE MRI based on the 3D gradient-echo volumetric interpolated breath-hold examination (VIBE) sequence using incoherent k-space sampling combined with a CS reconstruction followed by conventional DCE MRI.</AbstractText The diagnostic performance of the MS, TTE, AVI, and conventional kinetic analysis was analyzed and compared with histology.</AbstractText Wilcoxon rank sum test, receiver operating characteristic analysis.</AbstractText The MS was larger and the TTE and AVI were smaller for malignant lesions compared with benign lesions: MS: 29.3%/s and 18.4%/s (P < 0.001), TTE: 7.0 and 12.0 seconds (P < 0.001), AVI: 2.7 and 4.4 frames (P = 0.006) for malignant and benign lesions. The discriminating power of the MS (area under the curve [AUC], 0.76) was slightly better than that of conventional kinetic analysis (AUC, 0.69) and comparable to that of the TTE and AVI (AUC, 0.78 and 0.76 for TTE and AVI, respectively). Invasive lobular carcinoma had smaller MS (21.8%/s) among malignant lesions (29.3%/s).</AbstractText The MS, TTE, and AVI can be used to evaluate breast lesions with clinical performance equivalent to that of conventional kinetic analysis. These parameters vary among histologies.</AbstractText 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:164-174.</AbstractText
|
Modeling Laryngeal Dystonia through Spectral Analyses of Vocalizations in a Dystonia Mouse Model. Laryngeal dystonia is a task-specific, focal dystonia that disrupts vocal-motor control and significantly alters quality of life through impaired communication. Despite its early onset in many hereditary dystonias, effective treatments remain limited, in part due to the lack of a preclinical model that captures its circuit-level pathophysiology. Our experiment evaluates ultrasonic vocalizations (USVs) in <i
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40775657
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38831756
|
40610604
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Integrated molecular and detailed anatomical profiling identifies a prognostically adverse subtype of posterior fossa meningiomas: high-risk copy number alterations are associated with midline predilection and predict poor prognosis.
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Prognostic stratification of glioblastoma patients by unsupervised clustering of morphology patterns on whole slide images furthering our disease understanding.
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Molecular and functional diversity of the autonomic nervous system.
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Anatomical localization of meningiomas has been increasingly linked to their genetic alterations. However, studies focusing specifically on the genomic landscape and clinical implications of posterior fossa meningiomas remain limited. In this study, we investigated the genetic, anatomical, and clinical characteristics of posterior fossa meningiomas, aiming to clarify the association between genetic alterations, precise tumor localization, and prognosis. Whole-exome sequencing was performed on 132 consecutive tumors to identify driver mutations and copy number alterations (CNAs). Tumor localization was carefully assessed based on dural attachment, arterial supply, and intraoperative findings. Based on driver mutations and CNAs, tumors were classified into three molecular groups: Group A (no Merlin pathway alterations, n = 71 (54%)), Group B (NF2 mutation/22q loss without high-risk CNAs, n = 45 (34%)), and Group C (high-risk CNAs, n = 16 (12%)). Notably, Group C showed a strong anatomical predilection, with 81% arising from midline structures, including the medial incisura and clivus. Group C tumors were significantly associated with poor progression-free survival following gross total resection (P = 0.023), and this remained significant even when the analysis was anatomically restricted to tumors located in the medial incisura and clivus (P = 0.0003). In multivariable analysis, Group C (P = 0.020, HR 6.60) and preoperative tumor volume > 10 cc (P = 0.044, HR 9.41) independently predicted poor prognosis. Overall, the results demonstrated that approximately 10% of posterior fossa meningiomas harbored high-risk CNAs, predominantly in midline locations, and were associated with worse clinical outcomes. CNA profiling in addition to the identification of driver mutations may provide a valuable tool for risk stratification and decision-making regarding adjuvant therapy in posterior fossa meningiomas.</AbstractText
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Glioblastoma (GBM) is a highly aggressive malignant tumor of the central nervous system that displays varying molecular and morphological profiles, leading to challenging prognostic assessments. Stratifying GBM patients according to overall survival (OS) from H&E-stained whole slide images (WSI) using advanced computational methods is challenging, but with direct clinical implications.</AbstractText This work is focusing on GBM (IDH-wildtype, CNS WHO Gr.4) cases, identified from the TCGA-GBM and TCGA-LGG collections after considering the 2021 WHO classification criteria. The proposed approach starts with patch extraction in each WSI, followed by comprehensive patch-level curation to discard artifactual content, i.e., glass reflections, pen markings, dust on the slide, and tissue tearing. Each patch is then computationally described as a feature vector defined by a pre-trained VGG16 convolutional neural network. Principal component analysis provides a feature representation of reduced dimensionality, further facilitating identification of distinct groups of morphology patterns, via unsupervised k-means clustering.</AbstractText The optimal number of clusters, according to cluster reproducibility and separability, is automatically determined based on the rand index and silhouette coefficient, respectively. Our proposed approach achieved prognostic stratification accuracy of 83.33% on a multi-institutional independent unseen hold-out test set with sensitivity and specificity of 83.33%.</AbstractText We hypothesize that the quantification of these clusters of morphology patterns, reflect the tumor's spatial heterogeneity and yield prognostic relevant information to distinguish between short and long survivors using a decision tree classifier. The interpretability analysis of the obtained results can contribute to furthering and quantifying our understanding of GBM and potentially improving our diagnostic and prognostic predictions.</AbstractText
|
The autonomic nervous system (ANS) plays a pivotal role in regulating organ functions through descending brain-to-body signalling. The pathways involved are broadly categorized into two major branches: the sympathetic nervous system, which mediates 'fight or flight' responses, and the parasympathetic nervous system, which governs 'rest and digest' functions. Historically, the ANS was considered to mediate simple motor functions with limited neurochemical diversity. However, recent advances in neurotechnology have shown that brain-to-body communication is more complex and dynamic than previously appreciated. This review synthesizes current knowledge about the molecular, anatomical and functional diversity of autonomic motor neurons. Here we present a comparative analysis of the cellular architecture of the ANS and the suggested roles of distinct neuron populations. Additionally, we explore the emerging view that the ANS interacts with diverse systems involving metabolism, immunology and ageing, which extends its role beyond simple brain-organ modulation. Finally, we emphasize the need for cell-type-specific and longitudinal studies of the ANS to uncover novel mechanisms underlying body-brain interactions and to identify new translational opportunities for therapeutic interventions.</AbstractText
|
Integrated molecular and detailed anatomical profiling identifies a prognostically adverse subtype of posterior fossa meningiomas: high-risk copy number alterations are associated with midline predilection and predict poor prognosis. Anatomical localization of meningiomas has been increasingly linked to their genetic alterations. However, studies focusing specifically on the genomic landscape and clinical implications of posterior fossa meningiomas remain limited. In this study, we investigated the genetic, anatomical, and clinical characteristics of posterior fossa meningiomas, aiming to clarify the association between genetic alterations, precise tumor localization, and prognosis. Whole-exome sequencing was performed on 132 consecutive tumors to identify driver mutations and copy number alterations (CNAs). Tumor localization was carefully assessed based on dural attachment, arterial supply, and intraoperative findings. Based on driver mutations and CNAs, tumors were classified into three molecular groups: Group A (no Merlin pathway alterations, n = 71 (54%)), Group B (NF2 mutation/22q loss without high-risk CNAs, n = 45 (34%)), and Group C (high-risk CNAs, n = 16 (12%)). Notably, Group C showed a strong anatomical predilection, with 81% arising from midline structures, including the medial incisura and clivus. Group C tumors were significantly associated with poor progression-free survival following gross total resection (P = 0.023), and this remained significant even when the analysis was anatomically restricted to tumors located in the medial incisura and clivus (P = 0.0003). In multivariable analysis, Group C (P = 0.020, HR 6.60) and preoperative tumor volume > 10 cc (P = 0.044, HR 9.41) independently predicted poor prognosis. Overall, the results demonstrated that approximately 10% of posterior fossa meningiomas harbored high-risk CNAs, predominantly in midline locations, and were associated with worse clinical outcomes. CNA profiling in addition to the identification of driver mutations may provide a valuable tool for risk stratification and decision-making regarding adjuvant therapy in posterior fossa meningiomas.</AbstractText
|
Prognostic stratification of glioblastoma patients by unsupervised clustering of morphology patterns on whole slide images furthering our disease understanding. Glioblastoma (GBM) is a highly aggressive malignant tumor of the central nervous system that displays varying molecular and morphological profiles, leading to challenging prognostic assessments. Stratifying GBM patients according to overall survival (OS) from H&E-stained whole slide images (WSI) using advanced computational methods is challenging, but with direct clinical implications.</AbstractText This work is focusing on GBM (IDH-wildtype, CNS WHO Gr.4) cases, identified from the TCGA-GBM and TCGA-LGG collections after considering the 2021 WHO classification criteria. The proposed approach starts with patch extraction in each WSI, followed by comprehensive patch-level curation to discard artifactual content, i.e., glass reflections, pen markings, dust on the slide, and tissue tearing. Each patch is then computationally described as a feature vector defined by a pre-trained VGG16 convolutional neural network. Principal component analysis provides a feature representation of reduced dimensionality, further facilitating identification of distinct groups of morphology patterns, via unsupervised k-means clustering.</AbstractText The optimal number of clusters, according to cluster reproducibility and separability, is automatically determined based on the rand index and silhouette coefficient, respectively. Our proposed approach achieved prognostic stratification accuracy of 83.33% on a multi-institutional independent unseen hold-out test set with sensitivity and specificity of 83.33%.</AbstractText We hypothesize that the quantification of these clusters of morphology patterns, reflect the tumor's spatial heterogeneity and yield prognostic relevant information to distinguish between short and long survivors using a decision tree classifier. The interpretability analysis of the obtained results can contribute to furthering and quantifying our understanding of GBM and potentially improving our diagnostic and prognostic predictions.</AbstractText
|
Molecular and functional diversity of the autonomic nervous system. The autonomic nervous system (ANS) plays a pivotal role in regulating organ functions through descending brain-to-body signalling. The pathways involved are broadly categorized into two major branches: the sympathetic nervous system, which mediates 'fight or flight' responses, and the parasympathetic nervous system, which governs 'rest and digest' functions. Historically, the ANS was considered to mediate simple motor functions with limited neurochemical diversity. However, recent advances in neurotechnology have shown that brain-to-body communication is more complex and dynamic than previously appreciated. This review synthesizes current knowledge about the molecular, anatomical and functional diversity of autonomic motor neurons. Here we present a comparative analysis of the cellular architecture of the ANS and the suggested roles of distinct neuron populations. Additionally, we explore the emerging view that the ANS interacts with diverse systems involving metabolism, immunology and ageing, which extends its role beyond simple brain-organ modulation. Finally, we emphasize the need for cell-type-specific and longitudinal studies of the ANS to uncover novel mechanisms underlying body-brain interactions and to identify new translational opportunities for therapeutic interventions.</AbstractText
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40733502
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27687129
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40683805
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The Role of Autophagy in HIV Infection and Immunological Recovery of ART-Treated PLWH.
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Flux of signalling endosomes undergoing axonal retrograde transport is encoded by presynaptic activity and TrkB.
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Response of the Conox quantitative electroencephalographic monitor to neuromuscular block in awake volunteers.
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Human immunodeficiency virus (HIV) is responsible for acquired immunodeficiency syndrome (AIDS), a condition characterized by the depletion of CD4+ T lymphocytes, which predisposes individuals to opportunistic infections and, ultimately, death. Although antiretroviral therapy (ART) has substantially improved clinical outcomes, certain limitations persist. Notably, 15-30% of individuals undergoing ART achieve viral suppression but fail to restore adequate CD4+ T cell counts, being defined as immunological non-responders (INR) and remaining at increased risk of disease progression to AIDS. The impaired immune recovery in INRs is attributed to insufficient production and/or excessive destruction of CD4+ T lymphocytes, which can be modulated by autophagy process. This evolutionarily conserved mechanism is fundamental to lymphocyte development and activation as well as to programmed cell death pathways such as apoptosis, necroptosis, ferroptosis, and pyroptosis. These pathways are essential for understanding the impaired immune reconstitution observed in people living with HIV, whose inability to maintain immune homeostasis contributes to accelerated disease progression. This review explores the interplay between autophagy, HIV, and cell death mechanisms, highlighting its relevance in immunological recovery under ART and its potential as a therapeutic target.</AbstractText
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Axonal retrograde transport of signalling endosomes from the nerve terminal to the soma underpins survival. As each signalling endosome carries a quantal amount of activated receptors, we hypothesized that it is the frequency of endosomes reaching the soma that determines the scale of the trophic signal. Here we show that upregulating synaptic activity markedly increased the flux of plasma membrane-derived retrograde endosomes (labelled using cholera toxin subunit-B: CTB) in hippocampal neurons cultured in microfluidic devices, and live Drosophila larval motor neurons. Electron and super-resolution microscopy analyses revealed that the fast-moving sub-diffraction-limited CTB carriers contained the TrkB neurotrophin receptor, transiently activated by synaptic activity in a BDNF-independent manner. Pharmacological and genetic inhibition of TrkB activation selectively prevented the coupling between synaptic activity and the retrograde flux of signalling endosomes. TrkB activity therefore controls the encoding of synaptic activity experienced by nerve terminals, digitalized as the flux of retrogradely transported signalling endosomes.</AbstractText
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The Conox monitor analyses the frontal EEG to generate two indices of anaesthetic effects: qCON, intended to indicate the level of consciousness, and qNOX, designed to reflect responsiveness to noxious stimuli. Two similar quantitative EEG devices, BIS and Entropy, have been shown to require muscle activity (EMG) to generate accurate index values in awake individuals. Without EMG, these devices produce misleadingly low values and incorrectly suggest sedation or anaesthesia despite the cortical EEG showing the subjects are awake. As EMG affects frequency bands used by Conox, it too could be incorporating muscle activity to generate high values in awake individuals.</AbstractText We replayed EEGs recorded during awake paralysis to the Conox monitor via an electronic playback system to test whether it requires EMG to generate accurate values in awake subjects.</AbstractText Both qCON and qNOX decreased after neuromuscular block to values consistent with sedation or anaesthesia, despite subjects being fully awake. qCON decreased below 60 in 15 of 19 trials, and qNOX decreased below 60 in 11 of 19 trials. Overall, 42% of qCON values during paralysis were <60, the level supposedly indicating anaesthesia.</AbstractText Conox requires muscle activity to generate accurate values in awake individuals. Consequently, it might be an unreliable indicator of awareness in patients who have received neuromuscular blocking drugs. Studies conducted without neuromuscular block can provide misleading guidance when applied to Conox use in paralysed patients. Clinicians should approach manufacturer guidelines with caution and not rely solely on index values to guide dosing of anaesthetic drugs.</AbstractText
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The Role of Autophagy in HIV Infection and Immunological Recovery of ART-Treated PLWH. Human immunodeficiency virus (HIV) is responsible for acquired immunodeficiency syndrome (AIDS), a condition characterized by the depletion of CD4+ T lymphocytes, which predisposes individuals to opportunistic infections and, ultimately, death. Although antiretroviral therapy (ART) has substantially improved clinical outcomes, certain limitations persist. Notably, 15-30% of individuals undergoing ART achieve viral suppression but fail to restore adequate CD4+ T cell counts, being defined as immunological non-responders (INR) and remaining at increased risk of disease progression to AIDS. The impaired immune recovery in INRs is attributed to insufficient production and/or excessive destruction of CD4+ T lymphocytes, which can be modulated by autophagy process. This evolutionarily conserved mechanism is fundamental to lymphocyte development and activation as well as to programmed cell death pathways such as apoptosis, necroptosis, ferroptosis, and pyroptosis. These pathways are essential for understanding the impaired immune reconstitution observed in people living with HIV, whose inability to maintain immune homeostasis contributes to accelerated disease progression. This review explores the interplay between autophagy, HIV, and cell death mechanisms, highlighting its relevance in immunological recovery under ART and its potential as a therapeutic target.</AbstractText
|
Flux of signalling endosomes undergoing axonal retrograde transport is encoded by presynaptic activity and TrkB. Axonal retrograde transport of signalling endosomes from the nerve terminal to the soma underpins survival. As each signalling endosome carries a quantal amount of activated receptors, we hypothesized that it is the frequency of endosomes reaching the soma that determines the scale of the trophic signal. Here we show that upregulating synaptic activity markedly increased the flux of plasma membrane-derived retrograde endosomes (labelled using cholera toxin subunit-B: CTB) in hippocampal neurons cultured in microfluidic devices, and live Drosophila larval motor neurons. Electron and super-resolution microscopy analyses revealed that the fast-moving sub-diffraction-limited CTB carriers contained the TrkB neurotrophin receptor, transiently activated by synaptic activity in a BDNF-independent manner. Pharmacological and genetic inhibition of TrkB activation selectively prevented the coupling between synaptic activity and the retrograde flux of signalling endosomes. TrkB activity therefore controls the encoding of synaptic activity experienced by nerve terminals, digitalized as the flux of retrogradely transported signalling endosomes.</AbstractText
|
Response of the Conox quantitative electroencephalographic monitor to neuromuscular block in awake volunteers. The Conox monitor analyses the frontal EEG to generate two indices of anaesthetic effects: qCON, intended to indicate the level of consciousness, and qNOX, designed to reflect responsiveness to noxious stimuli. Two similar quantitative EEG devices, BIS and Entropy, have been shown to require muscle activity (EMG) to generate accurate index values in awake individuals. Without EMG, these devices produce misleadingly low values and incorrectly suggest sedation or anaesthesia despite the cortical EEG showing the subjects are awake. As EMG affects frequency bands used by Conox, it too could be incorporating muscle activity to generate high values in awake individuals.</AbstractText We replayed EEGs recorded during awake paralysis to the Conox monitor via an electronic playback system to test whether it requires EMG to generate accurate values in awake subjects.</AbstractText Both qCON and qNOX decreased after neuromuscular block to values consistent with sedation or anaesthesia, despite subjects being fully awake. qCON decreased below 60 in 15 of 19 trials, and qNOX decreased below 60 in 11 of 19 trials. Overall, 42% of qCON values during paralysis were <60, the level supposedly indicating anaesthesia.</AbstractText Conox requires muscle activity to generate accurate values in awake individuals. Consequently, it might be an unreliable indicator of awareness in patients who have received neuromuscular blocking drugs. Studies conducted without neuromuscular block can provide misleading guidance when applied to Conox use in paralysed patients. Clinicians should approach manufacturer guidelines with caution and not rely solely on index values to guide dosing of anaesthetic drugs.</AbstractText
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39664106
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38019287
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38417152
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Diagnostic Accuracy of Screening Tests for Diabetic Peripheral Neuropathy: An Umbrella Review.
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A diminished sciatic nerve structural integrity is associated with distinct peripheral sensory phenotypes in individuals with type 2 diabetes.
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Irregularity of instantaneous gamma frequency in the motor control network characterize visuomotor and proprioceptive information processing.
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Peripheral neuropathy is a common cause of morbidity in diabetes. Despite recent advancements in early diagnosis methods, there is a need for practical, highly sensitive, and cost-effective screening methods in clinical practice. This study summarizes evidence from systematic reviews and meta-analyses on the diagnostic accuracy of validated screening methods for diabetic peripheral neuropathy. Two independent reviewers assessed methodological quality and bias using AMSTAR and ROBIS tools. Seven reviews with 19,531 participants were included. The monofilament test showed inconsistent sensitivity (<i
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Quantitative sensory testing (QST) allows the identification of individuals with rapid progression of diabetic sensorimotor polyneuropathy (DSPN) based on certain sensory phenotypes. Hence, the aim of this study was to investigate the relationship of these phenotypes with the structural integrity of the sciatic nerve among individuals with type 2 diabetes.</AbstractText Seventy-six individuals with type 2 diabetes took part in this cross-sectional study and underwent QST of the right foot and high-resolution magnetic resonance neurography including diffusion tensor imaging of the right distal sciatic nerve to determine the sciatic nerve fractional anisotropy (FA) and cross-sectional area (CSA), both of which serve as markers of structural integrity of peripheral nerves. Participants were then assigned to four sensory phenotypes (participants with type 2 diabetes and healthy sensory profile [HSP], thermal hyperalgesia [TH], mechanical hyperalgesia [MH], sensory loss [SL]) by a standardised sorting algorithm based on QST.</AbstractText Objective neurological deficits showed a gradual increase across HSP, TH, MH and SL groups, being higher in MH compared with HSP and in SL compared with HSP and TH. The number of participants categorised as HSP, TH, MH and SL was 16, 24, 17 and 19, respectively. There was a gradual decrease of the sciatic nerve's FA (HSP 0.444, TH 0.437, MH 0.395, SL 0.382; p=0.005) and increase of CSA (HSP 21.7, TH 21.5, MH 25.9, SL 25.8 mm<sup The most severe sensory phenotypes of DSPN (MH and SL) showed diminishing sciatic nerve structural integrity indexed by lower FA, likely representing progressive axonal loss, as well as increasing CSA of the sciatic nerve, which cannot be detected in individuals with TH. Individuals with type 2 diabetes may experience a predefined cascade of nerve fibre damage in the course of the disease, from healthy to TH, to MH and finally SL, while structural changes in the proximal nerve seem to precede the sensory loss of peripheral nerves and indicate potential targets for the prevention of end-stage DSPN.</AbstractText ClinicalTrials.gov NCT03022721.</AbstractText
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<i
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Diagnostic Accuracy of Screening Tests for Diabetic Peripheral Neuropathy: An Umbrella Review. Peripheral neuropathy is a common cause of morbidity in diabetes. Despite recent advancements in early diagnosis methods, there is a need for practical, highly sensitive, and cost-effective screening methods in clinical practice. This study summarizes evidence from systematic reviews and meta-analyses on the diagnostic accuracy of validated screening methods for diabetic peripheral neuropathy. Two independent reviewers assessed methodological quality and bias using AMSTAR and ROBIS tools. Seven reviews with 19,531 participants were included. The monofilament test showed inconsistent sensitivity (<i
|
A diminished sciatic nerve structural integrity is associated with distinct peripheral sensory phenotypes in individuals with type 2 diabetes. Quantitative sensory testing (QST) allows the identification of individuals with rapid progression of diabetic sensorimotor polyneuropathy (DSPN) based on certain sensory phenotypes. Hence, the aim of this study was to investigate the relationship of these phenotypes with the structural integrity of the sciatic nerve among individuals with type 2 diabetes.</AbstractText Seventy-six individuals with type 2 diabetes took part in this cross-sectional study and underwent QST of the right foot and high-resolution magnetic resonance neurography including diffusion tensor imaging of the right distal sciatic nerve to determine the sciatic nerve fractional anisotropy (FA) and cross-sectional area (CSA), both of which serve as markers of structural integrity of peripheral nerves. Participants were then assigned to four sensory phenotypes (participants with type 2 diabetes and healthy sensory profile [HSP], thermal hyperalgesia [TH], mechanical hyperalgesia [MH], sensory loss [SL]) by a standardised sorting algorithm based on QST.</AbstractText Objective neurological deficits showed a gradual increase across HSP, TH, MH and SL groups, being higher in MH compared with HSP and in SL compared with HSP and TH. The number of participants categorised as HSP, TH, MH and SL was 16, 24, 17 and 19, respectively. There was a gradual decrease of the sciatic nerve's FA (HSP 0.444, TH 0.437, MH 0.395, SL 0.382; p=0.005) and increase of CSA (HSP 21.7, TH 21.5, MH 25.9, SL 25.8 mm<sup The most severe sensory phenotypes of DSPN (MH and SL) showed diminishing sciatic nerve structural integrity indexed by lower FA, likely representing progressive axonal loss, as well as increasing CSA of the sciatic nerve, which cannot be detected in individuals with TH. Individuals with type 2 diabetes may experience a predefined cascade of nerve fibre damage in the course of the disease, from healthy to TH, to MH and finally SL, while structural changes in the proximal nerve seem to precede the sensory loss of peripheral nerves and indicate potential targets for the prevention of end-stage DSPN.</AbstractText ClinicalTrials.gov NCT03022721.</AbstractText
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Irregularity of instantaneous gamma frequency in the motor control network characterize visuomotor and proprioceptive information processing. <i
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30486806
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21472377
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29654878
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Pediatric intramedullary schwannoma with syringomyelia: a case report and literature review.
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Balanced steady-state free-precession MR imaging for measuring pulsatile motion of cerebellar tonsils during the cardiac cycle: a reliability study.
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Inter-subject phase synchronization for exploratory analysis of task-fMRI.
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Intramedullary schwannomas without neurofibromatosis are exceedingly rare. They are rarer in children with only 8 cases reported so far. The association of intramedullary schwannomas with syringomyelia is also rare. Here, we present a case of intramedullary schwannoma with syringomyelia treated surgically in an 9-year-old boy.</AbstractText We reviewed the clinical course of a 9-year-old boy, who presented with both lower extremity weakness of 6-month duration. Neurophysical examination revealed a decreased sensation below the T10 dermatome. Magnetic resonance imaging (MRI) showed an well-demarcated intramedullary lesion located at the level of T8 vertebra with isointensity on T2WI and hypointensity on T1WI, which was homogeneous enhanced after gadolinium injection. There was associated syringomyelia extending from T7 down to the level of T10. A mild scoliotic deformity was also observed. The lesion was totally resected after an T7-T8 laminoplasty. Histopathological findings were consistent with schwannoma. Postoperative MRI did not reveal the presence of a residual tumor with syringomyelia reducted. By 2 weeks after treatment, the patient had experienced nearly complete recovery. Management with external bracing was performed on this patient for 3 months after surgery to prevent spinal deformity. However, mild spinal kyphosis occurred 5 months after surgery, and a progressive postoperative spinal kyphosis was observed during these 3 years of follow-up. Continued conservative management with observation was performed as there is no association with functional decline and impairment in health-related quality-of-life measures.</AbstractText Although extremely rare and uncommonly associated with syringomyelia, schwannomas need to be considered in the preoperative diagnosis of solitary intramedullary tumors in children as total resection can be achieved improving surgical outcome; Pediatric patients should be monitored closely for the development of spinal deformity following resection of intramedullary schwannoma, particularly possessing preoperative scoliotic deformity and/or tumor-associated syringomyelia.</AbstractText
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Assessment of the motion of the cerebellar tonsils is of interest in diseases affecting the CSF flow at the foramen magnum. Cardiac-gated balanced steady-state free-precession technique, which has recently been shown to demonstrate the pulsatile motion of neural structures, appears well suited to allow direct measurement of craniocaudal translation of cerebellar tonsils during the cardiac cycle. Our aim was to assess the intra-observer and inter-observer variability in the assessment of tonsillar motion utilizing this technique.</AbstractText We retrospectively identified 44 patients who had undergone MR imaging with cine TrueFISP sequence, as a part of CSF flow study. Two neuroradiologists independently assessed the images. The tonsillar pulsatility was subjectively characterized into none, minimal, and marked categories after review of the images on a cine loop. For patients with identifiable tonsillar motion, the maximal extent of translation of the inferior edge of the cerebellar tonsil was directly measured. Both readers repeated the measurements after a minimum interval of 2 weeks. Intra- and inter-observer variability was characterized by calculating the kappa statistics.</AbstractText The intra-observer agreement for subjective assessment of tonsillar pulsatility was near perfect while the inter-observer agreement was substantial. A good intra- and inter-observer correlation was also seen for the objective measurements of the tonsillar motion. A good correlation was found between the subjective categorization of the tonsillar pulsatility and the objective measurements.</AbstractText Steady-state balanced free-precession MR imaging technique allows for a reproducible subjective and objective assessment of tonsillar pulsatility.</AbstractText
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Analysis of task-based fMRI data is conventionally carried out using a hypothesis-driven approach, where blood-oxygen-level dependent (BOLD) time courses are correlated with a hypothesized temporal structure. In some experimental designs, this temporal structure can be difficult to define. In other cases, experimenters may wish to take a more exploratory, data-driven approach to detecting task-driven BOLD activity. In this study, we demonstrate the efficiency and power of an inter-subject synchronization approach for exploratory analysis of task-based fMRI data. Combining the tools of instantaneous phase synchronization and independent component analysis, we characterize whole-brain task-driven responses in terms of group-wise similarity in temporal signal dynamics of brain networks. We applied this framework to fMRI data collected during performance of a simple motor task and a social cognitive task. Analyses using an inter-subject phase synchronization approach revealed a large number of brain networks that dynamically synchronized to various features of the task, often not predicted by the hypothesized temporal structure of the task. We suggest that this methodological framework, along with readily available tools in the fMRI community, provides a powerful exploratory, data-driven approach for analysis of task-driven BOLD activity.</AbstractText
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Pediatric intramedullary schwannoma with syringomyelia: a case report and literature review. Intramedullary schwannomas without neurofibromatosis are exceedingly rare. They are rarer in children with only 8 cases reported so far. The association of intramedullary schwannomas with syringomyelia is also rare. Here, we present a case of intramedullary schwannoma with syringomyelia treated surgically in an 9-year-old boy.</AbstractText We reviewed the clinical course of a 9-year-old boy, who presented with both lower extremity weakness of 6-month duration. Neurophysical examination revealed a decreased sensation below the T10 dermatome. Magnetic resonance imaging (MRI) showed an well-demarcated intramedullary lesion located at the level of T8 vertebra with isointensity on T2WI and hypointensity on T1WI, which was homogeneous enhanced after gadolinium injection. There was associated syringomyelia extending from T7 down to the level of T10. A mild scoliotic deformity was also observed. The lesion was totally resected after an T7-T8 laminoplasty. Histopathological findings were consistent with schwannoma. Postoperative MRI did not reveal the presence of a residual tumor with syringomyelia reducted. By 2 weeks after treatment, the patient had experienced nearly complete recovery. Management with external bracing was performed on this patient for 3 months after surgery to prevent spinal deformity. However, mild spinal kyphosis occurred 5 months after surgery, and a progressive postoperative spinal kyphosis was observed during these 3 years of follow-up. Continued conservative management with observation was performed as there is no association with functional decline and impairment in health-related quality-of-life measures.</AbstractText Although extremely rare and uncommonly associated with syringomyelia, schwannomas need to be considered in the preoperative diagnosis of solitary intramedullary tumors in children as total resection can be achieved improving surgical outcome; Pediatric patients should be monitored closely for the development of spinal deformity following resection of intramedullary schwannoma, particularly possessing preoperative scoliotic deformity and/or tumor-associated syringomyelia.</AbstractText
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Balanced steady-state free-precession MR imaging for measuring pulsatile motion of cerebellar tonsils during the cardiac cycle: a reliability study. Assessment of the motion of the cerebellar tonsils is of interest in diseases affecting the CSF flow at the foramen magnum. Cardiac-gated balanced steady-state free-precession technique, which has recently been shown to demonstrate the pulsatile motion of neural structures, appears well suited to allow direct measurement of craniocaudal translation of cerebellar tonsils during the cardiac cycle. Our aim was to assess the intra-observer and inter-observer variability in the assessment of tonsillar motion utilizing this technique.</AbstractText We retrospectively identified 44 patients who had undergone MR imaging with cine TrueFISP sequence, as a part of CSF flow study. Two neuroradiologists independently assessed the images. The tonsillar pulsatility was subjectively characterized into none, minimal, and marked categories after review of the images on a cine loop. For patients with identifiable tonsillar motion, the maximal extent of translation of the inferior edge of the cerebellar tonsil was directly measured. Both readers repeated the measurements after a minimum interval of 2 weeks. Intra- and inter-observer variability was characterized by calculating the kappa statistics.</AbstractText The intra-observer agreement for subjective assessment of tonsillar pulsatility was near perfect while the inter-observer agreement was substantial. A good intra- and inter-observer correlation was also seen for the objective measurements of the tonsillar motion. A good correlation was found between the subjective categorization of the tonsillar pulsatility and the objective measurements.</AbstractText Steady-state balanced free-precession MR imaging technique allows for a reproducible subjective and objective assessment of tonsillar pulsatility.</AbstractText
|
Inter-subject phase synchronization for exploratory analysis of task-fMRI. Analysis of task-based fMRI data is conventionally carried out using a hypothesis-driven approach, where blood-oxygen-level dependent (BOLD) time courses are correlated with a hypothesized temporal structure. In some experimental designs, this temporal structure can be difficult to define. In other cases, experimenters may wish to take a more exploratory, data-driven approach to detecting task-driven BOLD activity. In this study, we demonstrate the efficiency and power of an inter-subject synchronization approach for exploratory analysis of task-based fMRI data. Combining the tools of instantaneous phase synchronization and independent component analysis, we characterize whole-brain task-driven responses in terms of group-wise similarity in temporal signal dynamics of brain networks. We applied this framework to fMRI data collected during performance of a simple motor task and a social cognitive task. Analyses using an inter-subject phase synchronization approach revealed a large number of brain networks that dynamically synchronized to various features of the task, often not predicted by the hypothesized temporal structure of the task. We suggest that this methodological framework, along with readily available tools in the fMRI community, provides a powerful exploratory, data-driven approach for analysis of task-driven BOLD activity.</AbstractText
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37848914
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34370119
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37432752
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Connective tissue nevus misdiagnosed as juvenile localized scleroderma.
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Imaging in non-bacterial osteomyelitis in children and adolescents: diagnosis, differential diagnosis and follow-up-an educational review based on a literature survey and own clinical experiences.
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Ecstatic or Mystical Experience through Epilepsy.
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Connective tissue nevi (CTN) are congenital hamartomas caused by excessive proliferation of dermis components. In children, CTN can mimic juvenile localized scleroderma (JLS), an immune mediated skin disorder that requires aggressive immunosuppression.</AbstractText Aim of our study was to describe a series of pediatric patients with CTN misdiagnosed as JLS and the discerning characteristics between the two conditions.</AbstractText Retrospective analysis of children referred to our Center during the last two decades for JLS who received a final diagnosis of CTN. Clinical, laboratory, histopathological and instrumental data (MRI and thermography) were collected and compared with those with JLS.</AbstractText Seventeen patients with mean age at onset 4.6 years entered the study. All came to our Center with a certain diagnosis of JLS (n = 15) or suspected JLS (n = 2). The indurated skin lesions were flat and resembled either circumscribed morphea or pansclerotic morphea. In 14 patients (82.4%) they were mainly localized at the lower limbs and in three (17.6%) at the upper limbs. No patient had laboratory inflammatory changes or positive autoantibodies. Skin biopsies confirmed the diagnosis of CTN: non-familial collagenoma in eleven (64.7%), mixed CTN in four (23.5%) and familial CTN in two (11.8%). Mean age at final diagnosis was 9.5 years, with a mean diagnostic delay of 4.8 years (range 1-15 years). Sixteen patients underwent musculoskeletal MRI that was normal in all except two who showed muscle perifascial enhancement. Thermography was normal in all patients. At our first evaluation, eleven patients (64.7%) were on systemic treatment (methotrexate 11, corticosteroids 7, biologics 2), three (17.6%) on topical corticosteroids and three untreated.</AbstractText CTN can be misdiagnosed as JLS and therefore aggressively treated with prolonged and inappropriate immunosuppression. The absence of inflammatory appearance of the skin lesions, normal instrumental and laboratory findings and the accurate evaluation of skin biopsy are crucial to address the right diagnosis.</AbstractText
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Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone disorder affecting children and adolescents. Previously classified as a rare disease, recent studies suggest a higher incidence of the disease. CNO may develop into the clinical presentation of chronic recurrent osteomyelitis (CRMO) with high relapse rate and multifocality.</AbstractText Diagnosis of CNO/CRMO is often delayed, with implications for disease severity and relapse rate. This can be significantly improved by knowledge of the disease entity and its characteristics. Imaging plays a key role in diagnosis, differential diagnosis and therapy monitoring. Magnetic resonance imaging (MRI) has several advantages compared to other imaging methods and is increasingly applied in clinical studies. Recent studies show that a whole-body (WB) coverage (WB-MRI) without contrast agent administration is a rational approach. This educational review is based on a systematic analysis of international peer-reviewed articles and presents our own clinical experiences. It provides an overview of disease entity, incidence and clinical diagnosis. The role of imaging, especially of whole-body MRI, is discussed in detail. Finally, practical advice for imaging, including flowcharts explaining when and how to apply imaging, is provided.</AbstractText Knowing the specifics of CNO/CRMO and the importance of MRI/whole-body MRI allows rapid and efficient diagnosis as well as therapy support and helps to avoid irreversible secondary damage.</AbstractText
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Ecstatic epilepsy is a rare form of focal epilepsy, so named because the seizures' first symptoms consist of an ecstatic/mystical experience, including feelings of increased self-awareness, mental clarity, and "unity with everything that exists," accompanied by a sense of bliss and physical well-being. In this perspective article, we first describe the phenomenology of ecstatic seizures, address their historical context, and describe the primary brain structure involved in the genesis of these peculiar epileptic seizures, the anterior insula. In the second part of the article, we move onto the possible neurocognitive underpinnings of ecstatic seizures. We first remind the reader of the insula's role in interoceptive processing and consciously experienced feelings, contextualized by the theory of predictive coding. This leads us to hypothesize that temporary disruptions to activity in the anterior insula could interrupt the generation of interoceptive prediction errors, and cause one to experience the absence of uncertainty, and thereby, a sense of bliss. The absence of interoceptive prediction errors would in fact mimic perfect prediction of the body's physiological state. This sudden clarity of bodily perception could explain the ecstatic quality of the experience, as the interoceptive system forms the basis for unified conscious experience. Our alternative hypothesis is that the anterior insula plays an overarching role in the processing of surprise and that the dysfunction caused by the epileptic discharge could interrupt any surprise exceeding expectations, resulting in a sense of complete control and oneness with the environment.</AbstractText
|
Connective tissue nevus misdiagnosed as juvenile localized scleroderma. Connective tissue nevi (CTN) are congenital hamartomas caused by excessive proliferation of dermis components. In children, CTN can mimic juvenile localized scleroderma (JLS), an immune mediated skin disorder that requires aggressive immunosuppression.</AbstractText Aim of our study was to describe a series of pediatric patients with CTN misdiagnosed as JLS and the discerning characteristics between the two conditions.</AbstractText Retrospective analysis of children referred to our Center during the last two decades for JLS who received a final diagnosis of CTN. Clinical, laboratory, histopathological and instrumental data (MRI and thermography) were collected and compared with those with JLS.</AbstractText Seventeen patients with mean age at onset 4.6 years entered the study. All came to our Center with a certain diagnosis of JLS (n = 15) or suspected JLS (n = 2). The indurated skin lesions were flat and resembled either circumscribed morphea or pansclerotic morphea. In 14 patients (82.4%) they were mainly localized at the lower limbs and in three (17.6%) at the upper limbs. No patient had laboratory inflammatory changes or positive autoantibodies. Skin biopsies confirmed the diagnosis of CTN: non-familial collagenoma in eleven (64.7%), mixed CTN in four (23.5%) and familial CTN in two (11.8%). Mean age at final diagnosis was 9.5 years, with a mean diagnostic delay of 4.8 years (range 1-15 years). Sixteen patients underwent musculoskeletal MRI that was normal in all except two who showed muscle perifascial enhancement. Thermography was normal in all patients. At our first evaluation, eleven patients (64.7%) were on systemic treatment (methotrexate 11, corticosteroids 7, biologics 2), three (17.6%) on topical corticosteroids and three untreated.</AbstractText CTN can be misdiagnosed as JLS and therefore aggressively treated with prolonged and inappropriate immunosuppression. The absence of inflammatory appearance of the skin lesions, normal instrumental and laboratory findings and the accurate evaluation of skin biopsy are crucial to address the right diagnosis.</AbstractText
|
Imaging in non-bacterial osteomyelitis in children and adolescents: diagnosis, differential diagnosis and follow-up-an educational review based on a literature survey and own clinical experiences. Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone disorder affecting children and adolescents. Previously classified as a rare disease, recent studies suggest a higher incidence of the disease. CNO may develop into the clinical presentation of chronic recurrent osteomyelitis (CRMO) with high relapse rate and multifocality.</AbstractText Diagnosis of CNO/CRMO is often delayed, with implications for disease severity and relapse rate. This can be significantly improved by knowledge of the disease entity and its characteristics. Imaging plays a key role in diagnosis, differential diagnosis and therapy monitoring. Magnetic resonance imaging (MRI) has several advantages compared to other imaging methods and is increasingly applied in clinical studies. Recent studies show that a whole-body (WB) coverage (WB-MRI) without contrast agent administration is a rational approach. This educational review is based on a systematic analysis of international peer-reviewed articles and presents our own clinical experiences. It provides an overview of disease entity, incidence and clinical diagnosis. The role of imaging, especially of whole-body MRI, is discussed in detail. Finally, practical advice for imaging, including flowcharts explaining when and how to apply imaging, is provided.</AbstractText Knowing the specifics of CNO/CRMO and the importance of MRI/whole-body MRI allows rapid and efficient diagnosis as well as therapy support and helps to avoid irreversible secondary damage.</AbstractText
|
Ecstatic or Mystical Experience through Epilepsy. Ecstatic epilepsy is a rare form of focal epilepsy, so named because the seizures' first symptoms consist of an ecstatic/mystical experience, including feelings of increased self-awareness, mental clarity, and "unity with everything that exists," accompanied by a sense of bliss and physical well-being. In this perspective article, we first describe the phenomenology of ecstatic seizures, address their historical context, and describe the primary brain structure involved in the genesis of these peculiar epileptic seizures, the anterior insula. In the second part of the article, we move onto the possible neurocognitive underpinnings of ecstatic seizures. We first remind the reader of the insula's role in interoceptive processing and consciously experienced feelings, contextualized by the theory of predictive coding. This leads us to hypothesize that temporary disruptions to activity in the anterior insula could interrupt the generation of interoceptive prediction errors, and cause one to experience the absence of uncertainty, and thereby, a sense of bliss. The absence of interoceptive prediction errors would in fact mimic perfect prediction of the body's physiological state. This sudden clarity of bodily perception could explain the ecstatic quality of the experience, as the interoceptive system forms the basis for unified conscious experience. Our alternative hypothesis is that the anterior insula plays an overarching role in the processing of surprise and that the dysfunction caused by the epileptic discharge could interrupt any surprise exceeding expectations, resulting in a sense of complete control and oneness with the environment.</AbstractText
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39934111
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26813123
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40759622
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Accelerated epigenetic aging in Huntington's disease involves polycomb repressive complex 1.
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Alzheimer's disease: Targeting the Cholinergic System.
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Novel miniplate designs to enhance biomechanical stability in mandibular symphyseal fracture fixation.
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Loss of epigenetic information during physiological aging compromises cellular identity, leading to de-repression of developmental genes. Here, we assessed the epigenomic landscape of vulnerable neurons in two reference mouse models of Huntington neurodegenerative disease (HD), using cell-type-specific multi-omics, including temporal analysis at three disease stages via FANS-CUT&Tag. We show accelerated de-repression of developmental genes in HD striatal neurons, involving histone re-acetylation and depletion of H2AK119 ubiquitination and H3K27 trimethylation marks, which are catalyzed by polycomb repressive complexes 1 and 2 (PRC1 and PRC2), respectively. We further identify a PRC1-dependent subcluster of bivalent developmental transcription factors that is re-activated in HD striatal neurons. This mechanism likely involves progressive paralog switching between PRC1-CBX genes, which promotes the upregulation of normally low-expressed PRC1-CBX2/4/8 isoforms in striatal neurons, alongside the down-regulation of predominant PRC1-CBX isoforms in these cells (e.g., CBX6/7). Collectively, our data provide evidence for PRC1-dependent accelerated epigenetic aging in HD vulnerable neurons.</AbstractText
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Acetylcholine (ACh) has a crucial role in the peripheral and central nervous systems. The enzyme choline acetyltransferase (ChAT) is responsible for synthesizing ACh from acetyl-CoA and choline in the cytoplasm and the vesicular acetylcholine transporter (VAChT) uptakes the neurotransmitter into synaptic vesicles. Following depolarization, ACh undergoes exocytosis reaching the synaptic cleft, where it can bind its receptors, including muscarinic and nicotinic receptors. ACh present at the synaptic cleft is promptly hydrolyzed by the enzyme acetylcholinesterase (AChE), forming acetate and choline, which is recycled into the presynaptic nerve terminal by the high-affinity choline transporter (CHT1). Cholinergic neurons located in the basal forebrain, including the neurons that form the nucleus basalis of Meynert, are severely lost in Alzheimer's disease (AD). AD is the most ordinary cause of dementia affecting 25 million people worldwide. The hallmarks of the disease are the accumulation of neurofibrillary tangles and amyloid plaques. However, there is no real correlation between levels of cortical plaques and AD-related cognitive impairment. Nevertheless, synaptic loss is the principal correlate of disease progression and loss of cholinergic neurons contributes to memory and attention deficits. Thus, drugs that act on the cholinergic system represent a promising option to treat AD patients.</AbstractText
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In this article, the performance of different geometries of specially designed fixation miniplates for mandibular symphyseal fracture is evaluated by investigating the effect of geometrical parameters on the biomechanical stability of the fracture. Experimental cone beam computed tomography (CBCT) images were used to generate and simulate the mandible model. Two novel miniplate geometries, including rectangular and elliptical designs, are presented to achieve better biomechanical performance than conventional design. Performance of each geometric design is evaluated in six different dimensional parameters to determine the appropriate parameters for the new miniplate designs. Three-dimensional stress analysis is performed to investigate the mechanical behavior of the novel miniplates, and the results are compared with the classic miniplate. The results reveal that the relative displacement in the symphysis bone of the fractured mandible area fixed by the new rectangular and elliptical designs is reduced 9.55 % and 15.4 %, respectively. In addition, the novel designs for miniplates reduce the number of screws by two in comparison to classic miniplates. The biomechanical advantages observed, such as reduced relative displacement and a decreased number of screws (implying less surgical trauma to the bone), suggest that the novel miniplate designs hold the potential to contribute to more favorable clinical outcomes, possibly influencing aspects such as patient recovery time. Findings of this research provide a foundation for future experimental and clinical investigations of potential clinical benefits.</AbstractText
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Accelerated epigenetic aging in Huntington's disease involves polycomb repressive complex 1. Loss of epigenetic information during physiological aging compromises cellular identity, leading to de-repression of developmental genes. Here, we assessed the epigenomic landscape of vulnerable neurons in two reference mouse models of Huntington neurodegenerative disease (HD), using cell-type-specific multi-omics, including temporal analysis at three disease stages via FANS-CUT&Tag. We show accelerated de-repression of developmental genes in HD striatal neurons, involving histone re-acetylation and depletion of H2AK119 ubiquitination and H3K27 trimethylation marks, which are catalyzed by polycomb repressive complexes 1 and 2 (PRC1 and PRC2), respectively. We further identify a PRC1-dependent subcluster of bivalent developmental transcription factors that is re-activated in HD striatal neurons. This mechanism likely involves progressive paralog switching between PRC1-CBX genes, which promotes the upregulation of normally low-expressed PRC1-CBX2/4/8 isoforms in striatal neurons, alongside the down-regulation of predominant PRC1-CBX isoforms in these cells (e.g., CBX6/7). Collectively, our data provide evidence for PRC1-dependent accelerated epigenetic aging in HD vulnerable neurons.</AbstractText
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Alzheimer's disease: Targeting the Cholinergic System. Acetylcholine (ACh) has a crucial role in the peripheral and central nervous systems. The enzyme choline acetyltransferase (ChAT) is responsible for synthesizing ACh from acetyl-CoA and choline in the cytoplasm and the vesicular acetylcholine transporter (VAChT) uptakes the neurotransmitter into synaptic vesicles. Following depolarization, ACh undergoes exocytosis reaching the synaptic cleft, where it can bind its receptors, including muscarinic and nicotinic receptors. ACh present at the synaptic cleft is promptly hydrolyzed by the enzyme acetylcholinesterase (AChE), forming acetate and choline, which is recycled into the presynaptic nerve terminal by the high-affinity choline transporter (CHT1). Cholinergic neurons located in the basal forebrain, including the neurons that form the nucleus basalis of Meynert, are severely lost in Alzheimer's disease (AD). AD is the most ordinary cause of dementia affecting 25 million people worldwide. The hallmarks of the disease are the accumulation of neurofibrillary tangles and amyloid plaques. However, there is no real correlation between levels of cortical plaques and AD-related cognitive impairment. Nevertheless, synaptic loss is the principal correlate of disease progression and loss of cholinergic neurons contributes to memory and attention deficits. Thus, drugs that act on the cholinergic system represent a promising option to treat AD patients.</AbstractText
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Novel miniplate designs to enhance biomechanical stability in mandibular symphyseal fracture fixation. In this article, the performance of different geometries of specially designed fixation miniplates for mandibular symphyseal fracture is evaluated by investigating the effect of geometrical parameters on the biomechanical stability of the fracture. Experimental cone beam computed tomography (CBCT) images were used to generate and simulate the mandible model. Two novel miniplate geometries, including rectangular and elliptical designs, are presented to achieve better biomechanical performance than conventional design. Performance of each geometric design is evaluated in six different dimensional parameters to determine the appropriate parameters for the new miniplate designs. Three-dimensional stress analysis is performed to investigate the mechanical behavior of the novel miniplates, and the results are compared with the classic miniplate. The results reveal that the relative displacement in the symphysis bone of the fractured mandible area fixed by the new rectangular and elliptical designs is reduced 9.55 % and 15.4 %, respectively. In addition, the novel designs for miniplates reduce the number of screws by two in comparison to classic miniplates. The biomechanical advantages observed, such as reduced relative displacement and a decreased number of screws (implying less surgical trauma to the bone), suggest that the novel miniplate designs hold the potential to contribute to more favorable clinical outcomes, possibly influencing aspects such as patient recovery time. Findings of this research provide a foundation for future experimental and clinical investigations of potential clinical benefits.</AbstractText
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38148753
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38797931
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35976729
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Clinical parameter-guided initial resuscitation in adult patients with septic shock: A systematic review and network meta-analysis.
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Lower admission stroke severity is associated with good collateral status in distal medium vessel occlusion stroke.
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Pronociceptive autoantibodies in the spinal cord mediate nociceptive sensitization, loss of function, and spontaneous pain in the lumbar disk puncture model of chronic back pain.
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To identify the most useful tissue perfusion parameter for initial resuscitation in sepsis/septic shock adults using a network meta-analysis.</AbstractText We searched major databases until December 2022 for randomized trials comparing four tissue perfusion parameters or against usual care. The primary outcome was short-term mortality up to 90 days. The Confidence in Network Meta-Analysis web application was used to assess the quality of evidence.</AbstractText Seventeen trials were identified. Lactate-guided therapy (risk ratios, 0.59; 95% confidence intervals [0.45-0.76]; high certainty) and capillary refill time-guided therapy (risk ratios, 0.53; 95% confidence intervals [0.33-0.86]; high certainty) were significantly associated with lower short-term mortality compared with usual care, whereas central venous oxygen saturation-guided therapy (risk ratio, 1.50; 95% confidence intervals [1.16-1.94]; moderate certainty) increased the risk of short-term mortality compared with lactate-guided therapy.</AbstractText Lactate or capillary refill time-guided initial resuscitation for sepsis/septic shock patients may decrease short-term mortality. More research is essential to personalize and optimize treatment strategies for septic shock resuscitation.</AbstractText
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Distal medium vessel occlusions (DMVOs) are a significant contributor to acute ischemic stroke (AIS), with collateral status (CS) playing a pivotal role in modulating ischemic damage progression. We aimed to explore baseline characteristics associated with CS in AIS-DMVO.</AbstractText This retrospective analysis of a prospectively collected database enrolled 130 AIS-DMVO patients from two comprehensive stroke centers. Baseline characteristics, including patient demographics, admission National Institutes of Health Stroke Scale (NIHSS) score, admission Los Angeles Motor Scale (LAMS) score, and co-morbidities, including hypertension, hyperlipidemia, diabetes, coronary artery disease, atrial fibrillation, and history of transient ischemic attack or stroke, were collected. The analysis was dichotomized to good CS, reflected by hypoperfusion index ratio (HIR) <.3, versus poor CS, reflected by HIR ≥.3.</AbstractText Good CS was observed in 34% of the patients. As to the occluded location, 43.8% occurred in proximal M2, 16.9% in mid M2, 35.4% in more distal middle cerebral artery, and 3.8% in distal anterior cerebral artery. In multivariate logistic analysis, a lower NIHSS score and a lower LAMS score were both independently associated with a good CS (odds ratio [OR]: 0.88, 95% confidence interval [CI]: 0.82-0.95, p < .001 and OR: 0.77, 95% CI: 0.62-0.96, p = .018, respectively). Patients with poor CS were more likely to manifest as moderate to severe stroke (29.1% vs. 4.5%, p < .001), while patients with good CS had a significantly higher chance of having a minor stroke clinically (40.9% vs. 12.8%, p < .001).</AbstractText CS remains an important determinant in the severity of AIS-DMVO. Collateral enhancement strategies may be a worthwhile pursuit in AIS-DMVO patients with more severe initial stroke presentation, which can be swiftly identified by the concise LAMS and serves as a proxy for underlying poor CS.</AbstractText
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Previously, we observed that B cells and autoantibodies mediated chronic nociceptive sensitization in the mouse tibia fracture model of complex regional pain syndrome and that complex regional pain syndrome patient antibodies were pronociceptive in fracture mice lacking mature B cells and antibodies (muMT). The current study used a lumbar spinal disk puncture (DP) model of low back pain in wild-type (WT) and muMT mice to evaluate pronociceptive adaptive immune responses. Spinal disks and cords were collected 3 weeks after DP for polymerase chain reaction and immunohistochemistry analyses. Wild-type DP mice developed 24 weeks of hindpaw mechanical allodynia and hyperalgesia, grip weakness, and a conditioned place preference response indicative of spontaneous pain, but pain responses were attenuated or absent in muMT DP mice. Spinal cord expression of inflammatory cytokines, immune cell markers, and complement components were increased in WT DP mice and in muMT DP mice. Dorsal horn immunostaining in WT DP mice demonstrated glial activation and increased complement 5a receptor expressionin spinal neurons. Serum collected from WT DP mice and injected into muMT DP mice caused nociceptive sensitization, as did intrathecal injection of IgM collected from WT DP mice, and IgM immune complexes were observed in lumbar spinal disks and cord of WT DP mice. Serum from WT tibia fracture mice was not pronociceptive in muMT DP mice and vice versa, evidence that each type of tissue trauma chronically generates its own unique antibodies and targeted antigens. These data further support the pronociceptive autoimmunity hypothesis for the transition from tissue injury to chronic musculoskeletal pain state.</AbstractText
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Clinical parameter-guided initial resuscitation in adult patients with septic shock: A systematic review and network meta-analysis. To identify the most useful tissue perfusion parameter for initial resuscitation in sepsis/septic shock adults using a network meta-analysis.</AbstractText We searched major databases until December 2022 for randomized trials comparing four tissue perfusion parameters or against usual care. The primary outcome was short-term mortality up to 90 days. The Confidence in Network Meta-Analysis web application was used to assess the quality of evidence.</AbstractText Seventeen trials were identified. Lactate-guided therapy (risk ratios, 0.59; 95% confidence intervals [0.45-0.76]; high certainty) and capillary refill time-guided therapy (risk ratios, 0.53; 95% confidence intervals [0.33-0.86]; high certainty) were significantly associated with lower short-term mortality compared with usual care, whereas central venous oxygen saturation-guided therapy (risk ratio, 1.50; 95% confidence intervals [1.16-1.94]; moderate certainty) increased the risk of short-term mortality compared with lactate-guided therapy.</AbstractText Lactate or capillary refill time-guided initial resuscitation for sepsis/septic shock patients may decrease short-term mortality. More research is essential to personalize and optimize treatment strategies for septic shock resuscitation.</AbstractText
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Lower admission stroke severity is associated with good collateral status in distal medium vessel occlusion stroke. Distal medium vessel occlusions (DMVOs) are a significant contributor to acute ischemic stroke (AIS), with collateral status (CS) playing a pivotal role in modulating ischemic damage progression. We aimed to explore baseline characteristics associated with CS in AIS-DMVO.</AbstractText This retrospective analysis of a prospectively collected database enrolled 130 AIS-DMVO patients from two comprehensive stroke centers. Baseline characteristics, including patient demographics, admission National Institutes of Health Stroke Scale (NIHSS) score, admission Los Angeles Motor Scale (LAMS) score, and co-morbidities, including hypertension, hyperlipidemia, diabetes, coronary artery disease, atrial fibrillation, and history of transient ischemic attack or stroke, were collected. The analysis was dichotomized to good CS, reflected by hypoperfusion index ratio (HIR) <.3, versus poor CS, reflected by HIR ≥.3.</AbstractText Good CS was observed in 34% of the patients. As to the occluded location, 43.8% occurred in proximal M2, 16.9% in mid M2, 35.4% in more distal middle cerebral artery, and 3.8% in distal anterior cerebral artery. In multivariate logistic analysis, a lower NIHSS score and a lower LAMS score were both independently associated with a good CS (odds ratio [OR]: 0.88, 95% confidence interval [CI]: 0.82-0.95, p < .001 and OR: 0.77, 95% CI: 0.62-0.96, p = .018, respectively). Patients with poor CS were more likely to manifest as moderate to severe stroke (29.1% vs. 4.5%, p < .001), while patients with good CS had a significantly higher chance of having a minor stroke clinically (40.9% vs. 12.8%, p < .001).</AbstractText CS remains an important determinant in the severity of AIS-DMVO. Collateral enhancement strategies may be a worthwhile pursuit in AIS-DMVO patients with more severe initial stroke presentation, which can be swiftly identified by the concise LAMS and serves as a proxy for underlying poor CS.</AbstractText
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Pronociceptive autoantibodies in the spinal cord mediate nociceptive sensitization, loss of function, and spontaneous pain in the lumbar disk puncture model of chronic back pain. Previously, we observed that B cells and autoantibodies mediated chronic nociceptive sensitization in the mouse tibia fracture model of complex regional pain syndrome and that complex regional pain syndrome patient antibodies were pronociceptive in fracture mice lacking mature B cells and antibodies (muMT). The current study used a lumbar spinal disk puncture (DP) model of low back pain in wild-type (WT) and muMT mice to evaluate pronociceptive adaptive immune responses. Spinal disks and cords were collected 3 weeks after DP for polymerase chain reaction and immunohistochemistry analyses. Wild-type DP mice developed 24 weeks of hindpaw mechanical allodynia and hyperalgesia, grip weakness, and a conditioned place preference response indicative of spontaneous pain, but pain responses were attenuated or absent in muMT DP mice. Spinal cord expression of inflammatory cytokines, immune cell markers, and complement components were increased in WT DP mice and in muMT DP mice. Dorsal horn immunostaining in WT DP mice demonstrated glial activation and increased complement 5a receptor expressionin spinal neurons. Serum collected from WT DP mice and injected into muMT DP mice caused nociceptive sensitization, as did intrathecal injection of IgM collected from WT DP mice, and IgM immune complexes were observed in lumbar spinal disks and cord of WT DP mice. Serum from WT tibia fracture mice was not pronociceptive in muMT DP mice and vice versa, evidence that each type of tissue trauma chronically generates its own unique antibodies and targeted antigens. These data further support the pronociceptive autoimmunity hypothesis for the transition from tissue injury to chronic musculoskeletal pain state.</AbstractText
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39517679
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31048300
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38421889
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Hybrid Reconstruction Approach for Polychromatic Computed Tomography in Highly Limited-Data Scenarios.
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Dynamic Contrast-Enhanced MRI to Differentiate Parotid Neoplasms Using Golden-Angle Radial Sparse Parallel Imaging.
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Can supplementing vitamin B12 improve mental health outcomes?: a literature review.
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Conventional strategies aimed at mitigating beam-hardening artifacts in computed tomography (CT) can be categorized into two main approaches: (1) postprocessing following conventional reconstruction and (2) iterative reconstruction incorporating a beam-hardening model. While the former fails in low-dose and/or limited-data cases, the latter substantially increases computational cost. Although deep learning-based methods have been proposed for several cases of limited-data CT, few works in the literature have dealt with beam-hardening artifacts, and none have addressed the problems caused by randomly selected projections and a highly limited span. We propose the deep learning-based prior image constrained (PICDL) framework, a hybrid method used to yield CT images free from beam-hardening artifacts in different limited-data scenarios based on the combination of a modified version of the Prior Image Constrained Compressed Sensing (PICCS) algorithm that incorporates the L2 norm (L2-PICCS) with a prior image generated from a preliminary FDK reconstruction with a deep learning (DL) algorithm. The model is based on a modification of the U-Net architecture, incorporating ResNet-34 as a replacement of the original encoder. Evaluation with rodent head studies in a small-animal CT scanner showed that the proposed method was able to correct beam-hardening artifacts, recover patient contours, and compensate streak and deformation artifacts in scenarios with a limited span and a limited number of projections randomly selected. Hallucinations present in the prior image caused by the deep learning model were eliminated, while the target information was effectively recovered by the L2-PICCS algorithm.</AbstractText
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Conventional imaging frequently shows overlapping features between benign and malignant parotid neoplasms. We investigated dynamic contrast-enhanced MR imaging using golden-angle radial sparse parallel imaging in differentiating parotid neoplasms.</AbstractText For this retrospective study, 41 consecutive parotid neoplasms were imaged with dynamic contrast-enhanced MR imaging with golden-angle radial sparse parallel imaging using 1-mm in-plane resolution. The temporal resolution was 3.4 seconds for 78.2 seconds and 8.8 seconds for the remaining acquisition. Three readers retrospectively and independently created and classified time-intensity curves as follows: 1) continuous wash-in; 2) rapid wash-in, subsequent plateau; and 3) rapid wash-in with washout. Additionally, time-intensity curve-derived semiquantitative metrics normalized to the ipsilateral common carotid artery were recorded. Diagnostic performance for the prediction of neoplasm type and malignancy was assessed. Subset multivariate analysis (<i Independent time-intensity curve classification of the 41 neoplasms produced moderate-to-substantial interreader agreement (κ = 0.50-0.79). The time-intensity curve classification threshold of ≥2 predicted malignancy with a positive predictive value of 56.0%-66.7%, and a negative predictive value of 92.0%-100%. The time-intensity curve classification threshold of <2 predicted pleomorphic adenoma with a positive predictive value of 87.0%-95.0% and a negative predictive value of 76.0%-95.0%. For all readers, type 2 and 3 curves were associated with malignant neoplasms (<i Golden-angle radial sparse parallel MR imaging allows high spatial and temporal resolution permeability characterization of parotid neoplasms, with a high negative predictive value for malignancy prediction. Combining time-to-maximum and ADC improves pleomorphic adenoma prediction compared with either metric alone.</AbstractText
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This study reviews research into the effects of the supplementation of B12 in the prevention and recovery of mental illness, and the potentiation of psychotropic medication.</AbstractText This literature review follows a systematic approach to searching databases CINAHL, EMBASE, Medline, and PsycINFO where 287 non-duplicated articles results were received. Appropriate articles were identified through title and abstract screening and inclusion and exclusion criteria were applied. Five articles were chosen to address the research question following critical appraisal. Thematic analysis was then conducted.</AbstractText This review identified five randomised controlled trials into the supplementation of various doses of B12 in conjunction with folic acid and B6. The supplement was measured against post-stroke depression prevention, the reduction of symptoms of depression in woman with cardiovascular disease, the effect on negative symptoms in schizophrenia, the reduction and prevention of depression in older adults, and the potentiation of psychotropic interventions. The papers reviewed showed inconclusive results, but evidence to support sub-groups and specific high-risk groups. Strong evidence showed supplementation of B12, folic acid and B6 has high rates of preventing post-stroke depression.</AbstractText The findings show that this area of research is still to be developed. The effects of B12 supplementation with other B vitamins on mental health have shown to be inconclusive. There is a case for its use to be considered within certain patient groups to aid recovery of mental health or in some high-risk patient groups. Recommendations are made for further research into high-risk groups of people that may have symptoms or symptoms that could be improved through the supplementation of B12.</AbstractText
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Hybrid Reconstruction Approach for Polychromatic Computed Tomography in Highly Limited-Data Scenarios. Conventional strategies aimed at mitigating beam-hardening artifacts in computed tomography (CT) can be categorized into two main approaches: (1) postprocessing following conventional reconstruction and (2) iterative reconstruction incorporating a beam-hardening model. While the former fails in low-dose and/or limited-data cases, the latter substantially increases computational cost. Although deep learning-based methods have been proposed for several cases of limited-data CT, few works in the literature have dealt with beam-hardening artifacts, and none have addressed the problems caused by randomly selected projections and a highly limited span. We propose the deep learning-based prior image constrained (PICDL) framework, a hybrid method used to yield CT images free from beam-hardening artifacts in different limited-data scenarios based on the combination of a modified version of the Prior Image Constrained Compressed Sensing (PICCS) algorithm that incorporates the L2 norm (L2-PICCS) with a prior image generated from a preliminary FDK reconstruction with a deep learning (DL) algorithm. The model is based on a modification of the U-Net architecture, incorporating ResNet-34 as a replacement of the original encoder. Evaluation with rodent head studies in a small-animal CT scanner showed that the proposed method was able to correct beam-hardening artifacts, recover patient contours, and compensate streak and deformation artifacts in scenarios with a limited span and a limited number of projections randomly selected. Hallucinations present in the prior image caused by the deep learning model were eliminated, while the target information was effectively recovered by the L2-PICCS algorithm.</AbstractText
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Dynamic Contrast-Enhanced MRI to Differentiate Parotid Neoplasms Using Golden-Angle Radial Sparse Parallel Imaging. Conventional imaging frequently shows overlapping features between benign and malignant parotid neoplasms. We investigated dynamic contrast-enhanced MR imaging using golden-angle radial sparse parallel imaging in differentiating parotid neoplasms.</AbstractText For this retrospective study, 41 consecutive parotid neoplasms were imaged with dynamic contrast-enhanced MR imaging with golden-angle radial sparse parallel imaging using 1-mm in-plane resolution. The temporal resolution was 3.4 seconds for 78.2 seconds and 8.8 seconds for the remaining acquisition. Three readers retrospectively and independently created and classified time-intensity curves as follows: 1) continuous wash-in; 2) rapid wash-in, subsequent plateau; and 3) rapid wash-in with washout. Additionally, time-intensity curve-derived semiquantitative metrics normalized to the ipsilateral common carotid artery were recorded. Diagnostic performance for the prediction of neoplasm type and malignancy was assessed. Subset multivariate analysis (<i Independent time-intensity curve classification of the 41 neoplasms produced moderate-to-substantial interreader agreement (κ = 0.50-0.79). The time-intensity curve classification threshold of ≥2 predicted malignancy with a positive predictive value of 56.0%-66.7%, and a negative predictive value of 92.0%-100%. The time-intensity curve classification threshold of <2 predicted pleomorphic adenoma with a positive predictive value of 87.0%-95.0% and a negative predictive value of 76.0%-95.0%. For all readers, type 2 and 3 curves were associated with malignant neoplasms (<i Golden-angle radial sparse parallel MR imaging allows high spatial and temporal resolution permeability characterization of parotid neoplasms, with a high negative predictive value for malignancy prediction. Combining time-to-maximum and ADC improves pleomorphic adenoma prediction compared with either metric alone.</AbstractText
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Can supplementing vitamin B12 improve mental health outcomes?: a literature review. This study reviews research into the effects of the supplementation of B12 in the prevention and recovery of mental illness, and the potentiation of psychotropic medication.</AbstractText This literature review follows a systematic approach to searching databases CINAHL, EMBASE, Medline, and PsycINFO where 287 non-duplicated articles results were received. Appropriate articles were identified through title and abstract screening and inclusion and exclusion criteria were applied. Five articles were chosen to address the research question following critical appraisal. Thematic analysis was then conducted.</AbstractText This review identified five randomised controlled trials into the supplementation of various doses of B12 in conjunction with folic acid and B6. The supplement was measured against post-stroke depression prevention, the reduction of symptoms of depression in woman with cardiovascular disease, the effect on negative symptoms in schizophrenia, the reduction and prevention of depression in older adults, and the potentiation of psychotropic interventions. The papers reviewed showed inconclusive results, but evidence to support sub-groups and specific high-risk groups. Strong evidence showed supplementation of B12, folic acid and B6 has high rates of preventing post-stroke depression.</AbstractText The findings show that this area of research is still to be developed. The effects of B12 supplementation with other B vitamins on mental health have shown to be inconclusive. There is a case for its use to be considered within certain patient groups to aid recovery of mental health or in some high-risk patient groups. Recommendations are made for further research into high-risk groups of people that may have symptoms or symptoms that could be improved through the supplementation of B12.</AbstractText
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39420888
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35185636
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38290849
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Mental health and weight regain after bariatric surgery: associations between weight regain and psychiatric and eating-related comorbidities.
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Joint Hypermobility Links Neurodivergence to Dysautonomia and Pain.
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The affective consequences of response inhibition determine no-go-based crosstalk effects in dual tasks.
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Weight regain is a common outcome of weight loss interventions. Mental health-related comorbidities, among other factors, can mediate weight regain regardless of the implemented treatment modality. This study explores whether postoperative psychopathological comorbidities are associated with weight regain after bariatric surgery.</AbstractText This cross-sectional study recruited 90 outpatients who underwent Roux-en-Y gastric bypass surgery. Anthropometric measurements were collected retrospectively from medical charts. The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorder-IV (DSM-IV) Axis I Disorders (SCID-I) was applied to evaluate psychiatry diagnoses. Validated self-report instruments were used to assess depression, anxiety, alcohol use, impulsivity, binge eating, and body image dissatisfaction. Weight regain was defined as a ≥20% increase from the maximum weight lost. Level of evidence: Level III, cross-sectional study based on a well-designed study.</AbstractText Overall, 55.6% of participants experienced weight regain. Notably, mental disorders such as current binge-eating disorder and lifetime diagnoses including bulimia nervosa, alcohol abuse/dependence, and obsessive-compulsive disorder were significantly associated with weight regain. However, controlled analysis found that, for mental disorders, only current binge-eating disorder (odds ratio [OR] 6.3, 95% confidence interval [CI] 1.26-31.06, p = 0.024) remained associated with weight regain. Eating-related psychopathologies also associated with weight regain included binge eating (d = 0.55; p = 0.013), eating disinhibition (d = 0.76; p = 0.001), higher hunger levels (d = 0.39; p = 0.004), and non-planning trait impulsivity (d = 0.69; p = 0.0001).</AbstractText Postoperative presence of psychopathological comorbidities, such as eating psychopathology and trait impulsivity, were associated with weight regain after bariatric surgery. These findings highlight the importance of addressing mental health in individuals experiencing postsurgical weight regain.</AbstractText
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Autism, attention deficit hyperactivity disorder (ADHD), and tic disorder (Tourette syndrome; TS) are neurodevelopmental conditions that frequently co-occur and impact psychological, social, and emotional processes. Increased likelihood of chronic physical symptoms, including fatigue and pain, are also recognized. The expression of joint hypermobility, reflecting a constitutional variant in connective tissue, predicts susceptibility to psychological symptoms alongside recognized physical symptoms. Here, we tested for increased prevalence of joint hypermobility, autonomic dysfunction, and musculoskeletal symptoms in 109 adults with neurodevelopmental condition diagnoses.</AbstractText Rates of generalized joint hypermobility (GJH, henceforth hypermobility) in adults with a formal diagnosis of neurodevelopmental conditions (henceforth neurodivergent group, <i The neurodivergent group manifested elevated prevalence of hypermobility (51%) compared to the general population rate of 20% and a comparison population (17.5%). Using a more stringent age specific cut-off, in the neurodivergent group this prevalence was 28.4%, more than double than the comparison group (12.5%). Odds ratio for presence of hypermobility in neurodivergent group, compared to the general population was 4.51 (95% CI 2.17-9.37), with greater odds in females than males. Using age specific cut-off, the odds ratio for GJH in neurodivergent group, compared to the comparison group, was 2.84 (95% CI 1.16-6.94). Neurodivergent participants reported significantly more symptoms of orthostatic intolerance and musculoskeletal skeletal pain than the comparison group. The number of hypermobile joints was found to mediate the relationship between neurodivergence and symptoms of both dysautonomia and pain.</AbstractText In neurodivergent adults, there is a strong link between the expression of joint hypermobility, dysautonomia, and pain, more so than in the comparison group. Moreover, joint hypermobility mediates the link between neurodivergence and symptoms of dysautonomia and pain. Increased awareness and understanding of this association may enhance the management of core symptoms and allied difficulties in neurodivergent people, including co-occurring physical symptoms, and guide service delivery in the future.</AbstractText
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Backward crosstalk effects (BCEs) are observed in dual-task studies when characteristics of Task 2 influence Task 1 performance. When Task 2 is a go/no-go task, responses in Task 1 are slower when Task 2 is a no-go as compared with a go trial. This no-go BCE has been argued to be due to response inhibition spilling over from Task 2 to Task 1. Growing evidence shows that response inhibition elicits negative affect leading to affective devaluation of associated stimuli. We tested for a functional role of the negative affective consequence of response inhibition in the no-go BCE by investigating its interaction with affective processing in Task 1. In four experiments, Task 1 was a valence categorisation task, and Task 2 a go/no-go task. In all experiments, the no-go BCE strongly depended on affective processing in Task 1. While this modulation could be attributed to an affective (mis)match between stimulus features in both tasks in Experiments 1 and 2, Experiments 3 and 4 provided evidence for an affective (mis)match between stimulus valence in Task 1 and affective consequences of Task 2 response inhibition. The results are discussed in the context of current theories of no-go BCEs in dual tasks.</AbstractText
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Mental health and weight regain after bariatric surgery: associations between weight regain and psychiatric and eating-related comorbidities. Weight regain is a common outcome of weight loss interventions. Mental health-related comorbidities, among other factors, can mediate weight regain regardless of the implemented treatment modality. This study explores whether postoperative psychopathological comorbidities are associated with weight regain after bariatric surgery.</AbstractText This cross-sectional study recruited 90 outpatients who underwent Roux-en-Y gastric bypass surgery. Anthropometric measurements were collected retrospectively from medical charts. The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorder-IV (DSM-IV) Axis I Disorders (SCID-I) was applied to evaluate psychiatry diagnoses. Validated self-report instruments were used to assess depression, anxiety, alcohol use, impulsivity, binge eating, and body image dissatisfaction. Weight regain was defined as a ≥20% increase from the maximum weight lost. Level of evidence: Level III, cross-sectional study based on a well-designed study.</AbstractText Overall, 55.6% of participants experienced weight regain. Notably, mental disorders such as current binge-eating disorder and lifetime diagnoses including bulimia nervosa, alcohol abuse/dependence, and obsessive-compulsive disorder were significantly associated with weight regain. However, controlled analysis found that, for mental disorders, only current binge-eating disorder (odds ratio [OR] 6.3, 95% confidence interval [CI] 1.26-31.06, p = 0.024) remained associated with weight regain. Eating-related psychopathologies also associated with weight regain included binge eating (d = 0.55; p = 0.013), eating disinhibition (d = 0.76; p = 0.001), higher hunger levels (d = 0.39; p = 0.004), and non-planning trait impulsivity (d = 0.69; p = 0.0001).</AbstractText Postoperative presence of psychopathological comorbidities, such as eating psychopathology and trait impulsivity, were associated with weight regain after bariatric surgery. These findings highlight the importance of addressing mental health in individuals experiencing postsurgical weight regain.</AbstractText
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Joint Hypermobility Links Neurodivergence to Dysautonomia and Pain. Autism, attention deficit hyperactivity disorder (ADHD), and tic disorder (Tourette syndrome; TS) are neurodevelopmental conditions that frequently co-occur and impact psychological, social, and emotional processes. Increased likelihood of chronic physical symptoms, including fatigue and pain, are also recognized. The expression of joint hypermobility, reflecting a constitutional variant in connective tissue, predicts susceptibility to psychological symptoms alongside recognized physical symptoms. Here, we tested for increased prevalence of joint hypermobility, autonomic dysfunction, and musculoskeletal symptoms in 109 adults with neurodevelopmental condition diagnoses.</AbstractText Rates of generalized joint hypermobility (GJH, henceforth hypermobility) in adults with a formal diagnosis of neurodevelopmental conditions (henceforth neurodivergent group, <i The neurodivergent group manifested elevated prevalence of hypermobility (51%) compared to the general population rate of 20% and a comparison population (17.5%). Using a more stringent age specific cut-off, in the neurodivergent group this prevalence was 28.4%, more than double than the comparison group (12.5%). Odds ratio for presence of hypermobility in neurodivergent group, compared to the general population was 4.51 (95% CI 2.17-9.37), with greater odds in females than males. Using age specific cut-off, the odds ratio for GJH in neurodivergent group, compared to the comparison group, was 2.84 (95% CI 1.16-6.94). Neurodivergent participants reported significantly more symptoms of orthostatic intolerance and musculoskeletal skeletal pain than the comparison group. The number of hypermobile joints was found to mediate the relationship between neurodivergence and symptoms of both dysautonomia and pain.</AbstractText In neurodivergent adults, there is a strong link between the expression of joint hypermobility, dysautonomia, and pain, more so than in the comparison group. Moreover, joint hypermobility mediates the link between neurodivergence and symptoms of dysautonomia and pain. Increased awareness and understanding of this association may enhance the management of core symptoms and allied difficulties in neurodivergent people, including co-occurring physical symptoms, and guide service delivery in the future.</AbstractText
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The affective consequences of response inhibition determine no-go-based crosstalk effects in dual tasks. Backward crosstalk effects (BCEs) are observed in dual-task studies when characteristics of Task 2 influence Task 1 performance. When Task 2 is a go/no-go task, responses in Task 1 are slower when Task 2 is a no-go as compared with a go trial. This no-go BCE has been argued to be due to response inhibition spilling over from Task 2 to Task 1. Growing evidence shows that response inhibition elicits negative affect leading to affective devaluation of associated stimuli. We tested for a functional role of the negative affective consequence of response inhibition in the no-go BCE by investigating its interaction with affective processing in Task 1. In four experiments, Task 1 was a valence categorisation task, and Task 2 a go/no-go task. In all experiments, the no-go BCE strongly depended on affective processing in Task 1. While this modulation could be attributed to an affective (mis)match between stimulus features in both tasks in Experiments 1 and 2, Experiments 3 and 4 provided evidence for an affective (mis)match between stimulus valence in Task 1 and affective consequences of Task 2 response inhibition. The results are discussed in the context of current theories of no-go BCEs in dual tasks.</AbstractText
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39433769
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27215221
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39031368
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Altered drug metabolism and increased susceptibility to fatty liver disease in a mouse model of myotonic dystrophy.
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Facioscapulohumeral Dystrophy.
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Social Dysfunction and Apathy: Transdiagnostic Domains in Late-Life Cognitive Disorders.
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Myotonic Dystrophy type 1 (DM1), a highly prevalent form of muscular dystrophy, is caused by (CTG)<sub
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Facioscapulohumeral muscular dystrophy (FSHD) is a clinically recognizable and relatively common muscular dystrophy. It is inherited mostly as an autosomal dominant disease or in a minority of cases, in a digenic pattern. The disease manifestation is variable and most likely dependent on genetic and epigenetic factors. We review the history, epidemiology, clinical presentation, and genetics of the disease, present the recently elucidated molecular pathogenesis, discuss the pathology and the possible consequence of the inflammation seen in the muscle biopsies, and consider future treatments.</AbstractText
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Social dysfunction is a maladaptive process of coping, problem solving, and achieving one's goals. A new definition of apathy was cross-linked to social dysfunction, with a reduced goal-directed behavior and social interaction as a separate dimension. We hypothesized that these two neuropsychiatric symptoms may be included in the mild behavioral impairment diagnostic framework, operationalizing and standardizing late-life neuropsychiatric symptom assessment, to improve risk determination of dementia. Social dysfunction and apathy were transdiagnostic and prodromic for late-life cognitive disorders. A transdiagnostic approach could provide a useful mean for a better understanding of apathy and related conditions such as social behavior.</AbstractText
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Altered drug metabolism and increased susceptibility to fatty liver disease in a mouse model of myotonic dystrophy. Myotonic Dystrophy type 1 (DM1), a highly prevalent form of muscular dystrophy, is caused by (CTG)<sub
|
Facioscapulohumeral Dystrophy. Facioscapulohumeral muscular dystrophy (FSHD) is a clinically recognizable and relatively common muscular dystrophy. It is inherited mostly as an autosomal dominant disease or in a minority of cases, in a digenic pattern. The disease manifestation is variable and most likely dependent on genetic and epigenetic factors. We review the history, epidemiology, clinical presentation, and genetics of the disease, present the recently elucidated molecular pathogenesis, discuss the pathology and the possible consequence of the inflammation seen in the muscle biopsies, and consider future treatments.</AbstractText
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Social Dysfunction and Apathy: Transdiagnostic Domains in Late-Life Cognitive Disorders. Social dysfunction is a maladaptive process of coping, problem solving, and achieving one's goals. A new definition of apathy was cross-linked to social dysfunction, with a reduced goal-directed behavior and social interaction as a separate dimension. We hypothesized that these two neuropsychiatric symptoms may be included in the mild behavioral impairment diagnostic framework, operationalizing and standardizing late-life neuropsychiatric symptom assessment, to improve risk determination of dementia. Social dysfunction and apathy were transdiagnostic and prodromic for late-life cognitive disorders. A transdiagnostic approach could provide a useful mean for a better understanding of apathy and related conditions such as social behavior.</AbstractText
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20631210
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19172643
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20360002
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Attentional modulation of affective versus sensory processing: functional connectivity and a top-down biased activation theory of selective attention.
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The free choice whether or not to respond after stimulus presentation.
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Axonal neuregulin 1 type III activates NF-kappaB in Schwann cells during myelin formation.
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Top-down selective attention to the affective properties of taste stimuli increases activation to the taste stimuli in the orbitofrontal cortex (OFC) and pregenual cingulate cortex (PGC), and selective attention to the intensity of the stimuli increases the activation in the insular taste cortex, but the origin of the top-down attentional biases is not known. Using psychophysiological interaction connectivity analyses, we showed that in the anterior lateral prefrontal cortex (LPFC) at Y = 53 mm the correlation with activity in OFC and PGC seed regions was greater when attention was to pleasantness compared with when attention was to intensity. Conversely, we showed that in a more posterior region of the LPFC at Y = 34 the correlation with activity in the anterior insula seed region was greater when attention was to intensity compared with when attention was to pleasantness. We also showed that correlations between areas in these separate processing streams were dependent on selective attention to affective value versus physical intensity of the stimulus. We then propose a biased activation theory of selective attention to account for the findings and contrast this with a biased competition theory of selective attention.</AbstractText
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The concept of 'willed' actions has attracted attention during the last few years. Free choices have been associated with activations on the medial frontal surface, the dorsolateral prefrontal cortex and the parietal lobe. Self-paced movements and free selection between various motor responses were typically used to investigate voluntary behavior. The aim of the present study was to determine neural correlates of voluntary motor responses and the voluntary inhibition of motor responses in a group of healthy subjects. Hence, a go/nogo/voluntary selection paradigm was used. In the voluntary selection condition subjects decided freely whether or not to respond with a button press after stimulus presentation. Functional MRI data and event-related potentials were acquired simultaneously in order to reliably investigate spatial and temporal characteristics of these responses. The results showed decision-related enhanced neural responses predominantly in the medial frontal gyrus/supplementary motor area, lateral frontal brain regions and the inferior parietal gyrus. Additional activations associated with voluntary movements were detected in the frontal eye field as well as brain regions directly linked to motor responses (e.g. somatosensory cortical areas). Altogether, decision processes were shown to be relatively independent of the kind of response chosen.</AbstractText
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The formation of myelin requires a series of complex signaling events initiated by the axon to surrounding glial cells, which ultimately respond by tightly wrapping the axon with layers of specialized plasma membrane thereby allowing for saltatory conduction. Activation of the transcription factor NF-kappaB in Schwann cells has been suggested to be critical for these cells to differentiate into a myelinating phenotype; however, the mechanisms by which it is activated have yet to be elucidated. Here, we demonstrate that axonal membranes are sufficient to promote NF-kappaB activation in cultured Schwann cells and identify neuregulin 1 (NRG1), specifically the membrane-bound type III isoform, as the signal responsible for activating this transcription factor. Surprisingly, neither membrane-bound type I nor the soluble NRG1 EGF domain could activate NF-kappaB, indicating that type III induces a qualitatively unique signal. The transcriptional activity of NF-kappaB was significantly enhanced by treatment with forskolin, indicating these two signals converge for maximal activation. Both ErbB2 and -3 receptors were required for transducing the NRG1 signal, because gene deletion of ErbB3 in Schwann cells or treatment with the ErbB2 selective inhibitor, PKI-166, prevented the stimulation of NF-kappaB by axonal membranes. Finally, PKI-166 blocked the activation of the transcription factor in myelinating neuron/Schwann cell co-cultures and in vivo, in developing sciatic nerves. Taken together, these data establish NRG1 type III as the activator of NF-kappaB during myelin formation.</AbstractText
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Attentional modulation of affective versus sensory processing: functional connectivity and a top-down biased activation theory of selective attention. Top-down selective attention to the affective properties of taste stimuli increases activation to the taste stimuli in the orbitofrontal cortex (OFC) and pregenual cingulate cortex (PGC), and selective attention to the intensity of the stimuli increases the activation in the insular taste cortex, but the origin of the top-down attentional biases is not known. Using psychophysiological interaction connectivity analyses, we showed that in the anterior lateral prefrontal cortex (LPFC) at Y = 53 mm the correlation with activity in OFC and PGC seed regions was greater when attention was to pleasantness compared with when attention was to intensity. Conversely, we showed that in a more posterior region of the LPFC at Y = 34 the correlation with activity in the anterior insula seed region was greater when attention was to intensity compared with when attention was to pleasantness. We also showed that correlations between areas in these separate processing streams were dependent on selective attention to affective value versus physical intensity of the stimulus. We then propose a biased activation theory of selective attention to account for the findings and contrast this with a biased competition theory of selective attention.</AbstractText
|
The free choice whether or not to respond after stimulus presentation. The concept of 'willed' actions has attracted attention during the last few years. Free choices have been associated with activations on the medial frontal surface, the dorsolateral prefrontal cortex and the parietal lobe. Self-paced movements and free selection between various motor responses were typically used to investigate voluntary behavior. The aim of the present study was to determine neural correlates of voluntary motor responses and the voluntary inhibition of motor responses in a group of healthy subjects. Hence, a go/nogo/voluntary selection paradigm was used. In the voluntary selection condition subjects decided freely whether or not to respond with a button press after stimulus presentation. Functional MRI data and event-related potentials were acquired simultaneously in order to reliably investigate spatial and temporal characteristics of these responses. The results showed decision-related enhanced neural responses predominantly in the medial frontal gyrus/supplementary motor area, lateral frontal brain regions and the inferior parietal gyrus. Additional activations associated with voluntary movements were detected in the frontal eye field as well as brain regions directly linked to motor responses (e.g. somatosensory cortical areas). Altogether, decision processes were shown to be relatively independent of the kind of response chosen.</AbstractText
|
Axonal neuregulin 1 type III activates NF-kappaB in Schwann cells during myelin formation. The formation of myelin requires a series of complex signaling events initiated by the axon to surrounding glial cells, which ultimately respond by tightly wrapping the axon with layers of specialized plasma membrane thereby allowing for saltatory conduction. Activation of the transcription factor NF-kappaB in Schwann cells has been suggested to be critical for these cells to differentiate into a myelinating phenotype; however, the mechanisms by which it is activated have yet to be elucidated. Here, we demonstrate that axonal membranes are sufficient to promote NF-kappaB activation in cultured Schwann cells and identify neuregulin 1 (NRG1), specifically the membrane-bound type III isoform, as the signal responsible for activating this transcription factor. Surprisingly, neither membrane-bound type I nor the soluble NRG1 EGF domain could activate NF-kappaB, indicating that type III induces a qualitatively unique signal. The transcriptional activity of NF-kappaB was significantly enhanced by treatment with forskolin, indicating these two signals converge for maximal activation. Both ErbB2 and -3 receptors were required for transducing the NRG1 signal, because gene deletion of ErbB3 in Schwann cells or treatment with the ErbB2 selective inhibitor, PKI-166, prevented the stimulation of NF-kappaB by axonal membranes. Finally, PKI-166 blocked the activation of the transcription factor in myelinating neuron/Schwann cell co-cultures and in vivo, in developing sciatic nerves. Taken together, these data establish NRG1 type III as the activator of NF-kappaB during myelin formation.</AbstractText
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36736647
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26945974
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36427753
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Developing an evidence-based approach to quality control.
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The first step for neuroimaging data analysis: DICOM to NIfTI conversion.
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Functionally and structurally distinct fusiform face area(s) in over 1000 participants.
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Effective Quality Control remains one of the pillars of Clinical Biochemistry. An understanding of the possible analytical errors that may occur, how to detect them efficiently and how to prevent them from causing patient harm are critical components of a Quality System. For some time, there have been questions about the theoretical basis of the models used to describe and detect analytical error. The current theory recognises two types of error, systematic and random and a system based on sampling the analytical process using a synthetic material to detect these errors. However, there are at least two other errors that are present. One is related to the QC material and the other, irregular errors. In this Opinion Piece, some of the underlying assumptions of Quality Control systems are described and analysed.</AbstractText
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Clinical imaging data are typically stored and transferred in the DICOM format, whereas the NIfTI format has been widely adopted by scientists in the neuroimaging community. Therefore, a vital initial step in processing the data is to convert images from the complicated DICOM format to the much simpler NIfTI format. While there are a number of tools that usually handle DICOM to NIfTI conversion seamlessly, some variations can disrupt this process.</AbstractText We provide some insight into the challenges faced with image conversion. First, different manufacturers implement the DICOM format differently which complicates the conversion. Second, different modalities and sub-modalities may need special treatment during conversion. Lastly, the image transferring and archiving can also impact the DICOM conversion.</AbstractText We present results in several error-prone domains, including the slice order for functional imaging, phase encoding direction for distortion correction, effect of diffusion gradient direction, and effect of gantry correction for some imaging modality.</AbstractText Conversion tools are often designed for a specific manufacturer or modality. The tools and insight we present here are aimed at different manufacturers or modalities.</AbstractText The imaging conversion is complicated by the variation of images. An understanding of the conversion basics can be helpful for identifying the source of the error. Here we provide users with simple methods for detecting and correcting problems. This also serves as an overview for developers who wish to either develop their own tools or adapt the open source tools created by the authors.</AbstractText
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The fusiform face area (FFA) is a widely studied region causally involved in face perception. Even though cognitive neuroscientists have been studying the FFA for over two decades, answers to foundational questions regarding the function, architecture, and connectivity of the FFA from a large (N>1000) group of participants are still lacking. To fill this gap in knowledge, we quantified these multimodal features of fusiform face-selective regions in 1053 participants in the Human Connectome Project. After manually defining over 4,000 fusiform face-selective regions, we report five main findings. First, 68.76% of hemispheres have two cortically separate regions (pFus-faces/FFA-1 and mFus-faces/FFA-2). Second, in 26.69% of hemispheres, pFus-faces/FFA-1 and mFus-faces/FFA-2 are spatially contiguous, yet are distinct based on functional, architectural, and connectivity metrics. Third, pFus-faces/FFA-1 is more face-selective than mFus-faces/FFA-2, and the two regions have distinct functional connectivity fingerprints. Fourth, pFus-faces/FFA-1 is cortically thinner and more heavily myelinated than mFus-faces/FFA-2. Fifth, face-selective patterns and functional connectivity fingerprints of each region are more similar in monozygotic than dizygotic twins and more so than architectural gradients. As we share our areal definitions with the field, future studies can explore how structural and functional features of these regions will inform theories regarding how visual categories are represented in the brain.</AbstractText
|
Developing an evidence-based approach to quality control. Effective Quality Control remains one of the pillars of Clinical Biochemistry. An understanding of the possible analytical errors that may occur, how to detect them efficiently and how to prevent them from causing patient harm are critical components of a Quality System. For some time, there have been questions about the theoretical basis of the models used to describe and detect analytical error. The current theory recognises two types of error, systematic and random and a system based on sampling the analytical process using a synthetic material to detect these errors. However, there are at least two other errors that are present. One is related to the QC material and the other, irregular errors. In this Opinion Piece, some of the underlying assumptions of Quality Control systems are described and analysed.</AbstractText
|
The first step for neuroimaging data analysis: DICOM to NIfTI conversion. Clinical imaging data are typically stored and transferred in the DICOM format, whereas the NIfTI format has been widely adopted by scientists in the neuroimaging community. Therefore, a vital initial step in processing the data is to convert images from the complicated DICOM format to the much simpler NIfTI format. While there are a number of tools that usually handle DICOM to NIfTI conversion seamlessly, some variations can disrupt this process.</AbstractText We provide some insight into the challenges faced with image conversion. First, different manufacturers implement the DICOM format differently which complicates the conversion. Second, different modalities and sub-modalities may need special treatment during conversion. Lastly, the image transferring and archiving can also impact the DICOM conversion.</AbstractText We present results in several error-prone domains, including the slice order for functional imaging, phase encoding direction for distortion correction, effect of diffusion gradient direction, and effect of gantry correction for some imaging modality.</AbstractText Conversion tools are often designed for a specific manufacturer or modality. The tools and insight we present here are aimed at different manufacturers or modalities.</AbstractText The imaging conversion is complicated by the variation of images. An understanding of the conversion basics can be helpful for identifying the source of the error. Here we provide users with simple methods for detecting and correcting problems. This also serves as an overview for developers who wish to either develop their own tools or adapt the open source tools created by the authors.</AbstractText
|
Functionally and structurally distinct fusiform face area(s) in over 1000 participants. The fusiform face area (FFA) is a widely studied region causally involved in face perception. Even though cognitive neuroscientists have been studying the FFA for over two decades, answers to foundational questions regarding the function, architecture, and connectivity of the FFA from a large (N>1000) group of participants are still lacking. To fill this gap in knowledge, we quantified these multimodal features of fusiform face-selective regions in 1053 participants in the Human Connectome Project. After manually defining over 4,000 fusiform face-selective regions, we report five main findings. First, 68.76% of hemispheres have two cortically separate regions (pFus-faces/FFA-1 and mFus-faces/FFA-2). Second, in 26.69% of hemispheres, pFus-faces/FFA-1 and mFus-faces/FFA-2 are spatially contiguous, yet are distinct based on functional, architectural, and connectivity metrics. Third, pFus-faces/FFA-1 is more face-selective than mFus-faces/FFA-2, and the two regions have distinct functional connectivity fingerprints. Fourth, pFus-faces/FFA-1 is cortically thinner and more heavily myelinated than mFus-faces/FFA-2. Fifth, face-selective patterns and functional connectivity fingerprints of each region are more similar in monozygotic than dizygotic twins and more so than architectural gradients. As we share our areal definitions with the field, future studies can explore how structural and functional features of these regions will inform theories regarding how visual categories are represented in the brain.</AbstractText
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39805185
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34022959
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40463109
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Ultrasmall iron-gallic acid coordination polymer nanoparticles for scavenging ROS and suppressing inflammation in tauopathy-induced Alzheimer's disease.
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Identifying degenerative effects of repetitive head trauma with neuroimaging: a clinically-oriented review.
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Synaptic dynamics govern spatial integration in mouse visual cortex.
|
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder globally, with no effective treatment available yet. A crucial pathological hallmark of AD is the accumulation of hyperphosphorylated tau protein, which is deteriorated by reactive oxygen species (ROS) and neuroinflammation in AD progression. Thus, alleviation of ROS and inflammation has become a potential therapeutic strategy in many studies. Herein, we reported ultrasmall coordination polymer nanoparticles formed by ferric ions and gallic acid (Fe-GA CPNs), which owned antioxidant and anti-inflammation properties for AD therapeutics. The facilely prepared Fe-GA CPNs exhibited remarkable superoxide dismutase-like, peroxidase-like enzyme activity, and ROS eliminating ability with great water solubility, compared with gallic acid. We demonstrated that Fe-GA CPNs effectively relieved oxidative stress, ameliorated inflammation by modulating microglial polarization towards anti-inflammation phenotype, and reduced hyperphosphorylated tau protein levels. Furthermore, Fe-GA CPNs treatment significantly improved cognitive function in tauopathy-induced AD rats, and achieved a neuroprotective effect against AD pathology. This study highlights the potential of coordination polymer nanoparticles as promising therapeutic candidates for AD and other tau-related neurodegenerative diseases.</AbstractText
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Varying severities and frequencies of head trauma may result in dynamic acute and chronic pathophysiologic responses in the brain. Heightened attention to long-term effects of head trauma, particularly repetitive head trauma, has sparked recent efforts to identify neuroimaging biomarkers of underlying disease processes. Imaging modalities like structural magnetic resonance imaging (MRI) and positron emission tomography (PET) are the most clinically applicable given their use in neurodegenerative disease diagnosis and differentiation. In recent years, researchers have targeted repetitive head trauma cohorts in hopes of identifying in vivo biomarkers for underlying biologic changes that might ultimately improve diagnosis of chronic traumatic encephalopathy (CTE) in living persons. These populations most often include collision sport athletes (e.g., American football, boxing) and military veterans with repetitive low-level blast exposure. We provide a clinically-oriented review of neuroimaging data from repetitive head trauma cohorts based on structural MRI, FDG-PET, Aβ-PET, and tau-PET. We supplement the review with two patient reports of neuropathology-confirmed, clinically impaired adults with prior repetitive head trauma who underwent structural MRI, FDG-PET, Aβ-PET, and tau-PET in addition to comprehensive clinical examinations before death.</AbstractText Group-level comparisons to controls without known head trauma have revealed inconsistent regional volume differences, with possible propensity for medial temporal, limbic, and subcortical (thalamus, corpus callosum) structures. Greater frequency and severity (i.e., length) of cavum septum pellucidum (CSP) is observed in repetitive head trauma cohorts compared to unexposed controls. It remains unclear whether CSP predicts a particular neurodegenerative process, but CSP presence should increase suspicion that clinical impairment is at least partly attributable to the individual's head trauma exposure (regardless of underlying disease). PET imaging similarly has not revealed a prototypical metabolic or molecular pattern associated with repetitive head trauma or predictive of CTE based on the most widely studied radiotracers. Given the range of clinical syndromes and neurodegenerative pathologies observed in a subset of adults with prior repetitive head trauma, structural MRI and PET imaging may still be useful for differential diagnosis (e.g., assessing suspected Alzheimer's disease).</AbstractText
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Neurons in primary visual cortex are often suppressed by stimuli extending beyond their receptive fields. This surround suppression is proposed to reduce the redundancy of encoding large stimuli and support scene segmentation. We find that surround suppression decreases firing rates in mouse primary visual cortex by accelerating the decay of visually-evoked responses and reducing response duration. The rapid decay of visual responses at large sizes is enhanced by increased contrast, reduced by locomotion, and invariant to stimulus orientation, consistent with the engagement of a network mechanism. While fast-spiking interneurons have faster dynamics relative to neighboring pyramidal cells, the dynamics of somatostatin-expressing interneurons are delayed. At the subthreshold level, the rapid decay of visual responses with increasing size is due to a delayed removal of both synaptic excitation and inhibition below baseline levels following visual input. We propose that the delayed activation of somatostatin-expressing interneurons drives a network-wide suppression and accelerates the decay of the visual response. Thus, these data identify a key role for synaptic network dynamics in regulating both spatial and temporal integration in mouse visual cortex.</AbstractText
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Ultrasmall iron-gallic acid coordination polymer nanoparticles for scavenging ROS and suppressing inflammation in tauopathy-induced Alzheimer's disease. Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder globally, with no effective treatment available yet. A crucial pathological hallmark of AD is the accumulation of hyperphosphorylated tau protein, which is deteriorated by reactive oxygen species (ROS) and neuroinflammation in AD progression. Thus, alleviation of ROS and inflammation has become a potential therapeutic strategy in many studies. Herein, we reported ultrasmall coordination polymer nanoparticles formed by ferric ions and gallic acid (Fe-GA CPNs), which owned antioxidant and anti-inflammation properties for AD therapeutics. The facilely prepared Fe-GA CPNs exhibited remarkable superoxide dismutase-like, peroxidase-like enzyme activity, and ROS eliminating ability with great water solubility, compared with gallic acid. We demonstrated that Fe-GA CPNs effectively relieved oxidative stress, ameliorated inflammation by modulating microglial polarization towards anti-inflammation phenotype, and reduced hyperphosphorylated tau protein levels. Furthermore, Fe-GA CPNs treatment significantly improved cognitive function in tauopathy-induced AD rats, and achieved a neuroprotective effect against AD pathology. This study highlights the potential of coordination polymer nanoparticles as promising therapeutic candidates for AD and other tau-related neurodegenerative diseases.</AbstractText
|
Identifying degenerative effects of repetitive head trauma with neuroimaging: a clinically-oriented review. Varying severities and frequencies of head trauma may result in dynamic acute and chronic pathophysiologic responses in the brain. Heightened attention to long-term effects of head trauma, particularly repetitive head trauma, has sparked recent efforts to identify neuroimaging biomarkers of underlying disease processes. Imaging modalities like structural magnetic resonance imaging (MRI) and positron emission tomography (PET) are the most clinically applicable given their use in neurodegenerative disease diagnosis and differentiation. In recent years, researchers have targeted repetitive head trauma cohorts in hopes of identifying in vivo biomarkers for underlying biologic changes that might ultimately improve diagnosis of chronic traumatic encephalopathy (CTE) in living persons. These populations most often include collision sport athletes (e.g., American football, boxing) and military veterans with repetitive low-level blast exposure. We provide a clinically-oriented review of neuroimaging data from repetitive head trauma cohorts based on structural MRI, FDG-PET, Aβ-PET, and tau-PET. We supplement the review with two patient reports of neuropathology-confirmed, clinically impaired adults with prior repetitive head trauma who underwent structural MRI, FDG-PET, Aβ-PET, and tau-PET in addition to comprehensive clinical examinations before death.</AbstractText Group-level comparisons to controls without known head trauma have revealed inconsistent regional volume differences, with possible propensity for medial temporal, limbic, and subcortical (thalamus, corpus callosum) structures. Greater frequency and severity (i.e., length) of cavum septum pellucidum (CSP) is observed in repetitive head trauma cohorts compared to unexposed controls. It remains unclear whether CSP predicts a particular neurodegenerative process, but CSP presence should increase suspicion that clinical impairment is at least partly attributable to the individual's head trauma exposure (regardless of underlying disease). PET imaging similarly has not revealed a prototypical metabolic or molecular pattern associated with repetitive head trauma or predictive of CTE based on the most widely studied radiotracers. Given the range of clinical syndromes and neurodegenerative pathologies observed in a subset of adults with prior repetitive head trauma, structural MRI and PET imaging may still be useful for differential diagnosis (e.g., assessing suspected Alzheimer's disease).</AbstractText
|
Synaptic dynamics govern spatial integration in mouse visual cortex. Neurons in primary visual cortex are often suppressed by stimuli extending beyond their receptive fields. This surround suppression is proposed to reduce the redundancy of encoding large stimuli and support scene segmentation. We find that surround suppression decreases firing rates in mouse primary visual cortex by accelerating the decay of visually-evoked responses and reducing response duration. The rapid decay of visual responses at large sizes is enhanced by increased contrast, reduced by locomotion, and invariant to stimulus orientation, consistent with the engagement of a network mechanism. While fast-spiking interneurons have faster dynamics relative to neighboring pyramidal cells, the dynamics of somatostatin-expressing interneurons are delayed. At the subthreshold level, the rapid decay of visual responses with increasing size is due to a delayed removal of both synaptic excitation and inhibition below baseline levels following visual input. We propose that the delayed activation of somatostatin-expressing interneurons drives a network-wide suppression and accelerates the decay of the visual response. Thus, these data identify a key role for synaptic network dynamics in regulating both spatial and temporal integration in mouse visual cortex.</AbstractText
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37214329
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35233664
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37433970
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A rare case of spontaneous thrombosis in saccular cerebral aneurysm in a patient with subarachnoid hemorrhage.
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Temporary vessel occlusion in cerebral aneurysm surgery guided by direct cortical motor evoked potentials.
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Functional abnormalities of the cerebellum in vascular mild cognitive impairment.
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Cerebral aneurysm is a known cause of spontaneous subarachnoid hemorrhage (SAH). Furthermore, this condition is often asymptomatic, but the occurrence of a rupture can lead to fatal complications. The incidence of spontaneous thrombosis in saccular aneurysm is rare, with an incidence rate of 1%-2%. The most common sites include the middle cerebral artery (MCA) (41%), posterior communicating artery (PCOMM) (15%), and posterior inferior cerebellar artery (PICA) (11%). A head computed tomography angiography (CTA) with contrast is a common diagnostic tool for detecting SAH in the temporoparietal area, hippocampal gyrus, and right fissure of Sylvie. In some cases, saccular aneurysm can be found in the segment bifurcation of the right middle cerebral artery. A cerebral angiography was carried out, specifically digital subtraction angiography, which revealed the presence of visible blister remnants of aneurysm in the form of spontaneous thrombosis. After 1 year, another angiography evaluation was performed to assess the condition of the patient. Furthermore, the results showed no evidence of recanalization and there were no new neurologic deficits. Although spontaneous thrombosis led to the healing of aneurysm in some cases, secondary recanalization remained a possibility. Therefore, it was essential to monitor any incidence of this complication. Precise knowledge of the mechanism of spontaneous thrombosis could lead to the development of new therapeutic approaches. Spontaneous thrombosis in cases of saccular aneurysm is a rare occurrence, which can provide temporary or permanent benefits to the patient. Therefore, periodic evaluation is required to assess the condition of the patient.</AbstractText
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Temporary clipping is an important tool in the vascular neurosurgeon's armamentarium. We routinely utilize intraoperative neurophysiological monitoring (IONM) for complex brain aneurysm surgery cases, relying on direct cortical motor evoked potential (DCMEP) alerts to guide the duration of temporary clipping. Previous studies have argued for relatively short and intermittent temporary clipping strategies. In this study, we sought to assess the maximal permissive temporary clipping time during complex aneurysm surgery. To do this, we assessed patient outcome in relation to temporary clip duration guided by DCMEP.</AbstractText We queried our prospectively collected neuromonitoring database for anterior circulation aneurysm cases where temporary clipping was utilized by a single cerebrovascular surgeon between 2018 and 2021. Operative and IONM reports were reviewed. Patients in whom the duration of temporary clipping could not be determined were excluded. The operative strategy permissively allowed continuous temporary clipping as long as no neuromonitoring alerts were encountered. Maximal permissive parent artery occlusion time (Clip<sub A total of 41 complex anterior circulation aneurysm clipping cases met criteria for this study. The mean Clip<sub This study demonstrates that using DCMEP can facilitate relatively long but safe temporary clipping durations in complex anterior circulation aneurysm surgery. In the endovascular era with only a limited subset of technically challenging aneurysms needing open surgical treatment, extended permissive temporary clipping guided by DCMEPs can significantly enhance a surgeon's ability to achieve excellent technical and clinical outcomes.</AbstractText
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The alterations in cerebellar activity that occur in vascular mild cognitive impairment remain largely unexplored. This study aimed to investigate potential associations between abnormal cerebellar functional connectivity (FC) and changes in cognitive function by examining intracerebellar and cerebellar-cerebral FC.</AbstractText MRI data were collected from seventy-two patients with vascular mild cognitive impairment (VMCI), comprising 38 patients with small vessel mild cognitive impairment (SVMCI) and 34 with poststroke mild cognitive impairment (PSMCI), and from 43 demographically matched healthy controls (HCs). Changes in FC between subregions within the cerebellum and from each cerebellar subregion to the selected cerebral seed points in VMCI patients were calculated, and the association of these changes with cognitive function was examined.</AbstractText Compared with HCs, we found that VMCI patients had 11 cerebellar subregions showing significant differences (mainly decreases) in FC with brain regions in the default-mode network (DMN), sensory-motor network (SMN), and frontoparietal network (FPN). In the intracerebellar FC analysis, 47 (8%) cerebellar connections had significant intergroup differences, mainly a reduced magnitude of FC in VMCI patients. In the correlation analysis, higher Montreal Cognitive Assessment (MoCA) scores were correlated with stronger intracerebellar FC (left crus II-right lobule VI, left crus II-right lobule VIIb) and cerebellar-cerebral FC (right lobule X-left precuneus, vermal lobule IX-right inferior parietal lobule) in both the SVMCI and PSMCI groups.</AbstractText These findings suggest prominent intracerebellar and cerebellar-cerebral FC abnormalities in VMCI patients, contributing evidence for a possible role of the cerebellum in cognitive processes.</AbstractText
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A rare case of spontaneous thrombosis in saccular cerebral aneurysm in a patient with subarachnoid hemorrhage. Cerebral aneurysm is a known cause of spontaneous subarachnoid hemorrhage (SAH). Furthermore, this condition is often asymptomatic, but the occurrence of a rupture can lead to fatal complications. The incidence of spontaneous thrombosis in saccular aneurysm is rare, with an incidence rate of 1%-2%. The most common sites include the middle cerebral artery (MCA) (41%), posterior communicating artery (PCOMM) (15%), and posterior inferior cerebellar artery (PICA) (11%). A head computed tomography angiography (CTA) with contrast is a common diagnostic tool for detecting SAH in the temporoparietal area, hippocampal gyrus, and right fissure of Sylvie. In some cases, saccular aneurysm can be found in the segment bifurcation of the right middle cerebral artery. A cerebral angiography was carried out, specifically digital subtraction angiography, which revealed the presence of visible blister remnants of aneurysm in the form of spontaneous thrombosis. After 1 year, another angiography evaluation was performed to assess the condition of the patient. Furthermore, the results showed no evidence of recanalization and there were no new neurologic deficits. Although spontaneous thrombosis led to the healing of aneurysm in some cases, secondary recanalization remained a possibility. Therefore, it was essential to monitor any incidence of this complication. Precise knowledge of the mechanism of spontaneous thrombosis could lead to the development of new therapeutic approaches. Spontaneous thrombosis in cases of saccular aneurysm is a rare occurrence, which can provide temporary or permanent benefits to the patient. Therefore, periodic evaluation is required to assess the condition of the patient.</AbstractText
|
Temporary vessel occlusion in cerebral aneurysm surgery guided by direct cortical motor evoked potentials. Temporary clipping is an important tool in the vascular neurosurgeon's armamentarium. We routinely utilize intraoperative neurophysiological monitoring (IONM) for complex brain aneurysm surgery cases, relying on direct cortical motor evoked potential (DCMEP) alerts to guide the duration of temporary clipping. Previous studies have argued for relatively short and intermittent temporary clipping strategies. In this study, we sought to assess the maximal permissive temporary clipping time during complex aneurysm surgery. To do this, we assessed patient outcome in relation to temporary clip duration guided by DCMEP.</AbstractText We queried our prospectively collected neuromonitoring database for anterior circulation aneurysm cases where temporary clipping was utilized by a single cerebrovascular surgeon between 2018 and 2021. Operative and IONM reports were reviewed. Patients in whom the duration of temporary clipping could not be determined were excluded. The operative strategy permissively allowed continuous temporary clipping as long as no neuromonitoring alerts were encountered. Maximal permissive parent artery occlusion time (Clip<sub A total of 41 complex anterior circulation aneurysm clipping cases met criteria for this study. The mean Clip<sub This study demonstrates that using DCMEP can facilitate relatively long but safe temporary clipping durations in complex anterior circulation aneurysm surgery. In the endovascular era with only a limited subset of technically challenging aneurysms needing open surgical treatment, extended permissive temporary clipping guided by DCMEPs can significantly enhance a surgeon's ability to achieve excellent technical and clinical outcomes.</AbstractText
|
Functional abnormalities of the cerebellum in vascular mild cognitive impairment. The alterations in cerebellar activity that occur in vascular mild cognitive impairment remain largely unexplored. This study aimed to investigate potential associations between abnormal cerebellar functional connectivity (FC) and changes in cognitive function by examining intracerebellar and cerebellar-cerebral FC.</AbstractText MRI data were collected from seventy-two patients with vascular mild cognitive impairment (VMCI), comprising 38 patients with small vessel mild cognitive impairment (SVMCI) and 34 with poststroke mild cognitive impairment (PSMCI), and from 43 demographically matched healthy controls (HCs). Changes in FC between subregions within the cerebellum and from each cerebellar subregion to the selected cerebral seed points in VMCI patients were calculated, and the association of these changes with cognitive function was examined.</AbstractText Compared with HCs, we found that VMCI patients had 11 cerebellar subregions showing significant differences (mainly decreases) in FC with brain regions in the default-mode network (DMN), sensory-motor network (SMN), and frontoparietal network (FPN). In the intracerebellar FC analysis, 47 (8%) cerebellar connections had significant intergroup differences, mainly a reduced magnitude of FC in VMCI patients. In the correlation analysis, higher Montreal Cognitive Assessment (MoCA) scores were correlated with stronger intracerebellar FC (left crus II-right lobule VI, left crus II-right lobule VIIb) and cerebellar-cerebral FC (right lobule X-left precuneus, vermal lobule IX-right inferior parietal lobule) in both the SVMCI and PSMCI groups.</AbstractText These findings suggest prominent intracerebellar and cerebellar-cerebral FC abnormalities in VMCI patients, contributing evidence for a possible role of the cerebellum in cognitive processes.</AbstractText
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40011705
|
35468551
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40647476
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Longitudinal associations between white matter integrity, early life adversities, and treatment response following cognitive-behavioral therapy in depression.
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DKI enhances the sensitivity and interpretability of age-related DTI patterns in the white matter of UK biobank participants.
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SPP-SegNet and SE-DenseNet201: A Dual-Model Approach for Cervical Cell Segmentation and Classification.
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Cognitive-behavioral therapy (CBT) is a primary treatment for depression. Although previous research has underscored the significant roles of white matter (WM) alterations and maladaptive parenting in depression risk, their associations with CBT response remain largely unknown. This longitudinal study investigated the interplay of WM integrity changes over time, treatment response, and parenting style in patients with depression. Diffusion-tensor-imaging and clinical data were assessed in n = 65 (55% female) patients with depression before and after 20 CBT sessions and n = 65 (68% female) healthy controls (HC) in a naturalistic design. Linear-mixed-effect models compared changes in fractional anisotropy (FA) between groups and tested associations between FA changes and symptom changes. It was investigated whether parenting style predicts depressive symptoms at follow-up and whether FA changes mediate this association. Patients showed differential FA changes over time in the corpus callosum and corona radiata compared to HC (p<sub
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Studies of healthy brain aging traditionally report diffusivity patterns associated with white matter degeneration using diffusion tensor imaging (DTI), which assumes that diffusion measured at typical b-values (approximately 1000 s/mm<sup
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Cervical cancer, the fourth most common malignancy in women worldwide, continues to pose a significant threat to global health. Manual examination of the Pap smear image is time-consuming, labor-intensive, and prone to human error due to the large number of slides and subjective judgment. This study proposes a novel SegNet-based spatial pyramid pooling (SPP-SegNet) deep learning model for segmentation and a Squeeze-and-Excitation-based (SE-DenseNet201) model for classification, aimed at improving the accuracy of cervical cancer detection.</AbstractText The model incorporates the SPP bottleneck and atrous convolution in the SegNet framework, allowing for the extraction of multiscale spatial features and improving segmentation performance. The segmentation output is used as input for the classification task. The proposed method is evaluated on the Pomeranian and SIPaKMeD datasets.</AbstractText Segmentation results show that SPP-SegNet achieves 98.53% accuracy on the Pomeranian data set, exceeding standard SegNet, 97.86%. It also achieves 94.15% accuracy on the SIPaKMeD dataset, outperforming the standard SegNet, which is 90.95%. For classification, SE-DenseNet201 achieves 93% and 99% accuracy for the Pomeranian and SIPaKMeD binary classification, respectively, using the bounding box input.</AbstractText These results show that SPP-SegNet and SE-DenseNet201 can potentially automate cervical cell segmentation and classification, facilitating the early detection and diagnosis of cervical cancer.</AbstractText
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Longitudinal associations between white matter integrity, early life adversities, and treatment response following cognitive-behavioral therapy in depression. Cognitive-behavioral therapy (CBT) is a primary treatment for depression. Although previous research has underscored the significant roles of white matter (WM) alterations and maladaptive parenting in depression risk, their associations with CBT response remain largely unknown. This longitudinal study investigated the interplay of WM integrity changes over time, treatment response, and parenting style in patients with depression. Diffusion-tensor-imaging and clinical data were assessed in n = 65 (55% female) patients with depression before and after 20 CBT sessions and n = 65 (68% female) healthy controls (HC) in a naturalistic design. Linear-mixed-effect models compared changes in fractional anisotropy (FA) between groups and tested associations between FA changes and symptom changes. It was investigated whether parenting style predicts depressive symptoms at follow-up and whether FA changes mediate this association. Patients showed differential FA changes over time in the corpus callosum and corona radiata compared to HC (p<sub
|
DKI enhances the sensitivity and interpretability of age-related DTI patterns in the white matter of UK biobank participants. Studies of healthy brain aging traditionally report diffusivity patterns associated with white matter degeneration using diffusion tensor imaging (DTI), which assumes that diffusion measured at typical b-values (approximately 1000 s/mm<sup
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SPP-SegNet and SE-DenseNet201: A Dual-Model Approach for Cervical Cell Segmentation and Classification. Cervical cancer, the fourth most common malignancy in women worldwide, continues to pose a significant threat to global health. Manual examination of the Pap smear image is time-consuming, labor-intensive, and prone to human error due to the large number of slides and subjective judgment. This study proposes a novel SegNet-based spatial pyramid pooling (SPP-SegNet) deep learning model for segmentation and a Squeeze-and-Excitation-based (SE-DenseNet201) model for classification, aimed at improving the accuracy of cervical cancer detection.</AbstractText The model incorporates the SPP bottleneck and atrous convolution in the SegNet framework, allowing for the extraction of multiscale spatial features and improving segmentation performance. The segmentation output is used as input for the classification task. The proposed method is evaluated on the Pomeranian and SIPaKMeD datasets.</AbstractText Segmentation results show that SPP-SegNet achieves 98.53% accuracy on the Pomeranian data set, exceeding standard SegNet, 97.86%. It also achieves 94.15% accuracy on the SIPaKMeD dataset, outperforming the standard SegNet, which is 90.95%. For classification, SE-DenseNet201 achieves 93% and 99% accuracy for the Pomeranian and SIPaKMeD binary classification, respectively, using the bounding box input.</AbstractText These results show that SPP-SegNet and SE-DenseNet201 can potentially automate cervical cell segmentation and classification, facilitating the early detection and diagnosis of cervical cancer.</AbstractText
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38036161
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22654749
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39308986
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Measures of individual differences in adult theory of mind: A systematic review.
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The role of prediction in social neuroscience.
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Immunotherapy for hepatocellular carcinoma.
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Theory of mind (ToM), the ability to understand and reason about mental states, has been extensively studied in young children and clinical populations. A growing interest in examining ToM in adults has emerged over the past two decades, but the extent to which existing measures are suitable for studying adults, especially in detecting individual differences, remains understudied. In this systematic review of 273 studies, 75 measures used to investigate individual differences in adults' ToM were identified. Their sensitivity to individual differences, reliability, and validity were examined. Results suggest that ceiling effects were prevalent, and there was limited evidence to establish the reliability or validity of these measures due to the lack of reports of psychometric properties. Interrelations among measures were inconsistent. These findings highlight the need for future empirical and theoretical work to broaden the evidence base regarding psychometric properties of measures, to develop new measures, and to lay out more specific hypotheses about the relevance of ToM for different social outcomes.</AbstractText
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Research has shown that the brain is constantly making predictions about future events. Theories of prediction in perception, action and learning suggest that the brain serves to reduce the discrepancies between expectation and actual experience, i.e., by reducing the prediction error. Forward models of action and perception propose the generation of a predictive internal representation of the expected sensory outcome, which is matched to the actual sensory feedback. Shared neural representations have been found when experiencing one's own and observing other's actions, rewards, errors, and emotions such as fear and pain. These general principles of the "predictive brain" are well established and have already begun to be applied to social aspects of cognition. The application and relevance of these predictive principles to social cognition are discussed in this article. Evidence is presented to argue that simple non-social cognitive processes can be extended to explain complex cognitive processes required for social interaction, with common neural activity seen for both social and non-social cognitions. A number of studies are included which demonstrate that bottom-up sensory input and top-down expectancies can be modulated by social information. The concept of competing social forward models and a partially distinct category of social prediction errors are introduced. The evolutionary implications of a "social predictive brain" are also mentioned, along with the implications on psychopathology. The review presents a number of testable hypotheses and novel comparisons that aim to stimulate further discussion and integration between currently disparate fields of research, with regard to computational models, behavioral and neurophysiological data. This promotes a relatively new platform for inquiry in social neuroscience with implications in social learning, theory of mind, empathy, the evolution of the social brain, and potential strategies for treating social cognitive deficits.</AbstractText
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Hepatocellular carcinoma (HCC) is a major global healthcare challenge, with >1 million patients predicted to be affected annually by 2025. In contrast to other cancers, both incidence and mortality rates continue to rise, and HCC is now the third leading cause of cancer-related death worldwide. Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for advanced HCC, with trials demonstrating a superior overall survival benefit compared to sorafenib in the first-line setting. Combination therapy with either atezolizumab (anti-PD-L1) and bevacizumab (anti-VEGF) or durvalumab (anti-PD-L1) and tremelimumab (anti-CTLA-4) is now recognised as standard of care for advanced HCC. More recently, two phase III studies of ICI-based combination therapy in the early and intermediate disease settings have successfully met their primary end points of improved recurrence- and progression-free survival, respectively. Despite these advances, and in contrast to other tumour types, there remain no validated predictive biomarkers of response to ICIs in HCC. Ongoing research efforts are focused on further characterising the tumour microenvironment in order to select patients most likely to benefit from ICI and identify novel therapeutic targets. Herein, we review the current understanding of the immune landscape in which HCC develops and the evidence for ICI-based therapeutic strategies in HCC. Additionally, we describe the state of biomarker development and novel immunotherapy approaches in HCC which have progressed beyond the pre-clinical stage and into early-phase trials.</AbstractText
|
Measures of individual differences in adult theory of mind: A systematic review. Theory of mind (ToM), the ability to understand and reason about mental states, has been extensively studied in young children and clinical populations. A growing interest in examining ToM in adults has emerged over the past two decades, but the extent to which existing measures are suitable for studying adults, especially in detecting individual differences, remains understudied. In this systematic review of 273 studies, 75 measures used to investigate individual differences in adults' ToM were identified. Their sensitivity to individual differences, reliability, and validity were examined. Results suggest that ceiling effects were prevalent, and there was limited evidence to establish the reliability or validity of these measures due to the lack of reports of psychometric properties. Interrelations among measures were inconsistent. These findings highlight the need for future empirical and theoretical work to broaden the evidence base regarding psychometric properties of measures, to develop new measures, and to lay out more specific hypotheses about the relevance of ToM for different social outcomes.</AbstractText
|
The role of prediction in social neuroscience. Research has shown that the brain is constantly making predictions about future events. Theories of prediction in perception, action and learning suggest that the brain serves to reduce the discrepancies between expectation and actual experience, i.e., by reducing the prediction error. Forward models of action and perception propose the generation of a predictive internal representation of the expected sensory outcome, which is matched to the actual sensory feedback. Shared neural representations have been found when experiencing one's own and observing other's actions, rewards, errors, and emotions such as fear and pain. These general principles of the "predictive brain" are well established and have already begun to be applied to social aspects of cognition. The application and relevance of these predictive principles to social cognition are discussed in this article. Evidence is presented to argue that simple non-social cognitive processes can be extended to explain complex cognitive processes required for social interaction, with common neural activity seen for both social and non-social cognitions. A number of studies are included which demonstrate that bottom-up sensory input and top-down expectancies can be modulated by social information. The concept of competing social forward models and a partially distinct category of social prediction errors are introduced. The evolutionary implications of a "social predictive brain" are also mentioned, along with the implications on psychopathology. The review presents a number of testable hypotheses and novel comparisons that aim to stimulate further discussion and integration between currently disparate fields of research, with regard to computational models, behavioral and neurophysiological data. This promotes a relatively new platform for inquiry in social neuroscience with implications in social learning, theory of mind, empathy, the evolution of the social brain, and potential strategies for treating social cognitive deficits.</AbstractText
|
Immunotherapy for hepatocellular carcinoma. Hepatocellular carcinoma (HCC) is a major global healthcare challenge, with >1 million patients predicted to be affected annually by 2025. In contrast to other cancers, both incidence and mortality rates continue to rise, and HCC is now the third leading cause of cancer-related death worldwide. Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for advanced HCC, with trials demonstrating a superior overall survival benefit compared to sorafenib in the first-line setting. Combination therapy with either atezolizumab (anti-PD-L1) and bevacizumab (anti-VEGF) or durvalumab (anti-PD-L1) and tremelimumab (anti-CTLA-4) is now recognised as standard of care for advanced HCC. More recently, two phase III studies of ICI-based combination therapy in the early and intermediate disease settings have successfully met their primary end points of improved recurrence- and progression-free survival, respectively. Despite these advances, and in contrast to other tumour types, there remain no validated predictive biomarkers of response to ICIs in HCC. Ongoing research efforts are focused on further characterising the tumour microenvironment in order to select patients most likely to benefit from ICI and identify novel therapeutic targets. Herein, we review the current understanding of the immune landscape in which HCC develops and the evidence for ICI-based therapeutic strategies in HCC. Additionally, we describe the state of biomarker development and novel immunotherapy approaches in HCC which have progressed beyond the pre-clinical stage and into early-phase trials.</AbstractText
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40424871
|
36342887
|
40426098
|
Predicting metabolite-disease associations based on dynamic adaptive feature learning architecture.
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GaitForeMer: Self-Supervised Pre-Training of Transformers via Human Motion Forecasting for Few-Shot Gait Impairment Severity Estimation.
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Associations between self-efficacy, social support, racial discrimination, and adolescents oral health.
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In recent years, the association between metabolites and complex human diseases has increasingly been recognized as a major research focus. Traditional wet-lab experiments are considered time-consuming and labor-intensive, while computational methods have been shown to significantly enhance research efficiency. However, existing methods for predicting metabolite-disease associations primarily depend on predefined similarity metrics and static network structures, often failing to capture the complex interactions among node neighborhoods within metabolite and disease networks. This limitation hinders the capture of deeper dynamic relationships between metabolites and diseases, resulting in information loss and noise that deteriorate prediction performance.</AbstractText An innovative dynamic adaptive feature learning architecture (DAF-LA) is proposed to predict metabolite-disease associations. This architecture integrates dynamic subgraph construction and an adaptive feature enhancement mechanism, enabling high-precision feature learning and association prediction through progressive optimization from initial to high-order feature representations.</AbstractText The architecture was evaluated through five-fold cross-validation, achieving an AUC of 0.9742 and an AUPR of 0.9734. Additionally, the case study demonstrates that DAF-LA accurately predicts metabolites associated with Alzheimer's disease, Type 2 diabetes mellitus and Parkinson's disease.</AbstractText The results demonstrate that our method effectively uncovers potential associations between metabolites and diseases through dynamic topological modeling and multi-scale collaborative learning. It enables faster identification of likely metabolite-disease relationships, reduces the time and resource costs associated with inefficient large-scale screening in traditional wet-lab experiments, and provides more targeted guidance for subsequent biological validation.</AbstractText
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Parkinson's disease (PD) is a neurological disorder that has a variety of observable motor-related symptoms such as slow movement, tremor, muscular rigidity, and impaired posture. PD is typically diagnosed by evaluating the severity of motor impairments according to scoring systems such as the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Automated severity prediction using video recordings of individuals provides a promising route for non-intrusive monitoring of motor impairments. However, the limited size of PD gait data hinders model ability and clinical potential. Because of this clinical data scarcity and inspired by the recent advances in self-supervised large-scale language models like GPT-3, we use human motion forecasting as an effective self-supervised pre-training task for the estimation of motor impairment severity. We introduce <b
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This study aimed to develop a conceptual model exploring the relationships between perceived social support (PSS), self-efficacy, racial discrimination, and oral health (OH) in adolescents.</AbstractText A cross-sectional study of adolescents aged 12-18 was conducted at a university dental clinic. Participants completed a questionnaire on demographics, OH, PSS, general self-efficacy, and task-specific self-efficacy (TSSE). Structural Equation Modeling (SEM) was used for analysis.</AbstractText A total of 252 adolescents participated in the study, with an average age of 14 years; 60% were female, 81% were born in Canada, 56% identified as White, and 20% perceived discrimination. PSS was positively associated with general self-efficacy (p = 0.002), TSSE for dental visits (p = 0.004), dietary habits (p = 0.004), and tooth-brushing (p = 0.002), while also elevating sugar consumption (p = 0.002). PSS (p = 0.048) and discrimination (p = 0.01) reduced tooth-brushing frequency. Self-efficacy for dietary habits (p = 0.005) and tooth-brushing (p = 0.002) positively correlated with increased tooth-brushing, while self-efficacy for dietary habits decreased sugar consumption (p = 0.001). Self-efficacy for tooth-brushing was linked to reduced dental visits (p = 0.02). PSS indirectly increased brushing frequency (p = 0.02) and reduced dental-care utilization (p = 0.004). Discrimination indirectly reduced self-efficacy for dental visits (p = 0.003) but increased self-efficacies for tooth-brushing (p = 0.01) and dietary habits (p = 0.03).</AbstractText PSS was directly related to increased self-efficacy, while discrimination indirectly affected OH. Oral health was associated with self-efficacy for dietary habits and tooth-brushing, but not dental visits alone.</AbstractText The findings underscore the critical need to address systemic inequities in oral health care access. By exploring the interplay between social support, discrimination, and self-efficacy, this study highlights actionable pathways to reduce disparities and improve oral health outcomes among adolescents.</AbstractText
|
Predicting metabolite-disease associations based on dynamic adaptive feature learning architecture. In recent years, the association between metabolites and complex human diseases has increasingly been recognized as a major research focus. Traditional wet-lab experiments are considered time-consuming and labor-intensive, while computational methods have been shown to significantly enhance research efficiency. However, existing methods for predicting metabolite-disease associations primarily depend on predefined similarity metrics and static network structures, often failing to capture the complex interactions among node neighborhoods within metabolite and disease networks. This limitation hinders the capture of deeper dynamic relationships between metabolites and diseases, resulting in information loss and noise that deteriorate prediction performance.</AbstractText An innovative dynamic adaptive feature learning architecture (DAF-LA) is proposed to predict metabolite-disease associations. This architecture integrates dynamic subgraph construction and an adaptive feature enhancement mechanism, enabling high-precision feature learning and association prediction through progressive optimization from initial to high-order feature representations.</AbstractText The architecture was evaluated through five-fold cross-validation, achieving an AUC of 0.9742 and an AUPR of 0.9734. Additionally, the case study demonstrates that DAF-LA accurately predicts metabolites associated with Alzheimer's disease, Type 2 diabetes mellitus and Parkinson's disease.</AbstractText The results demonstrate that our method effectively uncovers potential associations between metabolites and diseases through dynamic topological modeling and multi-scale collaborative learning. It enables faster identification of likely metabolite-disease relationships, reduces the time and resource costs associated with inefficient large-scale screening in traditional wet-lab experiments, and provides more targeted guidance for subsequent biological validation.</AbstractText
|
GaitForeMer: Self-Supervised Pre-Training of Transformers via Human Motion Forecasting for Few-Shot Gait Impairment Severity Estimation. Parkinson's disease (PD) is a neurological disorder that has a variety of observable motor-related symptoms such as slow movement, tremor, muscular rigidity, and impaired posture. PD is typically diagnosed by evaluating the severity of motor impairments according to scoring systems such as the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Automated severity prediction using video recordings of individuals provides a promising route for non-intrusive monitoring of motor impairments. However, the limited size of PD gait data hinders model ability and clinical potential. Because of this clinical data scarcity and inspired by the recent advances in self-supervised large-scale language models like GPT-3, we use human motion forecasting as an effective self-supervised pre-training task for the estimation of motor impairment severity. We introduce <b
|
Associations between self-efficacy, social support, racial discrimination, and adolescents oral health. This study aimed to develop a conceptual model exploring the relationships between perceived social support (PSS), self-efficacy, racial discrimination, and oral health (OH) in adolescents.</AbstractText A cross-sectional study of adolescents aged 12-18 was conducted at a university dental clinic. Participants completed a questionnaire on demographics, OH, PSS, general self-efficacy, and task-specific self-efficacy (TSSE). Structural Equation Modeling (SEM) was used for analysis.</AbstractText A total of 252 adolescents participated in the study, with an average age of 14 years; 60% were female, 81% were born in Canada, 56% identified as White, and 20% perceived discrimination. PSS was positively associated with general self-efficacy (p = 0.002), TSSE for dental visits (p = 0.004), dietary habits (p = 0.004), and tooth-brushing (p = 0.002), while also elevating sugar consumption (p = 0.002). PSS (p = 0.048) and discrimination (p = 0.01) reduced tooth-brushing frequency. Self-efficacy for dietary habits (p = 0.005) and tooth-brushing (p = 0.002) positively correlated with increased tooth-brushing, while self-efficacy for dietary habits decreased sugar consumption (p = 0.001). Self-efficacy for tooth-brushing was linked to reduced dental visits (p = 0.02). PSS indirectly increased brushing frequency (p = 0.02) and reduced dental-care utilization (p = 0.004). Discrimination indirectly reduced self-efficacy for dental visits (p = 0.003) but increased self-efficacies for tooth-brushing (p = 0.01) and dietary habits (p = 0.03).</AbstractText PSS was directly related to increased self-efficacy, while discrimination indirectly affected OH. Oral health was associated with self-efficacy for dietary habits and tooth-brushing, but not dental visits alone.</AbstractText The findings underscore the critical need to address systemic inequities in oral health care access. By exploring the interplay between social support, discrimination, and self-efficacy, this study highlights actionable pathways to reduce disparities and improve oral health outcomes among adolescents.</AbstractText
|
38164795
|
29396300
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39192588
|
Discovery and validation of genes driving drug-intake and related behavioral traits in mice.
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Traumatic Brain Injury and Alzheimer's Disease: The Cerebrovascular Link.
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Presentation matters: Surface text features and text quality in written narratives of Dutch high school students with and without dyslexia.
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Substance use disorders are heritable disorders characterized by compulsive drug use, the biological mechanisms for which remain largely unknown. Genetic correlations reveal that predisposing drug-naïve phenotypes, including anxiety, depression, novelty preference and sensation seeking, are predictive of drug-use phenotypes, thereby implicating shared genetic mechanisms. High-throughput behavioral screening in knockout (KO) mice allows efficient discovery of the function of genes. We used this strategy in two rounds of candidate prioritization in which we identified 33 drug-use candidate genes based upon predisposing drug-naïve phenotypes and ultimately validated the perturbation of 22 genes as causal drivers of substance intake. We selected 19/221 KO strains (8.5%) that had a difference from control on at least one drug-naïve predictive behavioral phenotype and determined that 15/19 (~80%) affected the consumption or preference for alcohol, methamphetamine or both. No mutant exhibited a difference in nicotine consumption or preference which was possibly confounded with saccharin. In the second round of prioritization, we employed a multivariate approach to identify outliers and performed validation using methamphetamine two-bottle choice and ethanol drinking-in-the-dark protocols. We identified 15/401 KO strains (3.7%, which included one gene from the first cohort) that differed most from controls for the predisposing phenotypes. 8 of 15 gene deletions (53%) affected intake or preference for alcohol, methamphetamine or both. Using multivariate and bioinformatic analyses, we observed multiple relations between predisposing behaviors and drug intake, revealing many distinct biobehavioral processes underlying these relationships. The set of mouse models identified in this study can be used to characterize these addiction-related processes further.</AbstractText
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Traumatic brain injury (TBI) and Alzheimer's disease (AD) are devastating neurological disorders, whose complex relationship is not completely understood. Cerebrovascular pathology, a key element in both conditions, could represent a mechanistic link between Aβ/tau deposition after TBI and the development of post concussive syndrome, dementia and chronic traumatic encephalopathy (CTE). In addition to debilitating acute effects, TBI-induced neurovascular injuries accelerate amyloid β (Aβ) production and perivascular accumulation, arterial stiffness, tau hyperphosphorylation and tau/Aβ-induced blood brain barrier damage, giving rise to a deleterious feed-forward loop. We postulate that TBI can initiate cerebrovascular pathology, which is causally involved in the development of multiple forms of neurodegeneration including AD-like dementias. In this review, we will explore how novel biomarkers, animal and human studies with a focus on cerebrovascular dysfunction are contributing to the understanding of the consequences of TBI on the development of AD-like pathology.</AbstractText
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Presentation features such as spelling, punctuation and handwriting can influence the evaluation of general text quality. High school students with dyslexia might therefore be at a disadvantage, as at least their spelling performance is typically poor(er). Furthermore, these students might show less sophisticated linguistic features of texts, such as word length and sentence complexity, that might also be related to text quality. We compared narratives written by Dutch high school students (mean age 13.7 years) with (n = 28) and without (n = 29) dyslexia. Students with dyslexia's texts contained more spelling errors and poorer handwriting quality, but not more punctuation errors. Teacher-rated general text quality was lower for the texts of students with dyslexia in uncorrected versions. When spelling and punctuation errors were corrected, no teacher-rated text quality differences emerged. No differences in linguistic text features were found. Furthermore, spelling, punctuation and, to a lesser extent, number of words per sentence clause were related to ratings of text quality across participants. These results confirm the influence of presentation features on text quality rating. They encourage teachers to be aware of this effect and emphasize the importance of spelling and writing support and interventions for students with dyslexia throughout education.</AbstractText
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Discovery and validation of genes driving drug-intake and related behavioral traits in mice. Substance use disorders are heritable disorders characterized by compulsive drug use, the biological mechanisms for which remain largely unknown. Genetic correlations reveal that predisposing drug-naïve phenotypes, including anxiety, depression, novelty preference and sensation seeking, are predictive of drug-use phenotypes, thereby implicating shared genetic mechanisms. High-throughput behavioral screening in knockout (KO) mice allows efficient discovery of the function of genes. We used this strategy in two rounds of candidate prioritization in which we identified 33 drug-use candidate genes based upon predisposing drug-naïve phenotypes and ultimately validated the perturbation of 22 genes as causal drivers of substance intake. We selected 19/221 KO strains (8.5%) that had a difference from control on at least one drug-naïve predictive behavioral phenotype and determined that 15/19 (~80%) affected the consumption or preference for alcohol, methamphetamine or both. No mutant exhibited a difference in nicotine consumption or preference which was possibly confounded with saccharin. In the second round of prioritization, we employed a multivariate approach to identify outliers and performed validation using methamphetamine two-bottle choice and ethanol drinking-in-the-dark protocols. We identified 15/401 KO strains (3.7%, which included one gene from the first cohort) that differed most from controls for the predisposing phenotypes. 8 of 15 gene deletions (53%) affected intake or preference for alcohol, methamphetamine or both. Using multivariate and bioinformatic analyses, we observed multiple relations between predisposing behaviors and drug intake, revealing many distinct biobehavioral processes underlying these relationships. The set of mouse models identified in this study can be used to characterize these addiction-related processes further.</AbstractText
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Traumatic Brain Injury and Alzheimer's Disease: The Cerebrovascular Link. Traumatic brain injury (TBI) and Alzheimer's disease (AD) are devastating neurological disorders, whose complex relationship is not completely understood. Cerebrovascular pathology, a key element in both conditions, could represent a mechanistic link between Aβ/tau deposition after TBI and the development of post concussive syndrome, dementia and chronic traumatic encephalopathy (CTE). In addition to debilitating acute effects, TBI-induced neurovascular injuries accelerate amyloid β (Aβ) production and perivascular accumulation, arterial stiffness, tau hyperphosphorylation and tau/Aβ-induced blood brain barrier damage, giving rise to a deleterious feed-forward loop. We postulate that TBI can initiate cerebrovascular pathology, which is causally involved in the development of multiple forms of neurodegeneration including AD-like dementias. In this review, we will explore how novel biomarkers, animal and human studies with a focus on cerebrovascular dysfunction are contributing to the understanding of the consequences of TBI on the development of AD-like pathology.</AbstractText
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Presentation matters: Surface text features and text quality in written narratives of Dutch high school students with and without dyslexia. Presentation features such as spelling, punctuation and handwriting can influence the evaluation of general text quality. High school students with dyslexia might therefore be at a disadvantage, as at least their spelling performance is typically poor(er). Furthermore, these students might show less sophisticated linguistic features of texts, such as word length and sentence complexity, that might also be related to text quality. We compared narratives written by Dutch high school students (mean age 13.7 years) with (n = 28) and without (n = 29) dyslexia. Students with dyslexia's texts contained more spelling errors and poorer handwriting quality, but not more punctuation errors. Teacher-rated general text quality was lower for the texts of students with dyslexia in uncorrected versions. When spelling and punctuation errors were corrected, no teacher-rated text quality differences emerged. No differences in linguistic text features were found. Furthermore, spelling, punctuation and, to a lesser extent, number of words per sentence clause were related to ratings of text quality across participants. These results confirm the influence of presentation features on text quality rating. They encourage teachers to be aware of this effect and emphasize the importance of spelling and writing support and interventions for students with dyslexia throughout education.</AbstractText
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40682369
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36206805
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40660102
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Adverse Drug-Drug Interaction Between Phenobarbital and Fluconazole in Two Dogs.
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Clinical efficacy and safety of cannabidiol for pediatric refractory epilepsy indications: A systematic review and meta-analysis.
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Predicting the molecular subtypes of 2021 WHO grade 4 glioma by a multiparametric MRI-based machine learning model.
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Phenobarbital (PB) is an antiseizure medication widely used in dogs that is metabolized by hepatic cytochrome P450 (CYP) enzymes. Fluconazole, a commonly prescribed antifungal medication, inhibits several CYP isoenzymes and can impair PB metabolism. Genetic polymorphisms such as the CYP2C41 gene deletion can alter CYP activity and influence drug interactions, although not well characterized in dogs. We describe two epileptic dogs on chronic PB treatment that developed marked sedation and ataxia, and increased serum PB concentrations after receiving fluconazole. Both dogs were homozygous for the CYP2C41 deletion. Discontinuation of fluconazole resulted in decreased PB concentrations and resolution of clinical signs. These findings suggest fluconazole can inhibit PB metabolism, leading to clinically relevant toxicity, and this interaction does not require CYP2C41 enzyme expression. Monitoring PB concentrations during fluconazole co-administration is advised. Further characterization of the role of CYP enzymes in PB metabolism in dogs is needed to better predict drug interactions.</AbstractText
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Antiseizure medications (ASMs) are the mainstay for the treatment of seizure disorders. However, about one-third of people with epilepsy remain refractory to current ASMs. Cannabidiol (CBD) has recently been approved as ASM for three refractory epilepsy syndrome indications in children and adults. In this study, we evaluated the overall clinical potential of an oral CBD to treat refractory epilepsy in patients with Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), and tuberous sclerosis complex (TSC) through a systematic review and meta-analysis. A comprehensive search of databases was conducted, including randomized controlled trials (RCTs) assessing the effect of CBD in epilepsy patients. The review was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The review focused on RCTs involving patients receiving highly purified oral CBD (Epidiolex, 10 to 50 mg/kg/day) for up to 16 weeks. A subgroup analysis by syndrome and CBD with or without concomitant clobazam was conducted. The key outcomes were reduction in seizure frequency, differences in 50% responder rates, adverse events, and interactions with clobazam as co-therapy. Odds ratio (OR) with 95% confidence interval (CI) were estimated. Of 1183 articles screened, we included 6 RCTs meeting our eligibility criteria. All studies were considered to have a low risk of bias. In the pooled analysis, CBD treatment was found to be more efficacious compared to placebo (OR = 2.45, 95% CI =1.81-3.32, p < 0.01). Subgroup analysis by syndrome demonstrated the odds of ≥50% reduction in seizures with CBD treatment in patients with DS (OR = 2.26, 95% CI:1.38-3.70), LGS (OR = 2.98, 95% CI:1.83-4.85) and TSC (OR = 1.99, 95% CI = 1.06-3.76). Compared with placebo, CBD was associated with increased adverse events (OR = 1.81, 95% CI = 1.33-2.46) such as diarrhea, somnolence, and sedation, and any serious adverse events (OR = 2.86, 95% CI = 1.63-5.05). Other factors, including dosage and clobazam co-therapy, were significantly associated with a greater effect on seizure control and side effects of CBD. In conclusion, the study shows that CBD is highly efficacious both as standalone and adjunct therapy with clobazam for controlling seizures in DS, LGS, and TSC conditions while limiting side effects. Further pharmacodynamic investigation of CBD actions, drug interaction assessments, and therapeutic management guidelines are warranted.</AbstractText
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Accurately distinguishing the different molecular subtypes of 2021 World Health Organization (WHO) grade 4 Central Nervous System (CNS) gliomas is highly relevant for prognostic stratification and personalized treatment.</AbstractText To develop and validate a machine learning (ML) model using multiparametric MRI for the preoperative differentiation of astrocytoma, CNS WHO grade 4, and glioblastoma (GBM), isocitrate dehydrogenase-wild-type (IDH-wt) (WHO 2021) (Task 1:grade 4 vs. GBM); and to stratify astrocytoma, CNS WHO grade 4, by distinguish astrocytoma, IDH-mutant (IDH-mut), CNS WHO grade 4 from astrocytoma, IDH-wild-type (IDH-wt), CNS WHO grade 4 (Task 2:IDH-mut <sup We retrospectively analyzed 320 glioma patients from three hospitals (training/testing, 7:3 ratio) and 99 patients from ‌The Cancer Genome Atlas (TCGA) database for external validation‌. Radiomic features were extracted from tumor and edema on contrast-enhanced T1-weighted imaging (CE-T1WI) and T2 fluid-attenuated inversion recovery (T2-FLAIR). Extreme gradient boosting (XGBoost) was utilized for constructing the ML, clinical, and combined models. Model performance was evaluated with receiver operating characteristic (ROC) curves, decision curves, and calibration curves. Stability was evaluated using six additional classifiers. Kaplan-Meier (KM) survival analysis and the log-rank test assessed the model's prognostic value.</AbstractText In Task 1 and Task 2, the combined model (AUC = 0.907, 0.852 and 0.830 for Task 1; AUC = 0.899, 0.895 and 0.792 for Task 2) and the optimal ML model (AUC = 0.902, 0.854 and 0.832 for Task 1; AUC = 0.904, 0.899 and 0.783 for Task 2) significantly outperformed the clinical model (AUC = 0.671, 0.656, and 0.543 for Task 1; AUC = 0.619, 0.605 and 0.400 for Task 2) in both the training, testing and validation sets. Survival analysis showed the combined model performed similarly to molecular subtype in both tasks (p = 0.964 and p = 0.746).</AbstractText The multiparametric MRI ML model effectively distinguished astrocytoma, CNS WHO grade 4 from GBM, IDH-wt (WHO 2021) and differentiated astrocytoma, IDH-mut from astrocytoma, IDH-wt, CNS WHO grade 4. Additionally, the model provided reliable survival stratification for glioma patients across different molecular subtypes.</AbstractText
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Adverse Drug-Drug Interaction Between Phenobarbital and Fluconazole in Two Dogs. Phenobarbital (PB) is an antiseizure medication widely used in dogs that is metabolized by hepatic cytochrome P450 (CYP) enzymes. Fluconazole, a commonly prescribed antifungal medication, inhibits several CYP isoenzymes and can impair PB metabolism. Genetic polymorphisms such as the CYP2C41 gene deletion can alter CYP activity and influence drug interactions, although not well characterized in dogs. We describe two epileptic dogs on chronic PB treatment that developed marked sedation and ataxia, and increased serum PB concentrations after receiving fluconazole. Both dogs were homozygous for the CYP2C41 deletion. Discontinuation of fluconazole resulted in decreased PB concentrations and resolution of clinical signs. These findings suggest fluconazole can inhibit PB metabolism, leading to clinically relevant toxicity, and this interaction does not require CYP2C41 enzyme expression. Monitoring PB concentrations during fluconazole co-administration is advised. Further characterization of the role of CYP enzymes in PB metabolism in dogs is needed to better predict drug interactions.</AbstractText
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Clinical efficacy and safety of cannabidiol for pediatric refractory epilepsy indications: A systematic review and meta-analysis. Antiseizure medications (ASMs) are the mainstay for the treatment of seizure disorders. However, about one-third of people with epilepsy remain refractory to current ASMs. Cannabidiol (CBD) has recently been approved as ASM for three refractory epilepsy syndrome indications in children and adults. In this study, we evaluated the overall clinical potential of an oral CBD to treat refractory epilepsy in patients with Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), and tuberous sclerosis complex (TSC) through a systematic review and meta-analysis. A comprehensive search of databases was conducted, including randomized controlled trials (RCTs) assessing the effect of CBD in epilepsy patients. The review was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The review focused on RCTs involving patients receiving highly purified oral CBD (Epidiolex, 10 to 50 mg/kg/day) for up to 16 weeks. A subgroup analysis by syndrome and CBD with or without concomitant clobazam was conducted. The key outcomes were reduction in seizure frequency, differences in 50% responder rates, adverse events, and interactions with clobazam as co-therapy. Odds ratio (OR) with 95% confidence interval (CI) were estimated. Of 1183 articles screened, we included 6 RCTs meeting our eligibility criteria. All studies were considered to have a low risk of bias. In the pooled analysis, CBD treatment was found to be more efficacious compared to placebo (OR = 2.45, 95% CI =1.81-3.32, p < 0.01). Subgroup analysis by syndrome demonstrated the odds of ≥50% reduction in seizures with CBD treatment in patients with DS (OR = 2.26, 95% CI:1.38-3.70), LGS (OR = 2.98, 95% CI:1.83-4.85) and TSC (OR = 1.99, 95% CI = 1.06-3.76). Compared with placebo, CBD was associated with increased adverse events (OR = 1.81, 95% CI = 1.33-2.46) such as diarrhea, somnolence, and sedation, and any serious adverse events (OR = 2.86, 95% CI = 1.63-5.05). Other factors, including dosage and clobazam co-therapy, were significantly associated with a greater effect on seizure control and side effects of CBD. In conclusion, the study shows that CBD is highly efficacious both as standalone and adjunct therapy with clobazam for controlling seizures in DS, LGS, and TSC conditions while limiting side effects. Further pharmacodynamic investigation of CBD actions, drug interaction assessments, and therapeutic management guidelines are warranted.</AbstractText
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Predicting the molecular subtypes of 2021 WHO grade 4 glioma by a multiparametric MRI-based machine learning model. Accurately distinguishing the different molecular subtypes of 2021 World Health Organization (WHO) grade 4 Central Nervous System (CNS) gliomas is highly relevant for prognostic stratification and personalized treatment.</AbstractText To develop and validate a machine learning (ML) model using multiparametric MRI for the preoperative differentiation of astrocytoma, CNS WHO grade 4, and glioblastoma (GBM), isocitrate dehydrogenase-wild-type (IDH-wt) (WHO 2021) (Task 1:grade 4 vs. GBM); and to stratify astrocytoma, CNS WHO grade 4, by distinguish astrocytoma, IDH-mutant (IDH-mut), CNS WHO grade 4 from astrocytoma, IDH-wild-type (IDH-wt), CNS WHO grade 4 (Task 2:IDH-mut <sup We retrospectively analyzed 320 glioma patients from three hospitals (training/testing, 7:3 ratio) and 99 patients from ‌The Cancer Genome Atlas (TCGA) database for external validation‌. Radiomic features were extracted from tumor and edema on contrast-enhanced T1-weighted imaging (CE-T1WI) and T2 fluid-attenuated inversion recovery (T2-FLAIR). Extreme gradient boosting (XGBoost) was utilized for constructing the ML, clinical, and combined models. Model performance was evaluated with receiver operating characteristic (ROC) curves, decision curves, and calibration curves. Stability was evaluated using six additional classifiers. Kaplan-Meier (KM) survival analysis and the log-rank test assessed the model's prognostic value.</AbstractText In Task 1 and Task 2, the combined model (AUC = 0.907, 0.852 and 0.830 for Task 1; AUC = 0.899, 0.895 and 0.792 for Task 2) and the optimal ML model (AUC = 0.902, 0.854 and 0.832 for Task 1; AUC = 0.904, 0.899 and 0.783 for Task 2) significantly outperformed the clinical model (AUC = 0.671, 0.656, and 0.543 for Task 1; AUC = 0.619, 0.605 and 0.400 for Task 2) in both the training, testing and validation sets. Survival analysis showed the combined model performed similarly to molecular subtype in both tasks (p = 0.964 and p = 0.746).</AbstractText The multiparametric MRI ML model effectively distinguished astrocytoma, CNS WHO grade 4 from GBM, IDH-wt (WHO 2021) and differentiated astrocytoma, IDH-mut from astrocytoma, IDH-wt, CNS WHO grade 4. Additionally, the model provided reliable survival stratification for glioma patients across different molecular subtypes.</AbstractText
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30211336
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18022950
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28774561
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Constitutive activity of transient receptor potential vanilloid type 1 triggers spontaneous firing in nerve growth factor-treated dorsal root ganglion neurons of rats.
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Deletion of voltage-gated channel affects glomerular refinement and odorant receptor expression in the mouse olfactory system.
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Personalized vaccinology: A review.
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Dorsal root ganglion (DRG) neurons cultured in the presence of nerve growth factor (NGF, 100 ng/ml) often show a spontaneous action potential. Underlying mechanisms of this spontaneous firing were examined using the patch clamp technique. The spontaneous firing in the on-cell configuration was abolished by a decrease in the Na<sup
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Olfactory sensory neurons (OSNs) expressing a specific odorant receptor (OR) gene send axonal projections to specific glomeruli, creating a stereotypic olfactory sensory map. Odorant receptor sequence, G-protein cAMP signaling, and axon guidance molecules have been shown to direct axons of OSNs toward central targets in the olfactory bulb (OB). Although the OR sequence may act as one determinant, our objective was to elucidate the extent by which voltage-dependent activity of postsynaptic projection neurons in the OB centrally influences peripheral development and target destination of OSNs. We bred OR-tagged transgenic mice to homozygosity with mice that had a gene-targeted deletion of the Shaker potassium ion channel (Kv1.3) to elucidate how activity modulates synaptic connections that formulate the sensory map. Here we report that the Kv1.3 ion channel, which is predominantly expressed in mitral cells and whose gene-targeted deletion causes a "super-smeller" phenotype, alters synaptic refinement of axonal projections from OSNs expressing P2, M72, and MOR28 ORs. Absence of Kv1.3 voltage-gated activity caused the formation of small, heterogeneous, and supernumerary glomeruli that failed to undergo neural pruning over development. These changes were accompanied by a significant decrease in the number of P2-, M72-, and MOR28-expressing OSNs, which contained an overexpression of OR protein and G-protein G(olf) in the cilia of the olfactory epithelium. These findings suggest that voltage-gated activity of projection neurons is essential to refine primary olfactory projections and that it regulates proper expression of the transduction machinery at the periphery.</AbstractText
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At the current time, the field of vaccinology remains empirical in many respects. Vaccine development, vaccine immunogenicity, and vaccine efficacy have, for the most part, historically been driven by an empiric "isolate-inactivate-inject" paradigm. In turn, a population-level public health paradigm of "the same dose for everyone for every disease" model has been the normative thinking in regard to prevention of vaccine-preventable infectious diseases. In addition, up until recently, no vaccines had been designed specifically to overcome the immunosenescence of aging, consistent with a post-WWII mentality of developing vaccines and vaccine programs for children. It is now recognized that the current lack of knowledge concerning how immune responses to vaccines are generated is a critical barrier to understanding poor vaccine responses in the elderly and in immunoimmaturity, discovery of new correlates of vaccine immunogenicity (vaccine response biomarkers), and a directed approach to new vaccine development. The new fields of vaccinomics and adversomics provide models that permit global profiling of the innate, humoral, and cellular immune responses integrated at a systems biology level. This has advanced the science beyond that of reductionist scientific approaches by revealing novel interactions between and within the immune system and other biological systems (beyond transcriptional level), which are critical to developing "downstream" adaptive humoral and cellular responses to infectious pathogens and vaccines. Others have applied systems level approaches to the study of antibody responses (a.k.a. "systems serology"), [1] high-dimensional cell subset immunophenotyping through CyTOF, [2,3] and vaccine induced metabolic changes [4]. In turn, this knowledge is being utilized to better understand the following: identifying who is at risk for which infections; the level of risk that exists regarding poor immunogenicity and/or serious adverse events; and the type or dose of vaccine needed to fully protect an individual. In toto, such approaches allow for a personalized approach to the practice of vaccinology, analogous to the substantial inroads that individualized medicine is playing in other fields of human health and medicine. Herein we briefly review the field of vaccinomics, adversomics, and personalized vaccinology.</AbstractText
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Constitutive activity of transient receptor potential vanilloid type 1 triggers spontaneous firing in nerve growth factor-treated dorsal root ganglion neurons of rats. Dorsal root ganglion (DRG) neurons cultured in the presence of nerve growth factor (NGF, 100 ng/ml) often show a spontaneous action potential. Underlying mechanisms of this spontaneous firing were examined using the patch clamp technique. The spontaneous firing in the on-cell configuration was abolished by a decrease in the Na<sup
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Deletion of voltage-gated channel affects glomerular refinement and odorant receptor expression in the mouse olfactory system. Olfactory sensory neurons (OSNs) expressing a specific odorant receptor (OR) gene send axonal projections to specific glomeruli, creating a stereotypic olfactory sensory map. Odorant receptor sequence, G-protein cAMP signaling, and axon guidance molecules have been shown to direct axons of OSNs toward central targets in the olfactory bulb (OB). Although the OR sequence may act as one determinant, our objective was to elucidate the extent by which voltage-dependent activity of postsynaptic projection neurons in the OB centrally influences peripheral development and target destination of OSNs. We bred OR-tagged transgenic mice to homozygosity with mice that had a gene-targeted deletion of the Shaker potassium ion channel (Kv1.3) to elucidate how activity modulates synaptic connections that formulate the sensory map. Here we report that the Kv1.3 ion channel, which is predominantly expressed in mitral cells and whose gene-targeted deletion causes a "super-smeller" phenotype, alters synaptic refinement of axonal projections from OSNs expressing P2, M72, and MOR28 ORs. Absence of Kv1.3 voltage-gated activity caused the formation of small, heterogeneous, and supernumerary glomeruli that failed to undergo neural pruning over development. These changes were accompanied by a significant decrease in the number of P2-, M72-, and MOR28-expressing OSNs, which contained an overexpression of OR protein and G-protein G(olf) in the cilia of the olfactory epithelium. These findings suggest that voltage-gated activity of projection neurons is essential to refine primary olfactory projections and that it regulates proper expression of the transduction machinery at the periphery.</AbstractText
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Personalized vaccinology: A review. At the current time, the field of vaccinology remains empirical in many respects. Vaccine development, vaccine immunogenicity, and vaccine efficacy have, for the most part, historically been driven by an empiric "isolate-inactivate-inject" paradigm. In turn, a population-level public health paradigm of "the same dose for everyone for every disease" model has been the normative thinking in regard to prevention of vaccine-preventable infectious diseases. In addition, up until recently, no vaccines had been designed specifically to overcome the immunosenescence of aging, consistent with a post-WWII mentality of developing vaccines and vaccine programs for children. It is now recognized that the current lack of knowledge concerning how immune responses to vaccines are generated is a critical barrier to understanding poor vaccine responses in the elderly and in immunoimmaturity, discovery of new correlates of vaccine immunogenicity (vaccine response biomarkers), and a directed approach to new vaccine development. The new fields of vaccinomics and adversomics provide models that permit global profiling of the innate, humoral, and cellular immune responses integrated at a systems biology level. This has advanced the science beyond that of reductionist scientific approaches by revealing novel interactions between and within the immune system and other biological systems (beyond transcriptional level), which are critical to developing "downstream" adaptive humoral and cellular responses to infectious pathogens and vaccines. Others have applied systems level approaches to the study of antibody responses (a.k.a. "systems serology"), [1] high-dimensional cell subset immunophenotyping through CyTOF, [2,3] and vaccine induced metabolic changes [4]. In turn, this knowledge is being utilized to better understand the following: identifying who is at risk for which infections; the level of risk that exists regarding poor immunogenicity and/or serious adverse events; and the type or dose of vaccine needed to fully protect an individual. In toto, such approaches allow for a personalized approach to the practice of vaccinology, analogous to the substantial inroads that individualized medicine is playing in other fields of human health and medicine. Herein we briefly review the field of vaccinomics, adversomics, and personalized vaccinology.</AbstractText
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33300253
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26110628
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34483827
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Hyperperfusion on Arterial Spin Labeling MRI Predicts the 90-Day Functional Outcome After Mechanical Thrombectomy in Ischemic Stroke.
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Prominent vessel sign on susceptibility-weighted imaging in acute stroke: prediction of infarct growth and clinical outcome.
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Co-registration Comparison of On-Scalp Magnetoencephalography and Magnetic Resonance Imaging.
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The prognostic significance of hyperperfusion after reperfusion therapy in patients with acute ischemic stroke (AIS) remains controversial.</AbstractText To investigate the clinical factors associated with hyperperfusion, and the 90-day prognostic value of hyperperfusion after mechanical thrombectomy in AIS patients.</AbstractText Retrospective.</AbstractText Fifty-four AIS patients who underwent mechanical thrombectomy.</AbstractText Time-of-flight MR angiography, pulsed arterial spin labeling (ASL), diffusion-weighted imaging (DWI), and susceptibility-weighted imaging were performed at 3.0T within 1 week after thrombectomy.</AbstractText Clinical factors including demographics, risk factors, stroke and treatment characteristics were collected and assessed. Hyperperfusion on ASL was defined as a focal increased cerebral blood flow on the affected side ≥130% of its mirror counterpart. Good clinical outcome at 90 days was defined as modified Rankin Scale score of 0-2.</AbstractText The interrater agreement was assessed using Cohen's kappa or the intraclass correlation coefficient. The relationship between hyperperfusion and clinical factors were analyzed by appropriate univariate statistics. Predictors of 90-day functional outcome were assessed by univariate analyses followed by multivariate logistic regression analysis and receiver-operating-characteristic curves.</AbstractText Thirty-six (66.7%) patients developed hyperperfusion on ASL after thrombectomy. Hyperperfusion was significantly correlated with successful recanalization (P < 0.05) and improvement of National Institutes of Health Stroke Scale scores at 24 hours (NIHSS<sub Hyperperfusion on ASL correlated with successful recanalization and may be an independent prognostic marker for good neurological outcomes at 90 days in AIS patients after mechanical thrombectomy.</AbstractText 4 TECHNICAL EFFICACY STAGE: 2.</AbstractText
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Predicting the risk of further infarct growth in stroke patients is critical to therapeutic decision making. We aimed to predict early infarct growth and clinical outcome from prominent vessel sign (PVS) identified on the first susceptibility-weighted image (SWI) after acute stroke.</AbstractText Twenty-two patients with middle cerebral artery (MCA) infarction had diffusion-weighted imaging, SWI, MR angiography, and clinical evaluation using the National Institutes of Health Stroke Scale at 7-60 hours and 5-14 days after stroke onset. Late-stage clinical evaluation at 1 and 3 months used the modified Rankin Scale. The infarct area and growth were scored from 10 (none) to 0 (infarct or growth in all 10 zones) using the Alberta Stroke Program Early CT Score (ASPECTS) system.</AbstractText Infarct growth on the second MRI occurred in 13 of 15 patients with PVS on the first MRI and not in any patient without PVS (n=7; r=0.86, P<0.001). The extent of PVS was significantly correlated with infarct growth (r=0.82, P<0.001) and early-stage outcome (P=0.02). No between-group difference in late-stage clinical outcome was found.</AbstractText PVS on the first SWI after acute MCA territory stroke is a useful predictor of early infarct growth. Extensive PVS within the large MCA territory is related to poor early-stage outcome and could be useful for clinical assessment of stroke.</AbstractText
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Magnetoencephalography (MEG) can non-invasively measure the electromagnetic activity of the brain. A new type of MEG, on-scalp MEG, has attracted the attention of researchers recently. Compared to the conventional SQUID-MEG, on-scalp MEG constructed with optically pumped magnetometers is wearable and has a high signal-to-noise ratio. While the co-registration between MEG and magnetic resonance imaging (MRI) significantly influences the source localization accuracy, co-registration error requires assessment, and quantification. Recent studies have evaluated the co-registration error of on-scalp MEG mainly based on the surface fit error or the repeatability error of different measurements, which do not reflect the true co-registration error. In this study, a three-dimensional-printed reference phantom was constructed to provide the ground truth of MEG sensor locations and orientations relative to MRI. The co-registration performances of commonly used three devices-electromagnetic digitization system, structured-light scanner, and laser scanner-were compared and quantified by the indices of final co-registration errors in the reference phantom and human experiments. Furthermore, the influence of the co-registration error on the performance of source localization was analyzed via simulations. The laser scanner had the best co-registration accuracy (rotation error of 0.23° and translation error of 0.76 mm based on the phantom experiment), whereas the structured-light scanner had the best cost performance. The results of this study provide recommendations and precautions for researchers regarding selecting and using an appropriate device for the co-registration of on-scalp MEG and MRI.</AbstractText
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Hyperperfusion on Arterial Spin Labeling MRI Predicts the 90-Day Functional Outcome After Mechanical Thrombectomy in Ischemic Stroke. The prognostic significance of hyperperfusion after reperfusion therapy in patients with acute ischemic stroke (AIS) remains controversial.</AbstractText To investigate the clinical factors associated with hyperperfusion, and the 90-day prognostic value of hyperperfusion after mechanical thrombectomy in AIS patients.</AbstractText Retrospective.</AbstractText Fifty-four AIS patients who underwent mechanical thrombectomy.</AbstractText Time-of-flight MR angiography, pulsed arterial spin labeling (ASL), diffusion-weighted imaging (DWI), and susceptibility-weighted imaging were performed at 3.0T within 1 week after thrombectomy.</AbstractText Clinical factors including demographics, risk factors, stroke and treatment characteristics were collected and assessed. Hyperperfusion on ASL was defined as a focal increased cerebral blood flow on the affected side ≥130% of its mirror counterpart. Good clinical outcome at 90 days was defined as modified Rankin Scale score of 0-2.</AbstractText The interrater agreement was assessed using Cohen's kappa or the intraclass correlation coefficient. The relationship between hyperperfusion and clinical factors were analyzed by appropriate univariate statistics. Predictors of 90-day functional outcome were assessed by univariate analyses followed by multivariate logistic regression analysis and receiver-operating-characteristic curves.</AbstractText Thirty-six (66.7%) patients developed hyperperfusion on ASL after thrombectomy. Hyperperfusion was significantly correlated with successful recanalization (P < 0.05) and improvement of National Institutes of Health Stroke Scale scores at 24 hours (NIHSS<sub Hyperperfusion on ASL correlated with successful recanalization and may be an independent prognostic marker for good neurological outcomes at 90 days in AIS patients after mechanical thrombectomy.</AbstractText 4 TECHNICAL EFFICACY STAGE: 2.</AbstractText
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Prominent vessel sign on susceptibility-weighted imaging in acute stroke: prediction of infarct growth and clinical outcome. Predicting the risk of further infarct growth in stroke patients is critical to therapeutic decision making. We aimed to predict early infarct growth and clinical outcome from prominent vessel sign (PVS) identified on the first susceptibility-weighted image (SWI) after acute stroke.</AbstractText Twenty-two patients with middle cerebral artery (MCA) infarction had diffusion-weighted imaging, SWI, MR angiography, and clinical evaluation using the National Institutes of Health Stroke Scale at 7-60 hours and 5-14 days after stroke onset. Late-stage clinical evaluation at 1 and 3 months used the modified Rankin Scale. The infarct area and growth were scored from 10 (none) to 0 (infarct or growth in all 10 zones) using the Alberta Stroke Program Early CT Score (ASPECTS) system.</AbstractText Infarct growth on the second MRI occurred in 13 of 15 patients with PVS on the first MRI and not in any patient without PVS (n=7; r=0.86, P<0.001). The extent of PVS was significantly correlated with infarct growth (r=0.82, P<0.001) and early-stage outcome (P=0.02). No between-group difference in late-stage clinical outcome was found.</AbstractText PVS on the first SWI after acute MCA territory stroke is a useful predictor of early infarct growth. Extensive PVS within the large MCA territory is related to poor early-stage outcome and could be useful for clinical assessment of stroke.</AbstractText
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Co-registration Comparison of On-Scalp Magnetoencephalography and Magnetic Resonance Imaging. Magnetoencephalography (MEG) can non-invasively measure the electromagnetic activity of the brain. A new type of MEG, on-scalp MEG, has attracted the attention of researchers recently. Compared to the conventional SQUID-MEG, on-scalp MEG constructed with optically pumped magnetometers is wearable and has a high signal-to-noise ratio. While the co-registration between MEG and magnetic resonance imaging (MRI) significantly influences the source localization accuracy, co-registration error requires assessment, and quantification. Recent studies have evaluated the co-registration error of on-scalp MEG mainly based on the surface fit error or the repeatability error of different measurements, which do not reflect the true co-registration error. In this study, a three-dimensional-printed reference phantom was constructed to provide the ground truth of MEG sensor locations and orientations relative to MRI. The co-registration performances of commonly used three devices-electromagnetic digitization system, structured-light scanner, and laser scanner-were compared and quantified by the indices of final co-registration errors in the reference phantom and human experiments. Furthermore, the influence of the co-registration error on the performance of source localization was analyzed via simulations. The laser scanner had the best co-registration accuracy (rotation error of 0.23° and translation error of 0.76 mm based on the phantom experiment), whereas the structured-light scanner had the best cost performance. The results of this study provide recommendations and precautions for researchers regarding selecting and using an appropriate device for the co-registration of on-scalp MEG and MRI.</AbstractText
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40598761
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19003734
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40093735
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Deletion of the gene encoding the magnesium chelatase I subunit resulted in a novel wheat leaf colour mutant.
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Protective effect of vitamin C on oxidative stress: a randomized controlled trial.
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Changes in cerebral cortex activation during upright standing tasks in individuals with chronic neck pain: an fNIRS study.
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Leaf colour mutants are ideal germplasm resources for investigating the mechanisms of chlorophyll (Chl) synthesis, chloroplast development and photosynthesis. In this study, we obtained a yellow-leaf mutant, designated SN288-2. The variant presented a yellow-leaf phenotype and halted the development of chloroplasts at the seedling stage, with reduced accumulation of Chl. The yellow-leaf phenotype reverted to the normal phenotype in the wheat revival stage. In addition, the ratio of the crucial Chl precursors protoporphyrin IX (Proto IX) and Mg-protoporphyrin IX (Mg-Proto IX) was relatively high in yellow leaves. Bulked segregant analysis sequencing (BSA-Seq) revealed that the aberrant phenotype was controlled by two recessive genes located on chromosomes 7A and 7D, designated Y1-7A and Y2-7D, respectively. Subsequent research focused on Y1-7A. We identified TraesCS7A03G1163900 as a viable candidate for Y1-7A, encoding a major subunit of Mg-chelatase that is essential for Chl synthesis. Whole-genome resequencing and Sanger sequencing revealed a 5.3 kb deletion on the long arm of chromosome 7A in SN388-2 that encompasses the entire Y1-7A sequence. Quantitative real-time PCR (qRT-PCR) revealed that the Y1-7A gene was predominantly expressed in green tissues and that the encoded protein was localized within the chloroplast. Moreover, weighted gene coexpression network analysis (WGCNA) revealed a gene module associated with leaf development and Chl content restoration. Consequently, these results provide a new theory regarding the regulation of Chl synthesis and chloroplast development. Overall, the loss of Y1-7A impaired the function of Mg-chelatase and blocked the conversion of Proto IX to Mg-Proto IX.</AbstractText
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Although a number of reports regarding the role of reactive oxygen species (ROS) as the first step in cancer induction exist, few studies have investigated how vitamin C influences ROS in human plasma.</AbstractText Using the ROS assay system, a method recently established by one of the authors, we aimed to evaluate the effect of vitamin C supplementation on serum ROS among subjects diagnosed with chronic gastritis.</AbstractText A total of 244 Japanese subjects with atrophic gastritis were randomized to take 5-year supplementation of either 50 mg or 500 mg of vitamin C.</AbstractText The adjusted difference in the changes of total ROS between baseline and after 5-year supplementation was statistically significant between the intervention groups: 2.70 decrease (corresponds to 1.26% decrease) in the high-dose group and 4.16 increase (corresponds to 3.79% increase) in the low-dose group, p for difference = 0.01.</AbstractText Vitamin C was suggested to reduce oxidative stress among subjects with atrophic gastritis.</AbstractText
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Studies show that individuals with chronic neck pain (CNP) exhibit postural control deficits, potentially contributing to persistent and recurrent pain. However, the neural mechanisms underlying these deficits in CNP remain unexplored despite their importance for developing effective rehabilitation strategies. Therefore, this study aimed to investigate the neural activity during postural control using functional near-infrared spectroscopy (fNIRS), providing insights into the central mechanism underlying postural control deficits in individuals with CNP.</AbstractText In this cross-sectional study, 10 individuals with CNP (CNP group) and 10 healthy controls (HC group) were assessed under three conditions: Task 1, standing on a force plate with eyes open and both feet; Task 2, standing on a force plate with eyes closed and both feet; Task 3, standing on a force plate with eyes closed and one foot. Cerebral cortex hemodynamic reactions, including bilateral prefrontal cortex (PFC), dorsolateral prefrontal cortex (DLPFC), pre-motor cortex and supplementary motor area (PMC/SMA), primary motor cortex (M1), and primary somatosensory cortex (S1) were measured using fNIRS. Balance parameters, including the sway area, total sway length, mean velocity, and center of pressure (COP) amplitude in the anterior-posterior (AP) and medial-lateral (ML) directions, were measured using a force plate.</AbstractText In Tasks 1 and 2, no differences were observed between both groups in balance parameters. However, the CNP group exhibited significantly higher activation in the left PMC/SMA (<i Our findings suggest that individuals with CNP exhibit distinct patterns of cerebral cortex activities and postural control deficits. The PFC, M1, and PMC/SMA were involved in maintaining upright standing balance, and cerebral cortex changes associated with upright standing balance provide a more sensitive indicator of postural control deficits than peripheral balance parameters in individuals with CNP.</AbstractText
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Deletion of the gene encoding the magnesium chelatase I subunit resulted in a novel wheat leaf colour mutant. Leaf colour mutants are ideal germplasm resources for investigating the mechanisms of chlorophyll (Chl) synthesis, chloroplast development and photosynthesis. In this study, we obtained a yellow-leaf mutant, designated SN288-2. The variant presented a yellow-leaf phenotype and halted the development of chloroplasts at the seedling stage, with reduced accumulation of Chl. The yellow-leaf phenotype reverted to the normal phenotype in the wheat revival stage. In addition, the ratio of the crucial Chl precursors protoporphyrin IX (Proto IX) and Mg-protoporphyrin IX (Mg-Proto IX) was relatively high in yellow leaves. Bulked segregant analysis sequencing (BSA-Seq) revealed that the aberrant phenotype was controlled by two recessive genes located on chromosomes 7A and 7D, designated Y1-7A and Y2-7D, respectively. Subsequent research focused on Y1-7A. We identified TraesCS7A03G1163900 as a viable candidate for Y1-7A, encoding a major subunit of Mg-chelatase that is essential for Chl synthesis. Whole-genome resequencing and Sanger sequencing revealed a 5.3 kb deletion on the long arm of chromosome 7A in SN388-2 that encompasses the entire Y1-7A sequence. Quantitative real-time PCR (qRT-PCR) revealed that the Y1-7A gene was predominantly expressed in green tissues and that the encoded protein was localized within the chloroplast. Moreover, weighted gene coexpression network analysis (WGCNA) revealed a gene module associated with leaf development and Chl content restoration. Consequently, these results provide a new theory regarding the regulation of Chl synthesis and chloroplast development. Overall, the loss of Y1-7A impaired the function of Mg-chelatase and blocked the conversion of Proto IX to Mg-Proto IX.</AbstractText
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Protective effect of vitamin C on oxidative stress: a randomized controlled trial. Although a number of reports regarding the role of reactive oxygen species (ROS) as the first step in cancer induction exist, few studies have investigated how vitamin C influences ROS in human plasma.</AbstractText Using the ROS assay system, a method recently established by one of the authors, we aimed to evaluate the effect of vitamin C supplementation on serum ROS among subjects diagnosed with chronic gastritis.</AbstractText A total of 244 Japanese subjects with atrophic gastritis were randomized to take 5-year supplementation of either 50 mg or 500 mg of vitamin C.</AbstractText The adjusted difference in the changes of total ROS between baseline and after 5-year supplementation was statistically significant between the intervention groups: 2.70 decrease (corresponds to 1.26% decrease) in the high-dose group and 4.16 increase (corresponds to 3.79% increase) in the low-dose group, p for difference = 0.01.</AbstractText Vitamin C was suggested to reduce oxidative stress among subjects with atrophic gastritis.</AbstractText
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Changes in cerebral cortex activation during upright standing tasks in individuals with chronic neck pain: an fNIRS study. Studies show that individuals with chronic neck pain (CNP) exhibit postural control deficits, potentially contributing to persistent and recurrent pain. However, the neural mechanisms underlying these deficits in CNP remain unexplored despite their importance for developing effective rehabilitation strategies. Therefore, this study aimed to investigate the neural activity during postural control using functional near-infrared spectroscopy (fNIRS), providing insights into the central mechanism underlying postural control deficits in individuals with CNP.</AbstractText In this cross-sectional study, 10 individuals with CNP (CNP group) and 10 healthy controls (HC group) were assessed under three conditions: Task 1, standing on a force plate with eyes open and both feet; Task 2, standing on a force plate with eyes closed and both feet; Task 3, standing on a force plate with eyes closed and one foot. Cerebral cortex hemodynamic reactions, including bilateral prefrontal cortex (PFC), dorsolateral prefrontal cortex (DLPFC), pre-motor cortex and supplementary motor area (PMC/SMA), primary motor cortex (M1), and primary somatosensory cortex (S1) were measured using fNIRS. Balance parameters, including the sway area, total sway length, mean velocity, and center of pressure (COP) amplitude in the anterior-posterior (AP) and medial-lateral (ML) directions, were measured using a force plate.</AbstractText In Tasks 1 and 2, no differences were observed between both groups in balance parameters. However, the CNP group exhibited significantly higher activation in the left PMC/SMA (<i Our findings suggest that individuals with CNP exhibit distinct patterns of cerebral cortex activities and postural control deficits. The PFC, M1, and PMC/SMA were involved in maintaining upright standing balance, and cerebral cortex changes associated with upright standing balance provide a more sensitive indicator of postural control deficits than peripheral balance parameters in individuals with CNP.</AbstractText
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35242362
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38914541
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36301030
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Modelling the simultaneous encoding/serial experience theory of the perceptual moment: a blink of meta-experience.
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Prefrontal coding of learned and inferred knowledge during REM and NREM sleep.
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Downregulated formyl peptide receptor 2 expression in the epileptogenic foci of patients with focal cortical dysplasia type IIb and tuberous sclerosis complex.
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One way to understand a system is to explore how its behaviour degrades when it is overloaded. This approach can be applied to understanding conscious perception by presenting stimuli in rapid succession in the 'same' perceptual event/moment. In previous work, we have identified a striking dissociation during the perceptual moment, between what is encoded into working memory [Lag-1 sparing in the attentional blink (AB)] and what is consciously perceived (Lag-1 impairing in the experiential blink). This paper links this dissociation to what, taking inspiration from the metacognition literature, could be called meta-experience; i.e. how the ability to track and comment on one's visual experience with subjectivity ratings reflects objective performance. Specifically, we provide evidence that the information (in bits) associated with an encoding into working memory decouples from the experiential reflection upon that perceptual/encoding event and that this decoupling is largest when there is the greatest perceptual overload. This is the meta-experiential blink. Meta-experiential self-observation is common to many computational models, including connectionist interpretations of consciousness, Bayesian observers and the readout-enhanced simultaneous type/serial token (reSTST) model. We assess how our meta-experiential blink data could be modelled using the concept of self-observation, providing model fits to behavioural and electroencephalogram responses in the reSTST model. We discuss the implications of our computational modelling of parallel encoding but serial experience for theories of conscious perception. Specifically, we (i) inform theories of Lag-1 sparing during the AB and (ii) consider the implications for the global workspace theory of conscious perception and higher-order theories of consciousness.</AbstractText
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Idling brain activity has been proposed to facilitate inference, insight, and innovative problem-solving. However, it remains unclear how and when the idling brain can create novel ideas. Here, we show that cortical offline activity is both necessary and sufficient for building unlearned inferential knowledge from previously acquired information. In a transitive inference paradigm, male C57BL/6J mice gained the inference 1 day after, but not shortly after, complete training. Inhibiting the neuronal computations in the anterior cingulate cortex (ACC) during post-learning either non-rapid eye movement (NREM) or rapid eye movement (REM) sleep, but not wakefulness, disrupted the inference without affecting the learned knowledge. In vivo Ca<sup
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Focal cortical dysplasia type IIb (FCDIIb) and tuberous sclerosis complex (TSC) show persistent neuroinflammation, which promotes epileptogenesis and epilepsy progression, suggesting that endogenous resolution of inflammation is inadequate to relieve neuronal network hyperexcitability. To explore the potential roles of formyl peptide receptor 2 (FPR2), which is a key regulator of inflammation resolution, in epilepsy caused by FCDIIb and TSC, we examined the expression and cellular distribution of FPR2.</AbstractText The expression of FPR2 and nuclear factor-κB (NF-κB) signaling pathway was examined by real-time PCR, western blots, and analyzed via one-way analysis of variance. The distribution of FPR2 was detected using immunostaining. The expression of resolvin D1 (RvD1, the endogenous ligand of FPR2) was observed via enzyme-linked immunosorbent assay. Pearson's correlation test was used to evaluate the correlation between the expression levels of FPR2 and RvD1 and the clinical variants.</AbstractText The expression of FPR2 was significantly lower in FCDIIb (p = .0146) and TSC (p = .0006) cortical lesions than in controls, as was the expression of RvD1 (FCDIIb: p = .00431; TSC: p = .0439). Weak FPR2 immunoreactivity was observed in dysmorphic neurons (DNs), balloon cells (BCs), and giant cells (GCs) in FCDIIb and TSC tissues. Moreover, FPR2 was mainly distributed in dysplastic neurons; it was sparse in microglia and nearly absent in astrocytes. The NF-κB pathway was significantly activated in patients with FCDIIb and TSC, and the protein level of NF-κB was negatively correlated with the protein level of FPR2 (FCDIIb: p = .00395; TSC: p = .0399). In addition, the protein level of FPR2 was negatively correlated with seizure frequency in FCDIIb (p = .0434) and TSC (p = .0351) patients.</AbstractText In summary, these results showed that the expression and specific distribution of FPR2 may be involved in epilepsy caused by FCDIIb and TSC, indicating that downregulation of FPR2 mediated the dysfunction of neuroinflammation resolution in FCDIIb and TSC.</AbstractText
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Modelling the simultaneous encoding/serial experience theory of the perceptual moment: a blink of meta-experience. One way to understand a system is to explore how its behaviour degrades when it is overloaded. This approach can be applied to understanding conscious perception by presenting stimuli in rapid succession in the 'same' perceptual event/moment. In previous work, we have identified a striking dissociation during the perceptual moment, between what is encoded into working memory [Lag-1 sparing in the attentional blink (AB)] and what is consciously perceived (Lag-1 impairing in the experiential blink). This paper links this dissociation to what, taking inspiration from the metacognition literature, could be called meta-experience; i.e. how the ability to track and comment on one's visual experience with subjectivity ratings reflects objective performance. Specifically, we provide evidence that the information (in bits) associated with an encoding into working memory decouples from the experiential reflection upon that perceptual/encoding event and that this decoupling is largest when there is the greatest perceptual overload. This is the meta-experiential blink. Meta-experiential self-observation is common to many computational models, including connectionist interpretations of consciousness, Bayesian observers and the readout-enhanced simultaneous type/serial token (reSTST) model. We assess how our meta-experiential blink data could be modelled using the concept of self-observation, providing model fits to behavioural and electroencephalogram responses in the reSTST model. We discuss the implications of our computational modelling of parallel encoding but serial experience for theories of conscious perception. Specifically, we (i) inform theories of Lag-1 sparing during the AB and (ii) consider the implications for the global workspace theory of conscious perception and higher-order theories of consciousness.</AbstractText
|
Prefrontal coding of learned and inferred knowledge during REM and NREM sleep. Idling brain activity has been proposed to facilitate inference, insight, and innovative problem-solving. However, it remains unclear how and when the idling brain can create novel ideas. Here, we show that cortical offline activity is both necessary and sufficient for building unlearned inferential knowledge from previously acquired information. In a transitive inference paradigm, male C57BL/6J mice gained the inference 1 day after, but not shortly after, complete training. Inhibiting the neuronal computations in the anterior cingulate cortex (ACC) during post-learning either non-rapid eye movement (NREM) or rapid eye movement (REM) sleep, but not wakefulness, disrupted the inference without affecting the learned knowledge. In vivo Ca<sup
|
Downregulated formyl peptide receptor 2 expression in the epileptogenic foci of patients with focal cortical dysplasia type IIb and tuberous sclerosis complex. Focal cortical dysplasia type IIb (FCDIIb) and tuberous sclerosis complex (TSC) show persistent neuroinflammation, which promotes epileptogenesis and epilepsy progression, suggesting that endogenous resolution of inflammation is inadequate to relieve neuronal network hyperexcitability. To explore the potential roles of formyl peptide receptor 2 (FPR2), which is a key regulator of inflammation resolution, in epilepsy caused by FCDIIb and TSC, we examined the expression and cellular distribution of FPR2.</AbstractText The expression of FPR2 and nuclear factor-κB (NF-κB) signaling pathway was examined by real-time PCR, western blots, and analyzed via one-way analysis of variance. The distribution of FPR2 was detected using immunostaining. The expression of resolvin D1 (RvD1, the endogenous ligand of FPR2) was observed via enzyme-linked immunosorbent assay. Pearson's correlation test was used to evaluate the correlation between the expression levels of FPR2 and RvD1 and the clinical variants.</AbstractText The expression of FPR2 was significantly lower in FCDIIb (p = .0146) and TSC (p = .0006) cortical lesions than in controls, as was the expression of RvD1 (FCDIIb: p = .00431; TSC: p = .0439). Weak FPR2 immunoreactivity was observed in dysmorphic neurons (DNs), balloon cells (BCs), and giant cells (GCs) in FCDIIb and TSC tissues. Moreover, FPR2 was mainly distributed in dysplastic neurons; it was sparse in microglia and nearly absent in astrocytes. The NF-κB pathway was significantly activated in patients with FCDIIb and TSC, and the protein level of NF-κB was negatively correlated with the protein level of FPR2 (FCDIIb: p = .00395; TSC: p = .0399). In addition, the protein level of FPR2 was negatively correlated with seizure frequency in FCDIIb (p = .0434) and TSC (p = .0351) patients.</AbstractText In summary, these results showed that the expression and specific distribution of FPR2 may be involved in epilepsy caused by FCDIIb and TSC, indicating that downregulation of FPR2 mediated the dysfunction of neuroinflammation resolution in FCDIIb and TSC.</AbstractText
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40321437
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32326995
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40778017
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Comprehensive Clinical and Behavioral Characteristics of Mild Cognitive Impairment According to Amyloid Positivity: A Large Multi-Center Korean Cohort.
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Type-2 diabetes and risk of dementia: observational and Mendelian randomisation studies in 1 million individuals.
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Experiencing pain: electromagnetic waves, consciousness, and the mind.
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Mild cognitive impairment (MCI) is a transitional stage to dementia, Alzheimer's disease being a major cause. Although amyloid beta-positive (Aβ+) MCI has been well-characterized, Aβ-negative (Aβ-) MCI has not. This study compared the comprehensive clinical and behavioral characteristics of Aβ+ and Aβ- MCI in a large multi-center cohort to better understand the heterogeneity of MCI, and to identify contributing factors to cognitive impairment.</AbstractText A total of 686 MCI participants were included. Aβ positivity was determined using Aβ positron emission tomography imaging with a direct conversion Centiloid cutoff value of 25.5. Standardized assessment and questionnaires were used to collect a wide range of clinical information, including vascular risk factors, cognition, daily living function, neuropsychiatric symptoms, and lifestyle behavior. Groups were compared using independent <i Aβ+ participants (n=406) were older, predominantly female, and more likely to be ApoE4 carriers. In contrast, Aβ- participants (n=280) showed higher vascular risk factors, including diabetes, elevated body mass index, and higher C-reactive protein levels. Aβ+ participants exhibited worse global cognition and functional decline, with a higher prevalence of delusions and appetite disturbances. Meanwhile, Aβ- participants reported greater social engagement, but poorer sleep quality.</AbstractText This study highlights the distinct clinical and lifestyle profiles of Aβ+ and Aβ- MCI, illuminating the heterogeneity of MCI and its underlying factors in the Korean population.</AbstractText
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In observational studies, type-2 diabetes is associated with increased risk of dementia; however, the causal nature of this association remains unanswered. In an unselected nationwide study of all Danes, we wanted to test whether type-2 diabetes is associated with dementia subtypes, and to test whether potential associations are of a causal nature.</AbstractText In the current study of nationwide observational registry data in all Danes above the age of 65 years (n = 784 434) combined with genetic consortia data on 213 370 individuals, we investigated the associations between type-2 diabetes and Alzheimer's disease, vascular dementia, unspecified dementia and all-cause dementia, and whether observational associations were of a causal nature by applying a two-sample Mendelian randomisation strategy. We addressed key biases inherent in Mendelian randomisation approaches.</AbstractText Important confounders (age, ethnicity, size of community, region, civil status and education level) were captured on all 784 434 individuals and adjusted for in the models. Multifactorial adjusted hazard ratios were 1.13 (1.06-1.21) for Alzheimer's disease, 1.98 (1.83-2.14) for vascular dementia, 1.53 (1.48-1.59) for unspecified dementia and 1.48 (1.44-1.53) for all-cause dementia in persons with type-2 diabetes v. without. Results were similar for men and women. The two-sample Mendelian randomisation estimate for the association between the genetic instrument and Alzheimer's disease was 1.04 (0.98-1.10), consistent with sensitivity estimates, addressing pleiotropy, measurement bias and weak instrument bias.</AbstractText In a nationwide study of all Danes above the age of 65 years, we show that type-2 diabetes is associated with major subtypes of dementia - with particularly strong associations for vascular dementia and unspecified dementia - the two types of dementia with the most obvious vascular pathologies. Although the present two-sample Mendelian randomisation approach using genetic consortia data suggests that type-2 diabetes is not a direct cause of Alzheimer's disease, we were unable to test the causal nature of type-2 diabetes for vascular dementia and unspecified dementia, because no publicly available genetic consortia data yet exist for these dementia endpoints. The causal nature of type-2 diabetes for dementia with vascular pathologies is pivotal questions to solve for future public health recommendations and therapeutic advice.</AbstractText
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Studies of nociception resulted in a theory in which the quality of pain - the suffering - arises when action potentials (APs) from the thalamus that encode information about an injury induce a long-term potentiation (LTP) at synapses on pyramidal neurons in a pain center (PC) within the anterior cingulate cortex (ACC). The LTP sensitizes transmission across the synapses via the activation of adenylate cyclase-1 (AC-1) and protein kinase A (PKA). It also generates Electromagnetic (EM) waves that now contain the information about the pain. The pain is experienced when the waves reach consciousness. Blocking the AC-1, PKA, or the waves attenuates the pain. The theory was founded on the response to a simple injury. I now discuss the role of other cortical centers involved in pain. Attention to pain is governed by circuits in the anterior insula cortex (IC); fear, which enhances the intensity of pain, involves circuits in the basal nucleus of the amygdala; and reward, which can attenuate pain, is regulated by activity in the nucleus accumbens (NucA). Evidence shows that injury-evoked APs induce LTP and the generation of EM waves in the IC, amygdala, and the NucA. Interactions between the waves from the PC with those from the amygdala or NucA can enhance or reduce pain, respectively. These findings reinforce the earlier theory that the information in the EM waves results in sensory experiences in consciousness. I now propose that the summation of the sensory experiences becomes knowledge in the mind, which is an entity distinct from the brain.</AbstractText
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Comprehensive Clinical and Behavioral Characteristics of Mild Cognitive Impairment According to Amyloid Positivity: A Large Multi-Center Korean Cohort. Mild cognitive impairment (MCI) is a transitional stage to dementia, Alzheimer's disease being a major cause. Although amyloid beta-positive (Aβ+) MCI has been well-characterized, Aβ-negative (Aβ-) MCI has not. This study compared the comprehensive clinical and behavioral characteristics of Aβ+ and Aβ- MCI in a large multi-center cohort to better understand the heterogeneity of MCI, and to identify contributing factors to cognitive impairment.</AbstractText A total of 686 MCI participants were included. Aβ positivity was determined using Aβ positron emission tomography imaging with a direct conversion Centiloid cutoff value of 25.5. Standardized assessment and questionnaires were used to collect a wide range of clinical information, including vascular risk factors, cognition, daily living function, neuropsychiatric symptoms, and lifestyle behavior. Groups were compared using independent <i Aβ+ participants (n=406) were older, predominantly female, and more likely to be ApoE4 carriers. In contrast, Aβ- participants (n=280) showed higher vascular risk factors, including diabetes, elevated body mass index, and higher C-reactive protein levels. Aβ+ participants exhibited worse global cognition and functional decline, with a higher prevalence of delusions and appetite disturbances. Meanwhile, Aβ- participants reported greater social engagement, but poorer sleep quality.</AbstractText This study highlights the distinct clinical and lifestyle profiles of Aβ+ and Aβ- MCI, illuminating the heterogeneity of MCI and its underlying factors in the Korean population.</AbstractText
|
Type-2 diabetes and risk of dementia: observational and Mendelian randomisation studies in 1 million individuals. In observational studies, type-2 diabetes is associated with increased risk of dementia; however, the causal nature of this association remains unanswered. In an unselected nationwide study of all Danes, we wanted to test whether type-2 diabetes is associated with dementia subtypes, and to test whether potential associations are of a causal nature.</AbstractText In the current study of nationwide observational registry data in all Danes above the age of 65 years (n = 784 434) combined with genetic consortia data on 213 370 individuals, we investigated the associations between type-2 diabetes and Alzheimer's disease, vascular dementia, unspecified dementia and all-cause dementia, and whether observational associations were of a causal nature by applying a two-sample Mendelian randomisation strategy. We addressed key biases inherent in Mendelian randomisation approaches.</AbstractText Important confounders (age, ethnicity, size of community, region, civil status and education level) were captured on all 784 434 individuals and adjusted for in the models. Multifactorial adjusted hazard ratios were 1.13 (1.06-1.21) for Alzheimer's disease, 1.98 (1.83-2.14) for vascular dementia, 1.53 (1.48-1.59) for unspecified dementia and 1.48 (1.44-1.53) for all-cause dementia in persons with type-2 diabetes v. without. Results were similar for men and women. The two-sample Mendelian randomisation estimate for the association between the genetic instrument and Alzheimer's disease was 1.04 (0.98-1.10), consistent with sensitivity estimates, addressing pleiotropy, measurement bias and weak instrument bias.</AbstractText In a nationwide study of all Danes above the age of 65 years, we show that type-2 diabetes is associated with major subtypes of dementia - with particularly strong associations for vascular dementia and unspecified dementia - the two types of dementia with the most obvious vascular pathologies. Although the present two-sample Mendelian randomisation approach using genetic consortia data suggests that type-2 diabetes is not a direct cause of Alzheimer's disease, we were unable to test the causal nature of type-2 diabetes for vascular dementia and unspecified dementia, because no publicly available genetic consortia data yet exist for these dementia endpoints. The causal nature of type-2 diabetes for dementia with vascular pathologies is pivotal questions to solve for future public health recommendations and therapeutic advice.</AbstractText
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Experiencing pain: electromagnetic waves, consciousness, and the mind. Studies of nociception resulted in a theory in which the quality of pain - the suffering - arises when action potentials (APs) from the thalamus that encode information about an injury induce a long-term potentiation (LTP) at synapses on pyramidal neurons in a pain center (PC) within the anterior cingulate cortex (ACC). The LTP sensitizes transmission across the synapses via the activation of adenylate cyclase-1 (AC-1) and protein kinase A (PKA). It also generates Electromagnetic (EM) waves that now contain the information about the pain. The pain is experienced when the waves reach consciousness. Blocking the AC-1, PKA, or the waves attenuates the pain. The theory was founded on the response to a simple injury. I now discuss the role of other cortical centers involved in pain. Attention to pain is governed by circuits in the anterior insula cortex (IC); fear, which enhances the intensity of pain, involves circuits in the basal nucleus of the amygdala; and reward, which can attenuate pain, is regulated by activity in the nucleus accumbens (NucA). Evidence shows that injury-evoked APs induce LTP and the generation of EM waves in the IC, amygdala, and the NucA. Interactions between the waves from the PC with those from the amygdala or NucA can enhance or reduce pain, respectively. These findings reinforce the earlier theory that the information in the EM waves results in sensory experiences in consciousness. I now propose that the summation of the sensory experiences becomes knowledge in the mind, which is an entity distinct from the brain.</AbstractText
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11736146
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32417703
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11250159
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Scaling of random spreading in small world networks.
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Human brain connectivity: Clinical applications for clinical neurophysiology.
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TBP is not universally required for zygotic RNA polymerase II transcription in zebrafish.
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In this study we have carried out computer simulations of random walks on Watts-Strogatz-type small world networks and measured the mean number of visited sites and the return probabilities. These quantities were found to obey scaling behavior with intuitively reasoned exponents as long as the probability p of having a long range bond was sufficiently low.</AbstractText
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This manuscript is the second part of a two-part description of the current status of understanding of the network function of the brain in health and disease. We start with the concept that brain function can be understood only by understanding its networks, how and why information flows in the brain. The first manuscript dealt with methods for network analysis, and the current manuscript focuses on the use of these methods to understand a wide variety of neurological and psychiatric disorders. Disorders considered are neurodegenerative disorders, such as Alzheimer disease and amyotrophic lateral sclerosis, stroke, movement disorders, including essential tremor, Parkinson disease, dystonia and apraxia, epilepsy, psychiatric disorders such as schizophrenia, and phantom limb pain. This state-of-the-art review makes clear the value of networks and brain models for understanding symptoms and signs of disease and can serve as a foundation for further work.</AbstractText
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General transcription factors TFIIA, B, D, E, F, H, and RNA polymerase II (Pol II) are required for accurate initiation of Pol II transcription. The TATA binding protein (TBP), a subunit of TFIID, is responsible for recognition of the TATA box, a core element shared by a category of class II promoters [1]. Recently, novel TBP-like factors (TLFs) have been described in metazoan organisms [2]. In spite of the numerous in vitro studies describing the general role of TBP in RNA polymerase II (Pol lI) transcription initiation, the precise function of TBP and the newly described TLF is poorly understood in vivo. We inhibited TBP and TLF function in zebrafish embryos to study the role of these factors during zygotic transcription. A dominant-negative variant of TLF mRNA and a TBP morpholino antisense oligo was used to block either TLF or TBP function. Both TBP- or TLF-blocked embryos developed normally until the midblastula stage; however, they then failed to gastrulate. Several zygotic regulatory genes were downregulated by a block in either TBP or TLF function, while others were differentially affected. These results suggest that TBP is not universally required for Pol II transcription in vertebrates and that there is a differential requirement for TBP and TLF during early embryogenesis.</AbstractText
|
Scaling of random spreading in small world networks. In this study we have carried out computer simulations of random walks on Watts-Strogatz-type small world networks and measured the mean number of visited sites and the return probabilities. These quantities were found to obey scaling behavior with intuitively reasoned exponents as long as the probability p of having a long range bond was sufficiently low.</AbstractText
|
Human brain connectivity: Clinical applications for clinical neurophysiology. This manuscript is the second part of a two-part description of the current status of understanding of the network function of the brain in health and disease. We start with the concept that brain function can be understood only by understanding its networks, how and why information flows in the brain. The first manuscript dealt with methods for network analysis, and the current manuscript focuses on the use of these methods to understand a wide variety of neurological and psychiatric disorders. Disorders considered are neurodegenerative disorders, such as Alzheimer disease and amyotrophic lateral sclerosis, stroke, movement disorders, including essential tremor, Parkinson disease, dystonia and apraxia, epilepsy, psychiatric disorders such as schizophrenia, and phantom limb pain. This state-of-the-art review makes clear the value of networks and brain models for understanding symptoms and signs of disease and can serve as a foundation for further work.</AbstractText
|
TBP is not universally required for zygotic RNA polymerase II transcription in zebrafish. General transcription factors TFIIA, B, D, E, F, H, and RNA polymerase II (Pol II) are required for accurate initiation of Pol II transcription. The TATA binding protein (TBP), a subunit of TFIID, is responsible for recognition of the TATA box, a core element shared by a category of class II promoters [1]. Recently, novel TBP-like factors (TLFs) have been described in metazoan organisms [2]. In spite of the numerous in vitro studies describing the general role of TBP in RNA polymerase II (Pol lI) transcription initiation, the precise function of TBP and the newly described TLF is poorly understood in vivo. We inhibited TBP and TLF function in zebrafish embryos to study the role of these factors during zygotic transcription. A dominant-negative variant of TLF mRNA and a TBP morpholino antisense oligo was used to block either TLF or TBP function. Both TBP- or TLF-blocked embryos developed normally until the midblastula stage; however, they then failed to gastrulate. Several zygotic regulatory genes were downregulated by a block in either TBP or TLF function, while others were differentially affected. These results suggest that TBP is not universally required for Pol II transcription in vertebrates and that there is a differential requirement for TBP and TLF during early embryogenesis.</AbstractText
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27539560
|
29206895
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26678554
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Brain-computer interfaces for communication and rehabilitation.
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Minimally conscious state or cortically mediated state?
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Characterization of the Escherichia coli YajL, YhbO and ElbB glyoxalases.
|
Brain-computer interfaces (BCIs) use brain activity to control external devices, thereby enabling severely disabled patients to interact with the environment. A variety of invasive and noninvasive techniques for controlling BCIs have been explored, most notably EEG, and more recently, near-infrared spectroscopy. Assistive BCIs are designed to enable paralyzed patients to communicate or control external robotic devices, such as prosthetics; rehabilitative BCIs are designed to facilitate recovery of neural function. In this Review, we provide an overview of the development of BCIs and the current technology available before discussing experimental and clinical studies of BCIs. We first consider the use of BCIs for communication in patients who are paralyzed, particularly those with locked-in syndrome or complete locked-in syndrome as a result of amyotrophic lateral sclerosis. We then discuss the use of BCIs for motor rehabilitation after severe stroke and spinal cord injury. We also describe the possible neurophysiological and learning mechanisms that underlie the clinical efficacy of BCIs.</AbstractText
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Durable impairments of consciousness are currently classified in three main neurological categories: comatose state, vegetative state (also recently coined unresponsive wakefulness syndrome) and minimally conscious state. While the introduction of minimally conscious state, in 2002, was a major progress to help clinicians recognize complex non-reflexive behaviours in the absence of functional communication, it raises several problems. The most important issue related to minimally conscious state lies in its criteria: while behavioural definition of minimally conscious state lacks any direct evidence of patient's conscious content or conscious state, it includes the adjective 'conscious'. I discuss this major problem in this review and propose a novel interpretation of minimally conscious state: its criteria do not inform us about the potential residual consciousness of patients, but they do inform us with certainty about the presence of a cortically mediated state. Based on this constructive criticism review, I suggest three proposals aiming at improving the way we describe the subjective and cognitive state of non-communicating patients. In particular, I present a tentative new classification of impairments of consciousness that combines behavioural evidence with functional brain imaging data, in order to probe directly and univocally residual conscious processes.</AbstractText
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The DJ-1 superfamily is a group of proteins that shares a similarity with the human DJ-1, known to be associated with Parkinson disease. Novel glyoxalase activity, converting α-oxoaldehydes to carboxylic acids, has been reported for DJ-1 homologs in humans, worms, plants and bacteria. The four Escherichia coli genes, hchA, yajL, yhbO and elbB, have been known to share sequence similarities and catalytic residues with other DJ-1 superfamily members. We investigated here whether they exhibit similar glyoxalase activity, as previously shown for HchA protein. Purified YajL, YhbO and ElbB exhibited glyoxalase activity with different substrate specificities, optimal pHs and metal effects. Overexpressions of the homologs enhance cellular protection from exogenously added glyoxals and reduce the glyoxal-dependent increase in intracellular advanced glycation end products. Based on their expression, primarily during the stationary phase, we speculate that their roles in cells as glyoxalases are manifested during the stationary phase.</AbstractText
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Brain-computer interfaces for communication and rehabilitation. Brain-computer interfaces (BCIs) use brain activity to control external devices, thereby enabling severely disabled patients to interact with the environment. A variety of invasive and noninvasive techniques for controlling BCIs have been explored, most notably EEG, and more recently, near-infrared spectroscopy. Assistive BCIs are designed to enable paralyzed patients to communicate or control external robotic devices, such as prosthetics; rehabilitative BCIs are designed to facilitate recovery of neural function. In this Review, we provide an overview of the development of BCIs and the current technology available before discussing experimental and clinical studies of BCIs. We first consider the use of BCIs for communication in patients who are paralyzed, particularly those with locked-in syndrome or complete locked-in syndrome as a result of amyotrophic lateral sclerosis. We then discuss the use of BCIs for motor rehabilitation after severe stroke and spinal cord injury. We also describe the possible neurophysiological and learning mechanisms that underlie the clinical efficacy of BCIs.</AbstractText
|
Minimally conscious state or cortically mediated state? Durable impairments of consciousness are currently classified in three main neurological categories: comatose state, vegetative state (also recently coined unresponsive wakefulness syndrome) and minimally conscious state. While the introduction of minimally conscious state, in 2002, was a major progress to help clinicians recognize complex non-reflexive behaviours in the absence of functional communication, it raises several problems. The most important issue related to minimally conscious state lies in its criteria: while behavioural definition of minimally conscious state lacks any direct evidence of patient's conscious content or conscious state, it includes the adjective 'conscious'. I discuss this major problem in this review and propose a novel interpretation of minimally conscious state: its criteria do not inform us about the potential residual consciousness of patients, but they do inform us with certainty about the presence of a cortically mediated state. Based on this constructive criticism review, I suggest three proposals aiming at improving the way we describe the subjective and cognitive state of non-communicating patients. In particular, I present a tentative new classification of impairments of consciousness that combines behavioural evidence with functional brain imaging data, in order to probe directly and univocally residual conscious processes.</AbstractText
|
Characterization of the Escherichia coli YajL, YhbO and ElbB glyoxalases. The DJ-1 superfamily is a group of proteins that shares a similarity with the human DJ-1, known to be associated with Parkinson disease. Novel glyoxalase activity, converting α-oxoaldehydes to carboxylic acids, has been reported for DJ-1 homologs in humans, worms, plants and bacteria. The four Escherichia coli genes, hchA, yajL, yhbO and elbB, have been known to share sequence similarities and catalytic residues with other DJ-1 superfamily members. We investigated here whether they exhibit similar glyoxalase activity, as previously shown for HchA protein. Purified YajL, YhbO and ElbB exhibited glyoxalase activity with different substrate specificities, optimal pHs and metal effects. Overexpressions of the homologs enhance cellular protection from exogenously added glyoxals and reduce the glyoxal-dependent increase in intracellular advanced glycation end products. Based on their expression, primarily during the stationary phase, we speculate that their roles in cells as glyoxalases are manifested during the stationary phase.</AbstractText
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38163852
|
32102280
|
38525292
|
Carbon Dots for Multiuse Platform: Intracellular pH Sensing and Complementary Intensified T1-T2 Dual Imaging Contrast Nanoprobes.
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MRI Relaxivity Changes of the Magnetic Nanoparticles Induced by Different Amino Acid Coatings.
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CMNet: deep learning model for colon polyp segmentation based on dual-branch structure.
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Measurement of pH in living cells is a great and decisive factor for providing an early and accurate diagnosis factor. Along with this, the multimodal transverse and longitudinal relaxivity enhancement potentiality over single modality within a single platform in the magnetic resonance imaging (MRI) field is a very challenging issue for diagnostic purposes in the biomedical field of application. Therefore, this work aims to design a versatile platform by fabricating a novel nanoprobe through holmium- and manganese-ion doping in carbon quantum dots (Ho-Mn-CQDs), which can show nearly neutral intracellular pH sensing and MRI imaging at the same time. These manufactured Ho-Mn-CQDs acted as excellent pH sensors in the near-neutral range (4.01-8.01) with the linearity between 6.01 and 8.01, which could be useful for the intracellular pH-sensing capability. An innumerable number of carboxyl and amino groups are present on the surface of the prepared nanoprobe, making it an excellent candidate for pH sensing through fluorescence intensity quenching phenomena. Cellular uptake and cell viability experiments were also executed to affirm the intracellular accepting ability of Ho-Mn-CQDs. Furthermore, with this pH-sensing quality, these Ho-Mn-CQDs are also capable of acting as T1-T2 dual modal imaging contrast agents in comparison with pristine Ho-doped and Mn-doped CQDs. The Ho-Mn-CQDs showed an increment of r1 and r2 relaxivity values simultaneously compared with only the negative contrast agent, holmium in holmium-doped CQDs, and the positive contrast agent, manganese in manganese-doped CQDs. The above-mentioned observations elucidate that its tiny size, excitation dependence of fluorescence behavior, low cytotoxicity, and dual modal contrast imaging capability make it an ideal candidate for pH monitoring in the near-neutral range and also as a dual modal MRI imaging contrast enhancement nanoprobe at the same time.</AbstractText
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In this study, we analysed the physico-chemical properties of positively charged magnetic fluids consisting of magnetic nanoparticles (MNPs) functionalised by different amino acids (AAs): glycine (Gly), lysine (Lys) and tryptophan (Trp), and the influence of AA-MNP complexes on the MRI relaxivity. We found that the AA coating affects the size of dispersed particles and isoelectric point, as well as the zeta potential of AA-MNPs differently, depending on the AA selected. Moreover, we showed that a change in hydrodynamic diameter results in a change to the relaxivity of AA-MNP complexes. On the one hand, we observed a decrease in the relaxivity values, <i
|
Colon cancer is one of the top three diseases in gastrointestinal cancers, and colon polyps are an important trigger of colon cancer. Early diagnosis and removal of colon polyps can avoid the incidence of colon cancer. Currently, colon polyp removal surgery is mainly based on artificial-intelligence (AI) colonoscopy, supplemented by deep-learning technology to help doctors remove colon polyps. With the development of deep learning, the use of advanced AI technology to assist in medical diagnosis has become mainstream and can maximize the doctor's diagnostic time and help doctors to better formulate medical plans.</AbstractText We propose a deep-learning model for segmenting colon polyps. The model adopts a dual-branch structure, combines a convolutional neural network (CNN) with a transformer, and replaces ordinary convolution with deeply separable convolution based on ResNet; a stripe pooling module is introduced to obtain more effective information. The aggregated attention module (AAM) is proposed for high-dimensional semantic information, which effectively combines two different structures for the high-dimensional information fusion problem. Deep supervision and multi-scale training are added in the model training process to enhance the learning effect and generalization performance of the model.</AbstractText The experimental results show that the proposed dual-branch structure is significantly better than the single-branch structure, and the model using the AAM has a significant performance improvement over the model not using the AAM. Our model leads 1.1% and 1.5% in mIoU and mDice, respectively, when compared with state-of-the-art models in a fivefold cross-validation on the Kvasir-SEG dataset.</AbstractText We propose and validate a deep learning model for segmenting colon polyps, using a dual-branch network structure. Our results demonstrate the feasibility of complementing traditional CNNs and transformer with each other. And we verified the feasibility of fusing different structures on high-dimensional semantics and successfully retained the high-dimensional information of different structures effectively.</AbstractText
|
Carbon Dots for Multiuse Platform: Intracellular pH Sensing and Complementary Intensified T1-T2 Dual Imaging Contrast Nanoprobes. Measurement of pH in living cells is a great and decisive factor for providing an early and accurate diagnosis factor. Along with this, the multimodal transverse and longitudinal relaxivity enhancement potentiality over single modality within a single platform in the magnetic resonance imaging (MRI) field is a very challenging issue for diagnostic purposes in the biomedical field of application. Therefore, this work aims to design a versatile platform by fabricating a novel nanoprobe through holmium- and manganese-ion doping in carbon quantum dots (Ho-Mn-CQDs), which can show nearly neutral intracellular pH sensing and MRI imaging at the same time. These manufactured Ho-Mn-CQDs acted as excellent pH sensors in the near-neutral range (4.01-8.01) with the linearity between 6.01 and 8.01, which could be useful for the intracellular pH-sensing capability. An innumerable number of carboxyl and amino groups are present on the surface of the prepared nanoprobe, making it an excellent candidate for pH sensing through fluorescence intensity quenching phenomena. Cellular uptake and cell viability experiments were also executed to affirm the intracellular accepting ability of Ho-Mn-CQDs. Furthermore, with this pH-sensing quality, these Ho-Mn-CQDs are also capable of acting as T1-T2 dual modal imaging contrast agents in comparison with pristine Ho-doped and Mn-doped CQDs. The Ho-Mn-CQDs showed an increment of r1 and r2 relaxivity values simultaneously compared with only the negative contrast agent, holmium in holmium-doped CQDs, and the positive contrast agent, manganese in manganese-doped CQDs. The above-mentioned observations elucidate that its tiny size, excitation dependence of fluorescence behavior, low cytotoxicity, and dual modal contrast imaging capability make it an ideal candidate for pH monitoring in the near-neutral range and also as a dual modal MRI imaging contrast enhancement nanoprobe at the same time.</AbstractText
|
MRI Relaxivity Changes of the Magnetic Nanoparticles Induced by Different Amino Acid Coatings. In this study, we analysed the physico-chemical properties of positively charged magnetic fluids consisting of magnetic nanoparticles (MNPs) functionalised by different amino acids (AAs): glycine (Gly), lysine (Lys) and tryptophan (Trp), and the influence of AA-MNP complexes on the MRI relaxivity. We found that the AA coating affects the size of dispersed particles and isoelectric point, as well as the zeta potential of AA-MNPs differently, depending on the AA selected. Moreover, we showed that a change in hydrodynamic diameter results in a change to the relaxivity of AA-MNP complexes. On the one hand, we observed a decrease in the relaxivity values, <i
|
CMNet: deep learning model for colon polyp segmentation based on dual-branch structure. Colon cancer is one of the top three diseases in gastrointestinal cancers, and colon polyps are an important trigger of colon cancer. Early diagnosis and removal of colon polyps can avoid the incidence of colon cancer. Currently, colon polyp removal surgery is mainly based on artificial-intelligence (AI) colonoscopy, supplemented by deep-learning technology to help doctors remove colon polyps. With the development of deep learning, the use of advanced AI technology to assist in medical diagnosis has become mainstream and can maximize the doctor's diagnostic time and help doctors to better formulate medical plans.</AbstractText We propose a deep-learning model for segmenting colon polyps. The model adopts a dual-branch structure, combines a convolutional neural network (CNN) with a transformer, and replaces ordinary convolution with deeply separable convolution based on ResNet; a stripe pooling module is introduced to obtain more effective information. The aggregated attention module (AAM) is proposed for high-dimensional semantic information, which effectively combines two different structures for the high-dimensional information fusion problem. Deep supervision and multi-scale training are added in the model training process to enhance the learning effect and generalization performance of the model.</AbstractText The experimental results show that the proposed dual-branch structure is significantly better than the single-branch structure, and the model using the AAM has a significant performance improvement over the model not using the AAM. Our model leads 1.1% and 1.5% in mIoU and mDice, respectively, when compared with state-of-the-art models in a fivefold cross-validation on the Kvasir-SEG dataset.</AbstractText We propose and validate a deep learning model for segmenting colon polyps, using a dual-branch network structure. Our results demonstrate the feasibility of complementing traditional CNNs and transformer with each other. And we verified the feasibility of fusing different structures on high-dimensional semantics and successfully retained the high-dimensional information of different structures effectively.</AbstractText
|
37664610
|
33694180
|
36094754
|
C9orf72 poly(PR) mediated neurodegeneration is associated with nucleolar stress.
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HDAC6 inhibition restores TDP-43 pathology and axonal transport defects in human motor neurons with TARDBP mutations.
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METTLing in Stem Cell and Cancer Biology.
|
The ALS/FTD-linked intronic hexanucleotide repeat expansion in the <i
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TDP-43 is the major component of pathological inclusions in most ALS patients and in up to 50% of patients with frontotemporal dementia (FTD). Heterozygous missense mutations in TARDBP, the gene encoding TDP-43, are one of the common causes of familial ALS. In this study, we investigate TDP-43 protein behavior in induced pluripotent stem cell (iPSC)-derived motor neurons from three ALS patients with different TARDBP mutations, three healthy controls and an isogenic control. TARDPB mutations induce several TDP-43 changes in spinal motor neurons, including cytoplasmic mislocalization and accumulation of insoluble TDP-43, C-terminal fragments, and phospho-TDP-43. By generating iPSC lines with allele-specific tagging of TDP-43, we find that mutant TDP-43 initiates the observed disease phenotypes and has an altered interactome as indicated by mass spectrometry. Our findings also indicate that TDP-43 proteinopathy results in a defect in mitochondrial transport. Lastly, we show that pharmacological inhibition of histone deacetylase 6 (HDAC6) restores the observed TDP-43 pathologies and the axonal mitochondrial motility, suggesting that HDAC6 inhibition may be an interesting therapeutic target for neurodegenerative disorders linked to TDP-43 pathology.</AbstractText
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The methyltransferase-like (METTL) family is a diverse group of methyltransferases that can methylate nucleotides, proteins, and small molecules. Despite this diverse array of substrates, they all share a characteristic seven-beta-strand catalytic domain, and recent evidence suggests many also share an important role in stem cell biology. The most well characterized family members METTL3 and METTL14 dimerize to form an N<sup
|
C9orf72 poly(PR) mediated neurodegeneration is associated with nucleolar stress. The ALS/FTD-linked intronic hexanucleotide repeat expansion in the <i
|
HDAC6 inhibition restores TDP-43 pathology and axonal transport defects in human motor neurons with TARDBP mutations. TDP-43 is the major component of pathological inclusions in most ALS patients and in up to 50% of patients with frontotemporal dementia (FTD). Heterozygous missense mutations in TARDBP, the gene encoding TDP-43, are one of the common causes of familial ALS. In this study, we investigate TDP-43 protein behavior in induced pluripotent stem cell (iPSC)-derived motor neurons from three ALS patients with different TARDBP mutations, three healthy controls and an isogenic control. TARDPB mutations induce several TDP-43 changes in spinal motor neurons, including cytoplasmic mislocalization and accumulation of insoluble TDP-43, C-terminal fragments, and phospho-TDP-43. By generating iPSC lines with allele-specific tagging of TDP-43, we find that mutant TDP-43 initiates the observed disease phenotypes and has an altered interactome as indicated by mass spectrometry. Our findings also indicate that TDP-43 proteinopathy results in a defect in mitochondrial transport. Lastly, we show that pharmacological inhibition of histone deacetylase 6 (HDAC6) restores the observed TDP-43 pathologies and the axonal mitochondrial motility, suggesting that HDAC6 inhibition may be an interesting therapeutic target for neurodegenerative disorders linked to TDP-43 pathology.</AbstractText
|
METTLing in Stem Cell and Cancer Biology. The methyltransferase-like (METTL) family is a diverse group of methyltransferases that can methylate nucleotides, proteins, and small molecules. Despite this diverse array of substrates, they all share a characteristic seven-beta-strand catalytic domain, and recent evidence suggests many also share an important role in stem cell biology. The most well characterized family members METTL3 and METTL14 dimerize to form an N<sup
|
40149639
|
36898840
|
40575365
|
Deciphering Pain and Pruritus in Keloids from the Perspective of Neurological Dysfunction: Where Are We Now?
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Endogenous Inflammatory Mediators Produced by Injury Activate TRPV1 and TRPA1 Nociceptors to Induce Sexually Dimorphic Cold Pain That Is Dependent on TRPM8 and GFRα3.
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A rare interstitial lung disease in young adulthood due to surfactant protein C gene mutation: Two case reports with brief literature review.
|
Keloids are a typical skin fibroproliferative disease that can cause severe aesthetic and functional concerns. Pain and pruritus are the most common clinical symptoms of keloids, but the mechanisms underlying these symptoms remain unclear. The peripheral nervous system plays a pivotal role in the transmission of superficial sensation signals. Mounting evidence has shown potential correlations between disturbance in the peripheral nervous system and pain and pruritus in keloids. Here, we summarize the role of neurological dysfunction in the development of pain and pruritus, with a specific focus on neuroanatomical alterations, the dysfunction of sensory nerves, and neurogenic inflammation.</AbstractText
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The detection of environmental temperatures is critical for survival, yet inappropriate responses to thermal stimuli can have a negative impact on overall health. The physiological effect of cold is distinct among somatosensory modalities in that it is soothing and analgesic, but also agonizing in the context of tissue damage. Inflammatory mediators produced during injury activate nociceptors to release neuropeptides, such as calcitonin gene-related peptide (CGRP) and substance P, inducing neurogenic inflammation, which further exasperates pain. Many inflammatory mediators induce sensitization to heat and mechanical stimuli but, conversely, inhibit cold responsiveness, and the identity of molecules inducing cold pain peripherally is enigmatic, as are the cellular and molecular mechanisms altering cold sensitivity. Here, we asked whether inflammatory mediators that induce neurogenic inflammation via the nociceptive ion channels TRPV1 (vanilloid subfamily of transient receptor potential channel) and TRPA1 (transient receptor potential ankyrin 1) lead to cold pain in mice. Specifically, we tested cold sensitivity in mice after intraplantar injection of lysophosphatidic acid or 4-hydroxy-2-nonenal, finding that each induces cold pain that is dependent on the cold-gated channel transient receptor potential melastatin 8 (TRPM8). Inhibition of CGRP, substance P, or toll-like receptor 4 (TLR4) signaling attenuates this phenotype, and each neuropeptide produces TRPM8-dependent cold pain directly. Further, the inhibition of CGRP or TLR4 signaling alleviates cold allodynia differentially by sex. Last, cold pain induced by both inflammatory mediators and neuropeptides requires TRPM8, as well as the neurotrophin artemin and its receptor GDNF receptor α3 (GFRα3). These results are consistent with artemin-induced cold allodynia requiring TRPM8, demonstrating that neurogenic inflammation alters cold sensitivity via localized artemin release that induces cold pain via GFRα3 and TRPM8.<b
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Interstitial lung disease associated with mutations in the surfactant protein C gene (SFTPC) is a rare condition. These mutations can be inherited as an autosomal dominant trait or occur sporadically due to a de novo mutation. The clinical symptoms of this disease can vary widely, ranging from fatal acute respiratory distress syndrome (RDS) in neonates to chronic lung disease in adults. We present 2 cases of young adults with SFTPC mutations related to interstitial lung disease (ILD). Chest CT findings in these cases included ground-glass opacities, reticulation, multiple cysts, and thickening of the interlobular septae.</AbstractText
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Deciphering Pain and Pruritus in Keloids from the Perspective of Neurological Dysfunction: Where Are We Now? Keloids are a typical skin fibroproliferative disease that can cause severe aesthetic and functional concerns. Pain and pruritus are the most common clinical symptoms of keloids, but the mechanisms underlying these symptoms remain unclear. The peripheral nervous system plays a pivotal role in the transmission of superficial sensation signals. Mounting evidence has shown potential correlations between disturbance in the peripheral nervous system and pain and pruritus in keloids. Here, we summarize the role of neurological dysfunction in the development of pain and pruritus, with a specific focus on neuroanatomical alterations, the dysfunction of sensory nerves, and neurogenic inflammation.</AbstractText
|
Endogenous Inflammatory Mediators Produced by Injury Activate TRPV1 and TRPA1 Nociceptors to Induce Sexually Dimorphic Cold Pain That Is Dependent on TRPM8 and GFRα3. The detection of environmental temperatures is critical for survival, yet inappropriate responses to thermal stimuli can have a negative impact on overall health. The physiological effect of cold is distinct among somatosensory modalities in that it is soothing and analgesic, but also agonizing in the context of tissue damage. Inflammatory mediators produced during injury activate nociceptors to release neuropeptides, such as calcitonin gene-related peptide (CGRP) and substance P, inducing neurogenic inflammation, which further exasperates pain. Many inflammatory mediators induce sensitization to heat and mechanical stimuli but, conversely, inhibit cold responsiveness, and the identity of molecules inducing cold pain peripherally is enigmatic, as are the cellular and molecular mechanisms altering cold sensitivity. Here, we asked whether inflammatory mediators that induce neurogenic inflammation via the nociceptive ion channels TRPV1 (vanilloid subfamily of transient receptor potential channel) and TRPA1 (transient receptor potential ankyrin 1) lead to cold pain in mice. Specifically, we tested cold sensitivity in mice after intraplantar injection of lysophosphatidic acid or 4-hydroxy-2-nonenal, finding that each induces cold pain that is dependent on the cold-gated channel transient receptor potential melastatin 8 (TRPM8). Inhibition of CGRP, substance P, or toll-like receptor 4 (TLR4) signaling attenuates this phenotype, and each neuropeptide produces TRPM8-dependent cold pain directly. Further, the inhibition of CGRP or TLR4 signaling alleviates cold allodynia differentially by sex. Last, cold pain induced by both inflammatory mediators and neuropeptides requires TRPM8, as well as the neurotrophin artemin and its receptor GDNF receptor α3 (GFRα3). These results are consistent with artemin-induced cold allodynia requiring TRPM8, demonstrating that neurogenic inflammation alters cold sensitivity via localized artemin release that induces cold pain via GFRα3 and TRPM8.<b
|
A rare interstitial lung disease in young adulthood due to surfactant protein C gene mutation: Two case reports with brief literature review. Interstitial lung disease associated with mutations in the surfactant protein C gene (SFTPC) is a rare condition. These mutations can be inherited as an autosomal dominant trait or occur sporadically due to a de novo mutation. The clinical symptoms of this disease can vary widely, ranging from fatal acute respiratory distress syndrome (RDS) in neonates to chronic lung disease in adults. We present 2 cases of young adults with SFTPC mutations related to interstitial lung disease (ILD). Chest CT findings in these cases included ground-glass opacities, reticulation, multiple cysts, and thickening of the interlobular septae.</AbstractText
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36322162
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22614249
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38001746
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Anxiolytic-like effects of citral in the mouse elevated plus maze: involvement of GABAergic and serotonergic transmissions.
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Monod-Wyman-Changeux allosteric mechanisms of action and the pharmacology of etomidate.
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Setup Uncertainty of Pediatric Brain Tumor Patients Receiving Proton Therapy: A Prospective Study.
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Citral, a monoterpene which is a part of the essential oil of several medicinal plants, is generally regarded as safe for human and animal consumption. Studies have introduced citral as a functional component of some essential oils in anxiolytic and antidepressant therapies; however, the neuropharmacological characteristics of citral have not yet been reported. In the present study, we evaluated the anxiolytic activities of citral in comparison to two standard anxiolytics, diazepam and buspirone, in Swiss albino mice by intraperitoneal administration of 1, 2, 5, 10, and 20 mg/kg using elevated plus maze (EPM) and open-field test (OFT). Moreover, we also examined whether the GABA<sub
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Formal Monod-Wyman-Changeux allosteric mechanisms have proven valuable in framing research on the mechanism of etomidate action on its major molecular targets, γ-aminobutyric acid type A (GABAA) receptors. However, the mathematical formalism of these mechanisms makes them difficult to comprehend.</AbstractText We illustrate how allosteric models represent shifting equilibria between various functional receptor states (closed versus open) and how co-agonism can be readily understood as simply addition of gating energy associated with occupation of distinct agonist sites. We use these models to illustrate how the functional effects of a point mutation, α1M236W, in GABAA receptors can be translated into an allosteric model phenotype.</AbstractText Allosteric co-agonism provides a robust framework for design and interpretation of structure-function experiments aimed at understanding where and how etomidate affects its GABAA receptor target molecules.</AbstractText
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This study quantifies setup uncertainty in brain tumor patients who received image-guided proton therapy. Patients analyzed include 165 children, adolescents, and young adults (median age at radiotherapy: 9 years (range: 10 months to 24 years); 80 anesthetized and 85 awake) enrolled in a single-institution prospective study from 2020 to 2023. Cone-beam computed tomography (CBCT) was performed daily to calculate and correct manual setup errors, once per course after setup correction to measure residual errors, and weekly after treatments to assess intrafractional motion. Orthogonal radiographs were acquired consecutively with CBCT for paired comparisons of 40 patients. Translational and rotational errors were converted from 6 degrees of freedom to a scalar by a statistical approach that considers the distance from the target to the isocenter. The 95th percentile of setup uncertainty was reduced by daily CBCT from 10 mm (manual positioning) to 1-1.5 mm (after correction) and increased to 2 mm by the end of fractional treatment. A larger variation existed between the roll corrections reported by radiographs vs. CBCT than for pitch and yaw, while there was no statistically significant difference in translational variation. A quantile mixed regression model showed that the 95th percentile of intrafractional motion was 0.40 mm lower for anesthetized patients (p=0.0016). Considering additional uncertainty in radiation-imaging isocentricity, the commonly used total plan robustness of 3 mm against positional uncertainty would be appropriate for our study cohort.</AbstractText
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Anxiolytic-like effects of citral in the mouse elevated plus maze: involvement of GABAergic and serotonergic transmissions. Citral, a monoterpene which is a part of the essential oil of several medicinal plants, is generally regarded as safe for human and animal consumption. Studies have introduced citral as a functional component of some essential oils in anxiolytic and antidepressant therapies; however, the neuropharmacological characteristics of citral have not yet been reported. In the present study, we evaluated the anxiolytic activities of citral in comparison to two standard anxiolytics, diazepam and buspirone, in Swiss albino mice by intraperitoneal administration of 1, 2, 5, 10, and 20 mg/kg using elevated plus maze (EPM) and open-field test (OFT). Moreover, we also examined whether the GABA<sub
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Monod-Wyman-Changeux allosteric mechanisms of action and the pharmacology of etomidate. Formal Monod-Wyman-Changeux allosteric mechanisms have proven valuable in framing research on the mechanism of etomidate action on its major molecular targets, γ-aminobutyric acid type A (GABAA) receptors. However, the mathematical formalism of these mechanisms makes them difficult to comprehend.</AbstractText We illustrate how allosteric models represent shifting equilibria between various functional receptor states (closed versus open) and how co-agonism can be readily understood as simply addition of gating energy associated with occupation of distinct agonist sites. We use these models to illustrate how the functional effects of a point mutation, α1M236W, in GABAA receptors can be translated into an allosteric model phenotype.</AbstractText Allosteric co-agonism provides a robust framework for design and interpretation of structure-function experiments aimed at understanding where and how etomidate affects its GABAA receptor target molecules.</AbstractText
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Setup Uncertainty of Pediatric Brain Tumor Patients Receiving Proton Therapy: A Prospective Study. This study quantifies setup uncertainty in brain tumor patients who received image-guided proton therapy. Patients analyzed include 165 children, adolescents, and young adults (median age at radiotherapy: 9 years (range: 10 months to 24 years); 80 anesthetized and 85 awake) enrolled in a single-institution prospective study from 2020 to 2023. Cone-beam computed tomography (CBCT) was performed daily to calculate and correct manual setup errors, once per course after setup correction to measure residual errors, and weekly after treatments to assess intrafractional motion. Orthogonal radiographs were acquired consecutively with CBCT for paired comparisons of 40 patients. Translational and rotational errors were converted from 6 degrees of freedom to a scalar by a statistical approach that considers the distance from the target to the isocenter. The 95th percentile of setup uncertainty was reduced by daily CBCT from 10 mm (manual positioning) to 1-1.5 mm (after correction) and increased to 2 mm by the end of fractional treatment. A larger variation existed between the roll corrections reported by radiographs vs. CBCT than for pitch and yaw, while there was no statistically significant difference in translational variation. A quantile mixed regression model showed that the 95th percentile of intrafractional motion was 0.40 mm lower for anesthetized patients (p=0.0016). Considering additional uncertainty in radiation-imaging isocentricity, the commonly used total plan robustness of 3 mm against positional uncertainty would be appropriate for our study cohort.</AbstractText
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30010197
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17562028
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29109052
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Alpha-band functional connectivity during cued versus implicit modality-specific anticipatory attention: EEG-source coherence analysis.
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Transcranial magnetic stimulation and synaptic plasticity: experimental framework and human models.
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Magnetic resonance imaging with RF encoding on curved natural slices.
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The anticipation of future events based on a background experience is one of the main components of any goal-directed behavior. Anticipatory attention can be either voluntary (explicit) or involuntary (implicit). We presumed that these two types of anticipatory attention differed in terms of cortical functional organization. We examined this assumption with an experimental model consisting of three experimental sessions (cued attention, implicit learning, and baseline) that were equal in terms of stimuli, motor responses, and cognitive task. Participants were asked to discriminate the temporal order of stimuli within a pair presented in either the visual or auditory sensory modality. Prestimulus functional connectivity was assessed via alpha-band coherence computed in the source space for preselected regions of interests. Functional links between the cortices of the frontoparietal control system increased during the cued attention condition and did not increase during the implicit anticipation condition. The buildup of implicit anticipation was accompanied by the strengthening of functional links between the intraparietal, ventral premotor, and presupplementary motor areas. It was discovered that both cued and implicit types of anticipation were underlain by functional modality-specific cortical links.</AbstractText
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Interest in the therapeutic potential of non-invasive human brain stimulation has been boosted by an improved understanding of the mechanisms of synaptic plasticity and the stimulus protocols that can induce plasticity in experimental preparations. A range of transcranial magnetic stimulation (TMS) protocols are available that have the potential to mimic these experimental protocols in the human. Repetitive TMS emulates aspects of activity-dependent plasticity, and theta-burst refinements may be able to take into account excitatory and inhibitory networks, paired associative stimulation can extend network considerations to incorporate sensorimotor integration, inhibitory networks may be targeted with short-interval paired stimulation and finally even the precision of spike-timing dependent plasticity may be accessible through I-(indirect)wave dynamics. This review will provide a synthesis of current concepts of activity- and time-dependent plasticity and their homeostatic regulation based on experimental studies, and relate these concepts to the promising range of TMS interventions that are available to target human brain plasticity.</AbstractText
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While the idea of using spatial encoding fields (SEM) for image formation has been proven, conventional wisdom still holds that a magnetic resonance imaging (MRI) system begins with a highly uniform magnetic field. In particular, radio frequency (RF) encoding MRIs designed and tested to date have largely used uniform magnetic fields. Here we demonstrate magnetic resonance imaging in a magnetic field with a built-in gradient that gives non-planar slices - curved surfaces - when the nuclear spins are excited with narrow band RF pulses. Image encoding on these naturally occurring non-planar slices was accomplished with RF encoding using a non-linear spatially varying B<sub
|
Alpha-band functional connectivity during cued versus implicit modality-specific anticipatory attention: EEG-source coherence analysis. The anticipation of future events based on a background experience is one of the main components of any goal-directed behavior. Anticipatory attention can be either voluntary (explicit) or involuntary (implicit). We presumed that these two types of anticipatory attention differed in terms of cortical functional organization. We examined this assumption with an experimental model consisting of three experimental sessions (cued attention, implicit learning, and baseline) that were equal in terms of stimuli, motor responses, and cognitive task. Participants were asked to discriminate the temporal order of stimuli within a pair presented in either the visual or auditory sensory modality. Prestimulus functional connectivity was assessed via alpha-band coherence computed in the source space for preselected regions of interests. Functional links between the cortices of the frontoparietal control system increased during the cued attention condition and did not increase during the implicit anticipation condition. The buildup of implicit anticipation was accompanied by the strengthening of functional links between the intraparietal, ventral premotor, and presupplementary motor areas. It was discovered that both cued and implicit types of anticipation were underlain by functional modality-specific cortical links.</AbstractText
|
Transcranial magnetic stimulation and synaptic plasticity: experimental framework and human models. Interest in the therapeutic potential of non-invasive human brain stimulation has been boosted by an improved understanding of the mechanisms of synaptic plasticity and the stimulus protocols that can induce plasticity in experimental preparations. A range of transcranial magnetic stimulation (TMS) protocols are available that have the potential to mimic these experimental protocols in the human. Repetitive TMS emulates aspects of activity-dependent plasticity, and theta-burst refinements may be able to take into account excitatory and inhibitory networks, paired associative stimulation can extend network considerations to incorporate sensorimotor integration, inhibitory networks may be targeted with short-interval paired stimulation and finally even the precision of spike-timing dependent plasticity may be accessible through I-(indirect)wave dynamics. This review will provide a synthesis of current concepts of activity- and time-dependent plasticity and their homeostatic regulation based on experimental studies, and relate these concepts to the promising range of TMS interventions that are available to target human brain plasticity.</AbstractText
|
Magnetic resonance imaging with RF encoding on curved natural slices. While the idea of using spatial encoding fields (SEM) for image formation has been proven, conventional wisdom still holds that a magnetic resonance imaging (MRI) system begins with a highly uniform magnetic field. In particular, radio frequency (RF) encoding MRIs designed and tested to date have largely used uniform magnetic fields. Here we demonstrate magnetic resonance imaging in a magnetic field with a built-in gradient that gives non-planar slices - curved surfaces - when the nuclear spins are excited with narrow band RF pulses. Image encoding on these naturally occurring non-planar slices was accomplished with RF encoding using a non-linear spatially varying B<sub
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40730634
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26415155
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40441883
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Enhanced remote sensing image feature classification using STFF-PSPNet.
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Supervised Evaluation of Image Segmentation and Object Proposal Techniques.
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NMDA receptor involvement in dopaminergic modulation of neuroplasticity induced by paired associative stimulation.
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Semantic segmentation of remotely sensed images is crucial for urban planning and change detection, yet faces issues like sample imbalance and low data quality. This study compiles a GF-2 image dataset and refines the PSPNet model. Weights of different class samples were adjusted to prioritize minority classes, mitigating sample imbalance's impact on classification. Data augmentation enhanced dataset quality. By replacing ResNet with the STFF network for better global feature extraction, adding attention modules, and using a combined loss function, the improved model shows excellent performance. It achieves a mAcc of 90.32 %, mIoU of 76.04 %, and a Dice coefficient of 85.15 %. Comparison with other models verifies its superiority, and tests on public datasets prove strong generalization, offering valuable insights for remote sensing image processing.</AbstractText
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This paper tackles the supervised evaluation of image segmentation and object proposal algorithms. It surveys, structures, and deduplicates the measures used to compare both segmentation results and object proposals with a ground truth database; and proposes a new measure: the precision-recall for objects and parts. To compare the quality of these measures, eight state-of-the-art object proposal techniques are analyzed and two quantitative meta-measures involving nine state of the art segmentation methods are presented. The meta-measures consist in assuming some plausible hypotheses about the results and assessing how well each measure reflects these hypotheses. As a conclusion of the performed experiments, this paper proposes the tandem of precision-recall curves for boundaries and for objects-and-parts as the tool of choice for the supervised evaluation of image segmentation. We make the datasets and code of all the measures publicly available.</AbstractText
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Dopamine (DA) modulates long-term potentiation (LTP)-like neuroplasticity. While particularly D1 and D2 receptors are thought to influence neuroplasticity through glutamatergic N-methyl-D-aspartate (NMDA) receptor and gamma-aminobutyric acid (GABA) modulation, the exact mechanisms are not completely clarified.</AbstractText We aimed to explore the relevance of NMDA receptor activity for DAergic modulation of focal LTP-like plasticity induced by excitatory paired associative stimulation (ePAS).</AbstractText In a double-blinded, randomized, and placebo-controlled design, 17 healthy participants received DAergic agents (100 mg L-Dopa for general DAergic enhancement, 10 mg bromocriptine for selective D2 receptor activation, or placebo) with different doses of the partial NMDA receptor agonist D-cycloserine (CYC; 50, 100, 200 mg, or placebo) and underwent ePAS. Cortical excitability was monitored via motor-evoked potentials induced by TMS over the left motor cortex for up to 2 hours post-stimulation.</AbstractText We did not find significant interactions between DAergic agents, CYC, and time across the entire sample, but significant group differences depending on sensitivity to ePAS. In high-sensitivity, but not low-sensitivity participants, ePAS induced LTP-like effects. CYC produced nonlinear, dose-dependent effects on plasticity in both groups. In the high-sensitivity group, LTP-like effects persisted under both DAergic agents, but were significantly reduced under bromocriptine. CYC had a nonlinear effect when combined with bromocriptine. In the low-sensitivity group, ePAS under DAergic agents did not induce LTP-like effects, and only additional intervention with medium-dose CYC restored facilitatory effects under L-Dopa.</AbstractText These findings suggest that optimal NMDA receptor activation is necessary for ePAS-induced neuroplasticity and that D2 receptor activity may reduce LTP-like effects by downregulating NMDA receptor function.</AbstractText
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Enhanced remote sensing image feature classification using STFF-PSPNet. Semantic segmentation of remotely sensed images is crucial for urban planning and change detection, yet faces issues like sample imbalance and low data quality. This study compiles a GF-2 image dataset and refines the PSPNet model. Weights of different class samples were adjusted to prioritize minority classes, mitigating sample imbalance's impact on classification. Data augmentation enhanced dataset quality. By replacing ResNet with the STFF network for better global feature extraction, adding attention modules, and using a combined loss function, the improved model shows excellent performance. It achieves a mAcc of 90.32 %, mIoU of 76.04 %, and a Dice coefficient of 85.15 %. Comparison with other models verifies its superiority, and tests on public datasets prove strong generalization, offering valuable insights for remote sensing image processing.</AbstractText
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Supervised Evaluation of Image Segmentation and Object Proposal Techniques. This paper tackles the supervised evaluation of image segmentation and object proposal algorithms. It surveys, structures, and deduplicates the measures used to compare both segmentation results and object proposals with a ground truth database; and proposes a new measure: the precision-recall for objects and parts. To compare the quality of these measures, eight state-of-the-art object proposal techniques are analyzed and two quantitative meta-measures involving nine state of the art segmentation methods are presented. The meta-measures consist in assuming some plausible hypotheses about the results and assessing how well each measure reflects these hypotheses. As a conclusion of the performed experiments, this paper proposes the tandem of precision-recall curves for boundaries and for objects-and-parts as the tool of choice for the supervised evaluation of image segmentation. We make the datasets and code of all the measures publicly available.</AbstractText
|
NMDA receptor involvement in dopaminergic modulation of neuroplasticity induced by paired associative stimulation. Dopamine (DA) modulates long-term potentiation (LTP)-like neuroplasticity. While particularly D1 and D2 receptors are thought to influence neuroplasticity through glutamatergic N-methyl-D-aspartate (NMDA) receptor and gamma-aminobutyric acid (GABA) modulation, the exact mechanisms are not completely clarified.</AbstractText We aimed to explore the relevance of NMDA receptor activity for DAergic modulation of focal LTP-like plasticity induced by excitatory paired associative stimulation (ePAS).</AbstractText In a double-blinded, randomized, and placebo-controlled design, 17 healthy participants received DAergic agents (100 mg L-Dopa for general DAergic enhancement, 10 mg bromocriptine for selective D2 receptor activation, or placebo) with different doses of the partial NMDA receptor agonist D-cycloserine (CYC; 50, 100, 200 mg, or placebo) and underwent ePAS. Cortical excitability was monitored via motor-evoked potentials induced by TMS over the left motor cortex for up to 2 hours post-stimulation.</AbstractText We did not find significant interactions between DAergic agents, CYC, and time across the entire sample, but significant group differences depending on sensitivity to ePAS. In high-sensitivity, but not low-sensitivity participants, ePAS induced LTP-like effects. CYC produced nonlinear, dose-dependent effects on plasticity in both groups. In the high-sensitivity group, LTP-like effects persisted under both DAergic agents, but were significantly reduced under bromocriptine. CYC had a nonlinear effect when combined with bromocriptine. In the low-sensitivity group, ePAS under DAergic agents did not induce LTP-like effects, and only additional intervention with medium-dose CYC restored facilitatory effects under L-Dopa.</AbstractText These findings suggest that optimal NMDA receptor activation is necessary for ePAS-induced neuroplasticity and that D2 receptor activity may reduce LTP-like effects by downregulating NMDA receptor function.</AbstractText
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23419808
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22112644
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23722210
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Your neighbors define your value: a study of spatial bias in number comparison.
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Verbal interference suppresses exact numerical representation.
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CLARITY for mapping the nervous system.
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Several chronometric biases in numerical cognition have informed our understanding of a mental number line (MNL). Complementing this approach, we investigated spatial performance in a magnitude comparison task. Participants located the larger or smaller number of a pair on a horizontal line representing the interval from 0 to 10. Experiments 1 and 2 used only number pairs one unit apart and found that digits were localized farther to the right with "select larger" instructions than with "select smaller" instructions. However, when numerical distance was varied (Experiment 3), digits were localized away from numerically near neighbors. This repulsion effect reveals context-specific distortions in number representation not previously noticed with chronometric measures.</AbstractText
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Language for number is an important case study of the relationship between language and cognition because the mechanisms of non-verbal numerical cognition are well-understood. When the Pirahã (an Amazonian hunter-gatherer tribe who have no exact number words) are tested in non-verbal numerical tasks, they are able to perform one-to-one matching tasks but make errors in more difficult tasks. Their pattern of errors suggests that they are using analog magnitude estimation, an evolutionarily- and developmentally-conserved mechanism for estimating quantities. Here we show that English-speaking participants rely on the same mechanisms when verbal number representations are unavailable due to verbal interference. Followup experiments demonstrate that the effects of verbal interference are primarily manifest during encoding of quantity information, and-using a new procedure for matching difficulty of interference tasks for individual participants-that the effects are restricted to verbal interference. These results are consistent with the hypothesis that number words are used online to encode, store, and manipulate numerical information. This linguistic strategy complements, rather than altering or replacing, non-verbal representations.</AbstractText
|
With potential relevance for brain-mapping work, hydrogel-based structures can now be built from within biological tissue to allow subsequent removal of lipids without mechanical disassembly of the tissue. This process creates a tissue-hydrogel hybrid that is physically stable, that preserves fine structure, proteins and nucleic acids, and that is permeable to both visible-spectrum photons and exogenous macromolecules. Here we highlight relevant challenges and opportunities of this approach, especially with regard to integration with complementary methodologies for brain-mapping studies.</AbstractText
|
Your neighbors define your value: a study of spatial bias in number comparison. Several chronometric biases in numerical cognition have informed our understanding of a mental number line (MNL). Complementing this approach, we investigated spatial performance in a magnitude comparison task. Participants located the larger or smaller number of a pair on a horizontal line representing the interval from 0 to 10. Experiments 1 and 2 used only number pairs one unit apart and found that digits were localized farther to the right with "select larger" instructions than with "select smaller" instructions. However, when numerical distance was varied (Experiment 3), digits were localized away from numerically near neighbors. This repulsion effect reveals context-specific distortions in number representation not previously noticed with chronometric measures.</AbstractText
|
Verbal interference suppresses exact numerical representation. Language for number is an important case study of the relationship between language and cognition because the mechanisms of non-verbal numerical cognition are well-understood. When the Pirahã (an Amazonian hunter-gatherer tribe who have no exact number words) are tested in non-verbal numerical tasks, they are able to perform one-to-one matching tasks but make errors in more difficult tasks. Their pattern of errors suggests that they are using analog magnitude estimation, an evolutionarily- and developmentally-conserved mechanism for estimating quantities. Here we show that English-speaking participants rely on the same mechanisms when verbal number representations are unavailable due to verbal interference. Followup experiments demonstrate that the effects of verbal interference are primarily manifest during encoding of quantity information, and-using a new procedure for matching difficulty of interference tasks for individual participants-that the effects are restricted to verbal interference. These results are consistent with the hypothesis that number words are used online to encode, store, and manipulate numerical information. This linguistic strategy complements, rather than altering or replacing, non-verbal representations.</AbstractText
|
CLARITY for mapping the nervous system. With potential relevance for brain-mapping work, hydrogel-based structures can now be built from within biological tissue to allow subsequent removal of lipids without mechanical disassembly of the tissue. This process creates a tissue-hydrogel hybrid that is physically stable, that preserves fine structure, proteins and nucleic acids, and that is permeable to both visible-spectrum photons and exogenous macromolecules. Here we highlight relevant challenges and opportunities of this approach, especially with regard to integration with complementary methodologies for brain-mapping studies.</AbstractText
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38605178
|
29146773
|
39635593
|
System-level time computation and representation in the suprachiasmatic nucleus revealed by large-scale calcium imaging and machine learning.
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Glyoxal as an alternative fixative to formaldehyde in immunostaining and super-resolution microscopy.
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Clinical team debriefing post-critical events: perceptions, benefits, and barriers among learners.
|
The suprachiasmatic nucleus (SCN) is the mammalian central circadian pacemaker with heterogeneous neurons acting in concert while each neuron harbors a self-sustained molecular clockwork. Nevertheless, how system-level SCN signals encode time of the day remains enigmatic. Here we show that population-level Ca<sup
|
Paraformaldehyde (PFA) is the most commonly used fixative for immunostaining of cells, but has been associated with various problems, ranging from loss of antigenicity to changes in morphology during fixation. We show here that the small dialdehyde glyoxal can successfully replace PFA Despite being less toxic than PFA, and, as most aldehydes, likely usable as a fixative, glyoxal has not yet been systematically tried in modern fluorescence microscopy. Here, we tested and optimized glyoxal fixation and surprisingly found it to be more efficient than PFA-based protocols. Glyoxal acted faster than PFA, cross-linked proteins more effectively, and improved the preservation of cellular morphology. We validated glyoxal fixation in multiple laboratories against different PFA-based protocols and confirmed that it enabled better immunostainings for a majority of the targets. Our data therefore support that glyoxal can be a valuable alternative to PFA for immunostaining.</AbstractText
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Clinical team debriefings (TD) following critical events are pivotal in promoting team learning and enhancing patient outcomes. Despite their importance, perceptions and practices surrounding these debriefings remain under-researched. The purpose of this study was to explore learners' perceptions and experiences regarding debriefing practices, investigate correlations or discrepancies within those perceptions and experiences, and identify recommendations and potential practice improvements for clinical educators.</AbstractText This was a cross-sectional anonymous survey of healthcare professionals, including medical students, medical residents, nursing students, and respiratory therapy students. The survey was sent to respiratory therapy programs, nursing programs, internal and emergency medicine and pediatric residency programs in southern California and Michigan. The variables surveyed included demographics, team debriefing experience, code experience, TD perceptions, emotional status, cognitive load, and the benefits and barriers of conducting post-code TD. Emotional status and cognitive load were assessed using validated surveys by Paas et al. and Barrett and Russell.</AbstractText Of the 184 participants, 56% (<i The results of this study show a relatively low TD occurrence despite the high value learners attribute to TD. Addressing this inconsistency requires structured approaches, dedicated time, and an understanding of barriers. Recognizing the significant cognitive and emotional loads on learners further accentuates the need for structured post-event debriefings. Addressing these challenges with multi-disciplinary participation can enhance debriefing outcomes.</AbstractText
|
System-level time computation and representation in the suprachiasmatic nucleus revealed by large-scale calcium imaging and machine learning. The suprachiasmatic nucleus (SCN) is the mammalian central circadian pacemaker with heterogeneous neurons acting in concert while each neuron harbors a self-sustained molecular clockwork. Nevertheless, how system-level SCN signals encode time of the day remains enigmatic. Here we show that population-level Ca<sup
|
Glyoxal as an alternative fixative to formaldehyde in immunostaining and super-resolution microscopy. Paraformaldehyde (PFA) is the most commonly used fixative for immunostaining of cells, but has been associated with various problems, ranging from loss of antigenicity to changes in morphology during fixation. We show here that the small dialdehyde glyoxal can successfully replace PFA Despite being less toxic than PFA, and, as most aldehydes, likely usable as a fixative, glyoxal has not yet been systematically tried in modern fluorescence microscopy. Here, we tested and optimized glyoxal fixation and surprisingly found it to be more efficient than PFA-based protocols. Glyoxal acted faster than PFA, cross-linked proteins more effectively, and improved the preservation of cellular morphology. We validated glyoxal fixation in multiple laboratories against different PFA-based protocols and confirmed that it enabled better immunostainings for a majority of the targets. Our data therefore support that glyoxal can be a valuable alternative to PFA for immunostaining.</AbstractText
|
Clinical team debriefing post-critical events: perceptions, benefits, and barriers among learners. Clinical team debriefings (TD) following critical events are pivotal in promoting team learning and enhancing patient outcomes. Despite their importance, perceptions and practices surrounding these debriefings remain under-researched. The purpose of this study was to explore learners' perceptions and experiences regarding debriefing practices, investigate correlations or discrepancies within those perceptions and experiences, and identify recommendations and potential practice improvements for clinical educators.</AbstractText This was a cross-sectional anonymous survey of healthcare professionals, including medical students, medical residents, nursing students, and respiratory therapy students. The survey was sent to respiratory therapy programs, nursing programs, internal and emergency medicine and pediatric residency programs in southern California and Michigan. The variables surveyed included demographics, team debriefing experience, code experience, TD perceptions, emotional status, cognitive load, and the benefits and barriers of conducting post-code TD. Emotional status and cognitive load were assessed using validated surveys by Paas et al. and Barrett and Russell.</AbstractText Of the 184 participants, 56% (<i The results of this study show a relatively low TD occurrence despite the high value learners attribute to TD. Addressing this inconsistency requires structured approaches, dedicated time, and an understanding of barriers. Recognizing the significant cognitive and emotional loads on learners further accentuates the need for structured post-event debriefings. Addressing these challenges with multi-disciplinary participation can enhance debriefing outcomes.</AbstractText
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34781680
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32488890
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33317317
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Novel Cyclic Endomorphin Analogues with Multiple Modifications and Oligoarginine Vector Exhibit Potent Antinociception with Reduced Opioid-like Side Effects.
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Brief Report: Relationship Between Cotinine Levels and Peripheral Endogenous Concentrations of Oxytocin, β-Endorphin, and Orexin in Individuals With Both Alcohol and Nicotine Use Disorders.
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Green Infrastructure and Health.
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Endomorphins (EMs) are potent pharmaceuticals for the treatment of pain. Herein, we investigated several novel EM analogues with multiple modifications and oligoarginine conjugation. Our results showed that analogues 1-6 behaved as potent μ-opioid agonists and enhanced stability and lipophilicity. Analogues 5 and 6 administered centrally and peripherally induced significant and prolonged antinociceptive effects in acute pain. Both analogues also produced long-acting antiallodynic effects against neuropathic and inflammatory pain. Furthermore, they showed a reduced acute antinociceptive tolerance. Analogue 6 decreased the extent of chronic antinociceptive tolerance, and analogue 5 exhibited no tolerance at the supraspinal level. Particularly, they displayed nontolerance-forming antinociception at the peripheral level. In addition, analogues 5 and 6 exhibited reduced or no opioid-like side effects on gastrointestinal transit, conditioned place preference (CPP), and motor impairment. The present investigation established that multiple modifications and oligoarginine-vector conjugation of EMs would be helpful in developing novel analgesics with fewer side effects.</AbstractText
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In this secondary analysis of a pilot clinical trial with individuals with alcohol and nicotine use disorders, we investigate the relationship between serum concentrations of oxytocin, β-endorphin, melatonin, α-melanocyte-stimulating hormone, substance P, and orexin, with objective biomarkers (salivary cotinine and serum γ-glutamyl transferase [GGT]) as well as with self-reported smoking and alcohol drinking.</AbstractText Biomarkers for a total of N = 19 participants were analyzed using multiplexed, competitive format immune-assay (peptides) and enzyme competitive immunoassay (saliva). A regression analysis using Pearson's correlation coefficient was utilized to determine correlations. We controlled for multiple comparisons, checked for collinearities, and ran two-sided statistical tests.</AbstractText We found significant positive correlations for cotinine and oxytocin (P = .002), β-endorphin (P = .008), and orexin (P < .001), but not for either GGT or self-reported smoking or alcohol drinking.</AbstractText These preliminary results suggest a relationship between cotinine and oxytocin, β-endorphin, and orexin, which opens up new potential hypotheses on the potential role of these endocrine pathways in tobacco smokers. (Am J Addict 2021;30:88-91).</AbstractText
|
The health benefits of green space are well known, but the health effects of green infrastructure less so. Green infrastructure goes well beyond the presence of green space and refers more to a strategically planned network of natural and seminatural areas, with other environmental features designed and managed to deliver a wide range of ecosystem services and possibly to improve human health. In this narrative review, we found that small green infrastructure, such as green roofs and walls, has the potential to mitigate urban flooding, attenuate indoor temperatures and heat islands, improve air quality, and muffle noise, among other benefits, but these effects have not been linked directly to health. Larger green infrastructure has been associated with reduced temperatures, air pollution, and crimes and violence, but less so with health, although some evidence suggests that it may be beneficial for health (e.g., good health, decreased mortality). Finally, parks and street trees show many health benefits, but it is not clear if they can always be considered green infrastructure.</AbstractText
|
Novel Cyclic Endomorphin Analogues with Multiple Modifications and Oligoarginine Vector Exhibit Potent Antinociception with Reduced Opioid-like Side Effects. Endomorphins (EMs) are potent pharmaceuticals for the treatment of pain. Herein, we investigated several novel EM analogues with multiple modifications and oligoarginine conjugation. Our results showed that analogues 1-6 behaved as potent μ-opioid agonists and enhanced stability and lipophilicity. Analogues 5 and 6 administered centrally and peripherally induced significant and prolonged antinociceptive effects in acute pain. Both analogues also produced long-acting antiallodynic effects against neuropathic and inflammatory pain. Furthermore, they showed a reduced acute antinociceptive tolerance. Analogue 6 decreased the extent of chronic antinociceptive tolerance, and analogue 5 exhibited no tolerance at the supraspinal level. Particularly, they displayed nontolerance-forming antinociception at the peripheral level. In addition, analogues 5 and 6 exhibited reduced or no opioid-like side effects on gastrointestinal transit, conditioned place preference (CPP), and motor impairment. The present investigation established that multiple modifications and oligoarginine-vector conjugation of EMs would be helpful in developing novel analgesics with fewer side effects.</AbstractText
|
Brief Report: Relationship Between Cotinine Levels and Peripheral Endogenous Concentrations of Oxytocin, β-Endorphin, and Orexin in Individuals With Both Alcohol and Nicotine Use Disorders. In this secondary analysis of a pilot clinical trial with individuals with alcohol and nicotine use disorders, we investigate the relationship between serum concentrations of oxytocin, β-endorphin, melatonin, α-melanocyte-stimulating hormone, substance P, and orexin, with objective biomarkers (salivary cotinine and serum γ-glutamyl transferase [GGT]) as well as with self-reported smoking and alcohol drinking.</AbstractText Biomarkers for a total of N = 19 participants were analyzed using multiplexed, competitive format immune-assay (peptides) and enzyme competitive immunoassay (saliva). A regression analysis using Pearson's correlation coefficient was utilized to determine correlations. We controlled for multiple comparisons, checked for collinearities, and ran two-sided statistical tests.</AbstractText We found significant positive correlations for cotinine and oxytocin (P = .002), β-endorphin (P = .008), and orexin (P < .001), but not for either GGT or self-reported smoking or alcohol drinking.</AbstractText These preliminary results suggest a relationship between cotinine and oxytocin, β-endorphin, and orexin, which opens up new potential hypotheses on the potential role of these endocrine pathways in tobacco smokers. (Am J Addict 2021;30:88-91).</AbstractText
|
Green Infrastructure and Health. The health benefits of green space are well known, but the health effects of green infrastructure less so. Green infrastructure goes well beyond the presence of green space and refers more to a strategically planned network of natural and seminatural areas, with other environmental features designed and managed to deliver a wide range of ecosystem services and possibly to improve human health. In this narrative review, we found that small green infrastructure, such as green roofs and walls, has the potential to mitigate urban flooding, attenuate indoor temperatures and heat islands, improve air quality, and muffle noise, among other benefits, but these effects have not been linked directly to health. Larger green infrastructure has been associated with reduced temperatures, air pollution, and crimes and violence, but less so with health, although some evidence suggests that it may be beneficial for health (e.g., good health, decreased mortality). Finally, parks and street trees show many health benefits, but it is not clear if they can always be considered green infrastructure.</AbstractText
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40594435
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32726254
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40469027
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Enhanced schizophrenia detection using multichannel EEG and CAOA-RST-based feature selection.
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Current Understanding of the Neurobiology of Agitation.
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Facile Ag(+)-assisted bonding strategy to build a low-defect hybrid layer with intrinsic antibacterial and enzymolysis inhibitory properties.
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Schizophrenia is a mental disorder characterized by hallucinations, delusions, disorganized thinking and behavior, and inappropriate affect. Early and accurate diagnosis of schizophrenia remains a challenge due to the disorder's complex nature and the limitations of state-of-the-art techniques. It is evident from the literature that electroencephalogram (EEG) signals provide valuable insights into brain activity, but their high dimensionality and complexity pose remain key challenges. Thus, our research introduces a novel approach by integrating the multichannel EGG, Crossover-Boosted Archimedes Optimization Algorithm (CAOA), and Rough Set Theory (RST) for schizophrenia detection. It is a four-stage model. In the first stage, Raw EGG data is collected. The data is passed to the next stage, which is called data preprocessing. This is used for artifact removal, band-pass filtering, and data normalization. The preprocessed data passed to the next stage. In the feature extraction stage, feature selection is performed using CAOA. In addition, classification is performed using a Support Vector Machine (SVM) based on features extracted through Multivariate Empirical Mode Function (MEMF) and entropy measures. The data interpretation stage displays the results to the end user using the data interpretation stage. We experimented and tested our proposed model using real EEG datasets. The simulation results prove that the proposed model achieved an average accuracy of 94.9%, sensitivity of 93.9%, specificity of 96.4%, and precision of 92.7%. Thus, our proposed model demonstrates significant improvements over state-of-the-art methods. In addition, the integration of CAOA and RST effectively addresses the challenges of high-dimensional EEG data, helps optimize the feature selection process, and increases accuracy. In future work, we suggest incorporating large-size datasets that include more diverse patient groups and refining the model with advanced machine-learning models and techniques.</AbstractText
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Managing agitation in the clinical setting is a challenge that many practitioners face regularly. Our evolving understanding of the etiological factors involved in aggressive acts has better informed our interventions through pharmacologic and behavioral strategies. This paper reviews the literature on the neurobiological underpinnings of aggressive behaviors, linking psychopathology with proposed mechanisms of action of psychiatric medications shown to be effective in mitigating agitation.</AbstractText We performed a review of the extant literature using PubMed as a primary database. Investigation focused on neurobiology of agitation and its relation to the current evidence base for particular interventions.</AbstractText There are well-established pathways that can lead to increased autonomic response and the potential for violence. Psychopathology and substance-induced perceptual distortions may lead to magnification and overestimation of environmental threat, heightening the potential for aggression. Additional challenges have arisen with the advent of several novel drugs of abuse, many of which lead to atypical clinical presentations and which can elude standard drug screens. Our interventions still lean on the evidence base found in Project BETA (Best Practices in Evaluation and Treatment of Agitation). Although not a new drug and not included in the Project BETA guidelines, ketamine and its use are also discussed, given its unique pharmacology and potential benefits when other protocoled interventions have failed.</AbstractText Aggression can occur due to manifold reasons in the clinical setting. Having an informed understanding of the possible determinants of agitation can help with more tailored responses to individual patients, limiting the unnecessary use of medications or of interventions that could be deemed forceful.</AbstractText
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As the most widely used material for dental tissue repair, dental resin composites face durability challenges, and their longevity critically depends on the hybrid layer's integrity. Incomplete adhesive infiltration within demineralized dentin matrix (DDM) creates structural defects in this layer, rendering it vulnerable to stress, enzymatic degradation, and bacterial invasion. These factors contribute to secondary caries, the predominant complication of resin-based restorations. Enhancing adhesive infiltration and the hybrid layer's antibacterial capacity is thus pivotal to extending the restoration lifespan. Previous studies have revealed that strong metal ion chelation can release confined water to facilitate hydrophobic monomer infiltration, significantly improving dentin bonding efficacy and durability. Therefore, in this study, leveraging the dual advantages of Ag<sup
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Enhanced schizophrenia detection using multichannel EEG and CAOA-RST-based feature selection. Schizophrenia is a mental disorder characterized by hallucinations, delusions, disorganized thinking and behavior, and inappropriate affect. Early and accurate diagnosis of schizophrenia remains a challenge due to the disorder's complex nature and the limitations of state-of-the-art techniques. It is evident from the literature that electroencephalogram (EEG) signals provide valuable insights into brain activity, but their high dimensionality and complexity pose remain key challenges. Thus, our research introduces a novel approach by integrating the multichannel EGG, Crossover-Boosted Archimedes Optimization Algorithm (CAOA), and Rough Set Theory (RST) for schizophrenia detection. It is a four-stage model. In the first stage, Raw EGG data is collected. The data is passed to the next stage, which is called data preprocessing. This is used for artifact removal, band-pass filtering, and data normalization. The preprocessed data passed to the next stage. In the feature extraction stage, feature selection is performed using CAOA. In addition, classification is performed using a Support Vector Machine (SVM) based on features extracted through Multivariate Empirical Mode Function (MEMF) and entropy measures. The data interpretation stage displays the results to the end user using the data interpretation stage. We experimented and tested our proposed model using real EEG datasets. The simulation results prove that the proposed model achieved an average accuracy of 94.9%, sensitivity of 93.9%, specificity of 96.4%, and precision of 92.7%. Thus, our proposed model demonstrates significant improvements over state-of-the-art methods. In addition, the integration of CAOA and RST effectively addresses the challenges of high-dimensional EEG data, helps optimize the feature selection process, and increases accuracy. In future work, we suggest incorporating large-size datasets that include more diverse patient groups and refining the model with advanced machine-learning models and techniques.</AbstractText
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Current Understanding of the Neurobiology of Agitation. Managing agitation in the clinical setting is a challenge that many practitioners face regularly. Our evolving understanding of the etiological factors involved in aggressive acts has better informed our interventions through pharmacologic and behavioral strategies. This paper reviews the literature on the neurobiological underpinnings of aggressive behaviors, linking psychopathology with proposed mechanisms of action of psychiatric medications shown to be effective in mitigating agitation.</AbstractText We performed a review of the extant literature using PubMed as a primary database. Investigation focused on neurobiology of agitation and its relation to the current evidence base for particular interventions.</AbstractText There are well-established pathways that can lead to increased autonomic response and the potential for violence. Psychopathology and substance-induced perceptual distortions may lead to magnification and overestimation of environmental threat, heightening the potential for aggression. Additional challenges have arisen with the advent of several novel drugs of abuse, many of which lead to atypical clinical presentations and which can elude standard drug screens. Our interventions still lean on the evidence base found in Project BETA (Best Practices in Evaluation and Treatment of Agitation). Although not a new drug and not included in the Project BETA guidelines, ketamine and its use are also discussed, given its unique pharmacology and potential benefits when other protocoled interventions have failed.</AbstractText Aggression can occur due to manifold reasons in the clinical setting. Having an informed understanding of the possible determinants of agitation can help with more tailored responses to individual patients, limiting the unnecessary use of medications or of interventions that could be deemed forceful.</AbstractText
|
Facile Ag(+)-assisted bonding strategy to build a low-defect hybrid layer with intrinsic antibacterial and enzymolysis inhibitory properties. As the most widely used material for dental tissue repair, dental resin composites face durability challenges, and their longevity critically depends on the hybrid layer's integrity. Incomplete adhesive infiltration within demineralized dentin matrix (DDM) creates structural defects in this layer, rendering it vulnerable to stress, enzymatic degradation, and bacterial invasion. These factors contribute to secondary caries, the predominant complication of resin-based restorations. Enhancing adhesive infiltration and the hybrid layer's antibacterial capacity is thus pivotal to extending the restoration lifespan. Previous studies have revealed that strong metal ion chelation can release confined water to facilitate hydrophobic monomer infiltration, significantly improving dentin bonding efficacy and durability. Therefore, in this study, leveraging the dual advantages of Ag<sup
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38555791
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24179289
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39401901
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Impaired glymphatic clearance in multiple system atrophy: A diffusion spectrum imaging study.
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Antidepressants and REM sleep behavior disorder: isolated side effect or neurodegenerative signal?
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Imaging-based chemogenetics for dissecting neural circuits in nonhuman primates.
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Impaired α-synuclein clearance is pivotal in the pathogenesis of neurodegenerative diseases. We evaluated glymphatic clearance in multiple system atrophy (MSA) patients using advanced imaging.</AbstractText Forty-four MSA patients (11 with MSA-parkinsonian type [MSA-P] and 33 with MSA-cerebellar type [MSA-C]) and 30 healthy controls were studied using diffusion spectrum magnetic resonance imaging (DSI-MRI). Diffusivities were measured along the x-, y-, and z-axes to calculate the Analysis Along the Perivascular Space (ALPS) index. Comparisons of the ALPS index were conducted between MSA patients and controls and among MSA subtypes. The ALPS index correlation with the Unified Multiple System Atrophy Rating Scale (UMSARS) scores was also analyzed.</AbstractText The ALPS index differed significantly between patients with MSA and healthy controls, with lower values observed in the former (1.46 ± 0.17 versus1.63 ± 0.12, p < 0.001). Both MSA-P and MSA-C patients had lower ALPS-index (1.40 ± 0.13, p < 0.001; 1.47 ± 0.18, p = 0.003, respectively), but there was no significant difference between the two (p = 0.22). No correlation was found between the ALPS index and clinical scores for UMASRS I (r = -0.08, p = 0.61), UMASRS II (r = -0.04, p = 0.81), or UMASRS I + II (r = -0.05, p = 0.74).</AbstractText MSA patients show reduced glymphatic clearance as measured by the ALPS index, underscoring the utility of this imaging method in neurodegenerative disease research.</AbstractText
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Antidepressants, among the most commonly prescribed medications, trigger symptoms of REM sleep behavior disorder (RBD) in up to 6% of users. Idiopathic RBD is a very strong prodromal marker of Parkinson disease and other synuclein-mediated neurodegenerative syndromes. It is therefore critically important to understand whether antidepressant-associated RBD is an independent pharmacologic syndrome or a sign of possible prodromal neurodegeneration.</AbstractText Prospective cohort study.</AbstractText Tertiary sleep disorders center.</AbstractText 100 patients with idiopathic RBD, all with diagnosis confirmed on polysomnography, stratified to baseline antidepressant use, with 45 matched controls.</AbstractText Of 100 patients, 27 were taking antidepressants. Compared to matched controls, RBD patients taking antidepressants demonstrated significant abnormalities of 12/14 neurodegenerative markers tested, including olfaction (P = 0.007), color vision (P = 0.004), Unified Parkinson Disease Rating Scale II and III (P < 0.001 and 0.007), timed up-and-go (P = 0.003), alternate tap test (P = 0.002), Purdue Pegboard (P = 0.007), systolic blood pressure drop (P = 0.029), erectile dysfunction (P = 0.002), constipation (P = 0.003), depression indices (P < 0.001), and prevalence of mild cognitive impairment (13% vs. 60%, P < 0.001). All these abnormalities were indistinguishable in severity from RBD patients not taking antidepressants. However, on prospective follow-up, RBD patients taking antidepressants had a lower risk of developing neurodegenerative disease than those without antidepressant use (5-year risk = 22% vs. 59%, RR = 0.22, 95%CI = 0.06, 0.74).</AbstractText Although patients with antidepressant-associated RBD have a lower risk of neurodegeneration than patients with "purely-idiopathic" RBD, markers of prodromal neurodegeneration are still clearly present. Development of RBD with antidepressants can be an early signal of an underlying neurodegenerative disease.</AbstractText
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Nonhuman primates, particularly macaque and marmoset monkeys, serve as invaluable models for studying complex brain functions and behavior. However, the lack of suitable genetic neuromodulation tools has constrained research at the network level. This review examines the application of a chemogenetic technology, specifically, designer receptors exclusively activated by designer drugs (DREADDs), to nonhuman primates. DREADDs offer a means of reversibly controlling neuronal activity within a specific cell type or neural pathway, effectively targeting multiple brain regions simultaneously. The combination of DREADDs with imaging techniques, such as positron emission tomography and magnetic resonance imaging, has significantly enhanced nonhuman primate research, facilitating the precise visualization and manipulation of specific brain circuits and enabling the detailed monitoring of changes in network activity, which can then be correlated with altered behavior. This review outlines these technological advances and considers their potential for enhancing our understanding of primate brain circuit function and developing novel therapeutic approaches for treating brain diseases.</AbstractText
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Impaired glymphatic clearance in multiple system atrophy: A diffusion spectrum imaging study. Impaired α-synuclein clearance is pivotal in the pathogenesis of neurodegenerative diseases. We evaluated glymphatic clearance in multiple system atrophy (MSA) patients using advanced imaging.</AbstractText Forty-four MSA patients (11 with MSA-parkinsonian type [MSA-P] and 33 with MSA-cerebellar type [MSA-C]) and 30 healthy controls were studied using diffusion spectrum magnetic resonance imaging (DSI-MRI). Diffusivities were measured along the x-, y-, and z-axes to calculate the Analysis Along the Perivascular Space (ALPS) index. Comparisons of the ALPS index were conducted between MSA patients and controls and among MSA subtypes. The ALPS index correlation with the Unified Multiple System Atrophy Rating Scale (UMSARS) scores was also analyzed.</AbstractText The ALPS index differed significantly between patients with MSA and healthy controls, with lower values observed in the former (1.46 ± 0.17 versus1.63 ± 0.12, p < 0.001). Both MSA-P and MSA-C patients had lower ALPS-index (1.40 ± 0.13, p < 0.001; 1.47 ± 0.18, p = 0.003, respectively), but there was no significant difference between the two (p = 0.22). No correlation was found between the ALPS index and clinical scores for UMASRS I (r = -0.08, p = 0.61), UMASRS II (r = -0.04, p = 0.81), or UMASRS I + II (r = -0.05, p = 0.74).</AbstractText MSA patients show reduced glymphatic clearance as measured by the ALPS index, underscoring the utility of this imaging method in neurodegenerative disease research.</AbstractText
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Antidepressants and REM sleep behavior disorder: isolated side effect or neurodegenerative signal? Antidepressants, among the most commonly prescribed medications, trigger symptoms of REM sleep behavior disorder (RBD) in up to 6% of users. Idiopathic RBD is a very strong prodromal marker of Parkinson disease and other synuclein-mediated neurodegenerative syndromes. It is therefore critically important to understand whether antidepressant-associated RBD is an independent pharmacologic syndrome or a sign of possible prodromal neurodegeneration.</AbstractText Prospective cohort study.</AbstractText Tertiary sleep disorders center.</AbstractText 100 patients with idiopathic RBD, all with diagnosis confirmed on polysomnography, stratified to baseline antidepressant use, with 45 matched controls.</AbstractText Of 100 patients, 27 were taking antidepressants. Compared to matched controls, RBD patients taking antidepressants demonstrated significant abnormalities of 12/14 neurodegenerative markers tested, including olfaction (P = 0.007), color vision (P = 0.004), Unified Parkinson Disease Rating Scale II and III (P < 0.001 and 0.007), timed up-and-go (P = 0.003), alternate tap test (P = 0.002), Purdue Pegboard (P = 0.007), systolic blood pressure drop (P = 0.029), erectile dysfunction (P = 0.002), constipation (P = 0.003), depression indices (P < 0.001), and prevalence of mild cognitive impairment (13% vs. 60%, P < 0.001). All these abnormalities were indistinguishable in severity from RBD patients not taking antidepressants. However, on prospective follow-up, RBD patients taking antidepressants had a lower risk of developing neurodegenerative disease than those without antidepressant use (5-year risk = 22% vs. 59%, RR = 0.22, 95%CI = 0.06, 0.74).</AbstractText Although patients with antidepressant-associated RBD have a lower risk of neurodegeneration than patients with "purely-idiopathic" RBD, markers of prodromal neurodegeneration are still clearly present. Development of RBD with antidepressants can be an early signal of an underlying neurodegenerative disease.</AbstractText
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Imaging-based chemogenetics for dissecting neural circuits in nonhuman primates. Nonhuman primates, particularly macaque and marmoset monkeys, serve as invaluable models for studying complex brain functions and behavior. However, the lack of suitable genetic neuromodulation tools has constrained research at the network level. This review examines the application of a chemogenetic technology, specifically, designer receptors exclusively activated by designer drugs (DREADDs), to nonhuman primates. DREADDs offer a means of reversibly controlling neuronal activity within a specific cell type or neural pathway, effectively targeting multiple brain regions simultaneously. The combination of DREADDs with imaging techniques, such as positron emission tomography and magnetic resonance imaging, has significantly enhanced nonhuman primate research, facilitating the precise visualization and manipulation of specific brain circuits and enabling the detailed monitoring of changes in network activity, which can then be correlated with altered behavior. This review outlines these technological advances and considers their potential for enhancing our understanding of primate brain circuit function and developing novel therapeutic approaches for treating brain diseases.</AbstractText
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40752470
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18074326
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39983627
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Psychometric performance of the Intuitive Eating Scale-2 in females with anorexia nervosa: An examination of factor structure and Item Response Theory.
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The patient's account of relapse and recovery in anorexia nervosa: a qualitative study.
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White matter microstructural subgroups of children with ADHD: Similar clinical presentations and distinct neuropsychological profiles.
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The Intuitive Eating Scale-2 (IES-2) is widely used to assess intuitive eating (IE) behaviors, attitudes, and beliefs, yet its application in anorexia nervosa (AN) remains unclear. Given the disrupted interoceptive awareness and heightened cognitive control over eating in AN, it is less certain how IE constructs apply during acute stages of this disorder. This study evaluated the factor structure and item-level performance of the IES-2 in a clinical sample of 150 adolescent and adult females diagnosed with AN, upon admission to a residential treatment facility. Confirmatory Factor Analysis supported a first-order factor structure, suggesting that the four subscales should be treated independently rather than combined into a total IE score, contradicting the original scoring approach. Item 12 ("I am able to cope with negative emotions (e.g., anxiety, sadness) without turning to food for comfort") demonstrated poor factor loadings on the Eating for Physical Rather than Emotional Reasons subscale. Item Response Theory further indicated that item 12 had poor discrimination across levels of the latent trait, supporting its removal. These findings indicate that certain subscales, particularly those assessing emotional eating, may not capture relevant eating behaviors in adolescents and adults with AN. We recommend scoring IES-2 subscales separately and reconsidering the inclusion of item 12 to enhance measurement accuracy in AN. Refining the IES-2 for clinical ED populations may improve its utility in tracking recovery and treatment outcomes.</AbstractText
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The purpose of this study was to explore the subjective accounts of weight-recovered female patients, who met DSMIV criteria for anorexia nervosa (AN), regarding their views of their illness following weight restoration.</AbstractText Qualitative semi-structured interviews were administered to 15 participants to ascertain their perspective of the factors that either contributed to their maintaining a healthy weight, or the factors involved in their having relapsed over the follow-up period.</AbstractText Qualitative analyses revealed six core categories: internal motivation to change, recovery as a work in progress, the perceived value of the treatment experience, developing supportive relationships, awareness and tolerance of negative emotion and self-validation.</AbstractText This study provides valuable information about the way in which AN patients experience their illness and highlight the factors that help or hinder recovery. These findings may help enhance relapse prevention programs and potentially enhance our ability to identify and target those individuals at the greatest risk of relapsing.</AbstractText
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The current study aimed to explore whether it is possible to subgroup ADHD using white matter microstructural characteristics.</AbstractText In a cohort comprising subjects with ADHD (n = 227) (all aged 6-15 years) and their healthy counterparts (n = 89), the Diffusion Tensor Imaging (DTI) was used to assess fractional anisotropy (FA) in several regions: the body, genu, and splenium of corpus callosum (CC), the bilateral anterior corona radiata, the bilateral internal capsule, and the bilateral superior longitudinal fasciculus. Clinical and neuropsychological profiles were assessed using the ADHD rating scale (ADHD-RS), the Child Behavior Checklist (CBCL), the Behavior Rating Inventory of Executive Function (BRIEF), and CANTAB. Responses to methylphenidate of some of the subjects with ADHD (n = 52) were documented in the Hospital Information System. Cluster analysis was applied to subgroup the ADHD participants. Subsequent between-group comparisons were analyzed using ANCOVA and logistic regression, controlling for age and sex.</AbstractText Cluster analysis stratified the ADHD subjects into two subgroups. Subsequent analysis revealed that there are no significant differences in those behavioral measures from ADHD-RS, CBCL, or BRIEF between the two ADHD subgroups (all P > .05). Compared with the control group, Cluster-2 exhibited lower FA and performed worse on processing speed, while Cluster-1 had higher FA but showed poorer response inhibition and sustained attention. Additionally, Cluster-2 exhibited a superior response to methylphenidate treatment compared to Cluster-1.</AbstractText Although with similar clinical features, ADHD participants could be stratified by their microstructural characteristics, which were further linked to distinct cognitive dysfunction and responses to methylphenidate.</AbstractText
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Psychometric performance of the Intuitive Eating Scale-2 in females with anorexia nervosa: An examination of factor structure and Item Response Theory. The Intuitive Eating Scale-2 (IES-2) is widely used to assess intuitive eating (IE) behaviors, attitudes, and beliefs, yet its application in anorexia nervosa (AN) remains unclear. Given the disrupted interoceptive awareness and heightened cognitive control over eating in AN, it is less certain how IE constructs apply during acute stages of this disorder. This study evaluated the factor structure and item-level performance of the IES-2 in a clinical sample of 150 adolescent and adult females diagnosed with AN, upon admission to a residential treatment facility. Confirmatory Factor Analysis supported a first-order factor structure, suggesting that the four subscales should be treated independently rather than combined into a total IE score, contradicting the original scoring approach. Item 12 ("I am able to cope with negative emotions (e.g., anxiety, sadness) without turning to food for comfort") demonstrated poor factor loadings on the Eating for Physical Rather than Emotional Reasons subscale. Item Response Theory further indicated that item 12 had poor discrimination across levels of the latent trait, supporting its removal. These findings indicate that certain subscales, particularly those assessing emotional eating, may not capture relevant eating behaviors in adolescents and adults with AN. We recommend scoring IES-2 subscales separately and reconsidering the inclusion of item 12 to enhance measurement accuracy in AN. Refining the IES-2 for clinical ED populations may improve its utility in tracking recovery and treatment outcomes.</AbstractText
|
The patient's account of relapse and recovery in anorexia nervosa: a qualitative study. The purpose of this study was to explore the subjective accounts of weight-recovered female patients, who met DSMIV criteria for anorexia nervosa (AN), regarding their views of their illness following weight restoration.</AbstractText Qualitative semi-structured interviews were administered to 15 participants to ascertain their perspective of the factors that either contributed to their maintaining a healthy weight, or the factors involved in their having relapsed over the follow-up period.</AbstractText Qualitative analyses revealed six core categories: internal motivation to change, recovery as a work in progress, the perceived value of the treatment experience, developing supportive relationships, awareness and tolerance of negative emotion and self-validation.</AbstractText This study provides valuable information about the way in which AN patients experience their illness and highlight the factors that help or hinder recovery. These findings may help enhance relapse prevention programs and potentially enhance our ability to identify and target those individuals at the greatest risk of relapsing.</AbstractText
|
White matter microstructural subgroups of children with ADHD: Similar clinical presentations and distinct neuropsychological profiles. The current study aimed to explore whether it is possible to subgroup ADHD using white matter microstructural characteristics.</AbstractText In a cohort comprising subjects with ADHD (n = 227) (all aged 6-15 years) and their healthy counterparts (n = 89), the Diffusion Tensor Imaging (DTI) was used to assess fractional anisotropy (FA) in several regions: the body, genu, and splenium of corpus callosum (CC), the bilateral anterior corona radiata, the bilateral internal capsule, and the bilateral superior longitudinal fasciculus. Clinical and neuropsychological profiles were assessed using the ADHD rating scale (ADHD-RS), the Child Behavior Checklist (CBCL), the Behavior Rating Inventory of Executive Function (BRIEF), and CANTAB. Responses to methylphenidate of some of the subjects with ADHD (n = 52) were documented in the Hospital Information System. Cluster analysis was applied to subgroup the ADHD participants. Subsequent between-group comparisons were analyzed using ANCOVA and logistic regression, controlling for age and sex.</AbstractText Cluster analysis stratified the ADHD subjects into two subgroups. Subsequent analysis revealed that there are no significant differences in those behavioral measures from ADHD-RS, CBCL, or BRIEF between the two ADHD subgroups (all P > .05). Compared with the control group, Cluster-2 exhibited lower FA and performed worse on processing speed, while Cluster-1 had higher FA but showed poorer response inhibition and sustained attention. Additionally, Cluster-2 exhibited a superior response to methylphenidate treatment compared to Cluster-1.</AbstractText Although with similar clinical features, ADHD participants could be stratified by their microstructural characteristics, which were further linked to distinct cognitive dysfunction and responses to methylphenidate.</AbstractText
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21603086
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16398417
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19004526
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A Wire Crossed-Loop-Resonator for Rapid Scan EPR.
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Rapid polarizing field cycling in magnetic resonance imaging.
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Age-related changes in neural activity associated with familiarity, recollection and false recognition.
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A crossed-loop (orthogonal mode) resonator (CLR) was constructed of fine wire to achieve design goals for rapid scan in vivo EPR imaging at VHF frequencies (in practice, near 250 MHz). This application requires the resonator to have a very open design to facilitate access to the animal for physiological support during the image acquisition. The rapid scan experiment uses large amplitude magnetic field scans, and sufficiently large resonator and detection bandwidths to record the rapidly-changing signal response. Rapid-scan EPR is sensitive to RF/microwave source noise and to baseline changes that are coherent with the field scan. The sensitivity to source noise is a primary incentive for using a CLR to isolate the detected signal from the RF source noise. Isolation from source noise of 44 and 47 dB was achieved in two resonator designs. Prior results showed that eddy currents contribute to background problems in rapid scan EPR, so the CLR design had to minimize conducting metal components. Using fine (AWG 38) wire for the resonators decreased eddy currents and lowered the resonator Q, thus providing larger resonator bandwidth. Mechanical resonances at specific scan frequencies are a major contributor to rapid scan backgrounds.</AbstractText
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We describe the electronics for controlling the independently pulsed polarizing coil in a prepolarized magnetic resonance imaging (PMRI) system and demonstrate performance with free induction decay measurements and in vivo imaging experiments. A PMRI scanner retains all the benefits of acquiring MRI data at low field, but with the higher signal of the polarizing field. Rapidly and efficiently ramping the polarizing coil without disturbing the data acquisition is one of the major challenges of PMRI. With our modular hardware design, we successfully ramp the 0.4-T polarizing coil of a wrist-sized PMRI scanner at up to 100 T/s without causing image artifacts or otherwise degrading data acquisition.</AbstractText
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Older adults often exhibit elevated false recognition for events that never occurred, while simultaneously experiencing difficulty in recognizing events that actually occurred. It has been proposed that reduced recollection in conjunction with an over-reliance on familiarity may contribute to this pattern of results. This explanation is somewhat inconsistent, however, with recent evidence suggesting that familiarity and associated neural activity are reduced in healthy aging. Alternatively, given that illusory memory may be based, in part, on veridical memory processes (recollection/familiarity), one might predict that older adults exhibit enhanced false alarm rates because the neural signatures associated with true recognition (hits) and false recognition (false alarms) are less distinguishable in old than in young adults. Here, we used event-related fMRI to measure the effects of aging on neural activity associated with recollection, familiarity and familiarity-based false alarms for objects in young and older adults. Compared to young adults, older adults exhibited elevated false alarm rates and impaired behavioral indices of recollection and familiarity. Imaging data showed that older adults exhibited reduced recollection effects in the left parietoccipital cortex. Furthermore, while similar regions in frontal, parietal, lateral and inferior temporal cortices contributed to familiarity-based true and false recognition, reduced familiarity-related activity in frontal and inferior temporal regions in the older adults resulted in decreased differentiation between true and false recognition effects in this group. Our results suggest that reductions in neural activity associated with both recollection and familiarity for studied items may contribute to elevated false recognition in older adults, via reduced differentiation between the neural activity associated with true and false memory.</AbstractText
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A Wire Crossed-Loop-Resonator for Rapid Scan EPR. A crossed-loop (orthogonal mode) resonator (CLR) was constructed of fine wire to achieve design goals for rapid scan in vivo EPR imaging at VHF frequencies (in practice, near 250 MHz). This application requires the resonator to have a very open design to facilitate access to the animal for physiological support during the image acquisition. The rapid scan experiment uses large amplitude magnetic field scans, and sufficiently large resonator and detection bandwidths to record the rapidly-changing signal response. Rapid-scan EPR is sensitive to RF/microwave source noise and to baseline changes that are coherent with the field scan. The sensitivity to source noise is a primary incentive for using a CLR to isolate the detected signal from the RF source noise. Isolation from source noise of 44 and 47 dB was achieved in two resonator designs. Prior results showed that eddy currents contribute to background problems in rapid scan EPR, so the CLR design had to minimize conducting metal components. Using fine (AWG 38) wire for the resonators decreased eddy currents and lowered the resonator Q, thus providing larger resonator bandwidth. Mechanical resonances at specific scan frequencies are a major contributor to rapid scan backgrounds.</AbstractText
|
Rapid polarizing field cycling in magnetic resonance imaging. We describe the electronics for controlling the independently pulsed polarizing coil in a prepolarized magnetic resonance imaging (PMRI) system and demonstrate performance with free induction decay measurements and in vivo imaging experiments. A PMRI scanner retains all the benefits of acquiring MRI data at low field, but with the higher signal of the polarizing field. Rapidly and efficiently ramping the polarizing coil without disturbing the data acquisition is one of the major challenges of PMRI. With our modular hardware design, we successfully ramp the 0.4-T polarizing coil of a wrist-sized PMRI scanner at up to 100 T/s without causing image artifacts or otherwise degrading data acquisition.</AbstractText
|
Age-related changes in neural activity associated with familiarity, recollection and false recognition. Older adults often exhibit elevated false recognition for events that never occurred, while simultaneously experiencing difficulty in recognizing events that actually occurred. It has been proposed that reduced recollection in conjunction with an over-reliance on familiarity may contribute to this pattern of results. This explanation is somewhat inconsistent, however, with recent evidence suggesting that familiarity and associated neural activity are reduced in healthy aging. Alternatively, given that illusory memory may be based, in part, on veridical memory processes (recollection/familiarity), one might predict that older adults exhibit enhanced false alarm rates because the neural signatures associated with true recognition (hits) and false recognition (false alarms) are less distinguishable in old than in young adults. Here, we used event-related fMRI to measure the effects of aging on neural activity associated with recollection, familiarity and familiarity-based false alarms for objects in young and older adults. Compared to young adults, older adults exhibited elevated false alarm rates and impaired behavioral indices of recollection and familiarity. Imaging data showed that older adults exhibited reduced recollection effects in the left parietoccipital cortex. Furthermore, while similar regions in frontal, parietal, lateral and inferior temporal cortices contributed to familiarity-based true and false recognition, reduced familiarity-related activity in frontal and inferior temporal regions in the older adults resulted in decreased differentiation between true and false recognition effects in this group. Our results suggest that reductions in neural activity associated with both recollection and familiarity for studied items may contribute to elevated false recognition in older adults, via reduced differentiation between the neural activity associated with true and false memory.</AbstractText
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38665298
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35068797
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38607989
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Magnetic resonance elastography for the prediction of hepatocellular carcinoma in chronic hepatitis B.
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Magnetic Resonance Elastography for the Clinical Risk Assessment of Fibrosis, Cirrhosis, and Portal Hypertension in Patients With NAFLD.
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Enzyme-Responsive Fluorescent Labeling Strategy for In Vivo Imaging of Gut Bacteria.
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Magnetic resonance elastography (MRE) is used for the evaluation of liver fibrosis; however, it remains unclear whether MRE-based liver stiffness is associated with hepatocellular carcinoma (HCC) development, particularly in patients with chronic hepatitis B.</AbstractText A total of 504 patients with chronic hepatitis B receiving MRE were enrolled. The <i In a cross-sectional analysis at the time of MRE measurement, the median (interquartile range) liver stiffness values in patients with presence or history of HCC and those without HCC were 3.68 (2.89-4.96) and 2.60 (2.22-3.45) kPa, respectively, and liver stiffness was significantly higher in patients with presence or history of HCC than in those without HCC (<i MRE-based liver stiffness is associated with HCC risk in patients with chronic hepatitis B and may be used for the early prediction of HCC development and determination of indications for treatment.</AbstractText
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Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming one of the most common causes of liver disease. The progressive subtype of NAFLD, nonalcoholic steatohepatitis (NASH), leads to cirrhosis, hepatocellular carcinoma, and mortality. Fibrosis is the strongest predictor for complications. Due to the invasive nature of liver biopsy, noninvasive testing methods have emerged to detect fibrosis and predict outcomes. Of these modalities, magnetic resonance elastography (MRE) has demonstrated the highest accuracy to detect fibrosis. In this review, we will focus on the emerging data regarding MRE and liver fibrosis, cirrhosis, and portal hypertension in NAFLD.</AbstractText
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Myrosinase (Myr), as a unique β-thioglucosidase enzyme capable of converting natural and gut bacterial metabolite glucosinolates into bioactive agents, has recently attracted a great deal of attention because of its essential functions in exerting homeostasis dynamics and promoting human health. Such nutraceutical and biomedical significance demands unique and reliable strategies for specific identification of Myr enzymes of gut bacterial origin in living systems, whereas the dearth of methods for bacterial Myr detection and visualization remains a challenging concern. Herein, we present a series of unique molecular probes for specific identification and imaging of Myr-expressing gut bacterial strains. Typically, an artificial glucosinolate with an azide group in aglycone was synthesized and sequentially linked with the probe moieties of versatile channels through simple click conjugation. Upon gut bacterial enzymatic cleavage, the as-prepared probe molecules could be converted into reactive isothiocyanate forms, which can further act as reactive electrophiles for the covalent labeling of gut bacteria, thus realizing their localized fluorescent imaging within a wide range of wavelength channels in live bacterial strains and animal models. Overall, our proposed method presents a novel technology for selective gut bacterial Myr enzyme labeling <i
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Magnetic resonance elastography for the prediction of hepatocellular carcinoma in chronic hepatitis B. Magnetic resonance elastography (MRE) is used for the evaluation of liver fibrosis; however, it remains unclear whether MRE-based liver stiffness is associated with hepatocellular carcinoma (HCC) development, particularly in patients with chronic hepatitis B.</AbstractText A total of 504 patients with chronic hepatitis B receiving MRE were enrolled. The <i In a cross-sectional analysis at the time of MRE measurement, the median (interquartile range) liver stiffness values in patients with presence or history of HCC and those without HCC were 3.68 (2.89-4.96) and 2.60 (2.22-3.45) kPa, respectively, and liver stiffness was significantly higher in patients with presence or history of HCC than in those without HCC (<i MRE-based liver stiffness is associated with HCC risk in patients with chronic hepatitis B and may be used for the early prediction of HCC development and determination of indications for treatment.</AbstractText
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Magnetic Resonance Elastography for the Clinical Risk Assessment of Fibrosis, Cirrhosis, and Portal Hypertension in Patients With NAFLD. Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming one of the most common causes of liver disease. The progressive subtype of NAFLD, nonalcoholic steatohepatitis (NASH), leads to cirrhosis, hepatocellular carcinoma, and mortality. Fibrosis is the strongest predictor for complications. Due to the invasive nature of liver biopsy, noninvasive testing methods have emerged to detect fibrosis and predict outcomes. Of these modalities, magnetic resonance elastography (MRE) has demonstrated the highest accuracy to detect fibrosis. In this review, we will focus on the emerging data regarding MRE and liver fibrosis, cirrhosis, and portal hypertension in NAFLD.</AbstractText
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Enzyme-Responsive Fluorescent Labeling Strategy for In Vivo Imaging of Gut Bacteria. Myrosinase (Myr), as a unique β-thioglucosidase enzyme capable of converting natural and gut bacterial metabolite glucosinolates into bioactive agents, has recently attracted a great deal of attention because of its essential functions in exerting homeostasis dynamics and promoting human health. Such nutraceutical and biomedical significance demands unique and reliable strategies for specific identification of Myr enzymes of gut bacterial origin in living systems, whereas the dearth of methods for bacterial Myr detection and visualization remains a challenging concern. Herein, we present a series of unique molecular probes for specific identification and imaging of Myr-expressing gut bacterial strains. Typically, an artificial glucosinolate with an azide group in aglycone was synthesized and sequentially linked with the probe moieties of versatile channels through simple click conjugation. Upon gut bacterial enzymatic cleavage, the as-prepared probe molecules could be converted into reactive isothiocyanate forms, which can further act as reactive electrophiles for the covalent labeling of gut bacteria, thus realizing their localized fluorescent imaging within a wide range of wavelength channels in live bacterial strains and animal models. Overall, our proposed method presents a novel technology for selective gut bacterial Myr enzyme labeling <i
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39455913
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34791407
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39656086
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KiNext: a portable and scalable workflow for the identification and classification of protein kinases.
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The European Genome-phenome Archive in 2021.
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Tissue-resident natural killer cells support survival in pancreatic cancer through promotion of cDC1-CD8 T activity.
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Protein kinases are a diverse superfamily of proteins common to organisms across the tree of life that are typically involved in signal transduction, allowing organisms to sense and respond to biotic or abiotic environmental factors. They have important roles in organismal physiology, including development, reproduction, acclimation to environmental stress, while their dysregulation can lead to disease, including several forms of cancer. Identifying the complement of protein kinases (the kinome) of any organism is useful for understanding its physiological capabilities, limitations and adaptations to environmental stress. The increasing availability of genomes makes it now possible to examine and compare the kinomes across a broad diversity of organisms. Here we present a pipeline respecting the FAIR principles (findable, accessible, interoperable and reusable) that facilitates the search and identification of protein kinases from a predicted proteome, and classifies them according to group of serine/threonine/tyrosine protein kinases present in eukaryotes.</AbstractText KiNext is a Nextflow pipeline that regroups a number of existing bioinformatic tools to search for and classify the protein kinases of an organism in a reproducible manner, starting from a set of amino acid sequences. Conventional eukaryotic protein kinases (ePKs) and atypical protein kinases (aPKs) are identified by using Hidden Markov Models (HMMs) generated from the catalytic domains of kinases. Furthermore, KiNext categorizes ePKs into the eight kinase groups by employing dedicated Hidden Markov Models (HMMs) tailored for each group. The performance of the KiNext pipeline was validated against previously identified kinomes obtained with other tools that were already published for two marine species, the Pacific oyster Crassostrea gigas and the unicellular green alga Ostreoccocus tauri. KiNext outperformed previous results by finding previously unidentified kinases and by attributing a large proportion of previously unclassified kinases to a group in both species. These results demonstrate improvements in kinase identification and classification, all while providing traceability and reproducibility of results in a FAIR pipeline. The default HMM models provided with KiNext are most suitable for eukaryotes, but the pipeline can be easily modified to include HMM models for other taxa of interest.</AbstractText The KiNext pipeline enables efficient and reproducible identification of kinomes based on predicted amino acid sequences (i.e. proteomes). KiNext was designed to be easy to use, automated, portable and scalable.</AbstractText
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The European Genome-phenome Archive (EGA - https://ega-archive.org/) is a resource for long term secure archiving of all types of potentially identifiable genetic, phenotypic, and clinical data resulting from biomedical research projects. Its mission is to foster hosted data reuse, enable reproducibility, and accelerate biomedical and translational research in line with the FAIR principles. Launched in 2008, the EGA has grown quickly, currently archiving over 4,500 studies from nearly one thousand institutions. The EGA operates a distributed data access model in which requests are made to the data controller, not to the EGA, therefore, the submitter keeps control on who has access to the data and under which conditions. Given the size and value of data hosted, the EGA is constantly improving its value chain, that is, how the EGA can contribute to enhancing the value of human health data by facilitating its submission, discovery, access, and distribution, as well as leading the design and implementation of standards and methods necessary to deliver the value chain. The EGA has become a key GA4GH Driver Project, leading multiple development efforts and implementing new standards and tools, and has been appointed as an ELIXIR Core Data Resource.</AbstractText
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The immunosuppressive microenvironment in pancreatic ductal adenocarcinoma (PDAC) prevents tumor control and strategies to restore anti-cancer immunity (i.e. by increasing CD8 T-cell activity) have had limited success. Here, we demonstrate how inducing localized physical damage using ionizing radiation (IR) unmasks the benefit of immunotherapy by increasing tissue-resident natural killer (trNK) cells that support CD8 T activity. Our data confirms that targeting mouse orthotopic PDAC tumors with IR together with CCR5 inhibition and PD1 blockade reduces E-cadherin positive tumor cells by recruiting a hypoactive NKG2D<sup
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KiNext: a portable and scalable workflow for the identification and classification of protein kinases. Protein kinases are a diverse superfamily of proteins common to organisms across the tree of life that are typically involved in signal transduction, allowing organisms to sense and respond to biotic or abiotic environmental factors. They have important roles in organismal physiology, including development, reproduction, acclimation to environmental stress, while their dysregulation can lead to disease, including several forms of cancer. Identifying the complement of protein kinases (the kinome) of any organism is useful for understanding its physiological capabilities, limitations and adaptations to environmental stress. The increasing availability of genomes makes it now possible to examine and compare the kinomes across a broad diversity of organisms. Here we present a pipeline respecting the FAIR principles (findable, accessible, interoperable and reusable) that facilitates the search and identification of protein kinases from a predicted proteome, and classifies them according to group of serine/threonine/tyrosine protein kinases present in eukaryotes.</AbstractText KiNext is a Nextflow pipeline that regroups a number of existing bioinformatic tools to search for and classify the protein kinases of an organism in a reproducible manner, starting from a set of amino acid sequences. Conventional eukaryotic protein kinases (ePKs) and atypical protein kinases (aPKs) are identified by using Hidden Markov Models (HMMs) generated from the catalytic domains of kinases. Furthermore, KiNext categorizes ePKs into the eight kinase groups by employing dedicated Hidden Markov Models (HMMs) tailored for each group. The performance of the KiNext pipeline was validated against previously identified kinomes obtained with other tools that were already published for two marine species, the Pacific oyster Crassostrea gigas and the unicellular green alga Ostreoccocus tauri. KiNext outperformed previous results by finding previously unidentified kinases and by attributing a large proportion of previously unclassified kinases to a group in both species. These results demonstrate improvements in kinase identification and classification, all while providing traceability and reproducibility of results in a FAIR pipeline. The default HMM models provided with KiNext are most suitable for eukaryotes, but the pipeline can be easily modified to include HMM models for other taxa of interest.</AbstractText The KiNext pipeline enables efficient and reproducible identification of kinomes based on predicted amino acid sequences (i.e. proteomes). KiNext was designed to be easy to use, automated, portable and scalable.</AbstractText
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The European Genome-phenome Archive in 2021. The European Genome-phenome Archive (EGA - https://ega-archive.org/) is a resource for long term secure archiving of all types of potentially identifiable genetic, phenotypic, and clinical data resulting from biomedical research projects. Its mission is to foster hosted data reuse, enable reproducibility, and accelerate biomedical and translational research in line with the FAIR principles. Launched in 2008, the EGA has grown quickly, currently archiving over 4,500 studies from nearly one thousand institutions. The EGA operates a distributed data access model in which requests are made to the data controller, not to the EGA, therefore, the submitter keeps control on who has access to the data and under which conditions. Given the size and value of data hosted, the EGA is constantly improving its value chain, that is, how the EGA can contribute to enhancing the value of human health data by facilitating its submission, discovery, access, and distribution, as well as leading the design and implementation of standards and methods necessary to deliver the value chain. The EGA has become a key GA4GH Driver Project, leading multiple development efforts and implementing new standards and tools, and has been appointed as an ELIXIR Core Data Resource.</AbstractText
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Tissue-resident natural killer cells support survival in pancreatic cancer through promotion of cDC1-CD8 T activity. The immunosuppressive microenvironment in pancreatic ductal adenocarcinoma (PDAC) prevents tumor control and strategies to restore anti-cancer immunity (i.e. by increasing CD8 T-cell activity) have had limited success. Here, we demonstrate how inducing localized physical damage using ionizing radiation (IR) unmasks the benefit of immunotherapy by increasing tissue-resident natural killer (trNK) cells that support CD8 T activity. Our data confirms that targeting mouse orthotopic PDAC tumors with IR together with CCR5 inhibition and PD1 blockade reduces E-cadherin positive tumor cells by recruiting a hypoactive NKG2D<sup
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36539937
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22636202
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37502130
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Power triggers moral reasoning aligned with active goals and moral flexibility across contexts.
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Liberating reason from the passions: overriding intuitionist moral judgments through emotion reappraisal.
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Perioperative Antiplatelet Therapy for the Stent-Assisted Coil Embolization: Results of the Questionnaire Survey.
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Three experiments tested the hypothesis that power elicits moral judgments in line with active goals, and moral flexibility across different contexts. Power and goals emanating from the mission associated with power were experimentally manipulated: person-centered mission, which benefits from outcome-focus, or regulation-centered mission, which benefits from rule-based focus. Power consistently elicited rule-based (deontological) moral reasoning under regulation-centered goals. However, power triggered outcome-based (utilitarian) moral reasoning under person-centered goals. Power enhanced goal serving morality due to greater goal commitment, with focal goal commitment mediating the interactive effects of power and focal goal on moral judgments. These findings show that the links between power and morality are context sensitive, flexible, and mediated by a greater commitment to active goals.</AbstractText
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A classic problem in moral psychology concerns whether and when moral judgments are driven by intuition versus deliberate reasoning. In this investigation, we explored the role of reappraisal, an emotion-regulation strategy that involves construing an emotion-eliciting situation in a way that diminishes the intensity of the emotional experience. We hypothesized that although emotional reactions evoke initial moral intuitions, reappraisal weakens the influence of these intuitions, leading to more deliberative moral judgments. Three studies of moral judgments in emotionally evocative, disgust-eliciting moral dilemmas supported our hypothesis. A greater tendency to reappraise was related to fewer intuition-based judgments (Study 1). Content analysis of open-ended descriptions of moral-reasoning processes revealed that reappraisal was associated with longer time spent in deliberation and with fewer intuitionist moral judgments (Study 2). Finally, in comparison with participants who simply watched an emotion-inducing film, participants who had been instructed to reappraise their reactions while watching the film subsequently reported less intense emotional reactions to moral dilemmas, and these dampened reactions led, in turn, to fewer intuitionist moral judgments (Study 3).</AbstractText
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This study aimed to determine the status of perioperative antiplatelet therapy in stent-assisted coil embolization (SAC) in Japan.</AbstractText The questionnaire consisted of 13 questions and used Google forms, and was sent to institutions where endovascular specialists were employed. The results were analyzed.</AbstractText The responses from 307 centers indicated that the timing of initiation of antiplatelet therapy was 14 days-1 month before treatment in half of centers, and 7-14 days before treatment in the other half. Platelet function tests were performed at 165 centers (56.2%), of which 136 centers (46.3%) performed these tests for all patients, with the VerifyNow system being the most widely used tool. The duration of postoperative dual antiplatelet therapy was 6, 3, and 12 months in 169 (57.7%), 70 (23.5%), and 42 (14.3%) centers, respectively. The antiplatelet agents used for monotherapy were P2Y12 receptor antagonists or aspirin, with a postoperative period of up to 12 months in 139 centers (47.3%), 24 months in 68 centers (23.1%), and longer than 24 months in 50 centers (17%).</AbstractText Current antiplatelet therapy for SAC in Japan varies widely among institutions. Moreover, each center has its own empirical rules for SAC. Therefore, the findings of this survey suggest the need to establish guidelines for optimal periprocedural antiplatelet therapy for SAC.</AbstractText
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Power triggers moral reasoning aligned with active goals and moral flexibility across contexts. Three experiments tested the hypothesis that power elicits moral judgments in line with active goals, and moral flexibility across different contexts. Power and goals emanating from the mission associated with power were experimentally manipulated: person-centered mission, which benefits from outcome-focus, or regulation-centered mission, which benefits from rule-based focus. Power consistently elicited rule-based (deontological) moral reasoning under regulation-centered goals. However, power triggered outcome-based (utilitarian) moral reasoning under person-centered goals. Power enhanced goal serving morality due to greater goal commitment, with focal goal commitment mediating the interactive effects of power and focal goal on moral judgments. These findings show that the links between power and morality are context sensitive, flexible, and mediated by a greater commitment to active goals.</AbstractText
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Liberating reason from the passions: overriding intuitionist moral judgments through emotion reappraisal. A classic problem in moral psychology concerns whether and when moral judgments are driven by intuition versus deliberate reasoning. In this investigation, we explored the role of reappraisal, an emotion-regulation strategy that involves construing an emotion-eliciting situation in a way that diminishes the intensity of the emotional experience. We hypothesized that although emotional reactions evoke initial moral intuitions, reappraisal weakens the influence of these intuitions, leading to more deliberative moral judgments. Three studies of moral judgments in emotionally evocative, disgust-eliciting moral dilemmas supported our hypothesis. A greater tendency to reappraise was related to fewer intuition-based judgments (Study 1). Content analysis of open-ended descriptions of moral-reasoning processes revealed that reappraisal was associated with longer time spent in deliberation and with fewer intuitionist moral judgments (Study 2). Finally, in comparison with participants who simply watched an emotion-inducing film, participants who had been instructed to reappraise their reactions while watching the film subsequently reported less intense emotional reactions to moral dilemmas, and these dampened reactions led, in turn, to fewer intuitionist moral judgments (Study 3).</AbstractText
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Perioperative Antiplatelet Therapy for the Stent-Assisted Coil Embolization: Results of the Questionnaire Survey. This study aimed to determine the status of perioperative antiplatelet therapy in stent-assisted coil embolization (SAC) in Japan.</AbstractText The questionnaire consisted of 13 questions and used Google forms, and was sent to institutions where endovascular specialists were employed. The results were analyzed.</AbstractText The responses from 307 centers indicated that the timing of initiation of antiplatelet therapy was 14 days-1 month before treatment in half of centers, and 7-14 days before treatment in the other half. Platelet function tests were performed at 165 centers (56.2%), of which 136 centers (46.3%) performed these tests for all patients, with the VerifyNow system being the most widely used tool. The duration of postoperative dual antiplatelet therapy was 6, 3, and 12 months in 169 (57.7%), 70 (23.5%), and 42 (14.3%) centers, respectively. The antiplatelet agents used for monotherapy were P2Y12 receptor antagonists or aspirin, with a postoperative period of up to 12 months in 139 centers (47.3%), 24 months in 68 centers (23.1%), and longer than 24 months in 50 centers (17%).</AbstractText Current antiplatelet therapy for SAC in Japan varies widely among institutions. Moreover, each center has its own empirical rules for SAC. Therefore, the findings of this survey suggest the need to establish guidelines for optimal periprocedural antiplatelet therapy for SAC.</AbstractText
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15690509
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16092102
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30706540
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Dual-velocity continuously moving table acquisition for contrast-enhanced peripheral magnetic resonance angiography.
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Cramér-Rao bounds for three-point decomposition of water and fat.
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Low-rank plus sparse compressed sensing for accelerated proton resonance frequency shift MR temperature imaging.
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Acquisition of MR angiographic data of the peripheral vasculature during continuous table motion offers certain advantages over fixed station approaches, such as the elimination of wasted time moving between stations and the ability to form a seamless image of the extended field of view. However, it has recently been demonstrated that there is an approximate twofold reduction in contrast bolus velocity as it moves from the thighs to the calves. This can potentially cause a mismatch of the moving table with the contrast peak, resulting in the table outpacing the contrast bolus distally. In this work we describe a modification to the continuous table motion technique allowing two table velocities: a high (ca. 3.6 cm/sec) velocity from the abdomen to the thighs and a low (ca. 1.6 cm/sec) velocity distally. Implications of the nonconstant velocity on k-space sampling are described, and it is shown that lateral resolution is improved for the low-velocity region. Correction for table deceleration during the transition time between high and low velocities is demonstrated. Contrast-enhanced studies in 15 volunteers are free of table-motion-related artifact and suggest improved depiction of the contrast bolus distally.</AbstractText
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The noise analysis for three-point decomposition of water and fat was extended to account for the uncertainty in the field map. This generalization leads to a nonlinear estimation problem. The Crámer-Rao bound (CRB) was used to study the variance of the estimates of the magnitude, phase, and field map by computing the maximum effective number of signals averaged (NSA) for any choice of echo time shifts. The analysis shows that the noise properties of the reconstructed magnitude, phase, and field map depend not only on the choice of echo time shifts but also on the amount of fat and water in each voxel and their alignment at the echo. The choice of echo time shifts for spin-echo, spoiled gradient echo, and steady-state free precession imaging techniques were optimized using the CRB. The noise analysis for the magnitude explains rough interfaces seen clinically in the boundary of fat and water with source images obtained symmetrically about the spin-echo. It also provides a solution by choosing appropriate echo time shifts (-pi/6+pik, pi/2+pik, 7pi/6+pik), with k an integer. With this choice of echo time shifts it is possible to achieve the maximum NSA uniformly across all fat:water ratios. The optimization is also carried out for the estimation of phase and field map. These theoretical results were verified using Monte Carlo simulations with a newly developed nonlinear least-squares reconstruction algorithm that achieves the CRB.</AbstractText
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To improve multichannel compressed sensing (CS) reconstruction for MR proton resonance frequency (PRF) shift thermography, with application to MRI-induced RF heating evaluation and MR guided high intensity focused ultrasound (MRgFUS) temperature monitoring.</AbstractText A new compressed sensing reconstruction is proposed that enforces joint low rank and sparsity of complex difference domain PRF data between post heating and baseline images. Validations were performed on 4 retrospectively undersampled dynamic data sets in PRF applications, by comparing the proposed method to a previously described L<sub In all 4 retrospective validations, the proposed reconstruction method outperformed the conventional L+S and L<sub The complex difference-based low rank and sparse model enhances compressibility for dynamic PRF temperature imaging applications. The proposed multichannel CS reconstruction method enables high acceleration factors for PRF applications including RF heating evaluation and MRgFUS sonication.</AbstractText
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Dual-velocity continuously moving table acquisition for contrast-enhanced peripheral magnetic resonance angiography. Acquisition of MR angiographic data of the peripheral vasculature during continuous table motion offers certain advantages over fixed station approaches, such as the elimination of wasted time moving between stations and the ability to form a seamless image of the extended field of view. However, it has recently been demonstrated that there is an approximate twofold reduction in contrast bolus velocity as it moves from the thighs to the calves. This can potentially cause a mismatch of the moving table with the contrast peak, resulting in the table outpacing the contrast bolus distally. In this work we describe a modification to the continuous table motion technique allowing two table velocities: a high (ca. 3.6 cm/sec) velocity from the abdomen to the thighs and a low (ca. 1.6 cm/sec) velocity distally. Implications of the nonconstant velocity on k-space sampling are described, and it is shown that lateral resolution is improved for the low-velocity region. Correction for table deceleration during the transition time between high and low velocities is demonstrated. Contrast-enhanced studies in 15 volunteers are free of table-motion-related artifact and suggest improved depiction of the contrast bolus distally.</AbstractText
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Cramér-Rao bounds for three-point decomposition of water and fat. The noise analysis for three-point decomposition of water and fat was extended to account for the uncertainty in the field map. This generalization leads to a nonlinear estimation problem. The Crámer-Rao bound (CRB) was used to study the variance of the estimates of the magnitude, phase, and field map by computing the maximum effective number of signals averaged (NSA) for any choice of echo time shifts. The analysis shows that the noise properties of the reconstructed magnitude, phase, and field map depend not only on the choice of echo time shifts but also on the amount of fat and water in each voxel and their alignment at the echo. The choice of echo time shifts for spin-echo, spoiled gradient echo, and steady-state free precession imaging techniques were optimized using the CRB. The noise analysis for the magnitude explains rough interfaces seen clinically in the boundary of fat and water with source images obtained symmetrically about the spin-echo. It also provides a solution by choosing appropriate echo time shifts (-pi/6+pik, pi/2+pik, 7pi/6+pik), with k an integer. With this choice of echo time shifts it is possible to achieve the maximum NSA uniformly across all fat:water ratios. The optimization is also carried out for the estimation of phase and field map. These theoretical results were verified using Monte Carlo simulations with a newly developed nonlinear least-squares reconstruction algorithm that achieves the CRB.</AbstractText
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Low-rank plus sparse compressed sensing for accelerated proton resonance frequency shift MR temperature imaging. To improve multichannel compressed sensing (CS) reconstruction for MR proton resonance frequency (PRF) shift thermography, with application to MRI-induced RF heating evaluation and MR guided high intensity focused ultrasound (MRgFUS) temperature monitoring.</AbstractText A new compressed sensing reconstruction is proposed that enforces joint low rank and sparsity of complex difference domain PRF data between post heating and baseline images. Validations were performed on 4 retrospectively undersampled dynamic data sets in PRF applications, by comparing the proposed method to a previously described L<sub In all 4 retrospective validations, the proposed reconstruction method outperformed the conventional L+S and L<sub The complex difference-based low rank and sparse model enhances compressibility for dynamic PRF temperature imaging applications. The proposed multichannel CS reconstruction method enables high acceleration factors for PRF applications including RF heating evaluation and MRgFUS sonication.</AbstractText
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40388838
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39105640
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39647601
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ChatGPT-4-Driven Liver Ultrasound Radiomics Analysis: Diagnostic Value and Drawbacks in a Comparative Study.
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Fully Automated Deep Learning Model to Detect Clinically Significant Prostate Cancer at MRI.
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The dual modulating effects of neuropeptide FF on morphine-induced analgesia at the spinal level.
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Artificial intelligence (AI) is transforming medical imaging, with large language models such as ChatGPT-4 emerging as potential tools for automated image interpretation. While AI-driven radiomics has shown promise in diagnostic imaging, the efficacy of ChatGPT-4 in liver ultrasound analysis remains largely unexamined.</AbstractText This study aimed to evaluate the capability of ChatGPT-4 in liver ultrasound radiomics, specifically its ability to differentiate fibrosis, steatosis, and normal liver tissue, compared with conventional image analysis software.</AbstractText Seventy grayscale ultrasound images from a preclinical liver disease model, including fibrosis (n=31), fatty liver (n=18), and normal liver (n=21), were analyzed. ChatGPT-4 extracted texture features, which were compared with those obtained using interactive data language (IDL), a traditional image analysis software. One-way ANOVA was used to identify statistically significant features differentiating liver conditions, and logistic regression models were used to assess diagnostic performance.</AbstractText ChatGPT-4 extracted 9 key textural features-echo intensity, heterogeneity, skewness, kurtosis, contrast, homogeneity, dissimilarity, angular second momentum, and entropy-all of which significantly differed across liver conditions (P<.05). Among individual features, echo intensity achieved the highest F<sub Despite slightly lower sensitivity than IDL, ChatGPT-4 demonstrated high feasibility for ultrasound radiomics, offering faster processing, high-throughput analysis, and automated multi-image evaluation. These findings support its potential integration into AI-driven imaging workflows, with further refinements needed to enhance feature reproducibility and diagnostic accuracy.</AbstractText
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Background Multiparametric MRI can help identify clinically significant prostate cancer (csPCa) (Gleason score ≥7) but is limited by reader experience and interobserver variability. In contrast, deep learning (DL) produces deterministic outputs. Purpose To develop a DL model to predict the presence of csPCa by using patient-level labels without information about tumor location and to compare its performance with that of radiologists. Materials and Methods Data from patients without known csPCa who underwent MRI from January 2017 to December 2019 at one of multiple sites of a single academic institution were retrospectively reviewed. A convolutional neural network was trained to predict csPCa from T2-weighted images, diffusion-weighted images, apparent diffusion coefficient maps, and T1-weighted contrast-enhanced images. The reference standard was pathologic diagnosis. Radiologist performance was evaluated as follows: Radiology reports were used for the internal test set, and four radiologists' PI-RADS ratings were used for the external (ProstateX) test set. The performance was compared using areas under the receiver operating characteristic curves (AUCs) and the DeLong test. Gradient-weighted class activation maps (Grad-CAMs) were used to show tumor localization. Results Among 5735 examinations in 5215 patients (mean age, 66 years ± 8 [SD]; all male), 1514 examinations (1454 patients) showed csPCa. In the internal test set (400 examinations), the AUC was 0.89 and 0.89 for the DL classifier and radiologists, respectively (<i
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Increasing evidence indicates that neuropeptide FF (NPFF) produces analgesic effects and augments opioid-induced analgesia at the spinal level. However, our recent research demonstrated that NPFF exerted complex opioid-modulating effects in an inflammatory pain model after intrathecal (i.t.) injection. Consistent with previous findings, we found that i.t. NPFF dose-dependently attenuated complete Freund's adjuvant-induced pain hypersensitivity. Interestingly, pharmacological results illustrated that NPFF exhibited opposite opioid-modulating effects at the spinal level depending on its administration dosage, wherein i.t. NPFF potentiated morphine-induced anti-allodynia at the dose of 10 nmol, while attenuated morphine analgesia at an ultra-low-dose of 10 pmol. Behavioral results obtained from neuropeptide FF receptor 2 (NPFFR2) knockout animals suggested that both pro- and anti-opioid effects of NPFF were mediated by NPFFR2. Moreover, these modulating effects of spinal NPFFR2 were selectively targeting mu-opioid receptor, had no effect on delta- and kappa-opioid receptor agonist-induced analgesia. Finally, the opioid-modulating effects of NPFF were further verified using in vitro calcium imaging assay, demonstrating that pretreated with NPFF in primary-cultured spinal neurons significantly attenuated the inhibitory effects of morphine on high-K<sup
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ChatGPT-4-Driven Liver Ultrasound Radiomics Analysis: Diagnostic Value and Drawbacks in a Comparative Study. Artificial intelligence (AI) is transforming medical imaging, with large language models such as ChatGPT-4 emerging as potential tools for automated image interpretation. While AI-driven radiomics has shown promise in diagnostic imaging, the efficacy of ChatGPT-4 in liver ultrasound analysis remains largely unexamined.</AbstractText This study aimed to evaluate the capability of ChatGPT-4 in liver ultrasound radiomics, specifically its ability to differentiate fibrosis, steatosis, and normal liver tissue, compared with conventional image analysis software.</AbstractText Seventy grayscale ultrasound images from a preclinical liver disease model, including fibrosis (n=31), fatty liver (n=18), and normal liver (n=21), were analyzed. ChatGPT-4 extracted texture features, which were compared with those obtained using interactive data language (IDL), a traditional image analysis software. One-way ANOVA was used to identify statistically significant features differentiating liver conditions, and logistic regression models were used to assess diagnostic performance.</AbstractText ChatGPT-4 extracted 9 key textural features-echo intensity, heterogeneity, skewness, kurtosis, contrast, homogeneity, dissimilarity, angular second momentum, and entropy-all of which significantly differed across liver conditions (P<.05). Among individual features, echo intensity achieved the highest F<sub Despite slightly lower sensitivity than IDL, ChatGPT-4 demonstrated high feasibility for ultrasound radiomics, offering faster processing, high-throughput analysis, and automated multi-image evaluation. These findings support its potential integration into AI-driven imaging workflows, with further refinements needed to enhance feature reproducibility and diagnostic accuracy.</AbstractText
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Fully Automated Deep Learning Model to Detect Clinically Significant Prostate Cancer at MRI. Background Multiparametric MRI can help identify clinically significant prostate cancer (csPCa) (Gleason score ≥7) but is limited by reader experience and interobserver variability. In contrast, deep learning (DL) produces deterministic outputs. Purpose To develop a DL model to predict the presence of csPCa by using patient-level labels without information about tumor location and to compare its performance with that of radiologists. Materials and Methods Data from patients without known csPCa who underwent MRI from January 2017 to December 2019 at one of multiple sites of a single academic institution were retrospectively reviewed. A convolutional neural network was trained to predict csPCa from T2-weighted images, diffusion-weighted images, apparent diffusion coefficient maps, and T1-weighted contrast-enhanced images. The reference standard was pathologic diagnosis. Radiologist performance was evaluated as follows: Radiology reports were used for the internal test set, and four radiologists' PI-RADS ratings were used for the external (ProstateX) test set. The performance was compared using areas under the receiver operating characteristic curves (AUCs) and the DeLong test. Gradient-weighted class activation maps (Grad-CAMs) were used to show tumor localization. Results Among 5735 examinations in 5215 patients (mean age, 66 years ± 8 [SD]; all male), 1514 examinations (1454 patients) showed csPCa. In the internal test set (400 examinations), the AUC was 0.89 and 0.89 for the DL classifier and radiologists, respectively (<i
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The dual modulating effects of neuropeptide FF on morphine-induced analgesia at the spinal level. Increasing evidence indicates that neuropeptide FF (NPFF) produces analgesic effects and augments opioid-induced analgesia at the spinal level. However, our recent research demonstrated that NPFF exerted complex opioid-modulating effects in an inflammatory pain model after intrathecal (i.t.) injection. Consistent with previous findings, we found that i.t. NPFF dose-dependently attenuated complete Freund's adjuvant-induced pain hypersensitivity. Interestingly, pharmacological results illustrated that NPFF exhibited opposite opioid-modulating effects at the spinal level depending on its administration dosage, wherein i.t. NPFF potentiated morphine-induced anti-allodynia at the dose of 10 nmol, while attenuated morphine analgesia at an ultra-low-dose of 10 pmol. Behavioral results obtained from neuropeptide FF receptor 2 (NPFFR2) knockout animals suggested that both pro- and anti-opioid effects of NPFF were mediated by NPFFR2. Moreover, these modulating effects of spinal NPFFR2 were selectively targeting mu-opioid receptor, had no effect on delta- and kappa-opioid receptor agonist-induced analgesia. Finally, the opioid-modulating effects of NPFF were further verified using in vitro calcium imaging assay, demonstrating that pretreated with NPFF in primary-cultured spinal neurons significantly attenuated the inhibitory effects of morphine on high-K<sup
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40760576
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31188153
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40431415
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Efficacy of OSTAP, ESP block, trocar site local anesthetic injection in elective laparoscopic cholecystectomy: A randomized controlled trial.
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Ultrasound-assisted vs. landmark-guided paramedian spinal anaesthesia in the elderly: A randomised controlled trial.
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Dietary Insulinogenic Amino Acid Restriction Improves Glucose Metabolism in a Neonatal Piglet Model.
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Effective postoperative pain control remains a clinical challenge in laparoscopic cholecystectomy (LC). Regional anesthesia techniques such as the erector spinae plane (ESP) block and the oblique subcostal transversus abdominis plane (OSTAP) block have gained popularity as potential alternatives to traditional analgesic methods. This double-blind, randomized controlled trial aimed to compare the analgesic efficacy of ESP block, OSTAP block, and trocar site local anesthetic (LA) infiltration in terms of postoperative pain scores and opioid consumption in patients undergoing LC.</AbstractText A total of 100 patients were equally randomized into 4 groups: ESP block (Group E), OSTAP block (Group T), trocar site LA infiltration (Group L), and a control group (Group C) receiving multimodal analgesia. ESP and OSTAP blocks were applied unilaterally prior to surgery. All patients were followed for 24 hours postoperatively. Pain intensity was evaluated using the visual analog scale (VAS), and cumulative tramadol consumption, additional analgesic requirements, nausea-vomiting scores, and incidence of shoulder pain were recorded. Data analysis was performed using SPSS, with Bonferroni correction applied for multiple comparisons.</AbstractText VAS scores at all-time points were significantly lower in Groups E and L compared to Group C (P < .05). Although Group T also showed lower scores than Group C, this difference was not statistically significant after correction. Total tramadol consumption was significantly lower in Group E (112.2 ± 105.4 mg) and Group T (163.6 ± 127.1 mg) compared to Group C (281.8 ± 144.8 mg) and Group L (291.8 ± 131.6 mg; P < .001). Additional analgesic requirement rates were significantly lower in Groups E, T, and L than in Group C (P < .05). No adverse events such as LA toxicity or allergic reactions were observed. Nausea-vomiting scores and shoulder pain incidence were comparable across all groups.</AbstractText Both ESP and OSTAP blocks effectively reduced postoperative opioid requirements, with the ESP block demonstrating greater efficacy in terms of pain control. These findings support the use of unilateral ESP and OSTAP blocks as effective components of multimodal analgesia protocols in LC.</AbstractText
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Neuraxial ultrasound might improve the efficacy of spinal anaesthesia but this has not been tested for the paramedian approach in the elderly.</AbstractText The current study aims to assess whether the ultrasound-assisted paramedian technique can decrease the number of needle passes required for success compared with the landmark-guided paramedian technique in the elderly.</AbstractText Randomised controlled study.</AbstractText Single-institution, tertiary-level hospital in Seoul, Republic of Korea from October 2017 to January 2018.</AbstractText Eighty patients aged at least 60 years undergoing orthopaedic surgery.</AbstractText All received paramedian spinal anaesthesia by either the landmark-guided or preprocedural ultrasound-assisted technique.</AbstractText The number of needle passes required for successful dural puncture.</AbstractText The number of needle passes (median [interquartile range]) was significantly lower (1.0 [1.0 to 2.0] vs. 4.5 [2.0 to 7.0]) and the success rate at first pass significantly higher at 65.0 vs. 17.5% in the ultrasound compared with the landmark group (both P < 0.001). The ultrasound-assisted technique required a longer time for establishing landmarks (117.5 s [85.5 to 150.7 s] vs. 17.5 s [14.0 to 23.0 s]) and for total procedure (181.5 s [133.5 to 212.5 s] vs. 92.5 s [62.5 to 176.5 s]) but a shorter time for administering spinal anaesthesia (39.5 s [31.5 to 71.3 s] vs. 77.0 s [45.8 to 136.5 s]; all, P < 0.001) than the palpation-guided technique. The ultrasound group showed lower periprocedural pain scores (3 [2 to 4] vs. 4 [4 to 6]; P = 0.009) and discomfort scores (2 [0 to 3] vs. 5 [2 to 6]; P = 0.003) than the landmark group.</AbstractText Compared with the landmark-guided paramedian technique, the ultrasound-assisted paramedian technique decreases the number of needle manipulations and periprocedural pain and discomfort scores in the elderly. Our results suggest that neuraxial ultrasonography facilitates the performance of spinal anaesthesia in the elderly.</AbstractText NCT03316352.</AbstractText
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<b
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Efficacy of OSTAP, ESP block, trocar site local anesthetic injection in elective laparoscopic cholecystectomy: A randomized controlled trial. Effective postoperative pain control remains a clinical challenge in laparoscopic cholecystectomy (LC). Regional anesthesia techniques such as the erector spinae plane (ESP) block and the oblique subcostal transversus abdominis plane (OSTAP) block have gained popularity as potential alternatives to traditional analgesic methods. This double-blind, randomized controlled trial aimed to compare the analgesic efficacy of ESP block, OSTAP block, and trocar site local anesthetic (LA) infiltration in terms of postoperative pain scores and opioid consumption in patients undergoing LC.</AbstractText A total of 100 patients were equally randomized into 4 groups: ESP block (Group E), OSTAP block (Group T), trocar site LA infiltration (Group L), and a control group (Group C) receiving multimodal analgesia. ESP and OSTAP blocks were applied unilaterally prior to surgery. All patients were followed for 24 hours postoperatively. Pain intensity was evaluated using the visual analog scale (VAS), and cumulative tramadol consumption, additional analgesic requirements, nausea-vomiting scores, and incidence of shoulder pain were recorded. Data analysis was performed using SPSS, with Bonferroni correction applied for multiple comparisons.</AbstractText VAS scores at all-time points were significantly lower in Groups E and L compared to Group C (P < .05). Although Group T also showed lower scores than Group C, this difference was not statistically significant after correction. Total tramadol consumption was significantly lower in Group E (112.2 ± 105.4 mg) and Group T (163.6 ± 127.1 mg) compared to Group C (281.8 ± 144.8 mg) and Group L (291.8 ± 131.6 mg; P < .001). Additional analgesic requirement rates were significantly lower in Groups E, T, and L than in Group C (P < .05). No adverse events such as LA toxicity or allergic reactions were observed. Nausea-vomiting scores and shoulder pain incidence were comparable across all groups.</AbstractText Both ESP and OSTAP blocks effectively reduced postoperative opioid requirements, with the ESP block demonstrating greater efficacy in terms of pain control. These findings support the use of unilateral ESP and OSTAP blocks as effective components of multimodal analgesia protocols in LC.</AbstractText
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Ultrasound-assisted vs. landmark-guided paramedian spinal anaesthesia in the elderly: A randomised controlled trial. Neuraxial ultrasound might improve the efficacy of spinal anaesthesia but this has not been tested for the paramedian approach in the elderly.</AbstractText The current study aims to assess whether the ultrasound-assisted paramedian technique can decrease the number of needle passes required for success compared with the landmark-guided paramedian technique in the elderly.</AbstractText Randomised controlled study.</AbstractText Single-institution, tertiary-level hospital in Seoul, Republic of Korea from October 2017 to January 2018.</AbstractText Eighty patients aged at least 60 years undergoing orthopaedic surgery.</AbstractText All received paramedian spinal anaesthesia by either the landmark-guided or preprocedural ultrasound-assisted technique.</AbstractText The number of needle passes required for successful dural puncture.</AbstractText The number of needle passes (median [interquartile range]) was significantly lower (1.0 [1.0 to 2.0] vs. 4.5 [2.0 to 7.0]) and the success rate at first pass significantly higher at 65.0 vs. 17.5% in the ultrasound compared with the landmark group (both P < 0.001). The ultrasound-assisted technique required a longer time for establishing landmarks (117.5 s [85.5 to 150.7 s] vs. 17.5 s [14.0 to 23.0 s]) and for total procedure (181.5 s [133.5 to 212.5 s] vs. 92.5 s [62.5 to 176.5 s]) but a shorter time for administering spinal anaesthesia (39.5 s [31.5 to 71.3 s] vs. 77.0 s [45.8 to 136.5 s]; all, P < 0.001) than the palpation-guided technique. The ultrasound group showed lower periprocedural pain scores (3 [2 to 4] vs. 4 [4 to 6]; P = 0.009) and discomfort scores (2 [0 to 3] vs. 5 [2 to 6]; P = 0.003) than the landmark group.</AbstractText Compared with the landmark-guided paramedian technique, the ultrasound-assisted paramedian technique decreases the number of needle manipulations and periprocedural pain and discomfort scores in the elderly. Our results suggest that neuraxial ultrasonography facilitates the performance of spinal anaesthesia in the elderly.</AbstractText NCT03316352.</AbstractText
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Dietary Insulinogenic Amino Acid Restriction Improves Glucose Metabolism in a Neonatal Piglet Model. <b
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37021359
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33723865
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37531978
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Point estimation for adaptive trial designs II: Practical considerations and guidance.
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Estimation of treatment effect in 2-in-1 adaptive design and some of its extensions.
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Evaluation of motor and sensory neuron populations in a mouse median nerve injury model.
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In adaptive clinical trials, the conventional end-of-trial point estimate of a treatment effect is prone to bias, that is, a systematic tendency to deviate from its true value. As stated in recent FDA guidance on adaptive designs, it is desirable to report estimates of treatment effects that reduce or remove this bias. However, it may be unclear which of the available estimators are preferable, and their use remains rare in practice. This article is the second in a two-part series that studies the issue of bias in point estimation for adaptive trials. Part I provided a methodological review of approaches to remove or reduce the potential bias in point estimation for adaptive designs. In part II, we discuss how bias can affect standard estimators and assess the negative impact this can have. We review current practice for reporting point estimates and illustrate the computation of different estimators using a real adaptive trial example (including code), which we use as a basis for a simulation study. We show that while on average the values of these estimators can be similar, for a particular trial realization they can give noticeably different values for the estimated treatment effect. Finally, we propose guidelines for researchers around the choice of estimators and the reporting of estimates following an adaptive design. The issue of bias should be considered throughout the whole lifecycle of an adaptive design, with the estimation strategy prespecified in the statistical analysis plan. When available, unbiased or bias-reduced estimates are to be preferred.</AbstractText
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The 2-in-1 adaptive design allows seamless expansion of an ongoing Phase II trial into a Phase III trial to expedite a drug development program. Since its publication, it has generated a lot of interest. So far, most of the related research focused on type I error control. Similar to most adaptive designs, 2-in-1 design could also pose a great challenge on estimation of treatment effect due to the data-driven adaptation. In addition, the use of intermediate endpoint for interim adaptive decision-making is a less well-studied field. In this paper, we investigate the bias and variances in estimation for 2-in-1 design and some of its extensions, and propose some bias-adjusted estimators for 2-in-1 design. The properties of the proposed estimators are further studied theoretically and/or numerically, so as to provide guidance on how to interpret the estimated treatment effect of 2-in-1 design.</AbstractText
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Peripheral nerves can regenerate and restore function after injury but this process is hindered by many factors including chronic denervation, motor end-plate resorption and Schwann cell senescence. Forelimb injury models in rodents are becoming increasingly popular as they more accurately reflect the physiology and biomechanics of upper extremity nerve injuries. However several aspects of this surgical model remain poorly characterized.</AbstractText C57Bl/6 mice underwent enumeration of median nerve motor and sensory neuron pools using retrograde labeling with or without nerve transection. Distal histomorphometry of uninjured mouse median nerves was also examined. Baseline reference values of volitional forelimb grip strength measurements were determined and the rate of neural elongation was also estimated.</AbstractText We identified 1363 ± 165 sensory and 216 ± 16 motor neurons within the uninjured dorsal root ganglia (DRG) and ventral spinal cord, respectively. Eight days following injury, approximately 34% of motoneurons had elongated a distance of 5 mm beyond the repair site 8 days following injury. Volitional grip strength decreased 50% with unilateral median nerve transection and was negligible with contralateral flexor tendon tenotomy.</AbstractText Our spinal cord and DRG harvesting technique presented here was technically straightforward and reliable. Estimates of motor and sensory neuron numbers for the mouse median nerve compared favourably with studies using intramuscular injection of retrograde neurotracer. Histomorphometry data was consistent with and reinforced reference values in the literature.</AbstractText This study provides data that further develops an increasingly popular surgical model for studying peripheral nerve injury and repair.</AbstractText
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Point estimation for adaptive trial designs II: Practical considerations and guidance. In adaptive clinical trials, the conventional end-of-trial point estimate of a treatment effect is prone to bias, that is, a systematic tendency to deviate from its true value. As stated in recent FDA guidance on adaptive designs, it is desirable to report estimates of treatment effects that reduce or remove this bias. However, it may be unclear which of the available estimators are preferable, and their use remains rare in practice. This article is the second in a two-part series that studies the issue of bias in point estimation for adaptive trials. Part I provided a methodological review of approaches to remove or reduce the potential bias in point estimation for adaptive designs. In part II, we discuss how bias can affect standard estimators and assess the negative impact this can have. We review current practice for reporting point estimates and illustrate the computation of different estimators using a real adaptive trial example (including code), which we use as a basis for a simulation study. We show that while on average the values of these estimators can be similar, for a particular trial realization they can give noticeably different values for the estimated treatment effect. Finally, we propose guidelines for researchers around the choice of estimators and the reporting of estimates following an adaptive design. The issue of bias should be considered throughout the whole lifecycle of an adaptive design, with the estimation strategy prespecified in the statistical analysis plan. When available, unbiased or bias-reduced estimates are to be preferred.</AbstractText
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Estimation of treatment effect in 2-in-1 adaptive design and some of its extensions. The 2-in-1 adaptive design allows seamless expansion of an ongoing Phase II trial into a Phase III trial to expedite a drug development program. Since its publication, it has generated a lot of interest. So far, most of the related research focused on type I error control. Similar to most adaptive designs, 2-in-1 design could also pose a great challenge on estimation of treatment effect due to the data-driven adaptation. In addition, the use of intermediate endpoint for interim adaptive decision-making is a less well-studied field. In this paper, we investigate the bias and variances in estimation for 2-in-1 design and some of its extensions, and propose some bias-adjusted estimators for 2-in-1 design. The properties of the proposed estimators are further studied theoretically and/or numerically, so as to provide guidance on how to interpret the estimated treatment effect of 2-in-1 design.</AbstractText
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Evaluation of motor and sensory neuron populations in a mouse median nerve injury model. Peripheral nerves can regenerate and restore function after injury but this process is hindered by many factors including chronic denervation, motor end-plate resorption and Schwann cell senescence. Forelimb injury models in rodents are becoming increasingly popular as they more accurately reflect the physiology and biomechanics of upper extremity nerve injuries. However several aspects of this surgical model remain poorly characterized.</AbstractText C57Bl/6 mice underwent enumeration of median nerve motor and sensory neuron pools using retrograde labeling with or without nerve transection. Distal histomorphometry of uninjured mouse median nerves was also examined. Baseline reference values of volitional forelimb grip strength measurements were determined and the rate of neural elongation was also estimated.</AbstractText We identified 1363 ± 165 sensory and 216 ± 16 motor neurons within the uninjured dorsal root ganglia (DRG) and ventral spinal cord, respectively. Eight days following injury, approximately 34% of motoneurons had elongated a distance of 5 mm beyond the repair site 8 days following injury. Volitional grip strength decreased 50% with unilateral median nerve transection and was negligible with contralateral flexor tendon tenotomy.</AbstractText Our spinal cord and DRG harvesting technique presented here was technically straightforward and reliable. Estimates of motor and sensory neuron numbers for the mouse median nerve compared favourably with studies using intramuscular injection of retrograde neurotracer. Histomorphometry data was consistent with and reinforced reference values in the literature.</AbstractText This study provides data that further develops an increasingly popular surgical model for studying peripheral nerve injury and repair.</AbstractText
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35008604
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32051341
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35125799
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Pathophysiology of the Different Clinical Phenotypes of Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP).
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Deciphering immune mechanisms in chronic inflammatory demyelinating polyneuropathies.
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Prevalence of Color Vision Anomalies among Dental Professionals.
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Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common form of autoimmune polyneuropathy. It is a chronic disease and may be monophasic, progressive or recurrent with exacerbations and incomplete remissions, causing accumulating disability. In recent years, there has been rapid progress in understanding the background of CIDP, which allowed us to distinguish specific phenotypes of this disease. This in turn allowed us to better understand the mechanism of response or non-response to various forms of therapy. On the basis of a review of the relevant literature, the authors present the current state of knowledge concerning the pathophysiology of the different clinical phenotypes of CIDP as well as ongoing research in this field, with reference to key points of immune-mediated processes involved in the background of CIDP.</AbstractText
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Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease of the peripheral nerves that presents with either chronic progression or relapsing disease. Recent studies in samples from patients with CIDP and mouse models have delineated how defects in central (thymic) and peripheral (extrathymic) immune tolerance mechanisms can cause PNS autoimmunity. Notably, nerve parenchymal cells actively contribute to local autoimmunity and also control disease outcome. Here, we outline how emerging technologies increasingly enable an integrated view of how immune cells and PNS parenchymal cells communicate in CIDP. We also relate the known heterogeneity of clinical presentation with specific underlying mechanisms. For example, a severe subtype of CIDP with tremor is associated with pathogenic IgG4 autoantibodies against nodal and paranodal proteins. An improved understanding of pathogenic mechanisms in CIDP will form the basis for more effective mechanism-based therapies.</AbstractText
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Color blindness is one of the potential disabilities affecting the ability of color perception by the eye. The aim of the present study was to evaluate the prevalence of color blindness among dental professionals.</AbstractText For the present study, a total of 198 dental professionals were randomly selected as subjects who were asked to fill the required questionnaire followed by which their color vision status was evaluated using the Ishihara test. The results obtained were subjected to statistical analysis. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) version 17.0 (SPSS Inc., Chicago, IL, USA). The prevalence of color blindness, age specificity, and the ratio of the occurrence of color blindness in relation to gender were assessed using Chi-square test for independence and Chi-square test with Yates's correction for independence when the expected frequency was <5. <i The present study reported 3.54% prevalence of color blindness among the study population. A higher number of cases were reported from males (9.26%) than females (1.39%). (<i The present study reported high prevalence of color blindness in dental professionals while they were totally unaware of it.</AbstractText
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Pathophysiology of the Different Clinical Phenotypes of Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP). Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common form of autoimmune polyneuropathy. It is a chronic disease and may be monophasic, progressive or recurrent with exacerbations and incomplete remissions, causing accumulating disability. In recent years, there has been rapid progress in understanding the background of CIDP, which allowed us to distinguish specific phenotypes of this disease. This in turn allowed us to better understand the mechanism of response or non-response to various forms of therapy. On the basis of a review of the relevant literature, the authors present the current state of knowledge concerning the pathophysiology of the different clinical phenotypes of CIDP as well as ongoing research in this field, with reference to key points of immune-mediated processes involved in the background of CIDP.</AbstractText
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Deciphering immune mechanisms in chronic inflammatory demyelinating polyneuropathies. Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease of the peripheral nerves that presents with either chronic progression or relapsing disease. Recent studies in samples from patients with CIDP and mouse models have delineated how defects in central (thymic) and peripheral (extrathymic) immune tolerance mechanisms can cause PNS autoimmunity. Notably, nerve parenchymal cells actively contribute to local autoimmunity and also control disease outcome. Here, we outline how emerging technologies increasingly enable an integrated view of how immune cells and PNS parenchymal cells communicate in CIDP. We also relate the known heterogeneity of clinical presentation with specific underlying mechanisms. For example, a severe subtype of CIDP with tremor is associated with pathogenic IgG4 autoantibodies against nodal and paranodal proteins. An improved understanding of pathogenic mechanisms in CIDP will form the basis for more effective mechanism-based therapies.</AbstractText
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Prevalence of Color Vision Anomalies among Dental Professionals. Color blindness is one of the potential disabilities affecting the ability of color perception by the eye. The aim of the present study was to evaluate the prevalence of color blindness among dental professionals.</AbstractText For the present study, a total of 198 dental professionals were randomly selected as subjects who were asked to fill the required questionnaire followed by which their color vision status was evaluated using the Ishihara test. The results obtained were subjected to statistical analysis. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) version 17.0 (SPSS Inc., Chicago, IL, USA). The prevalence of color blindness, age specificity, and the ratio of the occurrence of color blindness in relation to gender were assessed using Chi-square test for independence and Chi-square test with Yates's correction for independence when the expected frequency was <5. <i The present study reported 3.54% prevalence of color blindness among the study population. A higher number of cases were reported from males (9.26%) than females (1.39%). (<i The present study reported high prevalence of color blindness in dental professionals while they were totally unaware of it.</AbstractText
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40502118
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24707045
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40566770
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Identifying Space-Resolved Proteins of the Murine Thymus, by Combining MALDI Mass Spectrometry Imaging and Proteomics.
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Soybean SAT1 (Symbiotic Ammonium Transporter 1) encodes a bHLH transcription factor involved in nodule growth and NH4+ transport.
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[A study on electroencephalogram characteristics of depression in patients with aphasia based on resting state and emotional Stroop task].
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The identification of spatially resolved proteomes has recently seen significant breakthroughs, yet challenges persist, particularly in integrating protein identification with precise spatial localization within a single experimental workflow. Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) enables spatial protein mapping on tissue sections without the need for antibodies. While MALDI-MSI addresses several obstacles in proteomic mapping with spatial resolution, it remains limited in its capacity for definitive protein identification. To overcome these limitations, this study introduces a novel approach combining MALDI-MSI with liquid chromatography-mass spectrometry (LC-MS/MS) to map protein localization and spatial changes in thymic tissue. Using a mouse model of chemotherapy-induced thymic involution with time-dependent regeneration kinetics, we evaluated the capability of this pipeline to resolve proteomic changes in a spatiotemporal manner. Our approach incorporates a scoring system to align molecular signals from MALDI-MSI with proteomic data, enabling precise identification of proteins critical for thymic function. The results reveal key changes in protein expression, particularly in regions associated with cell migration, cytoskeletal remodeling, and endogenous thymic regeneration. By analyzing the spatial distribution of proteins such as Keratin 8 (KRT8), Nucleoporin TPR, Cysteineand Glycine-Rich Protein 3 (CSPR3), and Tubulin-Associated Chaperone-A (TBCA), we observed distinct shifts in thymic compartment architecture, underscoring the impact of chemotherapy on thymic tissue structure. From a translational viewpoint, this approach identifies new pathways and targetable candidates to enhance immune cell recovery in pediatric cancer patients undergoing cytoreductive treatments. From an analytical perspective, it provides an innovative framework for visualizing protein distribution in lymphoid and other tissues, significantly advancing the potential for translational proteomic research.</AbstractText
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Glycine max symbiotic ammonium transporter 1 was first documented as a putative ammonium (NH4(+)) channel localized to the symbiosome membrane of soybean root nodules. We show that Glycine max symbiotic ammonium transporter 1 is actually a membrane-localized basic helix-loop-helix (bHLH) DNA-binding transcription factor now renamed Glycine max bHLH membrane 1 (GmbHLHm1). In yeast, GmbHLHm1 enters the nucleus and transcriptionally activates a unique plasma membrane NH4(+) channel Saccharomyces cerevisiae ammonium facilitator 1. Ammonium facilitator 1 homologs are present in soybean and other plant species, where they often share chromosomal microsynteny with bHLHm1 loci. GmbHLHm1 is important to the soybean rhizobium symbiosis because loss of activity results in a reduction of nodule fitness and growth. Transcriptional changes in nodules highlight downstream signaling pathways involving circadian clock regulation, nutrient transport, hormone signaling, and cell wall modification. Collectively, these results show that GmbHLHm1 influences nodule development and activity and is linked to a novel mechanism for NH4(+) transport common to both yeast and plants.</AbstractText
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Post-stroke aphasia is associated with a significantly elevated risk of depression, yet the underlying mechanisms remain unclear. This study recorded 64-channel electroencephalogram data and depression scale scores from 12 aphasic patients with depression, 8 aphasic patients without depression, and 12 healthy controls during resting state and an emotional Stroop task. Spectral and microstate analyses were conducted to examine brain activity patterns across conditions. Results showed that depression scores significantly negatively explained the occurrence of microstate class C and positively explained the transition probability from microstate class A to B. Furthermore, aphasic patients with depression exhibited increased alpha-band activation in the frontal region. These findings suggest distinct neural features in aphasic patients with depression and offer new insights into the mechanisms contributing to their heightened vulnerability to depression.</AbstractText 卒中后失语症患者的抑郁风险显著上升,但这一风险增加是源于外部心理社会因素还是大脑结构或功能变化目前尚不明确。本研究采集了12名失语抑郁患者、8名失语非抑郁患者以及12名健康志愿者在静息态与面孔情绪词任务下的64导联湿电极脑电信号,并进行了抑郁量表评估。研究结合频谱分析与微状态分析方法,比较三组人群在不同任务条件下的脑区神经活动模式。结果显示,受试者的抑郁量表评分能够负向解释C类微状态的发生率,正向解释A类到B类微状态的转换概率;此外,失语抑郁患者前额区域Alpha频段激活程度较为明显。上述差异可能反映了失语抑郁患者特有的神经活动特征,为理解其抑郁风险上升的潜在机制提供了新的研究路径。.</AbstractText
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Identifying Space-Resolved Proteins of the Murine Thymus, by Combining MALDI Mass Spectrometry Imaging and Proteomics. The identification of spatially resolved proteomes has recently seen significant breakthroughs, yet challenges persist, particularly in integrating protein identification with precise spatial localization within a single experimental workflow. Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) enables spatial protein mapping on tissue sections without the need for antibodies. While MALDI-MSI addresses several obstacles in proteomic mapping with spatial resolution, it remains limited in its capacity for definitive protein identification. To overcome these limitations, this study introduces a novel approach combining MALDI-MSI with liquid chromatography-mass spectrometry (LC-MS/MS) to map protein localization and spatial changes in thymic tissue. Using a mouse model of chemotherapy-induced thymic involution with time-dependent regeneration kinetics, we evaluated the capability of this pipeline to resolve proteomic changes in a spatiotemporal manner. Our approach incorporates a scoring system to align molecular signals from MALDI-MSI with proteomic data, enabling precise identification of proteins critical for thymic function. The results reveal key changes in protein expression, particularly in regions associated with cell migration, cytoskeletal remodeling, and endogenous thymic regeneration. By analyzing the spatial distribution of proteins such as Keratin 8 (KRT8), Nucleoporin TPR, Cysteineand Glycine-Rich Protein 3 (CSPR3), and Tubulin-Associated Chaperone-A (TBCA), we observed distinct shifts in thymic compartment architecture, underscoring the impact of chemotherapy on thymic tissue structure. From a translational viewpoint, this approach identifies new pathways and targetable candidates to enhance immune cell recovery in pediatric cancer patients undergoing cytoreductive treatments. From an analytical perspective, it provides an innovative framework for visualizing protein distribution in lymphoid and other tissues, significantly advancing the potential for translational proteomic research.</AbstractText
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Soybean SAT1 (Symbiotic Ammonium Transporter 1) encodes a bHLH transcription factor involved in nodule growth and NH4+ transport. Glycine max symbiotic ammonium transporter 1 was first documented as a putative ammonium (NH4(+)) channel localized to the symbiosome membrane of soybean root nodules. We show that Glycine max symbiotic ammonium transporter 1 is actually a membrane-localized basic helix-loop-helix (bHLH) DNA-binding transcription factor now renamed Glycine max bHLH membrane 1 (GmbHLHm1). In yeast, GmbHLHm1 enters the nucleus and transcriptionally activates a unique plasma membrane NH4(+) channel Saccharomyces cerevisiae ammonium facilitator 1. Ammonium facilitator 1 homologs are present in soybean and other plant species, where they often share chromosomal microsynteny with bHLHm1 loci. GmbHLHm1 is important to the soybean rhizobium symbiosis because loss of activity results in a reduction of nodule fitness and growth. Transcriptional changes in nodules highlight downstream signaling pathways involving circadian clock regulation, nutrient transport, hormone signaling, and cell wall modification. Collectively, these results show that GmbHLHm1 influences nodule development and activity and is linked to a novel mechanism for NH4(+) transport common to both yeast and plants.</AbstractText
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[A study on electroencephalogram characteristics of depression in patients with aphasia based on resting state and emotional Stroop task]. Post-stroke aphasia is associated with a significantly elevated risk of depression, yet the underlying mechanisms remain unclear. This study recorded 64-channel electroencephalogram data and depression scale scores from 12 aphasic patients with depression, 8 aphasic patients without depression, and 12 healthy controls during resting state and an emotional Stroop task. Spectral and microstate analyses were conducted to examine brain activity patterns across conditions. Results showed that depression scores significantly negatively explained the occurrence of microstate class C and positively explained the transition probability from microstate class A to B. Furthermore, aphasic patients with depression exhibited increased alpha-band activation in the frontal region. These findings suggest distinct neural features in aphasic patients with depression and offer new insights into the mechanisms contributing to their heightened vulnerability to depression.</AbstractText 卒中后失语症患者的抑郁风险显著上升,但这一风险增加是源于外部心理社会因素还是大脑结构或功能变化目前尚不明确。本研究采集了12名失语抑郁患者、8名失语非抑郁患者以及12名健康志愿者在静息态与面孔情绪词任务下的64导联湿电极脑电信号,并进行了抑郁量表评估。研究结合频谱分析与微状态分析方法,比较三组人群在不同任务条件下的脑区神经活动模式。结果显示,受试者的抑郁量表评分能够负向解释C类微状态的发生率,正向解释A类到B类微状态的转换概率;此外,失语抑郁患者前额区域Alpha频段激活程度较为明显。上述差异可能反映了失语抑郁患者特有的神经活动特征,为理解其抑郁风险上升的潜在机制提供了新的研究路径。.</AbstractText
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40354353
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31384033
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40485144
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Neural Substrates Associated with Character Amnesia in Chinese Handwriting: A Functional Near-infrared Spectroscopy Study.
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The human imagination: the cognitive neuroscience of visual mental imagery.
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Supplementation of Omega-3 Increases Serum Levels of Brain-Derived Neurotrophic Factor and Decreases Depression Status in Patients With Bipolar Disorder: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.
|
Chinese speakers have long suffered from character amnesia in handwriting, failing to handwrite a character despite being able to recognize it. However, it remains unclear whether character amnesia arises from the failure in accessing orthographic representations in the orthographic lexicon, reduced graphemic information in the graphemic buffer, or/and weakened phonology-orthography links. To address this issue, we employed functional near-infrared spectroscopy to explore brain regions that are associated with character amnesia. In particular, we tested whether character amnesia is associated with deactivation in the fusiform gyrus (FG), the superior parietal gyrus (SPG), or the supramarginal gyrus (SMG), which have been shown to be respectively associated with the orthographic lexicon, graphemic buffer, and phonology-orthography conversion. In a handwriting-to-dictation task, 23 Cantonese-speaking adults handwrote a character according to a dictation prompt and then reported whether they correctly handwrote the character or suffered from character amnesia. Functional near-infrared spectroscopy results showed that, compared with correct handwriting, character amnesia elicited reduced activation in the bilateral FG, the SPG, and the SMG. Parametric analyses showed that character frequency and number of strokes positively correlated with activation of the FG and the SPG, respectively. Functional connectivity analyses demonstrated that, compared with correct handwriting, character amnesia was associated with decreased connectivity between the left FG and the left SMG, the right FG and the right SMG, the right FG and the right SPG, the right FG and the left SMG, and the right FG and the left SPG. Together, these results suggested that character amnesia is associated with the decayed orthographic representations (in the orthographic lexicon) and failure in phonology-orthography conversion, resulting in reduced orthographic information being retrieved (into the graphemic buffer) for handwriting execution.</AbstractText
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Mental imagery can be advantageous, unnecessary and even clinically disruptive. With methodological constraints now overcome, research has shown that visual imagery involves a network of brain areas from the frontal cortex to sensory areas, overlapping with the default mode network, and can function much like a weak version of afferent perception. Imagery vividness and strength range from completely absent (aphantasia) to photo-like (hyperphantasia). Both the anatomy and function of the primary visual cortex are related to visual imagery. The use of imagery as a tool has been linked to many compound cognitive processes and imagery plays both symptomatic and mechanistic roles in neurological and mental disorders and treatments.</AbstractText
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There is a direct relationship between omega-3 and major depression. This study was conducted to investigate the effect of supplementation of omega-3 fatty acids on serum levels of brain-derived neurotrophic factor (BDNF) and depression status in patients with bipolar disorder (BD).</AbstractText This double-blind clinical trial was conducted on 60 men with BD. The patients were grouped into two groups and received 2 g/day of omega-3 supplements or a placebo daily for 2 months. The serum concentrations of BDNF and depression scores were investigated before and after the intervention. Afterward, the data were analyzed using the non-parametric Wilcoxon and Mann-Whitney tests.</AbstractText The supplementation of omega-3 fatty acids significantly increased the serum concentration of BDNF compared to pre-intervention (0.449 ± 0.110 ng/mL vs. 0.756 ± 0.160 ng/mL) and also decreased the scores on the Hamilton test (40.13 ± 9.51 vs. 22.40 ± 7.49) (p < 0.05). The results also showed that supplementation with omega-3 fatty acids significantly increased the serum concentration of BDNF (0.756 ± 0.160 ng/mL vs. 0.504 ± 0.154 ng/mL) and decreased the scores on the Hamilton test compared to the placebo group (22.40 ± 7.49 vs. 29.35 ± 6.08) (p < 0.05).</AbstractText In conclusion, daily supplementation with 2 g of omega-3 fatty acids for 2 months decreased depression scores and increased serum concentrations of BDNF in BD patients compared to the placebo group.</AbstractText
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Neural Substrates Associated with Character Amnesia in Chinese Handwriting: A Functional Near-infrared Spectroscopy Study. Chinese speakers have long suffered from character amnesia in handwriting, failing to handwrite a character despite being able to recognize it. However, it remains unclear whether character amnesia arises from the failure in accessing orthographic representations in the orthographic lexicon, reduced graphemic information in the graphemic buffer, or/and weakened phonology-orthography links. To address this issue, we employed functional near-infrared spectroscopy to explore brain regions that are associated with character amnesia. In particular, we tested whether character amnesia is associated with deactivation in the fusiform gyrus (FG), the superior parietal gyrus (SPG), or the supramarginal gyrus (SMG), which have been shown to be respectively associated with the orthographic lexicon, graphemic buffer, and phonology-orthography conversion. In a handwriting-to-dictation task, 23 Cantonese-speaking adults handwrote a character according to a dictation prompt and then reported whether they correctly handwrote the character or suffered from character amnesia. Functional near-infrared spectroscopy results showed that, compared with correct handwriting, character amnesia elicited reduced activation in the bilateral FG, the SPG, and the SMG. Parametric analyses showed that character frequency and number of strokes positively correlated with activation of the FG and the SPG, respectively. Functional connectivity analyses demonstrated that, compared with correct handwriting, character amnesia was associated with decreased connectivity between the left FG and the left SMG, the right FG and the right SMG, the right FG and the right SPG, the right FG and the left SMG, and the right FG and the left SPG. Together, these results suggested that character amnesia is associated with the decayed orthographic representations (in the orthographic lexicon) and failure in phonology-orthography conversion, resulting in reduced orthographic information being retrieved (into the graphemic buffer) for handwriting execution.</AbstractText
|
The human imagination: the cognitive neuroscience of visual mental imagery. Mental imagery can be advantageous, unnecessary and even clinically disruptive. With methodological constraints now overcome, research has shown that visual imagery involves a network of brain areas from the frontal cortex to sensory areas, overlapping with the default mode network, and can function much like a weak version of afferent perception. Imagery vividness and strength range from completely absent (aphantasia) to photo-like (hyperphantasia). Both the anatomy and function of the primary visual cortex are related to visual imagery. The use of imagery as a tool has been linked to many compound cognitive processes and imagery plays both symptomatic and mechanistic roles in neurological and mental disorders and treatments.</AbstractText
|
Supplementation of Omega-3 Increases Serum Levels of Brain-Derived Neurotrophic Factor and Decreases Depression Status in Patients With Bipolar Disorder: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. There is a direct relationship between omega-3 and major depression. This study was conducted to investigate the effect of supplementation of omega-3 fatty acids on serum levels of brain-derived neurotrophic factor (BDNF) and depression status in patients with bipolar disorder (BD).</AbstractText This double-blind clinical trial was conducted on 60 men with BD. The patients were grouped into two groups and received 2 g/day of omega-3 supplements or a placebo daily for 2 months. The serum concentrations of BDNF and depression scores were investigated before and after the intervention. Afterward, the data were analyzed using the non-parametric Wilcoxon and Mann-Whitney tests.</AbstractText The supplementation of omega-3 fatty acids significantly increased the serum concentration of BDNF compared to pre-intervention (0.449 ± 0.110 ng/mL vs. 0.756 ± 0.160 ng/mL) and also decreased the scores on the Hamilton test (40.13 ± 9.51 vs. 22.40 ± 7.49) (p < 0.05). The results also showed that supplementation with omega-3 fatty acids significantly increased the serum concentration of BDNF (0.756 ± 0.160 ng/mL vs. 0.504 ± 0.154 ng/mL) and decreased the scores on the Hamilton test compared to the placebo group (22.40 ± 7.49 vs. 29.35 ± 6.08) (p < 0.05).</AbstractText In conclusion, daily supplementation with 2 g of omega-3 fatty acids for 2 months decreased depression scores and increased serum concentrations of BDNF in BD patients compared to the placebo group.</AbstractText
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37507032
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31749516
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37055008
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The influence of static portal pressure on liver biophysical properties.
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Acoustic radiation force optical coherence elastography for elasticity assessment of soft tissues.
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Neurotensin receptor 1-biased ligand attenuates neurotensin-mediated excitation of ventral tegmental area dopamine neurons and dopamine release in the nucleus accumbens.
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The liver is a highly vascularized organ where fluid properties, including vascular pressure, vessel integrity and fluid viscosity, play a critical role in gross mechanical properties. To study the effects of portal pressure, liver confinement, fluid viscosity, and tissue crosslinking on liver stiffness, water diffusion, and vessel size, we applied multiparametric magnetic resonance imaging (mpMRI), including multifrequency magnetic resonance elastography (MRE) and apparent diffusion coefficient (ADC) measurements, to ex vivo livers from healthy male rats (13.6±1.6 weeks) at room temperature. Four scenarios including altered liver confinement, tissue crosslinking, and vascular fluid viscosity were investigated with mpMRI at different portal pressure levels (0-17.5 cmH<sub
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Biomechanical properties of soft tissues are important indicators of tissue functions which can be used for clinical diagnosis and disease monitoring. Elastography, incorporating the principles of elasticity measurements into imaging modalities, provides quantitative assessment of elastic properties of biological tissues. Benefiting from high-resolution, noninvasive and three-dimensional optical coherence tomography (OCT), optical coherence elastography (OCE) is an emerging optical imaging modality to characterize and map biomechanical properties of soft tissues. Recently, acoustic radiation force (ARF) OCE has been developed for elasticity measurements of ocular tissues, detection of vascular lesions and monitoring of blood coagulation based on remote and noninvasive ARF excitation to both internal and superficial tissues. Here, we describe the advantages of the ARF-OCE technique, the measurement methods in ARF-OCE, the applications in biomedical detection, current challenges and advances. ARF-OCE technology has the potential to become a powerful tool for <i
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Strong expression of the G protein-coupled receptor (GPCR) neurotensin receptor 1 (NTR1) in ventral tegmental area (VTA) dopamine (DA) neurons and terminals makes it an attractive target to modulate DA neuron activity and normalize DA-related pathologies. Recent studies have identified a novel class of NTR1 ligand that shows promising effects in preclinical models of addiction. A lead molecule, SBI-0654553 (SBI-553), can act as a positive allosteric modulator of NTR1 β-arrestin recruitment while simultaneously antagonizing NTR1 Gq protein signaling. Using cell-attached recordings from mouse VTA DA neurons we discovered that, unlike neurotensin (NT), SBI-553 did not independently increase spontaneous firing. Instead, SBI-553 blocked the NT-mediated increase in firing. SBI-553 also antagonized the effects of NT on dopamine D2 auto-receptor signaling, potentially through its inhibitory effects on G-protein signaling. We also measured DA release directly, using fast-scan cyclic voltammetry in the nucleus accumbens and observed antagonist effects of SBI-553 on an NT-induced increase in DA release. Further, in vivo administration of SBI-553 did not notably change basal or cocaine-evoked DA release measured in NAc using fiber photometry. Overall, these results indicate that SBI-553 blunts NT's effects on spontaneous DA neuron firing, D2 auto-receptor function, and DA release, without independently affecting these measures. In the presence of NT, SBI-553 has an inhibitory effect on mesolimbic DA activity, which could contribute to its efficacy in animal models of psychostimulant use.</AbstractText
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The influence of static portal pressure on liver biophysical properties. The liver is a highly vascularized organ where fluid properties, including vascular pressure, vessel integrity and fluid viscosity, play a critical role in gross mechanical properties. To study the effects of portal pressure, liver confinement, fluid viscosity, and tissue crosslinking on liver stiffness, water diffusion, and vessel size, we applied multiparametric magnetic resonance imaging (mpMRI), including multifrequency magnetic resonance elastography (MRE) and apparent diffusion coefficient (ADC) measurements, to ex vivo livers from healthy male rats (13.6±1.6 weeks) at room temperature. Four scenarios including altered liver confinement, tissue crosslinking, and vascular fluid viscosity were investigated with mpMRI at different portal pressure levels (0-17.5 cmH<sub
|
Acoustic radiation force optical coherence elastography for elasticity assessment of soft tissues. Biomechanical properties of soft tissues are important indicators of tissue functions which can be used for clinical diagnosis and disease monitoring. Elastography, incorporating the principles of elasticity measurements into imaging modalities, provides quantitative assessment of elastic properties of biological tissues. Benefiting from high-resolution, noninvasive and three-dimensional optical coherence tomography (OCT), optical coherence elastography (OCE) is an emerging optical imaging modality to characterize and map biomechanical properties of soft tissues. Recently, acoustic radiation force (ARF) OCE has been developed for elasticity measurements of ocular tissues, detection of vascular lesions and monitoring of blood coagulation based on remote and noninvasive ARF excitation to both internal and superficial tissues. Here, we describe the advantages of the ARF-OCE technique, the measurement methods in ARF-OCE, the applications in biomedical detection, current challenges and advances. ARF-OCE technology has the potential to become a powerful tool for <i
|
Neurotensin receptor 1-biased ligand attenuates neurotensin-mediated excitation of ventral tegmental area dopamine neurons and dopamine release in the nucleus accumbens. Strong expression of the G protein-coupled receptor (GPCR) neurotensin receptor 1 (NTR1) in ventral tegmental area (VTA) dopamine (DA) neurons and terminals makes it an attractive target to modulate DA neuron activity and normalize DA-related pathologies. Recent studies have identified a novel class of NTR1 ligand that shows promising effects in preclinical models of addiction. A lead molecule, SBI-0654553 (SBI-553), can act as a positive allosteric modulator of NTR1 β-arrestin recruitment while simultaneously antagonizing NTR1 Gq protein signaling. Using cell-attached recordings from mouse VTA DA neurons we discovered that, unlike neurotensin (NT), SBI-553 did not independently increase spontaneous firing. Instead, SBI-553 blocked the NT-mediated increase in firing. SBI-553 also antagonized the effects of NT on dopamine D2 auto-receptor signaling, potentially through its inhibitory effects on G-protein signaling. We also measured DA release directly, using fast-scan cyclic voltammetry in the nucleus accumbens and observed antagonist effects of SBI-553 on an NT-induced increase in DA release. Further, in vivo administration of SBI-553 did not notably change basal or cocaine-evoked DA release measured in NAc using fiber photometry. Overall, these results indicate that SBI-553 blunts NT's effects on spontaneous DA neuron firing, D2 auto-receptor function, and DA release, without independently affecting these measures. In the presence of NT, SBI-553 has an inhibitory effect on mesolimbic DA activity, which could contribute to its efficacy in animal models of psychostimulant use.</AbstractText
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24726812
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20851852
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24052383
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A preliminary study of functional connectivity of medication naïve children with obsessive-compulsive disorder.
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The prenatal origin of hemispheric asymmetry: an in utero neuroimaging study.
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Measuring membrane voltage with microbial rhodopsins.
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Evidence suggests that obsessive-compulsive disorder (OCD) is associated with a dysfunction in the cortico-striatal-thalamic-cortical (CSTC) circuitry. Resting state functional connectivity magnetic resonance imaging (rs-fcMRI) allows measurements of resting state networks (RSNs), brain networks that are present at 'rest'. However, although OCD has a typical onset during childhood or adolescence, only two other studies have performed rs-fcMRI comparisons of RSNs in children and adolescents with OCD against healthy controls.</AbstractText In the present study, we performed resting state functional magnetic resonance imaging using a 3 Tesla MRI, in 11 medication-naïve children and adolescents with OCD and 9 healthy controls. In contrast to previous studies that relied on a priori determination of RSNs, we determined resting state functional connectivity with a data-driven independent component analysis (ICA).</AbstractText Consistent with previous reports in healthy adults, we identified 13 RSNs. Case-control un-adjusted statistical significance (p<0.05) was found for two networks. Firstly, increased connectivity (OCD>control) in the right section of Brodmann area 43 of the auditory network; Secondly, decreased connectivity in the right section of Brodmann area 8 and Brodmann area 40 in the cingulate network.</AbstractText Our preliminary findings of case-control differences in RSNs lend further support to the CSTC hypothesis of OCD, as well as implicating other regions of the brain outside of the CSTC.</AbstractText
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Anatomical and functional hemispheric lateralization originates from differential gene expression and leads to asymmetric structural brain development, which initially appears in the perisylvian regions by 26 gestational weeks (GWs). In this in vivo neuroimaging study, we demonstrated a predominant pattern of temporal lobe (TL) asymmetry in a large cohort of human fetuses between 18 and 37 GWs. Over two-thirds of fetuses showed a larger, left-sided TL, combined with the earlier appearance of the right superior temporal sulcus by 23 GWs (vs. 25 GWs on the left side), which was also deeper than its left counterpart in the majority of cases (94.2%). Shape analysis detected highly significant differences in the contour of the right and left TLs by 20 GWs. Thus, fetal hemispheric asymmetry can be detected in utero, opening new diagnostic possibilities for the assessment of diseases that are believed to be linked to atypical hemispheric lateralization.</AbstractText
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Membrane voltage (Vm) is a fundamental biological parameter that is essential for neuronal communication, cardiac activity, transmembrane transport, regulation of signaling, and bacterial motility. Optical measurements of Vm promise new insights into how voltage propagates within and between cells, but effective optical contrast agents have been lacking. Microbial rhodopsin-based fluorescent voltage indicators are exquisitely sensitive and fast, but very dim, necessitating careful attention to experimental procedures. This chapter describes how to make optical voltage measurements with microbial rhodopsins.</AbstractText
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A preliminary study of functional connectivity of medication naïve children with obsessive-compulsive disorder. Evidence suggests that obsessive-compulsive disorder (OCD) is associated with a dysfunction in the cortico-striatal-thalamic-cortical (CSTC) circuitry. Resting state functional connectivity magnetic resonance imaging (rs-fcMRI) allows measurements of resting state networks (RSNs), brain networks that are present at 'rest'. However, although OCD has a typical onset during childhood or adolescence, only two other studies have performed rs-fcMRI comparisons of RSNs in children and adolescents with OCD against healthy controls.</AbstractText In the present study, we performed resting state functional magnetic resonance imaging using a 3 Tesla MRI, in 11 medication-naïve children and adolescents with OCD and 9 healthy controls. In contrast to previous studies that relied on a priori determination of RSNs, we determined resting state functional connectivity with a data-driven independent component analysis (ICA).</AbstractText Consistent with previous reports in healthy adults, we identified 13 RSNs. Case-control un-adjusted statistical significance (p<0.05) was found for two networks. Firstly, increased connectivity (OCD>control) in the right section of Brodmann area 43 of the auditory network; Secondly, decreased connectivity in the right section of Brodmann area 8 and Brodmann area 40 in the cingulate network.</AbstractText Our preliminary findings of case-control differences in RSNs lend further support to the CSTC hypothesis of OCD, as well as implicating other regions of the brain outside of the CSTC.</AbstractText
|
The prenatal origin of hemispheric asymmetry: an in utero neuroimaging study. Anatomical and functional hemispheric lateralization originates from differential gene expression and leads to asymmetric structural brain development, which initially appears in the perisylvian regions by 26 gestational weeks (GWs). In this in vivo neuroimaging study, we demonstrated a predominant pattern of temporal lobe (TL) asymmetry in a large cohort of human fetuses between 18 and 37 GWs. Over two-thirds of fetuses showed a larger, left-sided TL, combined with the earlier appearance of the right superior temporal sulcus by 23 GWs (vs. 25 GWs on the left side), which was also deeper than its left counterpart in the majority of cases (94.2%). Shape analysis detected highly significant differences in the contour of the right and left TLs by 20 GWs. Thus, fetal hemispheric asymmetry can be detected in utero, opening new diagnostic possibilities for the assessment of diseases that are believed to be linked to atypical hemispheric lateralization.</AbstractText
|
Measuring membrane voltage with microbial rhodopsins. Membrane voltage (Vm) is a fundamental biological parameter that is essential for neuronal communication, cardiac activity, transmembrane transport, regulation of signaling, and bacterial motility. Optical measurements of Vm promise new insights into how voltage propagates within and between cells, but effective optical contrast agents have been lacking. Microbial rhodopsin-based fluorescent voltage indicators are exquisitely sensitive and fast, but very dim, necessitating careful attention to experimental procedures. This chapter describes how to make optical voltage measurements with microbial rhodopsins.</AbstractText
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35844217
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19126760
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28744191
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Importin α3 (KPNA3) Deficiency Augments Effortful Reward-Seeking Behavior in Mice.
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Endocannabinoid-mediated control of synaptic transmission.
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Event-Related Potentials in a Cued Go-NoGo Task Associated with Executive Functions in Adolescents with Autism Spectrum Disorder; A Case-Control Study.
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Importin α3 (Gene: <i
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The discovery of cannabinoid receptors and subsequent identification of their endogenous ligands (endocannabinoids) in early 1990s have greatly accelerated research on cannabinoid actions in the brain. Then, the discovery in 2001 that endocannabinoids mediate retrograde synaptic signaling has opened up a new era for cannabinoid research and also established a new concept how diffusible messengers modulate synaptic efficacy and neural activity. The last 7 years have witnessed remarkable advances in our understanding of the endocannabinoid system. It is now well accepted that endocannabinoids are released from postsynaptic neurons, activate presynaptic cannabinoid CB(1) receptors, and cause transient and long-lasting reduction of neurotransmitter release. In this review, we aim to integrate our current understanding of functions of the endocannabinoid system, especially focusing on the control of synaptic transmission in the brain. We summarize recent electrophysiological studies carried out on synapses of various brain regions and discuss how synaptic transmission is regulated by endocannabinoid signaling. Then we refer to recent anatomical studies on subcellular distribution of the molecules involved in endocannabinoid signaling and discuss how these signaling molecules are arranged around synapses. In addition, we make a brief overview of studies on cannabinoid receptors and their intracellular signaling, biochemical studies on endocannabinoid metabolism, and behavioral studies on the roles of the endocannabinoid system in various aspects of neural functions.</AbstractText
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Executive functions are often affected in autism spectrum disorders (ASD). The underlying biology is however not well known. In the DSM-5, ASD is characterized by difficulties in two domains: Social Interaction and Repetitive and Restricted Behavior, RRB. Insistence of Sameness is part of RRB and has been reported related to executive functions. We aimed to identify differences between ASD and typically developing (TD) adolescents in Event Related Potentials (ERPs) associated with response preparation, conflict monitoring and response inhibition using a cued Go-NoGo paradigm. We also studied the effect of age and emotional content of paradigm related to these ERPs. We investigated 49 individuals with ASD and 49 TD aged 12-21 years, split into two groups below (young) and above (old) 16 years of age. ASD characteristics were quantified by the Social Communication Questionnaire (SCQ) and executive functions were assessed with the Behavior Rating Inventory of Executive Function (BRIEF), both parent-rated. Behavioral performance and ERPs were recorded during a cued visual Go-NoGo task which included neutral pictures (VCPT) and pictures of emotional faces (ECPT). The amplitudes of ERPs associated with response preparation, conflict monitoring, and response inhibition were analyzed. The ASD group showed markedly higher scores than TD in both SCQ and BRIEF. Behavioral data showed no case-control differences in either the VCPT or ECPT in the whole group. While there were no significant case-control differences in ERPs from the combined VCPT and ECPT in the whole sample, the Contingent Negative Variation (CNV) was significantly enhanced in the old ASD group (<i
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Importin α3 (KPNA3) Deficiency Augments Effortful Reward-Seeking Behavior in Mice. Importin α3 (Gene: <i
|
Endocannabinoid-mediated control of synaptic transmission. The discovery of cannabinoid receptors and subsequent identification of their endogenous ligands (endocannabinoids) in early 1990s have greatly accelerated research on cannabinoid actions in the brain. Then, the discovery in 2001 that endocannabinoids mediate retrograde synaptic signaling has opened up a new era for cannabinoid research and also established a new concept how diffusible messengers modulate synaptic efficacy and neural activity. The last 7 years have witnessed remarkable advances in our understanding of the endocannabinoid system. It is now well accepted that endocannabinoids are released from postsynaptic neurons, activate presynaptic cannabinoid CB(1) receptors, and cause transient and long-lasting reduction of neurotransmitter release. In this review, we aim to integrate our current understanding of functions of the endocannabinoid system, especially focusing on the control of synaptic transmission in the brain. We summarize recent electrophysiological studies carried out on synapses of various brain regions and discuss how synaptic transmission is regulated by endocannabinoid signaling. Then we refer to recent anatomical studies on subcellular distribution of the molecules involved in endocannabinoid signaling and discuss how these signaling molecules are arranged around synapses. In addition, we make a brief overview of studies on cannabinoid receptors and their intracellular signaling, biochemical studies on endocannabinoid metabolism, and behavioral studies on the roles of the endocannabinoid system in various aspects of neural functions.</AbstractText
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Event-Related Potentials in a Cued Go-NoGo Task Associated with Executive Functions in Adolescents with Autism Spectrum Disorder; A Case-Control Study. Executive functions are often affected in autism spectrum disorders (ASD). The underlying biology is however not well known. In the DSM-5, ASD is characterized by difficulties in two domains: Social Interaction and Repetitive and Restricted Behavior, RRB. Insistence of Sameness is part of RRB and has been reported related to executive functions. We aimed to identify differences between ASD and typically developing (TD) adolescents in Event Related Potentials (ERPs) associated with response preparation, conflict monitoring and response inhibition using a cued Go-NoGo paradigm. We also studied the effect of age and emotional content of paradigm related to these ERPs. We investigated 49 individuals with ASD and 49 TD aged 12-21 years, split into two groups below (young) and above (old) 16 years of age. ASD characteristics were quantified by the Social Communication Questionnaire (SCQ) and executive functions were assessed with the Behavior Rating Inventory of Executive Function (BRIEF), both parent-rated. Behavioral performance and ERPs were recorded during a cued visual Go-NoGo task which included neutral pictures (VCPT) and pictures of emotional faces (ECPT). The amplitudes of ERPs associated with response preparation, conflict monitoring, and response inhibition were analyzed. The ASD group showed markedly higher scores than TD in both SCQ and BRIEF. Behavioral data showed no case-control differences in either the VCPT or ECPT in the whole group. While there were no significant case-control differences in ERPs from the combined VCPT and ECPT in the whole sample, the Contingent Negative Variation (CNV) was significantly enhanced in the old ASD group (<i
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37401447
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36502350
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38145674
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Modification to the placement of the navigation reference frame in posterior corrective fusion of spinal deformity with myelomeningocele: a series of 6 cases.
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Functional level of lesion scale: Validating fourteen years of research with the national spina bifida patient registry.
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A portfolio decision analysis approach for selecting a subset of interdependent actions: The case of a regional climate roadmap in Finland.
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To show a modified placement of the navigation reference frame in posterior corrective fusion of spinal deformity with myelomeningocele. This was a retrospective, single-surgeon case series, and IRB-approved study. Six consecutive patients (one male and five females) who were diagnosed with spinal deformity with myelomeningocele underwent posterior corrective fusion surgery from the upper thoracic spine to the pelvis with preoperative computed tomography navigation (pCTN). At the level of the spina bifida, where posterior elements such as the spinous process were missing, the reference frame of the pCTN was placed on the flipped lamina or pedicles, and a pedicle screw (PS) or iliac screw (IS) was inserted. Screw deviation was investigated by using postoperative CT. A total of 55 screws were placed at the spina bifida level and pelvis. Of these, 12 ISs were placed on each side in each case. The screws placed using the pCTN were not reinserted or removed intraoperatively or postoperatively. However, only one PS was found to have perforated the spinal canal on postoperative CT but was left in place because it caused no neurological problem. By modifying the placement of the reference frame, such as placing it on the flipped lamina or pedicles, pCTN could be used even at the levels of the spina bifida, where the posterior elements are missing, to accurately place PSs and various types of ISs.</AbstractText
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Functional level of lesion (FLOL) is a grading of the level of neurological function in patients with myelomeningocele and other forms of spina bifida. It has been widely used as an independent variable in studies of spina bifida, but its inter-rater reliability has not previously been tested. The purpose of this study was to measure inter-rater reliability of FLOL testing and compare testing performed by a non-medically trained research associate to testing performed by a pediatric rehabilitation medicine specialist.</AbstractText Children in a multi-disciplinary spina bifida clinic underwent FLOL grading by a non-medically trained research associate. On the same day, these children were also graded by a pediatric rehabilitation medicine specialist. Cohen's weighted kappa statistic was used to compare grading, with the rehabilitation medicine specialist considered the gold standard.</AbstractText A total of 71 patients participated. FLOL was graded for left and right leg for each participant, resulting in 142 measurements. Cohen's weighted kappa was κ= 0.809, with a standard error of 0.034 and 95% confidence interval 0.723-0.875, indicating substantial agreement.</AbstractText FLOL as measured according to the instructions of the National Spina Bifida Patient Registry by a non-medically trained researcher is a reliable method to grade lower extremity function in spina bifida.</AbstractText
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In this paper, we present a structured approach based on portfolio decision analysis to support the consideration of interdependencies between actions (i.e. interactions) in the selection of an efficient portfolio. One of the main challenges in modelling interactions is that the possible number of them between the pairs of actions increases exponentially with the number of actions. In environmental management, the problems can include tens of possible actions potentially leading to hundreds of pairwise interactions between them. For example, a strategy for mitigating climate change can consist of various actions in different sectors for improving technology, reducing emissions and the sequestration of carbon. Our approach aims to reduce the burden of assessing interactions by initially selecting a shortlist of actions based on specific heuristics and focusing on modelling interactions exclusively within this chosen set of actions. Another feature of the approach is the use of holistic evaluation of interactions to further reduce the cognitive load of stakeholders making the assessment. As a possible disadvantage, these features may increase the imprecision related to the results of the model. To analyse the impacts of this imprecision, we propose a way to carry out sensitivity analysis on the basis of how intensively the interactions would be taken into account in the modelling. The applicability of the approach was tested in a case related to the roadmap to a carbon neutral North Savo region in Finland by the year 2035. The approach helped to better understand synergies and trade-offs when putting the actions of the roadmap into practice, which is expected to lead to better results in terms of preparedness and adaptation to climate change.</AbstractText
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Modification to the placement of the navigation reference frame in posterior corrective fusion of spinal deformity with myelomeningocele: a series of 6 cases. To show a modified placement of the navigation reference frame in posterior corrective fusion of spinal deformity with myelomeningocele. This was a retrospective, single-surgeon case series, and IRB-approved study. Six consecutive patients (one male and five females) who were diagnosed with spinal deformity with myelomeningocele underwent posterior corrective fusion surgery from the upper thoracic spine to the pelvis with preoperative computed tomography navigation (pCTN). At the level of the spina bifida, where posterior elements such as the spinous process were missing, the reference frame of the pCTN was placed on the flipped lamina or pedicles, and a pedicle screw (PS) or iliac screw (IS) was inserted. Screw deviation was investigated by using postoperative CT. A total of 55 screws were placed at the spina bifida level and pelvis. Of these, 12 ISs were placed on each side in each case. The screws placed using the pCTN were not reinserted or removed intraoperatively or postoperatively. However, only one PS was found to have perforated the spinal canal on postoperative CT but was left in place because it caused no neurological problem. By modifying the placement of the reference frame, such as placing it on the flipped lamina or pedicles, pCTN could be used even at the levels of the spina bifida, where the posterior elements are missing, to accurately place PSs and various types of ISs.</AbstractText
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Functional level of lesion scale: Validating fourteen years of research with the national spina bifida patient registry. Functional level of lesion (FLOL) is a grading of the level of neurological function in patients with myelomeningocele and other forms of spina bifida. It has been widely used as an independent variable in studies of spina bifida, but its inter-rater reliability has not previously been tested. The purpose of this study was to measure inter-rater reliability of FLOL testing and compare testing performed by a non-medically trained research associate to testing performed by a pediatric rehabilitation medicine specialist.</AbstractText Children in a multi-disciplinary spina bifida clinic underwent FLOL grading by a non-medically trained research associate. On the same day, these children were also graded by a pediatric rehabilitation medicine specialist. Cohen's weighted kappa statistic was used to compare grading, with the rehabilitation medicine specialist considered the gold standard.</AbstractText A total of 71 patients participated. FLOL was graded for left and right leg for each participant, resulting in 142 measurements. Cohen's weighted kappa was κ= 0.809, with a standard error of 0.034 and 95% confidence interval 0.723-0.875, indicating substantial agreement.</AbstractText FLOL as measured according to the instructions of the National Spina Bifida Patient Registry by a non-medically trained researcher is a reliable method to grade lower extremity function in spina bifida.</AbstractText
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A portfolio decision analysis approach for selecting a subset of interdependent actions: The case of a regional climate roadmap in Finland. In this paper, we present a structured approach based on portfolio decision analysis to support the consideration of interdependencies between actions (i.e. interactions) in the selection of an efficient portfolio. One of the main challenges in modelling interactions is that the possible number of them between the pairs of actions increases exponentially with the number of actions. In environmental management, the problems can include tens of possible actions potentially leading to hundreds of pairwise interactions between them. For example, a strategy for mitigating climate change can consist of various actions in different sectors for improving technology, reducing emissions and the sequestration of carbon. Our approach aims to reduce the burden of assessing interactions by initially selecting a shortlist of actions based on specific heuristics and focusing on modelling interactions exclusively within this chosen set of actions. Another feature of the approach is the use of holistic evaluation of interactions to further reduce the cognitive load of stakeholders making the assessment. As a possible disadvantage, these features may increase the imprecision related to the results of the model. To analyse the impacts of this imprecision, we propose a way to carry out sensitivity analysis on the basis of how intensively the interactions would be taken into account in the modelling. The applicability of the approach was tested in a case related to the roadmap to a carbon neutral North Savo region in Finland by the year 2035. The approach helped to better understand synergies and trade-offs when putting the actions of the roadmap into practice, which is expected to lead to better results in terms of preparedness and adaptation to climate change.</AbstractText
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40334931
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39593731
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40430343
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Unification of alpha, mu, and tau rhythms and their beta-band harmonics via eigenmodes: spectral peaks, topography, and reactivity.
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Improving EEG Forward Modeling Using High-Resolution Five-Layer BEM-FMM Head Models: Effect on Source Reconstruction Accuracy.
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Synthesis of 3-Carboxy-6-sulfamoylquinolones and Mefloquine-Based Compounds as Panx1 Blockers: Molecular Docking, Electrophysiological and Cell Culture Studies.
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The alpha, mu, and tau rhythms all have frequencies of around 10 Hz in normal adult humans, with a range of 7-13 Hz. The beta rhythm, mu-associated activity, and tau-associated activity, are found at around twice those frequencies. The present objective is to use neural field theory (NFT) to explain the observed frequency structure and spatial topography, and to suggest a mechanism of reactivity, of all these rhythms in a unified way, and to predict other features not yet reported experimentally.</AbstractText NFT averages over the activity of large numbers of neurons to predict mean firing rates and EEG characteristics. It predicts the existence of natural modes of activity, each with characteristic spatial structure and frequencies. The lowest modes dominate large-scale activity and the first four are used here to predict spectra, topography, and reactivity of alpha, mu, and tau rhythms and their second harmonics, including split peaks.</AbstractText Corticothalamic loop delays determine the basic ∼10 Hz frequency of the alpha rhythm, the ∼20 Hz frequency of the beta rhythm, and explain their frequency correlations on an individual-subject level. Differential effects of cortical geometry on individual modes cause observed frequency splitting of the alpha and beta rhythms and we predict analogous splitting of mu and tau and their harmonics. Spatial topographies of alpha, mu, and tau are explained by modal structure, with amplitudes superposed rather than powers, and we predict that the harmonic of each rhythm will tend to have similar topography to its fundamental, although specific exceptions can occur. Similar results are obtained when modal eigenfrequencies differ sufficiently to give rise to split peaks. Dynamics of rotating patterns and wavefronts are also explained in terms of pairs of modes. Blocking or "desynchronization" of each rhythm can be accounted for by modest decreases in corticothalamic loop gains, magnified by proximity to a critical state, and we predict that fundamental and harmonic will tend to be blocked in tandem, an effect that has already been observed for alpha and beta. Paradoxically, modal analysis implies that blocking in one region can correlate with enhancement in another, which may account for the phenomenon of event-related synchronization.</AbstractText A unified explanation of alpha, mu, tau, and their harmonics is obtained in terms of just four corticothalamic eigenmodes. The results are consistent with a wide variety of experimental observations and experimentally testable predictions of new features are made.</AbstractText A century after the first observations of human EEG, this work explains and unifies alpha, the earliest detected rhythm, with its relatives and their harmonics to form a single family. This provides a strong theoretical basis for analysis and monitoring of activity and its underlying physiology and, via NFT, for linking these rhythms to other phenomena such as evoked responses.</AbstractText
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Electroencephalographic (EEG) source localization is a fundamental tool for clinical diagnoses and brain-computer interfaces. We investigate the impact of model complexity on reconstruction accuracy by comparing the widely used three-layer boundary element method (BEM) as an inverse method against a five-layer BEM accelerated by the fast multipole method (BEM-FMM) and coupled with adaptive mesh refinement (AMR) as forward solver. Modern BEM-FMM with AMR can solve high-resolution multi-tissue models efficiently and accurately. We generated noiseless 256-channel EEG data from 15 subjects in the Connectome Young Adult dataset, using four anatomically relevant dipole positions, three conductivity sets, and two head segmentations; we mapped localization errors across the entire grey matter from 4000 dipole positions. The average location error among our four selected dipoles is ∼5mm (±2mm) with an orientation error of ∼12∘ (±7∘). The average source localization error across the entire grey matter is ∼9mm (±4mm), with a tendency for smaller errors on the occipital lobe. Our findings indicate that while three-layer models are robust under noiseless conditions, substantial localization errors (10-20mm) are common. Therefore, models of five or more layers may be needed for accurate source reconstruction in critical applications involving noisy EEG data.</AbstractText
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The membrane channel protein Panx1 is a promising therapeutic target since its involvement was demonstrated in a variety of pathologies such as neuropathic pain, ischemic stroke and cancer. As a continuation of our previous work in this field, we report here the synthesis and biological evaluation of two classes of compounds as Panx1 blockers: 3-carboxy-6-sulphonamidoquinolone derivatives and new Mefloquine analogs. The series of 3-carboxy-6-sulphonamidoquinolones gave interesting results, affording powerful Panx1 channel blockers with 73.2 < I% < 100 at 50 µM. In particular, <b
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Unification of alpha, mu, and tau rhythms and their beta-band harmonics via eigenmodes: spectral peaks, topography, and reactivity. The alpha, mu, and tau rhythms all have frequencies of around 10 Hz in normal adult humans, with a range of 7-13 Hz. The beta rhythm, mu-associated activity, and tau-associated activity, are found at around twice those frequencies. The present objective is to use neural field theory (NFT) to explain the observed frequency structure and spatial topography, and to suggest a mechanism of reactivity, of all these rhythms in a unified way, and to predict other features not yet reported experimentally.</AbstractText NFT averages over the activity of large numbers of neurons to predict mean firing rates and EEG characteristics. It predicts the existence of natural modes of activity, each with characteristic spatial structure and frequencies. The lowest modes dominate large-scale activity and the first four are used here to predict spectra, topography, and reactivity of alpha, mu, and tau rhythms and their second harmonics, including split peaks.</AbstractText Corticothalamic loop delays determine the basic ∼10 Hz frequency of the alpha rhythm, the ∼20 Hz frequency of the beta rhythm, and explain their frequency correlations on an individual-subject level. Differential effects of cortical geometry on individual modes cause observed frequency splitting of the alpha and beta rhythms and we predict analogous splitting of mu and tau and their harmonics. Spatial topographies of alpha, mu, and tau are explained by modal structure, with amplitudes superposed rather than powers, and we predict that the harmonic of each rhythm will tend to have similar topography to its fundamental, although specific exceptions can occur. Similar results are obtained when modal eigenfrequencies differ sufficiently to give rise to split peaks. Dynamics of rotating patterns and wavefronts are also explained in terms of pairs of modes. Blocking or "desynchronization" of each rhythm can be accounted for by modest decreases in corticothalamic loop gains, magnified by proximity to a critical state, and we predict that fundamental and harmonic will tend to be blocked in tandem, an effect that has already been observed for alpha and beta. Paradoxically, modal analysis implies that blocking in one region can correlate with enhancement in another, which may account for the phenomenon of event-related synchronization.</AbstractText A unified explanation of alpha, mu, tau, and their harmonics is obtained in terms of just four corticothalamic eigenmodes. The results are consistent with a wide variety of experimental observations and experimentally testable predictions of new features are made.</AbstractText A century after the first observations of human EEG, this work explains and unifies alpha, the earliest detected rhythm, with its relatives and their harmonics to form a single family. This provides a strong theoretical basis for analysis and monitoring of activity and its underlying physiology and, via NFT, for linking these rhythms to other phenomena such as evoked responses.</AbstractText
|
Improving EEG Forward Modeling Using High-Resolution Five-Layer BEM-FMM Head Models: Effect on Source Reconstruction Accuracy. Electroencephalographic (EEG) source localization is a fundamental tool for clinical diagnoses and brain-computer interfaces. We investigate the impact of model complexity on reconstruction accuracy by comparing the widely used three-layer boundary element method (BEM) as an inverse method against a five-layer BEM accelerated by the fast multipole method (BEM-FMM) and coupled with adaptive mesh refinement (AMR) as forward solver. Modern BEM-FMM with AMR can solve high-resolution multi-tissue models efficiently and accurately. We generated noiseless 256-channel EEG data from 15 subjects in the Connectome Young Adult dataset, using four anatomically relevant dipole positions, three conductivity sets, and two head segmentations; we mapped localization errors across the entire grey matter from 4000 dipole positions. The average location error among our four selected dipoles is ∼5mm (±2mm) with an orientation error of ∼12∘ (±7∘). The average source localization error across the entire grey matter is ∼9mm (±4mm), with a tendency for smaller errors on the occipital lobe. Our findings indicate that while three-layer models are robust under noiseless conditions, substantial localization errors (10-20mm) are common. Therefore, models of five or more layers may be needed for accurate source reconstruction in critical applications involving noisy EEG data.</AbstractText
|
Synthesis of 3-Carboxy-6-sulfamoylquinolones and Mefloquine-Based Compounds as Panx1 Blockers: Molecular Docking, Electrophysiological and Cell Culture Studies. The membrane channel protein Panx1 is a promising therapeutic target since its involvement was demonstrated in a variety of pathologies such as neuropathic pain, ischemic stroke and cancer. As a continuation of our previous work in this field, we report here the synthesis and biological evaluation of two classes of compounds as Panx1 blockers: 3-carboxy-6-sulphonamidoquinolone derivatives and new Mefloquine analogs. The series of 3-carboxy-6-sulphonamidoquinolones gave interesting results, affording powerful Panx1 channel blockers with 73.2 < I% < 100 at 50 µM. In particular, <b
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38853562
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22740813
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39154205
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Src dependency of the regulation of LTP by alternative splicing of GRIN1 exon 5.
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Role of a redox-based methylation switch in mRNA life cycle (pre- and post-transcriptional maturation) and protein turnover: implications in neurological disorders.
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Uncommon Streptococcus Constellatus Meningitis Leading to Pulmonary Abscess and Brainstem Infarct in an Immunocompetent Patient.
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Alternative splicing of <i
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Homeostatic synaptic scaling in response to neuronal stimulus or activation, and due to changes in cellular niche, is an important phenomenon for memory consolidation, retrieval, and other similar cognitive functions (Turrigiano and Nelson, 2004). Neurological disorders and cognitive disabilities in autism, Rett syndrome, schizophrenia, dementia, etc., are strongly correlated to alterations in protein expression (both synaptic and cytoplasmic; Cajigas et al., 2010). This correlation suggests that efficient temporal regulation of synaptic protein expression is important for synaptic plasticity. In addition, equilibrium between mRNA processing, protein translation, and protein turnover is a critical sensor/trigger for recording synaptic information, normal cognition, and behavior (Cajigas et al., 2010). Thus a regulatory switch, which controls the lifespan, maturation, and processing of mRNA, might influence cognition and adaptive behavior. Here, we propose a two part novel hypothesis that methylation might act as this suggested coordinating switch to critically regulate mRNA maturation at (1) the pre-transcription level, by regulating precursor-RNA processing into mRNA, via other non-coding RNAs and their influence on splicing phenomenon, and (2) the post-transcription level by modulating the regulatory functions of ribonucleoproteins and RNA binding proteins in mRNA translation, dendritic translocation as well as protein synthesis and synaptic turnover. DNA methylation changes are well recognized and highly correlated to gene expression levels as well as, learning and memory; however, RNA methylation changes are recently characterized and yet their functional implications are not established. This review article provides some insight on the intriguing consequences of changes in methylation levels on mRNA life-cycle. We also suggest that, since methylation is under the control of glutathione anti-oxidant levels (Lertratanangkoon et al., 1997), the redox status of neurons might be the central regulatory switch for methylation-based changes in mRNA processing, protein expression, and turnover. Lastly, we also describe experimental methods and techniques which might help researchers to evaluate the suggested hypothesis.</AbstractText
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BACKGROUND Except for neonates, streptococci other than Streptococcus pneumoniae are a rare cause of acute bacterial meningitis. Streptococcus constellatus is a member of the Streptococcus anginosus group of gram-positive streptococci. It is a commensal microbe of the mucosae of the oral cavity, gastrointestinal tract, and urogenital tract. Rarely, it becomes pathogenic and causes contiguous or distant infections after mucosal damage. This report describes a 19-year-old immunocompetent man who developed bacterial meningitis, lung abscess, and brainstem infarct secondary to Streptococcus constellatus. CASE REPORT A 19-year-old immunocompetent man presented to the Emergency Department with a 4-week history of headache and neck pain. He was febrile on arrival. Physical examination revealed ataxia, upper-limb discoordination, and a positive Brudzinski sign. Cerebrospinal fluid and blood cultures were positive for Streptococcus constellatus, identified by matrix-assisted laser desorption ionization - time of flight mass spectrometry. Computed tomography of the chest demonstrated a lung abscess measuring 7×3.5×3 cm. A magnetic resonance imaging scan of the head revealed a 1.8×0.7 cm acute infarct in the right pons. The patient was treated initially with intravenous ceftriaxone and vancomycin before culture and sensitivity results, in addition to intravenous dexamethasone. After culture and sensitivities resulted, antibiotics were transitioned to a 4-week course of intravenous penicillin. The patient survived with no neurological consequences upon discharge. CONCLUSIONS Streptococcus constellatus should be suspected as an etiological agent for bacterial meningitis and other rare complications such as brainstem infarction and lung abscess, even in immunocompetent patients.</AbstractText
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Src dependency of the regulation of LTP by alternative splicing of GRIN1 exon 5. Alternative splicing of <i
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Role of a redox-based methylation switch in mRNA life cycle (pre- and post-transcriptional maturation) and protein turnover: implications in neurological disorders. Homeostatic synaptic scaling in response to neuronal stimulus or activation, and due to changes in cellular niche, is an important phenomenon for memory consolidation, retrieval, and other similar cognitive functions (Turrigiano and Nelson, 2004). Neurological disorders and cognitive disabilities in autism, Rett syndrome, schizophrenia, dementia, etc., are strongly correlated to alterations in protein expression (both synaptic and cytoplasmic; Cajigas et al., 2010). This correlation suggests that efficient temporal regulation of synaptic protein expression is important for synaptic plasticity. In addition, equilibrium between mRNA processing, protein translation, and protein turnover is a critical sensor/trigger for recording synaptic information, normal cognition, and behavior (Cajigas et al., 2010). Thus a regulatory switch, which controls the lifespan, maturation, and processing of mRNA, might influence cognition and adaptive behavior. Here, we propose a two part novel hypothesis that methylation might act as this suggested coordinating switch to critically regulate mRNA maturation at (1) the pre-transcription level, by regulating precursor-RNA processing into mRNA, via other non-coding RNAs and their influence on splicing phenomenon, and (2) the post-transcription level by modulating the regulatory functions of ribonucleoproteins and RNA binding proteins in mRNA translation, dendritic translocation as well as protein synthesis and synaptic turnover. DNA methylation changes are well recognized and highly correlated to gene expression levels as well as, learning and memory; however, RNA methylation changes are recently characterized and yet their functional implications are not established. This review article provides some insight on the intriguing consequences of changes in methylation levels on mRNA life-cycle. We also suggest that, since methylation is under the control of glutathione anti-oxidant levels (Lertratanangkoon et al., 1997), the redox status of neurons might be the central regulatory switch for methylation-based changes in mRNA processing, protein expression, and turnover. Lastly, we also describe experimental methods and techniques which might help researchers to evaluate the suggested hypothesis.</AbstractText
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Uncommon Streptococcus Constellatus Meningitis Leading to Pulmonary Abscess and Brainstem Infarct in an Immunocompetent Patient. BACKGROUND Except for neonates, streptococci other than Streptococcus pneumoniae are a rare cause of acute bacterial meningitis. Streptococcus constellatus is a member of the Streptococcus anginosus group of gram-positive streptococci. It is a commensal microbe of the mucosae of the oral cavity, gastrointestinal tract, and urogenital tract. Rarely, it becomes pathogenic and causes contiguous or distant infections after mucosal damage. This report describes a 19-year-old immunocompetent man who developed bacterial meningitis, lung abscess, and brainstem infarct secondary to Streptococcus constellatus. CASE REPORT A 19-year-old immunocompetent man presented to the Emergency Department with a 4-week history of headache and neck pain. He was febrile on arrival. Physical examination revealed ataxia, upper-limb discoordination, and a positive Brudzinski sign. Cerebrospinal fluid and blood cultures were positive for Streptococcus constellatus, identified by matrix-assisted laser desorption ionization - time of flight mass spectrometry. Computed tomography of the chest demonstrated a lung abscess measuring 7×3.5×3 cm. A magnetic resonance imaging scan of the head revealed a 1.8×0.7 cm acute infarct in the right pons. The patient was treated initially with intravenous ceftriaxone and vancomycin before culture and sensitivity results, in addition to intravenous dexamethasone. After culture and sensitivities resulted, antibiotics were transitioned to a 4-week course of intravenous penicillin. The patient survived with no neurological consequences upon discharge. CONCLUSIONS Streptococcus constellatus should be suspected as an etiological agent for bacterial meningitis and other rare complications such as brainstem infarction and lung abscess, even in immunocompetent patients.</AbstractText
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29892002
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25570630
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30537949
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Modelling Peri-Perceptual Brain Processes in a Deep Learning Spiking Neural Network Architecture.
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Latent state-space models for neural decoding.
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Genetic ancestry, admixture and health determinants in Latin America.
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Familiarity of marketing stimuli may affect consumer behaviour at a peri-perceptual processing level. The current study introduces a method for deep learning of electroencephalogram (EEG) data using a spiking neural network (SNN) approach that reveals the complexity of peri-perceptual processes of familiarity. The method is applied to data from 20 participants viewing familiar and unfamiliar logos. The results support the potential of SNN models as novel tools in the exploration of peri-perceptual mechanisms that respond differentially to familiar and unfamiliar stimuli. Specifically, the activation pattern of the time-locked response identified by the proposed SNN model at approximately 200 milliseconds post-stimulus suggests greater connectivity and more widespread dynamic spatio-temporal patterns for familiar than unfamiliar logos. The proposed SNN approach can be applied to study other peri-perceptual or perceptual brain processes in cognitive and computational neuroscience.</AbstractText
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Ensembles of single-neurons in motor cortex can show strong low-dimensional collective dynamics. In this study, we explore an approach where neural decoding is applied to estimated low-dimensional dynamics instead of to the full recorded neuronal population. A latent state-space model (SSM) approach is used to estimate the low-dimensional neural dynamics from the measured spiking activity in population of neurons. A second state-space model representation is then used to decode kinematics, via a Kalman filter, from the estimated low-dimensional dynamics. The latent SSM-based decoding approach is illustrated on neuronal activity recorded from primary motor cortex in a monkey performing naturalistic 3-D reach and grasp movements. Our analysis show that 3-D reach decoding performance based on estimated low-dimensional dynamics is comparable to the decoding performance based on the full recorded neuronal population.</AbstractText
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Modern Latin American populations were formed via genetic admixture among ancestral source populations from Africa, the Americas and Europe. We are interested in studying how combinations of genetic ancestry in admixed Latin American populations may impact genomic determinants of health and disease. For this study, we characterized the impact of ancestry and admixture on genetic variants that underlie health- and disease-related phenotypes in population genomic samples from Colombia, Mexico, Peru, and Puerto Rico.</AbstractText We analyzed a total of 347 admixed Latin American genomes along with 1102 putative ancestral source genomes from Africans, Europeans, and Native Americans. We characterized the genetic ancestry, relatedness, and admixture patterns for each of the admixed Latin American genomes, finding a spectrum of ancestry proportions within and between populations. We then identified single nucleotide polymorphisms (SNPs) with anomalous ancestry-enrichment patterns, i.e. SNPs that exist in any given Latin American population at a higher frequency than expected based on the population's genetic ancestry profile. For this set of ancestry-enriched SNPs, we inspected their phenotypic impact on disease, metabolism, and the immune system. All four of the Latin American populations show ancestry-enrichment for a number of shared pathways, yielding evidence of similar selection pressures on these populations during their evolution. For example, all four populations show ancestry-enriched SNPs in multiple genes from immune system pathways, such as the cytokine receptor interaction, T cell receptor signaling, and antigen presentation pathways. We also found SNPs with excess African or European ancestry that are associated with ancestry-specific gene expression patterns and play crucial roles in the immune system and infectious disease responses. Genes from both the innate and adaptive immune system were found to be regulated by ancestry-enriched SNPs with population-specific regulatory effects.</AbstractText Ancestry-enriched SNPs in Latin American populations have a substantial effect on health- and disease-related phenotypes. The concordant impact observed for same phenotypes across populations points to a process of adaptive introgression, whereby ancestry-enriched SNPs with specific functional utility appear to have been retained in modern populations by virtue of their effects on health and fitness.</AbstractText
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Modelling Peri-Perceptual Brain Processes in a Deep Learning Spiking Neural Network Architecture. Familiarity of marketing stimuli may affect consumer behaviour at a peri-perceptual processing level. The current study introduces a method for deep learning of electroencephalogram (EEG) data using a spiking neural network (SNN) approach that reveals the complexity of peri-perceptual processes of familiarity. The method is applied to data from 20 participants viewing familiar and unfamiliar logos. The results support the potential of SNN models as novel tools in the exploration of peri-perceptual mechanisms that respond differentially to familiar and unfamiliar stimuli. Specifically, the activation pattern of the time-locked response identified by the proposed SNN model at approximately 200 milliseconds post-stimulus suggests greater connectivity and more widespread dynamic spatio-temporal patterns for familiar than unfamiliar logos. The proposed SNN approach can be applied to study other peri-perceptual or perceptual brain processes in cognitive and computational neuroscience.</AbstractText
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Latent state-space models for neural decoding. Ensembles of single-neurons in motor cortex can show strong low-dimensional collective dynamics. In this study, we explore an approach where neural decoding is applied to estimated low-dimensional dynamics instead of to the full recorded neuronal population. A latent state-space model (SSM) approach is used to estimate the low-dimensional neural dynamics from the measured spiking activity in population of neurons. A second state-space model representation is then used to decode kinematics, via a Kalman filter, from the estimated low-dimensional dynamics. The latent SSM-based decoding approach is illustrated on neuronal activity recorded from primary motor cortex in a monkey performing naturalistic 3-D reach and grasp movements. Our analysis show that 3-D reach decoding performance based on estimated low-dimensional dynamics is comparable to the decoding performance based on the full recorded neuronal population.</AbstractText
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Genetic ancestry, admixture and health determinants in Latin America. Modern Latin American populations were formed via genetic admixture among ancestral source populations from Africa, the Americas and Europe. We are interested in studying how combinations of genetic ancestry in admixed Latin American populations may impact genomic determinants of health and disease. For this study, we characterized the impact of ancestry and admixture on genetic variants that underlie health- and disease-related phenotypes in population genomic samples from Colombia, Mexico, Peru, and Puerto Rico.</AbstractText We analyzed a total of 347 admixed Latin American genomes along with 1102 putative ancestral source genomes from Africans, Europeans, and Native Americans. We characterized the genetic ancestry, relatedness, and admixture patterns for each of the admixed Latin American genomes, finding a spectrum of ancestry proportions within and between populations. We then identified single nucleotide polymorphisms (SNPs) with anomalous ancestry-enrichment patterns, i.e. SNPs that exist in any given Latin American population at a higher frequency than expected based on the population's genetic ancestry profile. For this set of ancestry-enriched SNPs, we inspected their phenotypic impact on disease, metabolism, and the immune system. All four of the Latin American populations show ancestry-enrichment for a number of shared pathways, yielding evidence of similar selection pressures on these populations during their evolution. For example, all four populations show ancestry-enriched SNPs in multiple genes from immune system pathways, such as the cytokine receptor interaction, T cell receptor signaling, and antigen presentation pathways. We also found SNPs with excess African or European ancestry that are associated with ancestry-specific gene expression patterns and play crucial roles in the immune system and infectious disease responses. Genes from both the innate and adaptive immune system were found to be regulated by ancestry-enriched SNPs with population-specific regulatory effects.</AbstractText Ancestry-enriched SNPs in Latin American populations have a substantial effect on health- and disease-related phenotypes. The concordant impact observed for same phenotypes across populations points to a process of adaptive introgression, whereby ancestry-enriched SNPs with specific functional utility appear to have been retained in modern populations by virtue of their effects on health and fitness.</AbstractText
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40681770
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38884672
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40701581
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Innovations in clinical PET image reconstruction: advances in Bayesian penalized likelihood algorithm and deep learning.
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Y-90 PET/MR imaging optimization with a Bayesian penalized likelihood reconstruction algorithm.
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Using community engagement to adapt anxiety cognitive behavioural therapy for autistic youth receiving services in Michigan community-based organisations: protocol for a mixed methods study.
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Recent advances in PET image reconstruction have focused on achieving high image quality and quantitative accuracy. Bayesian penalized likelihood (BPL) algorithms, such as Q.Clear and HYPER Iterative that have been integrated into commercial PET systems offer robust image noise suppression and edge preservation through regularization. In parallel, methods based on deep learning such as SubtlePET, AiCE, uAI<sup
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Positron Emission Tomography (PET) imaging after <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"
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Anxiety disorders are among the most common co-occurring mental health conditions experienced by autistic youth. Without appropriate intervention, anxiety disorders and related difficulties experienced by autistic youth can remain well into adulthood, causing reduced quality of life. Behavioral Interventions for Anxiety in Children with Autism (BIACA) is a manualised, modular evidence-based cognitive behavioural therapy with demonstrated efficacy in reducing or fully remitting anxiety symptoms and improving overall adaptive functioning for autistic youth. However, BIACA has been developed and tested mostly in academic research laboratories and has involved a limited number of community clinicians. Thus, certain characteristics (eg, length, complexity) may require adaptation to facilitate adoption and use in community settings.</AbstractText This mixed methods study will use and evaluate a community-engaged, intervention adaptation method (ie, Adapted version of the Method for Program Adaptation through Community Engagement (AM-PACE)) to develop an adapted version of BIACA for community use. In the current study, the AM-PACE method will involve: (1) a Community Advisory Board (CAB), (2) structured process to identify core components, (3) community feedback via surveys and semistructured interviews and (4) role play exercises with intended clients. Thereafter, community-based providers (<i Ethics approval was obtained from the Michigan State University Institutional Review Board. Research findings will be published in peer-reviewed journals, presented at international conferences and disseminated in alignment with CAB recommendations.</AbstractText This study has been registered on Open Science Framework: https://doi.org/10.17605/OSF.IO/Z54MD.</AbstractText
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Innovations in clinical PET image reconstruction: advances in Bayesian penalized likelihood algorithm and deep learning. Recent advances in PET image reconstruction have focused on achieving high image quality and quantitative accuracy. Bayesian penalized likelihood (BPL) algorithms, such as Q.Clear and HYPER Iterative that have been integrated into commercial PET systems offer robust image noise suppression and edge preservation through regularization. In parallel, methods based on deep learning such as SubtlePET, AiCE, uAI<sup
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Y-90 PET/MR imaging optimization with a Bayesian penalized likelihood reconstruction algorithm. Positron Emission Tomography (PET) imaging after <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"
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Using community engagement to adapt anxiety cognitive behavioural therapy for autistic youth receiving services in Michigan community-based organisations: protocol for a mixed methods study. Anxiety disorders are among the most common co-occurring mental health conditions experienced by autistic youth. Without appropriate intervention, anxiety disorders and related difficulties experienced by autistic youth can remain well into adulthood, causing reduced quality of life. Behavioral Interventions for Anxiety in Children with Autism (BIACA) is a manualised, modular evidence-based cognitive behavioural therapy with demonstrated efficacy in reducing or fully remitting anxiety symptoms and improving overall adaptive functioning for autistic youth. However, BIACA has been developed and tested mostly in academic research laboratories and has involved a limited number of community clinicians. Thus, certain characteristics (eg, length, complexity) may require adaptation to facilitate adoption and use in community settings.</AbstractText This mixed methods study will use and evaluate a community-engaged, intervention adaptation method (ie, Adapted version of the Method for Program Adaptation through Community Engagement (AM-PACE)) to develop an adapted version of BIACA for community use. In the current study, the AM-PACE method will involve: (1) a Community Advisory Board (CAB), (2) structured process to identify core components, (3) community feedback via surveys and semistructured interviews and (4) role play exercises with intended clients. Thereafter, community-based providers (<i Ethics approval was obtained from the Michigan State University Institutional Review Board. Research findings will be published in peer-reviewed journals, presented at international conferences and disseminated in alignment with CAB recommendations.</AbstractText This study has been registered on Open Science Framework: https://doi.org/10.17605/OSF.IO/Z54MD.</AbstractText
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34103532
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34219649
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34181914
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A molecular pathology, neurobiology, biochemical, genetic and neuroimaging study of progressive apraxia of speech.
|
Connectional asymmetry of the inferior parietal lobule shapes hemispheric specialization in humans, chimpanzees, and rhesus macaques.
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Treatment of type 2 diabetes: challenges, hopes, and anticipated successes.
|
Progressive apraxia of speech is a neurodegenerative syndrome affecting spoken communication. Molecular pathology, biochemistry, genetics, and longitudinal imaging were investigated in 32 autopsy-confirmed patients with progressive apraxia of speech who were followed over 10 years. Corticobasal degeneration and progressive supranuclear palsy (4R-tauopathies) were the most common underlying pathologies. Perceptually distinct speech characteristics, combined with age-at-onset, predicted specific 4R-tauopathy; phonetic subtype and younger age predicted corticobasal degeneration, and prosodic subtype and older age predicted progressive supranuclear palsy. Phonetic and prosodic subtypes showed differing relationships within the cortico-striato-pallido-nigro-luysial network. Biochemical analysis revealed no distinct differences in aggregated 4R-tau while tau H1 haplotype frequency (69%) was lower compared to 1000+ autopsy-confirmed 4R-tauopathies. Corticobasal degeneration patients had faster rates of decline, greater cortical degeneration, and shorter illness duration than progressive supranuclear palsy. These findings help define the pathobiology of progressive apraxia of speech and may have consequences for development of 4R-tau targeting treatment.</AbstractText
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The inferior parietal lobule (IPL) is one of the most expanded cortical regions in humans relative to other primates. It is also among the most structurally and functionally asymmetric regions in the human cerebral cortex. Whether the structural and connectional asymmetries of IPL subdivisions differ across primate species and how this relates to functional asymmetries remain unclear. We identified IPL subregions that exhibited positive allometric in both hemispheres, scaling across rhesus macaque monkeys, chimpanzees, and humans. The patterns of IPL subregions asymmetry were similar in chimpanzees and humans, but no IPL asymmetries were evident in macaques. Among the comparative sample of primates, humans showed the most widespread asymmetric connections in the frontal, parietal, and temporal cortices, constituting leftward asymmetric networks that may provide an anatomical basis for language and tool use. Unique human asymmetric connectivity between the IPL and primary motor cortex might be related to handedness. These findings suggest that structural and connectional asymmetries may underlie hemispheric specialization of the human brain.</AbstractText
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Despite the successful development of new therapies for the treatment of type 2 diabetes, such as glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 inhibitors, the search for novel treatment options that can provide better glycaemic control and at reduce complications is a continuous effort. The present Review aims to present an overview of novel targets and mechanisms and focuses on glucose-lowering effects guiding this search and developments. We discuss not only novel developments of insulin therapy (eg, so-called smart insulin preparation with a glucose-dependent mode of action), but also a group of drug classes for which extensive research efforts have not been rewarded with obvious clinical impact. We discuss the potential clinical use of the salutary adipokine adiponectin and the hepatokine fibroblast growth factor (FGF) 21, among others. A GLP-1 peptide receptor agonist (semaglutide) is now available for oral absorption, and small molecules activating GLP-1 receptors appear on the horizon. Bariatric surgery and its accompanying changes in the gut hormonal milieu offer a background for unimolecular peptides interacting with two or more receptors (for GLP-1, glucose-dependent insulinotropic polypeptide, glucagon, and peptide YY) and provide more substantial glycaemic control and bodyweight reduction compared with selective GLP-1 receptor agonists. These and additional approaches will help expand the toolbox of effective medications needed for optimising the treatment of well delineated subgroups of type 2 diabetes or help develop personalised approaches for glucose-lowering drugs based on individual characteristics of our patients.</AbstractText
|
A molecular pathology, neurobiology, biochemical, genetic and neuroimaging study of progressive apraxia of speech. Progressive apraxia of speech is a neurodegenerative syndrome affecting spoken communication. Molecular pathology, biochemistry, genetics, and longitudinal imaging were investigated in 32 autopsy-confirmed patients with progressive apraxia of speech who were followed over 10 years. Corticobasal degeneration and progressive supranuclear palsy (4R-tauopathies) were the most common underlying pathologies. Perceptually distinct speech characteristics, combined with age-at-onset, predicted specific 4R-tauopathy; phonetic subtype and younger age predicted corticobasal degeneration, and prosodic subtype and older age predicted progressive supranuclear palsy. Phonetic and prosodic subtypes showed differing relationships within the cortico-striato-pallido-nigro-luysial network. Biochemical analysis revealed no distinct differences in aggregated 4R-tau while tau H1 haplotype frequency (69%) was lower compared to 1000+ autopsy-confirmed 4R-tauopathies. Corticobasal degeneration patients had faster rates of decline, greater cortical degeneration, and shorter illness duration than progressive supranuclear palsy. These findings help define the pathobiology of progressive apraxia of speech and may have consequences for development of 4R-tau targeting treatment.</AbstractText
|
Connectional asymmetry of the inferior parietal lobule shapes hemispheric specialization in humans, chimpanzees, and rhesus macaques. The inferior parietal lobule (IPL) is one of the most expanded cortical regions in humans relative to other primates. It is also among the most structurally and functionally asymmetric regions in the human cerebral cortex. Whether the structural and connectional asymmetries of IPL subdivisions differ across primate species and how this relates to functional asymmetries remain unclear. We identified IPL subregions that exhibited positive allometric in both hemispheres, scaling across rhesus macaque monkeys, chimpanzees, and humans. The patterns of IPL subregions asymmetry were similar in chimpanzees and humans, but no IPL asymmetries were evident in macaques. Among the comparative sample of primates, humans showed the most widespread asymmetric connections in the frontal, parietal, and temporal cortices, constituting leftward asymmetric networks that may provide an anatomical basis for language and tool use. Unique human asymmetric connectivity between the IPL and primary motor cortex might be related to handedness. These findings suggest that structural and connectional asymmetries may underlie hemispheric specialization of the human brain.</AbstractText
|
Treatment of type 2 diabetes: challenges, hopes, and anticipated successes. Despite the successful development of new therapies for the treatment of type 2 diabetes, such as glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 inhibitors, the search for novel treatment options that can provide better glycaemic control and at reduce complications is a continuous effort. The present Review aims to present an overview of novel targets and mechanisms and focuses on glucose-lowering effects guiding this search and developments. We discuss not only novel developments of insulin therapy (eg, so-called smart insulin preparation with a glucose-dependent mode of action), but also a group of drug classes for which extensive research efforts have not been rewarded with obvious clinical impact. We discuss the potential clinical use of the salutary adipokine adiponectin and the hepatokine fibroblast growth factor (FGF) 21, among others. A GLP-1 peptide receptor agonist (semaglutide) is now available for oral absorption, and small molecules activating GLP-1 receptors appear on the horizon. Bariatric surgery and its accompanying changes in the gut hormonal milieu offer a background for unimolecular peptides interacting with two or more receptors (for GLP-1, glucose-dependent insulinotropic polypeptide, glucagon, and peptide YY) and provide more substantial glycaemic control and bodyweight reduction compared with selective GLP-1 receptor agonists. These and additional approaches will help expand the toolbox of effective medications needed for optimising the treatment of well delineated subgroups of type 2 diabetes or help develop personalised approaches for glucose-lowering drugs based on individual characteristics of our patients.</AbstractText
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39870473
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39069572
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40188029
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Post-infectious acute cerebellar ataxia in a young adult.
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Difference in the immediate effect on positional nystagmus for head positions with interval time during Epley maneuver: a randomized trial.
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Targeted NMDA receptor knockdown in recall-activated neuronal ensembles impairs remote fear extinction.
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Acute cerebellar ataxia is a clinical syndrome that involves loss of balance and coordination, typically within less than 72 hours. It usually presents in children and rarely affect adults. A woman in her early 20s presented with acute onset dizziness, vertigo, truncal ataxia and dysarthria 2 weeks following an acute viral illness. Cerebral MRI identified evidence of dural enhancement, and positron emission topography brain imaging showed cortical reduction of glucose metabolism, consistent with an encephalopathic process. Lumbar puncture established a normal cerebrospinal fluid protein and glucose, with seven white cells ×10<sup
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The Epley maneuver (EM) shows immediate effect, wherein disappearance of positional nystagmus occurs soon after the EM. Our previous study showed that setting interval times during the EM reduced the immediate effect. The purpose of this study is to identify the head position for which interval time reduces the immediate effect.</AbstractText Fifty-one patients with posterior canal type of benign paroxysmal positional vertigo (BPPV) were randomly assigned to the following three groups: 10 min interval time set at the first head position of the EM in group A, at the third head position in group B, and at the fourth head position in group C. The primary outcome measure (POM) was the ratio of maximum slow-phase eye velocity of positional nystagmus soon after the EM, compared with that measured before the EM. A large ratio value indicates a poor immediate effect of the EM.</AbstractText The POM in group A (0.07) was smallest (B: 0.36, C: 0.49) (p < 0.001).</AbstractText The interval times at the third and fourth head positions reduced the immediate effect of the EM. Our previous study showed that the effect of BPPV fatigue is continued by maintaining the first head position of the EM. BPPV fatigue constitutes fatigability of positional nystagmus with repeated performance of the Dix-Hallpike test. Our findings may be interpreted in accordance with the theory that the immediate effect of the EM is BPPV fatigue itself, because we observed that the effect of BPPV fatigue is strongest in group A.</AbstractText
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Fear extinction training in rodents decreases fear responses, providing a model for the development of post-traumatic stress disorder therapeutics. Fear memory recall reactivates the consolidated fear memory trace across multiple brain regions, and several studies have suggested that these recall-activated neurons are re-engaged during extinction. However, the molecular mechanisms linking this reactivation to extinction remain largely elusive. Here, we investigated the role of N-Methyl-D-Aspartate receptors (NMDARs) in remote memory recall-activated neurons within the basolateral amygdala and the medial prefrontal cortex during extinction training in mice. We found that Grin1 knockdown in these specific ensembles impaired extinction of remote fear memory, but did not reduce their reactivation during retrieval of the extinguished memory. These data suggest that while reactivation of these neuronal populations persists, their NMDARs are crucial for driving the synaptic plasticity needed to extinguish remote fear memories.</AbstractText
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Post-infectious acute cerebellar ataxia in a young adult. Acute cerebellar ataxia is a clinical syndrome that involves loss of balance and coordination, typically within less than 72 hours. It usually presents in children and rarely affect adults. A woman in her early 20s presented with acute onset dizziness, vertigo, truncal ataxia and dysarthria 2 weeks following an acute viral illness. Cerebral MRI identified evidence of dural enhancement, and positron emission topography brain imaging showed cortical reduction of glucose metabolism, consistent with an encephalopathic process. Lumbar puncture established a normal cerebrospinal fluid protein and glucose, with seven white cells ×10<sup
|
Difference in the immediate effect on positional nystagmus for head positions with interval time during Epley maneuver: a randomized trial. The Epley maneuver (EM) shows immediate effect, wherein disappearance of positional nystagmus occurs soon after the EM. Our previous study showed that setting interval times during the EM reduced the immediate effect. The purpose of this study is to identify the head position for which interval time reduces the immediate effect.</AbstractText Fifty-one patients with posterior canal type of benign paroxysmal positional vertigo (BPPV) were randomly assigned to the following three groups: 10 min interval time set at the first head position of the EM in group A, at the third head position in group B, and at the fourth head position in group C. The primary outcome measure (POM) was the ratio of maximum slow-phase eye velocity of positional nystagmus soon after the EM, compared with that measured before the EM. A large ratio value indicates a poor immediate effect of the EM.</AbstractText The POM in group A (0.07) was smallest (B: 0.36, C: 0.49) (p < 0.001).</AbstractText The interval times at the third and fourth head positions reduced the immediate effect of the EM. Our previous study showed that the effect of BPPV fatigue is continued by maintaining the first head position of the EM. BPPV fatigue constitutes fatigability of positional nystagmus with repeated performance of the Dix-Hallpike test. Our findings may be interpreted in accordance with the theory that the immediate effect of the EM is BPPV fatigue itself, because we observed that the effect of BPPV fatigue is strongest in group A.</AbstractText
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Targeted NMDA receptor knockdown in recall-activated neuronal ensembles impairs remote fear extinction. Fear extinction training in rodents decreases fear responses, providing a model for the development of post-traumatic stress disorder therapeutics. Fear memory recall reactivates the consolidated fear memory trace across multiple brain regions, and several studies have suggested that these recall-activated neurons are re-engaged during extinction. However, the molecular mechanisms linking this reactivation to extinction remain largely elusive. Here, we investigated the role of N-Methyl-D-Aspartate receptors (NMDARs) in remote memory recall-activated neurons within the basolateral amygdala and the medial prefrontal cortex during extinction training in mice. We found that Grin1 knockdown in these specific ensembles impaired extinction of remote fear memory, but did not reduce their reactivation during retrieval of the extinguished memory. These data suggest that while reactivation of these neuronal populations persists, their NMDARs are crucial for driving the synaptic plasticity needed to extinguish remote fear memories.</AbstractText
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27992380
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29987616
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30525000
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Noninvasive amide proton transfer magnetic resonance imaging in evaluating the grading and cellularity of gliomas.
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Differentiation of Malignant and Benign Head and Neck Tumors with Amide Proton Transfer-Weighted MR Imaging.
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EXPERIENCE WITH MANAGING PENETRATING ANTERIOR NECK INJURIES IN LAGOS, NIGERIA.
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Using noninvasive magnetic resonance imaging techniques to accurately evaluate the grading and cellularity of gliomas is beneficial for improving the patient outcomes. Amide proton transfer imaging is a noninvasive molecular magnetic resonance imaging technique based on chemical exchange saturation transfer mechanism that detects endogenous mobile proteins and peptides in biological tissues. Between August 2012 and November 2015, a total number of 44 patients with pathologically proven gliomas were included in this study. We compared the capability of amide proton transfer magnetic resonance imaging with that of noninvasive diffusion-weighted imaging and noninvasive 3-dimensional pseudo-continuous arterial spin imaging in evaluating the grading and cellularity of gliomas. Our results reveal that amide proton transfer magnetic resonance imaging is a superior imaging technique to diffusion-weighted imaging and 3-dimensional pseudo-continuous arterial spin imaging in the grading of gliomas. In addition, our results showed that the Ki-67 index correlated better with the amide proton transfer-weighted signal intensity than with the apparent diffusion coefficient value or the cerebral blood flow value in the gliomas. Amide proton transfer magnetic resonance imaging is a promising method for predicting the grading and cellularity of gliomas.</AbstractText
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To prospectively evaluate the feasibility and capability of amide proton transfer-weighted (APTw) imaging for the characterization of head and neck tumors.</AbstractText Twenty-nine consecutive patients with suspected head and neck tumors were enrolled in this study and underwent APTw magnetic resonance imaging (MRI) on a 3.0-T MRI scanner. The patients were divided into malignant (n = 16) and benign (n = 13) groups, based on pathological results. A map of magnetization transfer ratio asymmetry at 3.5 ppm [MTR<sub The intraclass correlation coefficients of the malignant and benign groups were 0.96 and 0.90, respectively, which indicated a good interobserver agreement. MTR<sub APTw MRI is feasible for use in the head and neck tumors and is a valuable imaging biomarker for distinguishing malignant from benign lesions.</AbstractText
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Penetrating anterior neck injuries are potentially life threatening and the causes vary across countries of the world. Studies in Nigeria have been mainly isolated case reports and few retrospective studies.</AbstractText The aim of this study was to assess the causes, severity and management outcome of patients treated in our centre.</AbstractText This is a retrospective study of penetrating anterior neck injuries treated at the Lagos University Teaching Hospital over a 25-year period. The case records were retrieved and demographic data as well as the causes, site, extent of injuries and treatment outcome were analyzed.</AbstractText The mean age of the 39 patients in this study was 30.5yrs ± 7.9 SD with a male: female ratio of 6.8:1. Inflicted cut throat injuries accounted for 46% followed by vehicular accidents in 21%. Zone II site of the neck was the commonest site of injury 61.6% of the patients; while 71.8% of the patients presented within 24hrs of the injury, 46% of them had immediate blood transfusion. Tracheostomy was the main method of securing the airway. Primary soft tissue repair was performed on all the patients. Laryngopharyngeal repair was done in 61.5%. Peri-operative mortality was 7.7% and 83.3% had prolonged hospital admission with wound infection in 27.8% and laryngotracheal stenosis in 22.2% as the commonest complications.</AbstractText This study has shown that penetrating anterior neck injuries is not uncommon in Nigeria and commonly due to cut throat and vehicular accidents. Proper documentation and following established management protocols will improve outcome.</AbstractText
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Noninvasive amide proton transfer magnetic resonance imaging in evaluating the grading and cellularity of gliomas. Using noninvasive magnetic resonance imaging techniques to accurately evaluate the grading and cellularity of gliomas is beneficial for improving the patient outcomes. Amide proton transfer imaging is a noninvasive molecular magnetic resonance imaging technique based on chemical exchange saturation transfer mechanism that detects endogenous mobile proteins and peptides in biological tissues. Between August 2012 and November 2015, a total number of 44 patients with pathologically proven gliomas were included in this study. We compared the capability of amide proton transfer magnetic resonance imaging with that of noninvasive diffusion-weighted imaging and noninvasive 3-dimensional pseudo-continuous arterial spin imaging in evaluating the grading and cellularity of gliomas. Our results reveal that amide proton transfer magnetic resonance imaging is a superior imaging technique to diffusion-weighted imaging and 3-dimensional pseudo-continuous arterial spin imaging in the grading of gliomas. In addition, our results showed that the Ki-67 index correlated better with the amide proton transfer-weighted signal intensity than with the apparent diffusion coefficient value or the cerebral blood flow value in the gliomas. Amide proton transfer magnetic resonance imaging is a promising method for predicting the grading and cellularity of gliomas.</AbstractText
|
Differentiation of Malignant and Benign Head and Neck Tumors with Amide Proton Transfer-Weighted MR Imaging. To prospectively evaluate the feasibility and capability of amide proton transfer-weighted (APTw) imaging for the characterization of head and neck tumors.</AbstractText Twenty-nine consecutive patients with suspected head and neck tumors were enrolled in this study and underwent APTw magnetic resonance imaging (MRI) on a 3.0-T MRI scanner. The patients were divided into malignant (n = 16) and benign (n = 13) groups, based on pathological results. A map of magnetization transfer ratio asymmetry at 3.5 ppm [MTR<sub The intraclass correlation coefficients of the malignant and benign groups were 0.96 and 0.90, respectively, which indicated a good interobserver agreement. MTR<sub APTw MRI is feasible for use in the head and neck tumors and is a valuable imaging biomarker for distinguishing malignant from benign lesions.</AbstractText
|
EXPERIENCE WITH MANAGING PENETRATING ANTERIOR NECK INJURIES IN LAGOS, NIGERIA. Penetrating anterior neck injuries are potentially life threatening and the causes vary across countries of the world. Studies in Nigeria have been mainly isolated case reports and few retrospective studies.</AbstractText The aim of this study was to assess the causes, severity and management outcome of patients treated in our centre.</AbstractText This is a retrospective study of penetrating anterior neck injuries treated at the Lagos University Teaching Hospital over a 25-year period. The case records were retrieved and demographic data as well as the causes, site, extent of injuries and treatment outcome were analyzed.</AbstractText The mean age of the 39 patients in this study was 30.5yrs ± 7.9 SD with a male: female ratio of 6.8:1. Inflicted cut throat injuries accounted for 46% followed by vehicular accidents in 21%. Zone II site of the neck was the commonest site of injury 61.6% of the patients; while 71.8% of the patients presented within 24hrs of the injury, 46% of them had immediate blood transfusion. Tracheostomy was the main method of securing the airway. Primary soft tissue repair was performed on all the patients. Laryngopharyngeal repair was done in 61.5%. Peri-operative mortality was 7.7% and 83.3% had prolonged hospital admission with wound infection in 27.8% and laryngotracheal stenosis in 22.2% as the commonest complications.</AbstractText This study has shown that penetrating anterior neck injuries is not uncommon in Nigeria and commonly due to cut throat and vehicular accidents. Proper documentation and following established management protocols will improve outcome.</AbstractText
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30069290
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29995210
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28119135
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Posterior cortical atrophy: A rare variant of Alzheimer's disease.
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Bidirectional modulation of Alzheimer phenotype by alpha-synuclein in mice and primary neurons.
|
Relative latency and temporal variability of hemodynamic responses at the human primary visual cortex.
|
Posterior cortical atrophy is a rare condition first described in 1988 involving progressive degeneration and atrophy of the occipital cortex, often recognized after an unexplained homonymous hemianopsia may be discovered. We report a case in association with Alzheimer's disease in a 77-year-old female, who underwent brain single-photon emission computed tomography as well brain positron emission tomography using Florbetapir to further evaluate progressive cognitive decline. The patient had also been followed in Ophthalmology for glaucoma, where a progressive unexplained change in her visual field maps were noted over one year consistent with a progressive right homonymous hemianopsia. This rare combination of findings in association with her dementia led to a detailed review of all her imaging studies, concluding with the surprising recognition for a clear hemi-atrophy of the primary left occipital cortex was occurring, consistent with Alzheimer's disease affecting the primary visual cortex. Further awareness of this disease pattern is needed, as Alzheimer's disease typically does not affect the primary visual cortex; other conditions to consider in general include Lewy Body dementia, cortico-basal degeneration and prion disease.</AbstractText
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α-Synuclein (αSyn) histopathology defines several neurodegenerative disorders, including Parkinson's disease, Lewy body dementia, and Alzheimer's disease (AD). However, the functional link between soluble αSyn and disease etiology remains elusive, especially in AD. We, therefore, genetically targeted αSyn in APP transgenic mice modeling AD and mouse primary neurons. Our results demonstrate bidirectional modulation of behavioral deficits and pathophysiology by αSyn. Overexpression of human wild-type αSyn in APP animals markedly reduced amyloid deposition but, counter-intuitively, exacerbated deficits in spatial memory. It also increased extracellular amyloid-β oligomers (AβOs), αSyn oligomers, exacerbated tau conformational and phosphorylation variants associated with AD, and enhanced neuronal cell cycle re-entry (CCR), a frequent prelude to neuron death in AD. Conversely, ablation of the SNCA gene encoding for αSyn in APP mice improved memory retention in spite of increased plaque burden. Reminiscent of the effect of MAPT ablation in APP mice, SNCA deletion prevented premature mortality. Moreover, the absence of αSyn decreased extracellular AβOs, ameliorated CCR, and rescued postsynaptic marker deficits. In summary, this complementary, bidirectional genetic approach implicates αSyn as an essential mediator of key phenotypes in AD and offers new functional insight into αSyn pathophysiology.</AbstractText
|
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
|
Posterior cortical atrophy: A rare variant of Alzheimer's disease. Posterior cortical atrophy is a rare condition first described in 1988 involving progressive degeneration and atrophy of the occipital cortex, often recognized after an unexplained homonymous hemianopsia may be discovered. We report a case in association with Alzheimer's disease in a 77-year-old female, who underwent brain single-photon emission computed tomography as well brain positron emission tomography using Florbetapir to further evaluate progressive cognitive decline. The patient had also been followed in Ophthalmology for glaucoma, where a progressive unexplained change in her visual field maps were noted over one year consistent with a progressive right homonymous hemianopsia. This rare combination of findings in association with her dementia led to a detailed review of all her imaging studies, concluding with the surprising recognition for a clear hemi-atrophy of the primary left occipital cortex was occurring, consistent with Alzheimer's disease affecting the primary visual cortex. Further awareness of this disease pattern is needed, as Alzheimer's disease typically does not affect the primary visual cortex; other conditions to consider in general include Lewy Body dementia, cortico-basal degeneration and prion disease.</AbstractText
|
Bidirectional modulation of Alzheimer phenotype by alpha-synuclein in mice and primary neurons. α-Synuclein (αSyn) histopathology defines several neurodegenerative disorders, including Parkinson's disease, Lewy body dementia, and Alzheimer's disease (AD). However, the functional link between soluble αSyn and disease etiology remains elusive, especially in AD. We, therefore, genetically targeted αSyn in APP transgenic mice modeling AD and mouse primary neurons. Our results demonstrate bidirectional modulation of behavioral deficits and pathophysiology by αSyn. Overexpression of human wild-type αSyn in APP animals markedly reduced amyloid deposition but, counter-intuitively, exacerbated deficits in spatial memory. It also increased extracellular amyloid-β oligomers (AβOs), αSyn oligomers, exacerbated tau conformational and phosphorylation variants associated with AD, and enhanced neuronal cell cycle re-entry (CCR), a frequent prelude to neuron death in AD. Conversely, ablation of the SNCA gene encoding for αSyn in APP mice improved memory retention in spite of increased plaque burden. Reminiscent of the effect of MAPT ablation in APP mice, SNCA deletion prevented premature mortality. Moreover, the absence of αSyn decreased extracellular AβOs, ameliorated CCR, and rescued postsynaptic marker deficits. In summary, this complementary, bidirectional genetic approach implicates αSyn as an essential mediator of key phenotypes in AD and offers new functional insight into αSyn pathophysiology.</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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20637656
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17881519
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21197019
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Absence epilepsy and periventricular nodular heterotopia.
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Nicotine-induced dystonic arousal complex in a mouse line harboring a human autosomal-dominant nocturnal frontal lobe epilepsy mutation.
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Terahertz and far infrared spectroscopy of alanine-rich peptides having variable ellipticity.
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We report a case of a girl who presented with typical absence seizures at age of 4.5 years. EEG showed absence seizures of sudden onset with 3 Hz spike-and-waves that also correlated with the clinical absences. The seizure semiology included subtle deviation of the eyes which prompted MRI investigation of the brain. This showed a periventricular nodular heterotopia in the mid to anterior horn of the right lateral ventricle. Although possibly coincidental, periventricular heterotopia are considered to be epileptogenic and this association has been reported once before. Migration disorders, such as in the periventricular heterotopia of our patient, may influence the formation and excitability of the striato-thalamo-cortical network involved in the generation of 3 Hz spike-waves.</AbstractText
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We generated a mouse line harboring an autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE) mutation: the alpha4 nicotinic receptor S248F knock-in strain. In this mouse, modest nicotine doses (1-2 mg/kg) elicit a novel behavior termed the dystonic arousal complex (DAC). The DAC includes stereotypical head movements, body jerking, and forelimb dystonia; these behaviors resemble some core features of ADNFLE. A marked Straub tail is an additional component of the DAC. Similar to attacks in ADNFLE, the DAC can be partially suppressed by the sodium channel blocker carbamazepine or by pre-exposure to a very low dose of nicotine (0.1 mg/kg). The DAC is centrally mediated, genetically highly penetrant, and, surprisingly, not associated with overt ictal electrical activity as assessed by (1) epidural or frontal lobe depth-electrode electroencephalography or (2) hippocampal c-fos-regulated gene expression. Heterozygous knock-in mice are partially protected from nicotine-induced seizures. The noncompetitive antagonist mecamylamine does not suppress the DAC, although it suppresses high-dose nicotine-induced wild-type-like seizures. Experiments on agonist-induced 86Rb+ and neurotransmitter efflux from synaptosomes and on alpha4S248Fbeta2 receptors expressed in oocytes confirm that the S248F mutation confers resistance to mecamylamine blockade. Genetic background, gender, and mutant gene expression levels modulate expression of the DAC phenotype in mice. The S248F mouse thus appears to provide a model for the paroxysmal dystonic element of ADNFLE semiology. Our model complements what is seen in other ADNFLE animal models. Together, these mice cover the spectrum of behavioral and electrographic events seen in the human condition.</AbstractText
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Terahertz spectra of four alanine-rich peptides with known secondary structures were studied by terahertz time domain spectroscopy (THz-TDS) and by Fourier transform infrared spectroscopy (FTIR) using a synchrotron light source and a liquid-helium cooled bolometer. At ambient temperatures the usable bandwidth was restricted to 0.2-1.5 THz by the absorbance of water. The existence of a solvation shell around the peptide in solution was observed and its size estimated to be between 11 and 17 Å. By cooling the peptide solution to 80 K in order to reduce the water absorbance the bandwidth was increased to 0.1-3.0 THz for both THz-TDS and FTIR. Spectra were consistent with monotonic absorbance of the peptide and the existence of a solid amorphous low density solvation shell.</AbstractText
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Absence epilepsy and periventricular nodular heterotopia. We report a case of a girl who presented with typical absence seizures at age of 4.5 years. EEG showed absence seizures of sudden onset with 3 Hz spike-and-waves that also correlated with the clinical absences. The seizure semiology included subtle deviation of the eyes which prompted MRI investigation of the brain. This showed a periventricular nodular heterotopia in the mid to anterior horn of the right lateral ventricle. Although possibly coincidental, periventricular heterotopia are considered to be epileptogenic and this association has been reported once before. Migration disorders, such as in the periventricular heterotopia of our patient, may influence the formation and excitability of the striato-thalamo-cortical network involved in the generation of 3 Hz spike-waves.</AbstractText
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Nicotine-induced dystonic arousal complex in a mouse line harboring a human autosomal-dominant nocturnal frontal lobe epilepsy mutation. We generated a mouse line harboring an autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE) mutation: the alpha4 nicotinic receptor S248F knock-in strain. In this mouse, modest nicotine doses (1-2 mg/kg) elicit a novel behavior termed the dystonic arousal complex (DAC). The DAC includes stereotypical head movements, body jerking, and forelimb dystonia; these behaviors resemble some core features of ADNFLE. A marked Straub tail is an additional component of the DAC. Similar to attacks in ADNFLE, the DAC can be partially suppressed by the sodium channel blocker carbamazepine or by pre-exposure to a very low dose of nicotine (0.1 mg/kg). The DAC is centrally mediated, genetically highly penetrant, and, surprisingly, not associated with overt ictal electrical activity as assessed by (1) epidural or frontal lobe depth-electrode electroencephalography or (2) hippocampal c-fos-regulated gene expression. Heterozygous knock-in mice are partially protected from nicotine-induced seizures. The noncompetitive antagonist mecamylamine does not suppress the DAC, although it suppresses high-dose nicotine-induced wild-type-like seizures. Experiments on agonist-induced 86Rb+ and neurotransmitter efflux from synaptosomes and on alpha4S248Fbeta2 receptors expressed in oocytes confirm that the S248F mutation confers resistance to mecamylamine blockade. Genetic background, gender, and mutant gene expression levels modulate expression of the DAC phenotype in mice. The S248F mouse thus appears to provide a model for the paroxysmal dystonic element of ADNFLE semiology. Our model complements what is seen in other ADNFLE animal models. Together, these mice cover the spectrum of behavioral and electrographic events seen in the human condition.</AbstractText
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Terahertz and far infrared spectroscopy of alanine-rich peptides having variable ellipticity. Terahertz spectra of four alanine-rich peptides with known secondary structures were studied by terahertz time domain spectroscopy (THz-TDS) and by Fourier transform infrared spectroscopy (FTIR) using a synchrotron light source and a liquid-helium cooled bolometer. At ambient temperatures the usable bandwidth was restricted to 0.2-1.5 THz by the absorbance of water. The existence of a solvation shell around the peptide in solution was observed and its size estimated to be between 11 and 17 Å. By cooling the peptide solution to 80 K in order to reduce the water absorbance the bandwidth was increased to 0.1-3.0 THz for both THz-TDS and FTIR. Spectra were consistent with monotonic absorbance of the peptide and the existence of a solid amorphous low density solvation shell.</AbstractText
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40214014
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28302591
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40658737
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Mental fatigue, skill performance and activity profile in elite male Australian Football match play.
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Benchmarking of participant-level confound regression strategies for the control of motion artifact in studies of functional connectivity.
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A major trade-off between growth and defense in Arabidopsis thaliana can vanish in field conditions.
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The aim of this study was to identify relationships between mental fatigue (MF), match activity profile and skill execution in elite Australian Football (AF) match play. Thirty-nine elite male AF athletes (24.6 ± 4.5y) rated their MFs on a visual analogue scale on each training day of a 25 week, 23 match seasons. Match activity profile was measured by global navigation satellite system (GNSS) and match statistics measured by official Australian Football League (AFL) statistics in 23 AFL matches. Match statistics were coded based on an offensive or defensive skill and association with positive or negative outcomes. Linear mixed models were used to determine relationships between weekly median MF, measures of match activity profile and match statistics. Increased MF was significantly associated with decreased match running intensity, low velocity running intensity and PlayerLoad™ intensity (all <i
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Since initial reports regarding the impact of motion artifact on measures of functional connectivity, there has been a proliferation of participant-level confound regression methods to limit its impact. However, many of the most commonly used techniques have not been systematically evaluated using a broad range of outcome measures. Here, we provide a systematic evaluation of 14 participant-level confound regression methods in 393 youths. Specifically, we compare methods according to four benchmarks, including the residual relationship between motion and connectivity, distance-dependent effects of motion on connectivity, network identifiability, and additional degrees of freedom lost in confound regression. Our results delineate two clear trade-offs among methods. First, methods that include global signal regression minimize the relationship between connectivity and motion, but result in distance-dependent artifact. In contrast, censoring methods mitigate both motion artifact and distance-dependence, but use additional degrees of freedom. Importantly, less effective de-noising methods are also unable to identify modular network structure in the connectome. Taken together, these results emphasize the heterogeneous efficacy of existing methods, and suggest that different confound regression strategies may be appropriate in the context of specific scientific goals.</AbstractText
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When wild plants defend themselves from pathogens, this often comes with a trade-off: the same genes that protect a plant from disease can also reduce its growth and fecundity in the absence of pathogens. One protein implicated in a major growth-defense trade-off is ACCELERATED CELL DEATH 6 (ACD6), an ion channel that modulates salicylic acid (SA) synthesis to potentiate a wide range of defenses. Wild Arabidopsis thaliana populations maintain significant functional variation at the ACD6 locus, with some alleles making the protein hyperactive. In the greenhouse, plants with hyperactive ACD6 alleles are resistant to diverse pathogens, yet they are of smaller stature, their leaves senesce earlier, and they set fewer seeds compared to plants with the standard allele. We hypothesized that ACD6 hyperactivity would not only affect the growth of microbial pathogens but also more generally change leaf microbiome assembly. To test this in an ecologically meaningful context, we compared plants with hyperactive, standard, and defective ACD6 alleles in the same field-collected soil, both outdoors and in naturally lit and climate-controlled indoor conditions, taking advantage of near-isogenic lines as well as a natural accession and a CRISPR-edited derivative. We surveyed visual phenotypes, gene expression, hormone levels, seed production, and the microbiome in each environment. The genetic precision of CRISPR-edited plants allowed us to conclude that ACD6 genotype had no effect on mature field plants in our setting, despite reproducibly dramatic effects on greenhouse plants. We conclude that additional abiotic and/or microbial signals present outdoors-but not in the greenhouse-greatly modulate ACD6 activity. This raises the possibility that the fitness costs of other commonly studied immune system genes may be grossly misjudged without field studies.</AbstractText
|
Mental fatigue, skill performance and activity profile in elite male Australian Football match play. The aim of this study was to identify relationships between mental fatigue (MF), match activity profile and skill execution in elite Australian Football (AF) match play. Thirty-nine elite male AF athletes (24.6 ± 4.5y) rated their MFs on a visual analogue scale on each training day of a 25 week, 23 match seasons. Match activity profile was measured by global navigation satellite system (GNSS) and match statistics measured by official Australian Football League (AFL) statistics in 23 AFL matches. Match statistics were coded based on an offensive or defensive skill and association with positive or negative outcomes. Linear mixed models were used to determine relationships between weekly median MF, measures of match activity profile and match statistics. Increased MF was significantly associated with decreased match running intensity, low velocity running intensity and PlayerLoad™ intensity (all <i
|
Benchmarking of participant-level confound regression strategies for the control of motion artifact in studies of functional connectivity. Since initial reports regarding the impact of motion artifact on measures of functional connectivity, there has been a proliferation of participant-level confound regression methods to limit its impact. However, many of the most commonly used techniques have not been systematically evaluated using a broad range of outcome measures. Here, we provide a systematic evaluation of 14 participant-level confound regression methods in 393 youths. Specifically, we compare methods according to four benchmarks, including the residual relationship between motion and connectivity, distance-dependent effects of motion on connectivity, network identifiability, and additional degrees of freedom lost in confound regression. Our results delineate two clear trade-offs among methods. First, methods that include global signal regression minimize the relationship between connectivity and motion, but result in distance-dependent artifact. In contrast, censoring methods mitigate both motion artifact and distance-dependence, but use additional degrees of freedom. Importantly, less effective de-noising methods are also unable to identify modular network structure in the connectome. Taken together, these results emphasize the heterogeneous efficacy of existing methods, and suggest that different confound regression strategies may be appropriate in the context of specific scientific goals.</AbstractText
|
A major trade-off between growth and defense in Arabidopsis thaliana can vanish in field conditions. When wild plants defend themselves from pathogens, this often comes with a trade-off: the same genes that protect a plant from disease can also reduce its growth and fecundity in the absence of pathogens. One protein implicated in a major growth-defense trade-off is ACCELERATED CELL DEATH 6 (ACD6), an ion channel that modulates salicylic acid (SA) synthesis to potentiate a wide range of defenses. Wild Arabidopsis thaliana populations maintain significant functional variation at the ACD6 locus, with some alleles making the protein hyperactive. In the greenhouse, plants with hyperactive ACD6 alleles are resistant to diverse pathogens, yet they are of smaller stature, their leaves senesce earlier, and they set fewer seeds compared to plants with the standard allele. We hypothesized that ACD6 hyperactivity would not only affect the growth of microbial pathogens but also more generally change leaf microbiome assembly. To test this in an ecologically meaningful context, we compared plants with hyperactive, standard, and defective ACD6 alleles in the same field-collected soil, both outdoors and in naturally lit and climate-controlled indoor conditions, taking advantage of near-isogenic lines as well as a natural accession and a CRISPR-edited derivative. We surveyed visual phenotypes, gene expression, hormone levels, seed production, and the microbiome in each environment. The genetic precision of CRISPR-edited plants allowed us to conclude that ACD6 genotype had no effect on mature field plants in our setting, despite reproducibly dramatic effects on greenhouse plants. We conclude that additional abiotic and/or microbial signals present outdoors-but not in the greenhouse-greatly modulate ACD6 activity. This raises the possibility that the fitness costs of other commonly studied immune system genes may be grossly misjudged without field studies.</AbstractText
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40208003
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31736722
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40249202
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Modulatory role of the right ventrolateral prefrontal cortex in crowd emotional perception following social exclusion.
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Biomarkers Obtained by Transcranial Magnetic Stimulation of the Motor Cortex in Epilepsy.
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Structural Insights into the Mechanical Behavior of Large-Area 2D Covalent Organic Framework Nanofilms.
|
The right ventrolateral prefrontal cortex (rVLPFC) is a crucial region involved in modulating social exclusion. Although prior studies have focused primarily on how social exclusion influences the perception of single faces, the effect of social exclusion on the crowd emotional perception and the neural mechanisms remain elusive. The current research examined whether social exclusion causes a biased perception of crowd emotions, and whether this effect would be modulated by transcranial magnetic stimulation (TMS) over the rVLPFC. Participants were either socially included or excluded, while TMS stimulation was applied over the rVLPFC or the vertex. Next, they viewed sets of happy or disgusted faces and assessed the mean emotions of each set. Socially excluded participants overestimated the mean emotions for disgusted crowd faces compared to socially included participants, which was positively correlated with need threat. Compared to the vertex, stimulating the rVLPFC reduced socially excluded participants' biased perception of disgusted crowd faces. Moreover, stimulation of the rVLPFC decreased discrimination performance for crowd faces expressing disgust but increased it for happy crowd faces. The results provide a causal test for the role of rVLPFC in alleviating the biased perception of negative crowd emotions following social exclusion.</AbstractText
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Epilepsy is associated with numerous neurodevelopmental disorders. Transcranial magnetic stimulation (TMS) of the motor cortex coupled with electromyography (EMG) enables biomarkers that provide measures of cortical excitation and inhibition that are particularly relevant to epilepsy and related disorders. The motor threshold (MT), cortical silent period (CSP), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), and long interval intracortical inhibition (LICI) are among TMS-derived metrics that are modulated by antiepileptic drugs. TMS may have a practical role in optimization of antiepileptic medication regimens, as studies demonstrate dose-dependent relationships between TMS metrics and acute medication administration. A close association between seizure freedom and normalization of cortical excitability with long-term antiepileptic drug use highlights a plausible utility of TMS in measures of anti-epileptic drug efficacy. Finally, TMS-derived biomarkers distinguish patients with various epilepsies from healthy controls and thus may enable development of disorder-specific biomarkers and therapies both within and outside of the epilepsy realm.</AbstractText
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Two-dimensional covalent organic frameworks (2D COFs) are periodic, permanently porous, lightweight solids with remarkable structural modularity, enabling precise control over their properties. As thin films, they have shown promising applications in chemical separations and organic electronics, making it crucial to understand their stability under mechanical stress. Here, we investigate how two different chemical linkages commonly used for 2D COFs, specifically imine and enamine, influence the mechanical properties of nanoscale thick films. Centimeter-scale 2D COF films with a thickness below 100 nm were synthesized by a condensation reaction at a liquid-liquid interface and subsequently transferred onto patterned substrates for mechanical testing. By employing a custom-made nanotensile testing platform, we achieved a comprehensive mechanical characterization of freestanding 2D COF films over a large area (0.5 mm<sup
|
Modulatory role of the right ventrolateral prefrontal cortex in crowd emotional perception following social exclusion. The right ventrolateral prefrontal cortex (rVLPFC) is a crucial region involved in modulating social exclusion. Although prior studies have focused primarily on how social exclusion influences the perception of single faces, the effect of social exclusion on the crowd emotional perception and the neural mechanisms remain elusive. The current research examined whether social exclusion causes a biased perception of crowd emotions, and whether this effect would be modulated by transcranial magnetic stimulation (TMS) over the rVLPFC. Participants were either socially included or excluded, while TMS stimulation was applied over the rVLPFC or the vertex. Next, they viewed sets of happy or disgusted faces and assessed the mean emotions of each set. Socially excluded participants overestimated the mean emotions for disgusted crowd faces compared to socially included participants, which was positively correlated with need threat. Compared to the vertex, stimulating the rVLPFC reduced socially excluded participants' biased perception of disgusted crowd faces. Moreover, stimulation of the rVLPFC decreased discrimination performance for crowd faces expressing disgust but increased it for happy crowd faces. The results provide a causal test for the role of rVLPFC in alleviating the biased perception of negative crowd emotions following social exclusion.</AbstractText
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Biomarkers Obtained by Transcranial Magnetic Stimulation of the Motor Cortex in Epilepsy. Epilepsy is associated with numerous neurodevelopmental disorders. Transcranial magnetic stimulation (TMS) of the motor cortex coupled with electromyography (EMG) enables biomarkers that provide measures of cortical excitation and inhibition that are particularly relevant to epilepsy and related disorders. The motor threshold (MT), cortical silent period (CSP), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), and long interval intracortical inhibition (LICI) are among TMS-derived metrics that are modulated by antiepileptic drugs. TMS may have a practical role in optimization of antiepileptic medication regimens, as studies demonstrate dose-dependent relationships between TMS metrics and acute medication administration. A close association between seizure freedom and normalization of cortical excitability with long-term antiepileptic drug use highlights a plausible utility of TMS in measures of anti-epileptic drug efficacy. Finally, TMS-derived biomarkers distinguish patients with various epilepsies from healthy controls and thus may enable development of disorder-specific biomarkers and therapies both within and outside of the epilepsy realm.</AbstractText
|
Structural Insights into the Mechanical Behavior of Large-Area 2D Covalent Organic Framework Nanofilms. Two-dimensional covalent organic frameworks (2D COFs) are periodic, permanently porous, lightweight solids with remarkable structural modularity, enabling precise control over their properties. As thin films, they have shown promising applications in chemical separations and organic electronics, making it crucial to understand their stability under mechanical stress. Here, we investigate how two different chemical linkages commonly used for 2D COFs, specifically imine and enamine, influence the mechanical properties of nanoscale thick films. Centimeter-scale 2D COF films with a thickness below 100 nm were synthesized by a condensation reaction at a liquid-liquid interface and subsequently transferred onto patterned substrates for mechanical testing. By employing a custom-made nanotensile testing platform, we achieved a comprehensive mechanical characterization of freestanding 2D COF films over a large area (0.5 mm<sup
|
38410466
|
30291280
|
39046914
|
Association between Large Neutral Amino Acids and Brain Integrity in Middle-Aged Adults at Metabolic Risk.
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Evidence of a Causal Role for mid-Ventrolateral Prefrontal Cortex Based Functional Networks in Retrieving High-Fidelity Memory.
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Generalized inhomogeneity-resilient relaxation along a fictitious field (girRAFF) for improved robustness in rotating frame relaxometry at 3T.
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This investigation delves into the interplay between large neutral amino acids (LNAA) and metabolic syndrome (MetS) in midlife adults, examining their collective influence on brain structure and cognitive function. While LNAA, such as tryptophan and phenylalanine, are known to bolster cognition in youth, our study hypothesizes a reversal of these benefits in older adults with MetS, potentially signaling premature cognitive aging. Eighty participants between 40-61 years underwent MetS component quantification, LNAA measurement via high-performance liquid chromatography, and brain imaging to evaluate white matter hyperintensity (WMH) volume and medial temporal lobe (MTL) cortical thickness. Our linear regression analysis, adjusting for sex, age, and education, revealed that phenylalanine levels moderated the relationship between MetS and WMH volume (<i
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Functional neuroimaging studies have implicated regions of both ventrolateral prefrontal cortex (VLPFC) and angular gyrus in processes associated with retrieving goal-relevant information, which increases the fidelity and richness of long-term memory (LTM). To further investigate the roles of these cortical regions as nodes in functional networks with memory regions of the medial temporal lobe (MTL), we used fMRI-guided, 1 Hz repetitive transcranial magnetic stimulation (rTMS) to perturb normal neuronal function. The aim was to test the causal roles of left mid-VLPFC and left angular gyrus (AG) in MTL-VLPFC-parietal networks that have been associated with high-fidelity memory retrieval. rTMS treatments were administered immediately before blocks in an old/new recognition test, which was based on a mnemonic similarity task requiring discrimination of previously studied pictures of common objects. Capability for mnemonic discrimination was evaluated after each of three conditions: placebo control (rTMS at somatosensory cortex), mid-VLPFC target (rTMS at left pars triangularis) and parietal target (rTMS at left AG). The results showed the effect of rTMS perturbation of mid-VLPFC diminished subsequent discrimination-based memory performance, relative to placebo control, and no significant effect of perturbation of AG. These findings show a causal role for functional networks with left mid-VLPFC in high-fidelity retrieval.</AbstractText
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To optimize Relaxation along a Fictitious Field (RAFF) pulses for rotating frame relaxometry with improved robustness in the presence of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" The resilience of RAFF pulses against <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" Optimized girRAFF preparations yielded improved preparation efficiency (0.95/0.91 simulations/phantom) with respect to RAFF (0.36/0.67 simulations/phantom). <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" RAFF pulses display residual sensitivity to off-resonance and pronounced sensitivity to <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"
|
Association between Large Neutral Amino Acids and Brain Integrity in Middle-Aged Adults at Metabolic Risk. This investigation delves into the interplay between large neutral amino acids (LNAA) and metabolic syndrome (MetS) in midlife adults, examining their collective influence on brain structure and cognitive function. While LNAA, such as tryptophan and phenylalanine, are known to bolster cognition in youth, our study hypothesizes a reversal of these benefits in older adults with MetS, potentially signaling premature cognitive aging. Eighty participants between 40-61 years underwent MetS component quantification, LNAA measurement via high-performance liquid chromatography, and brain imaging to evaluate white matter hyperintensity (WMH) volume and medial temporal lobe (MTL) cortical thickness. Our linear regression analysis, adjusting for sex, age, and education, revealed that phenylalanine levels moderated the relationship between MetS and WMH volume (<i
|
Evidence of a Causal Role for mid-Ventrolateral Prefrontal Cortex Based Functional Networks in Retrieving High-Fidelity Memory. Functional neuroimaging studies have implicated regions of both ventrolateral prefrontal cortex (VLPFC) and angular gyrus in processes associated with retrieving goal-relevant information, which increases the fidelity and richness of long-term memory (LTM). To further investigate the roles of these cortical regions as nodes in functional networks with memory regions of the medial temporal lobe (MTL), we used fMRI-guided, 1 Hz repetitive transcranial magnetic stimulation (rTMS) to perturb normal neuronal function. The aim was to test the causal roles of left mid-VLPFC and left angular gyrus (AG) in MTL-VLPFC-parietal networks that have been associated with high-fidelity memory retrieval. rTMS treatments were administered immediately before blocks in an old/new recognition test, which was based on a mnemonic similarity task requiring discrimination of previously studied pictures of common objects. Capability for mnemonic discrimination was evaluated after each of three conditions: placebo control (rTMS at somatosensory cortex), mid-VLPFC target (rTMS at left pars triangularis) and parietal target (rTMS at left AG). The results showed the effect of rTMS perturbation of mid-VLPFC diminished subsequent discrimination-based memory performance, relative to placebo control, and no significant effect of perturbation of AG. These findings show a causal role for functional networks with left mid-VLPFC in high-fidelity retrieval.</AbstractText
|
Generalized inhomogeneity-resilient relaxation along a fictitious field (girRAFF) for improved robustness in rotating frame relaxometry at 3T. To optimize Relaxation along a Fictitious Field (RAFF) pulses for rotating frame relaxometry with improved robustness in the presence of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" The resilience of RAFF pulses against <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" Optimized girRAFF preparations yielded improved preparation efficiency (0.95/0.91 simulations/phantom) with respect to RAFF (0.36/0.67 simulations/phantom). <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" RAFF pulses display residual sensitivity to off-resonance and pronounced sensitivity to <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"
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40550205
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35196874
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39899718
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Management and outcomes for thoracic anterior spinal artery aneurysms: illustrative case.
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Iron Deposition in the Brain After Aneurysmal Subarachnoid Hemorrhage.
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Bonobos point more for ignorant than knowledgeable social partners.
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Anterior spinal artery (ASA) aneurysms are uncommon and difficult to diagnose due to their variable presentation and limited visibility with traditional imaging. They often present with severe back pain from rupture and spinal subarachnoid hemorrhage (SAH). There are few published studies and no established treatment recommendations. This study reports a ruptured thoracic ASA aneurysm treated with clip reconstruction and reviews the literature.</AbstractText A man in his late 40s presented with sudden, intense interscapular pain that progressed to paraplegia and sensory loss below T5. He regained neurological function within 6 hours, with residual back pain. Imaging showed SAH and an aneurysm from the left ASA at T5. After a left T4 costotransversectomy, the aneurysm was clipped, and postoperative angiography confirmed ASA patency and aneurysm occlusion. A review of 31 patients (mean [SD] age 43.4 [17.8] years) showed varied treatments: microsurgery (n = 13, 42%), endovascular embolization (n = 3, 10%), conservative management (n = 13, 42%), and surgical exploration followed by conservative management (n = 1, 3%). Complete symptom resolution occurred in 45% (n = 14) of cases.</AbstractText Thoracic ASA aneurysms present diagnostic and treatment challenges. This case illustrates that open microsurgical treatment can successfully decompress the spinal cord and occlude the aneurysm while preserving parent artery flow. https://thejns.org/doi/10.3171/CASE24649.</AbstractText
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After aneurysmal subarachnoid hemorrhage (SAH), thrombus forms over the cerebral cortex and releases hemoglobin. When extracellular, hemoglobin is toxic to neurones. High local hemoglobin concentration overwhelms the clearance capacity of macrophages expressing the hemoglobin-haptoglobin scavenger receptor CD163. We hypothesized that iron is deposited in the cortex after SAH and would associate with outcome.</AbstractText Two complementary cross-sectional studies were conducted. Postmortem brain tissue from 39 SAH (mean postictal interval of 9 days) and 22 control cases was studied with Perls' staining for iron and immunolabeling for CD163, ADAM17 (a disintegrin and metallopeptidase domain 17), CD68, and Iba1 (ionized calcium binding adaptor molecule 1). In parallel, to study the persistence of cortical iron and its relationship to clinical outcome, we conducted a susceptibility-weighted imaging study of 21 SAH patients 6 months postictus and 10 control individuals.</AbstractText In brain tissue from patients dying soon after SAH, the distribution of iron deposition followed a gradient that diminished with distance from the brain surface. Iron was located intracellularly (mainly in macrophages, and occasionally in microglia, neurones, and glial cells) and extracellularly. Microglial activation and motility markers were increased after SAH, with a similar inward diminishing gradient. In controls, there was a positive correlation between CD163 and iron, which was lost after SAH. In SAH survivors, iron-sensitive imaging 6 months post-SAH confirmed persistence of cortical iron, related to the size and location of the blood clot immediately after SAH, and associated with cognitive outcome.</AbstractText After SAH, iron deposits in the cortical gray matter in a pattern that reflects proximity to the brain surface and thrombus and is related to cognitive outcome. These observations support therapeutic manoeuvres which prevent the permeation of hemoglobin into the cortex after SAH.</AbstractText
|
Numerous uniquely human phenomena, from teaching to our most complex forms of cooperation, depend on our ability to tailor our communication to the knowledge and ignorance states of our social partners. Despite four decades of research into the "theory of mind" capacities of nonhuman primates, there remains no evidence that primates can communicate on the basis of their mental state attributions, to enable feats of coordination. Moreover, recent reevaluation of the experimental literature has questioned whether primates can represent others' ignorance at all. The present preregistered study investigated whether bonobos are capable of attributing knowledge or ignorance about the location of a hidden food reward to a cooperative human partner, and utilizing this attribution to modify their communicative behavior in the service of coordination. Bonobos could receive a reward that they had watched being hidden under one of several cups, if their human partner could locate the reward. If bonobos can represent a partner's ignorance and are motivated to communicate based on this mental state attribution, they should point more frequently, and more quickly, to the hidden food's location when their partner is ignorant about that location than when he is knowledgeable. Bonobos indeed flexibly adapted the frequency and speed of their communication to their partner's mental state. These findings suggest that apes can represent (and act on) others' ignorance in some form, strategically and appropriately communicating to effectively coordinate with an ignorant partner and change his behavior.</AbstractText
|
Management and outcomes for thoracic anterior spinal artery aneurysms: illustrative case. Anterior spinal artery (ASA) aneurysms are uncommon and difficult to diagnose due to their variable presentation and limited visibility with traditional imaging. They often present with severe back pain from rupture and spinal subarachnoid hemorrhage (SAH). There are few published studies and no established treatment recommendations. This study reports a ruptured thoracic ASA aneurysm treated with clip reconstruction and reviews the literature.</AbstractText A man in his late 40s presented with sudden, intense interscapular pain that progressed to paraplegia and sensory loss below T5. He regained neurological function within 6 hours, with residual back pain. Imaging showed SAH and an aneurysm from the left ASA at T5. After a left T4 costotransversectomy, the aneurysm was clipped, and postoperative angiography confirmed ASA patency and aneurysm occlusion. A review of 31 patients (mean [SD] age 43.4 [17.8] years) showed varied treatments: microsurgery (n = 13, 42%), endovascular embolization (n = 3, 10%), conservative management (n = 13, 42%), and surgical exploration followed by conservative management (n = 1, 3%). Complete symptom resolution occurred in 45% (n = 14) of cases.</AbstractText Thoracic ASA aneurysms present diagnostic and treatment challenges. This case illustrates that open microsurgical treatment can successfully decompress the spinal cord and occlude the aneurysm while preserving parent artery flow. https://thejns.org/doi/10.3171/CASE24649.</AbstractText
|
Iron Deposition in the Brain After Aneurysmal Subarachnoid Hemorrhage. After aneurysmal subarachnoid hemorrhage (SAH), thrombus forms over the cerebral cortex and releases hemoglobin. When extracellular, hemoglobin is toxic to neurones. High local hemoglobin concentration overwhelms the clearance capacity of macrophages expressing the hemoglobin-haptoglobin scavenger receptor CD163. We hypothesized that iron is deposited in the cortex after SAH and would associate with outcome.</AbstractText Two complementary cross-sectional studies were conducted. Postmortem brain tissue from 39 SAH (mean postictal interval of 9 days) and 22 control cases was studied with Perls' staining for iron and immunolabeling for CD163, ADAM17 (a disintegrin and metallopeptidase domain 17), CD68, and Iba1 (ionized calcium binding adaptor molecule 1). In parallel, to study the persistence of cortical iron and its relationship to clinical outcome, we conducted a susceptibility-weighted imaging study of 21 SAH patients 6 months postictus and 10 control individuals.</AbstractText In brain tissue from patients dying soon after SAH, the distribution of iron deposition followed a gradient that diminished with distance from the brain surface. Iron was located intracellularly (mainly in macrophages, and occasionally in microglia, neurones, and glial cells) and extracellularly. Microglial activation and motility markers were increased after SAH, with a similar inward diminishing gradient. In controls, there was a positive correlation between CD163 and iron, which was lost after SAH. In SAH survivors, iron-sensitive imaging 6 months post-SAH confirmed persistence of cortical iron, related to the size and location of the blood clot immediately after SAH, and associated with cognitive outcome.</AbstractText After SAH, iron deposits in the cortical gray matter in a pattern that reflects proximity to the brain surface and thrombus and is related to cognitive outcome. These observations support therapeutic manoeuvres which prevent the permeation of hemoglobin into the cortex after SAH.</AbstractText
|
Bonobos point more for ignorant than knowledgeable social partners. Numerous uniquely human phenomena, from teaching to our most complex forms of cooperation, depend on our ability to tailor our communication to the knowledge and ignorance states of our social partners. Despite four decades of research into the "theory of mind" capacities of nonhuman primates, there remains no evidence that primates can communicate on the basis of their mental state attributions, to enable feats of coordination. Moreover, recent reevaluation of the experimental literature has questioned whether primates can represent others' ignorance at all. The present preregistered study investigated whether bonobos are capable of attributing knowledge or ignorance about the location of a hidden food reward to a cooperative human partner, and utilizing this attribution to modify their communicative behavior in the service of coordination. Bonobos could receive a reward that they had watched being hidden under one of several cups, if their human partner could locate the reward. If bonobos can represent a partner's ignorance and are motivated to communicate based on this mental state attribution, they should point more frequently, and more quickly, to the hidden food's location when their partner is ignorant about that location than when he is knowledgeable. Bonobos indeed flexibly adapted the frequency and speed of their communication to their partner's mental state. These findings suggest that apes can represent (and act on) others' ignorance in some form, strategically and appropriately communicating to effectively coordinate with an ignorant partner and change his behavior.</AbstractText
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35434739
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29932344
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36248528
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Relationship Between Level of American Football Playing and Diagnosis of Chronic Traumatic Encephalopathy in a Selection Bias Analysis.
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Repeated Mild Closed Head Injuries Induce Long-Term White Matter Pathology and Neuronal Loss That Are Correlated With Behavioral Deficits.
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Learned uncertainty: The free energy principle in anxiety.
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Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts such as those from American football. Our understanding of this association is based on research in autopsied brains, since CTE can only be diagnosed postmortem. Such studies are susceptible to selection bias, which needs to be accounted for to ensure a generalizable estimate of the association between repetitive head impacts and CTE. We evaluated the relationship between level of American football playing and CTE diagnosis after adjusting for selection bias. The sample included 290 deceased male former American football players who donated their brains to the Veterans Affairs-Boston University-Concussion Legacy Foundation (VA-BU-CLF) Brain Bank between 2008 and 2019. After adjustment for selection bias, college-level and professional football players had 2.38 (95% simulation interval (SI): 1.16, 5.94) and 2.47 (95% SI: 1.46, 4.79) times the risk of being diagnosed with CTE as high-school-level players, respectively; these estimates are larger than estimates with no selection bias adjustment. Since CTE is currently diagnosed only postmortem, we additionally provide plausible scenarios for CTE risk ratios for each level of play during the former players' lifetime. This study provides further evidence to support a dose-response relationship between American football playing and CTE.</AbstractText
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An estimated 5.3 million Americans are living with a disability from a traumatic brain injury (TBI). There is emerging evidence of the detrimental effects from repeated mild TBIs (rmTBIs). rmTBI manifests its own unique set of behavioral and neuropathological changes. A subset of individuals exposed to rmTBI develop permanent behavioral and pathological consequences, defined postmortem as chronic traumatic encephalopathy. We have combined components of two classic rodent models of TBI, the controlled cortical impact model and the weight drop model, to develop a repeated mild closed head injury (rmCHI) that produces long-term deficits in several behaviors that correlate with neuropathological changes. Mice receiving rmCHI performed differently from 1-hit or sham controls on the elevated plus maze; these deficits persist up to 6 months postinjury (MPI). rmCHI mice performed worse than 1-hit and control sham mice at 2 MPI and 6 MPI on the Morris water maze. Mice receiving rmCHI exhibited significant atrophy of the corpus callosum at both 2 MPI and 6 MPI, as assessed by stereological volume analysis. Stereological analysis also revealed significant loss of cortical neurons in comparison with 1-hit and controls. Moreover, both of these pathological changes correlated with behavioral impairments. In human tau transgenic mice, rmCHI induced increases in hyperphosphorylated paired helical filament 1 tau in the hippocampus. This suggests that strategies to restore myelination or reduce neuronal loss may ameliorate the behavioral deficits observed following rmCHI and that rmCHI may model chronic traumatic encephalopathy in human tau mice.</AbstractText
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Generalized anxiety disorder is among the world's most prevalent psychiatric disorders and often manifests as persistent and difficult to control apprehension. Despite its prevalence, there is no integrative, formal model of how anxiety and anxiety disorders arise. Here, we offer a perspective derived from the free energy principle; one that shares similarities with established constructs such as <i
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Relationship Between Level of American Football Playing and Diagnosis of Chronic Traumatic Encephalopathy in a Selection Bias Analysis. Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts such as those from American football. Our understanding of this association is based on research in autopsied brains, since CTE can only be diagnosed postmortem. Such studies are susceptible to selection bias, which needs to be accounted for to ensure a generalizable estimate of the association between repetitive head impacts and CTE. We evaluated the relationship between level of American football playing and CTE diagnosis after adjusting for selection bias. The sample included 290 deceased male former American football players who donated their brains to the Veterans Affairs-Boston University-Concussion Legacy Foundation (VA-BU-CLF) Brain Bank between 2008 and 2019. After adjustment for selection bias, college-level and professional football players had 2.38 (95% simulation interval (SI): 1.16, 5.94) and 2.47 (95% SI: 1.46, 4.79) times the risk of being diagnosed with CTE as high-school-level players, respectively; these estimates are larger than estimates with no selection bias adjustment. Since CTE is currently diagnosed only postmortem, we additionally provide plausible scenarios for CTE risk ratios for each level of play during the former players' lifetime. This study provides further evidence to support a dose-response relationship between American football playing and CTE.</AbstractText
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Repeated Mild Closed Head Injuries Induce Long-Term White Matter Pathology and Neuronal Loss That Are Correlated With Behavioral Deficits. An estimated 5.3 million Americans are living with a disability from a traumatic brain injury (TBI). There is emerging evidence of the detrimental effects from repeated mild TBIs (rmTBIs). rmTBI manifests its own unique set of behavioral and neuropathological changes. A subset of individuals exposed to rmTBI develop permanent behavioral and pathological consequences, defined postmortem as chronic traumatic encephalopathy. We have combined components of two classic rodent models of TBI, the controlled cortical impact model and the weight drop model, to develop a repeated mild closed head injury (rmCHI) that produces long-term deficits in several behaviors that correlate with neuropathological changes. Mice receiving rmCHI performed differently from 1-hit or sham controls on the elevated plus maze; these deficits persist up to 6 months postinjury (MPI). rmCHI mice performed worse than 1-hit and control sham mice at 2 MPI and 6 MPI on the Morris water maze. Mice receiving rmCHI exhibited significant atrophy of the corpus callosum at both 2 MPI and 6 MPI, as assessed by stereological volume analysis. Stereological analysis also revealed significant loss of cortical neurons in comparison with 1-hit and controls. Moreover, both of these pathological changes correlated with behavioral impairments. In human tau transgenic mice, rmCHI induced increases in hyperphosphorylated paired helical filament 1 tau in the hippocampus. This suggests that strategies to restore myelination or reduce neuronal loss may ameliorate the behavioral deficits observed following rmCHI and that rmCHI may model chronic traumatic encephalopathy in human tau mice.</AbstractText
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Learned uncertainty: The free energy principle in anxiety. Generalized anxiety disorder is among the world's most prevalent psychiatric disorders and often manifests as persistent and difficult to control apprehension. Despite its prevalence, there is no integrative, formal model of how anxiety and anxiety disorders arise. Here, we offer a perspective derived from the free energy principle; one that shares similarities with established constructs such as <i
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31980969
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22209809
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32892629
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Brain activity underlying face and face pareidolia processing: an ERP study.
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Differentiating BOLD and non-BOLD signals in fMRI time series using multi-echo EPI.
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Real-Time Resting-State Functional Magnetic Resonance Imaging Using Averaged Sliding Windows with Partial Correlations and Regression of Confounding Signals.
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Face pareidolia is described as an interpretation of any unrelated object seen for the first time as a face. It is still unclear how to face pareidolia is processed. In this study, the neural basis of face and face pareidolia processing was investigated through recording event-related potentials (ERPs).</AbstractText The ERPs were recorded from 35 right-handed and healthy participants in response to faces and face pareidolia. Amplitudes and latencies of N170, vertex-positive potential (VPP), and N250 components were analyzed, and current source density (CSD) maps relevant to these components were obtained.</AbstractText N170 response was earlier and larger in response to faces compared to face pareidolias. VPP is also evoked earlier in response to faces as in the case of N170; however, the VPP amplitude was larger for face pareidolias than for faces. Statistical analyses did not reveal any differences between faces and face pareidolias in terms of N250 component.</AbstractText The results indicated that faces and face pareidolias are processed in the early stages of visual perception. In addition, the N250 component does not reflect the neural processing of faces and face pareidolias.</AbstractText
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A central challenge in the fMRI based study of functional connectivity is distinguishing neuronally related signal fluctuations from the effects of motion, physiology, and other nuisance sources. Conventional techniques for removing nuisance effects include modeling of noise time courses based on external measurements followed by temporal filtering. These techniques have limited effectiveness. Previous studies have shown using multi-echo fMRI that neuronally related fluctuations are Blood Oxygen Level Dependent (BOLD) signals that can be characterized in terms of changes in R(2)* and initial signal intensity (S(0)) based on the analysis of echo-time (TE) dependence. We hypothesized that if TE-dependence could be used to differentiate BOLD and non-BOLD signals, non-BOLD signal could be removed to denoise data without conventional noise modeling. To test this hypothesis, whole brain multi-echo data were acquired at 3 TEs and decomposed with Independent Components Analysis (ICA) after spatially concatenating data across space and TE. Components were analyzed for the degree to which their signal changes fit models for R(2)* and S(0) change, and summary scores were developed to characterize each component as BOLD-like or not BOLD-like. These scores clearly differentiated BOLD-like "functional network" components from non BOLD-like components related to motion, pulsatility, and other nuisance effects. Using non BOLD-like component time courses as noise regressors dramatically improved seed-based correlation mapping by reducing the effects of high and low frequency non-BOLD fluctuations. A comparison with seed-based correlation mapping using conventional noise regressors demonstrated the superiority of the proposed technique for both individual and group level seed-based connectivity analysis, especially in mapping subcortical-cortical connectivity. The differentiation of BOLD and non-BOLD components based on TE-dependence was highly robust, which allowed for the identification of BOLD-like components and the removal of non BOLD-like components to be implemented as a fully automated procedure.</AbstractText
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<b
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Brain activity underlying face and face pareidolia processing: an ERP study. Face pareidolia is described as an interpretation of any unrelated object seen for the first time as a face. It is still unclear how to face pareidolia is processed. In this study, the neural basis of face and face pareidolia processing was investigated through recording event-related potentials (ERPs).</AbstractText The ERPs were recorded from 35 right-handed and healthy participants in response to faces and face pareidolia. Amplitudes and latencies of N170, vertex-positive potential (VPP), and N250 components were analyzed, and current source density (CSD) maps relevant to these components were obtained.</AbstractText N170 response was earlier and larger in response to faces compared to face pareidolias. VPP is also evoked earlier in response to faces as in the case of N170; however, the VPP amplitude was larger for face pareidolias than for faces. Statistical analyses did not reveal any differences between faces and face pareidolias in terms of N250 component.</AbstractText The results indicated that faces and face pareidolias are processed in the early stages of visual perception. In addition, the N250 component does not reflect the neural processing of faces and face pareidolias.</AbstractText
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Differentiating BOLD and non-BOLD signals in fMRI time series using multi-echo EPI. A central challenge in the fMRI based study of functional connectivity is distinguishing neuronally related signal fluctuations from the effects of motion, physiology, and other nuisance sources. Conventional techniques for removing nuisance effects include modeling of noise time courses based on external measurements followed by temporal filtering. These techniques have limited effectiveness. Previous studies have shown using multi-echo fMRI that neuronally related fluctuations are Blood Oxygen Level Dependent (BOLD) signals that can be characterized in terms of changes in R(2)* and initial signal intensity (S(0)) based on the analysis of echo-time (TE) dependence. We hypothesized that if TE-dependence could be used to differentiate BOLD and non-BOLD signals, non-BOLD signal could be removed to denoise data without conventional noise modeling. To test this hypothesis, whole brain multi-echo data were acquired at 3 TEs and decomposed with Independent Components Analysis (ICA) after spatially concatenating data across space and TE. Components were analyzed for the degree to which their signal changes fit models for R(2)* and S(0) change, and summary scores were developed to characterize each component as BOLD-like or not BOLD-like. These scores clearly differentiated BOLD-like "functional network" components from non BOLD-like components related to motion, pulsatility, and other nuisance effects. Using non BOLD-like component time courses as noise regressors dramatically improved seed-based correlation mapping by reducing the effects of high and low frequency non-BOLD fluctuations. A comparison with seed-based correlation mapping using conventional noise regressors demonstrated the superiority of the proposed technique for both individual and group level seed-based connectivity analysis, especially in mapping subcortical-cortical connectivity. The differentiation of BOLD and non-BOLD components based on TE-dependence was highly robust, which allowed for the identification of BOLD-like components and the removal of non BOLD-like components to be implemented as a fully automated procedure.</AbstractText
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Real-Time Resting-State Functional Magnetic Resonance Imaging Using Averaged Sliding Windows with Partial Correlations and Regression of Confounding Signals. <b
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27383592
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21616985
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26989192
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Temporal Dynamics of Sensorimotor Networks in Effort-Based Cost-Benefit Valuation: Early Emergence and Late Net Value Integration.
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The contribution of emotion and cognition to moral sensitivity: a neurodevelopmental study.
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A mutation in the tuft mouse disrupts TET1 activity and alters the expression of genes that are crucial for neural tube closure.
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Although physical effort can impose significant costs on decision-making, when and how effort cost information is incorporated into choice remains contested, reflecting a larger debate over the role of sensorimotor networks in specifying behavior. Serial information processing models, in which motor circuits simply implement the output of cognitive systems, hypothesize that effort cost factors into decisions relatively late, via integration with stimulus values into net (combined) value signals in dorsomedial frontal cortex (dmFC). In contrast, ethology-inspired approaches suggest a more active role for the dorsal sensorimotor stream, with effort cost signals emerging rapidly after stimulus onset. Here we investigated the time course of effort cost integration using event-related potentials in hungry human subjects while they made decisions about expending physical effort for appetitive foods. Consistent with the ethological perspective, we found that effort cost was represented from as early as 100-250 ms after stimulus onset, localized to dorsal sensorimotor regions including middle cingulate, somatosensory, and motor/premotor cortices. However, examining the same data time-locked to motor output revealed net value signals combining stimulus value and effort cost approximately -400 ms before response, originating from sensorimotor areas including dmFC, precuneus, and posterior parietal cortex. Granger causal connectivity analysis of the motor effector signal in the time leading to response showed interactions between these sensorimotor regions and ventrolateral prefrontal cortex, a structure associated with adjusting behavior-response mappings. These results suggest that rapid activation of sensorimotor regions interacts with cognitive valuation systems, producing a net value signal reflecting both physical effort and reward contingencies.</AbstractText Although physical effort imposes a cost on choice, when and how effort cost influences neural correlates of decision-making remains contested. This dispute reflects a larger disagreement between cognitive neuroscience and ethology over the role of sensorimotor systems in behavior: are sensorimotor circuits merely implementing the late-stage output of cognitive systems, or engaged rapidly and interactively from early in decision-making? We find that, although early representation of effort cost is associated with sensorimotor regions, these signals are also integrated with cognitive stimulus value representations in the time leading up to motor response. These data suggest that sensorimotor networks interact dynamically with cognitive systems to guide decision-making, providing a first step toward reconciling differing perspectives on sensorimotor roles in valuation and choice.</AbstractText
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Whether emotion is a source of moral judgments remains controversial. This study combined neurophysiological measures, including functional magnetic resonance imaging, eye-tracking, and pupillary response with behavioral measures assessing affective and moral judgments across age. One hundred and twenty-six participants aged between 4 and 37 years viewed scenarios depicting intentional versus accidental actions that caused harm/damage to people and objects. Morally, salient scenarios evoked stronger empathic sadness in young participants and were associated with enhanced activity in the amygdala, insula, and temporal poles. While intentional harm was evaluated as equally wrong across all participants, ratings of deserved punishments and malevolent intent gradually became more differentiated with age. Furthermore, age-related increase in activity was detected in the ventromedial prefrontal cortex in response to intentional harm to people, as well as increased functional connectivity between this region and the amygdala. Our study provides evidence that moral reasoning involves a complex integration between affective and cognitive processes that gradually changes with age and can be viewed in dynamic transaction across the course of ontogenesis. The findings support the view that negative emotion alerts the individual to the moral salience of a situation by bringing discomfort and thus can serve as an antecedent to moral judgment.</AbstractText
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Genetic variations affecting neural tube closure along the head result in malformations of the face and brain. Neural tube defects (NTDs) are among the most common birth defects in humans. We previously reported a mouse mutant called tuft that arose spontaneously in our wild-type 3H1 colony. Adult tuft mice present midline craniofacial malformations with or without an anterior cephalocele. In addition, affected embryos presented neural tube closure defects resulting in insufficient closure of the anterior neuropore or exencephaly. Here, through whole-genome sequencing, we identified a nonsense mutation in the Tet1 gene, which encodes a methylcytosine dioxygenase (TET1), co-segregating with the tuft phenotype. This mutation resulted in premature termination that disrupts the catalytic domain that is involved in the demethylation of cytosine. We detected a significant loss of TET enzyme activity in the heads of tuft embryos that were homozygous for the mutation and had NTDs. RNA-Seq transcriptome analysis indicated that multiple gene pathways associated with neural tube closure were dysregulated in tuft embryo heads. Among them, the expressions of Cecr2, Epha7 and Grhl2 were significantly reduced in some embryos presenting neural tube closure defects, whereas one or more components of the non-canonical WNT signaling pathway mediating planar cell polarity and convergent extension were affected in others. We further show that the recombinant mutant TET1 protein was capable of entering the nucleus and affected the expression of endogenous Grhl2 in IMCD-3 (inner medullary collecting duct) cells. These results indicate that TET1 is an epigenetic determinant for regulating genes that are crucial to closure of the anterior neural tube and its mutation has implications to craniofacial development, as presented by the tuft mouse.</AbstractText
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Temporal Dynamics of Sensorimotor Networks in Effort-Based Cost-Benefit Valuation: Early Emergence and Late Net Value Integration. Although physical effort can impose significant costs on decision-making, when and how effort cost information is incorporated into choice remains contested, reflecting a larger debate over the role of sensorimotor networks in specifying behavior. Serial information processing models, in which motor circuits simply implement the output of cognitive systems, hypothesize that effort cost factors into decisions relatively late, via integration with stimulus values into net (combined) value signals in dorsomedial frontal cortex (dmFC). In contrast, ethology-inspired approaches suggest a more active role for the dorsal sensorimotor stream, with effort cost signals emerging rapidly after stimulus onset. Here we investigated the time course of effort cost integration using event-related potentials in hungry human subjects while they made decisions about expending physical effort for appetitive foods. Consistent with the ethological perspective, we found that effort cost was represented from as early as 100-250 ms after stimulus onset, localized to dorsal sensorimotor regions including middle cingulate, somatosensory, and motor/premotor cortices. However, examining the same data time-locked to motor output revealed net value signals combining stimulus value and effort cost approximately -400 ms before response, originating from sensorimotor areas including dmFC, precuneus, and posterior parietal cortex. Granger causal connectivity analysis of the motor effector signal in the time leading to response showed interactions between these sensorimotor regions and ventrolateral prefrontal cortex, a structure associated with adjusting behavior-response mappings. These results suggest that rapid activation of sensorimotor regions interacts with cognitive valuation systems, producing a net value signal reflecting both physical effort and reward contingencies.</AbstractText Although physical effort imposes a cost on choice, when and how effort cost influences neural correlates of decision-making remains contested. This dispute reflects a larger disagreement between cognitive neuroscience and ethology over the role of sensorimotor systems in behavior: are sensorimotor circuits merely implementing the late-stage output of cognitive systems, or engaged rapidly and interactively from early in decision-making? We find that, although early representation of effort cost is associated with sensorimotor regions, these signals are also integrated with cognitive stimulus value representations in the time leading up to motor response. These data suggest that sensorimotor networks interact dynamically with cognitive systems to guide decision-making, providing a first step toward reconciling differing perspectives on sensorimotor roles in valuation and choice.</AbstractText
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The contribution of emotion and cognition to moral sensitivity: a neurodevelopmental study. Whether emotion is a source of moral judgments remains controversial. This study combined neurophysiological measures, including functional magnetic resonance imaging, eye-tracking, and pupillary response with behavioral measures assessing affective and moral judgments across age. One hundred and twenty-six participants aged between 4 and 37 years viewed scenarios depicting intentional versus accidental actions that caused harm/damage to people and objects. Morally, salient scenarios evoked stronger empathic sadness in young participants and were associated with enhanced activity in the amygdala, insula, and temporal poles. While intentional harm was evaluated as equally wrong across all participants, ratings of deserved punishments and malevolent intent gradually became more differentiated with age. Furthermore, age-related increase in activity was detected in the ventromedial prefrontal cortex in response to intentional harm to people, as well as increased functional connectivity between this region and the amygdala. Our study provides evidence that moral reasoning involves a complex integration between affective and cognitive processes that gradually changes with age and can be viewed in dynamic transaction across the course of ontogenesis. The findings support the view that negative emotion alerts the individual to the moral salience of a situation by bringing discomfort and thus can serve as an antecedent to moral judgment.</AbstractText
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A mutation in the tuft mouse disrupts TET1 activity and alters the expression of genes that are crucial for neural tube closure. Genetic variations affecting neural tube closure along the head result in malformations of the face and brain. Neural tube defects (NTDs) are among the most common birth defects in humans. We previously reported a mouse mutant called tuft that arose spontaneously in our wild-type 3H1 colony. Adult tuft mice present midline craniofacial malformations with or without an anterior cephalocele. In addition, affected embryos presented neural tube closure defects resulting in insufficient closure of the anterior neuropore or exencephaly. Here, through whole-genome sequencing, we identified a nonsense mutation in the Tet1 gene, which encodes a methylcytosine dioxygenase (TET1), co-segregating with the tuft phenotype. This mutation resulted in premature termination that disrupts the catalytic domain that is involved in the demethylation of cytosine. We detected a significant loss of TET enzyme activity in the heads of tuft embryos that were homozygous for the mutation and had NTDs. RNA-Seq transcriptome analysis indicated that multiple gene pathways associated with neural tube closure were dysregulated in tuft embryo heads. Among them, the expressions of Cecr2, Epha7 and Grhl2 were significantly reduced in some embryos presenting neural tube closure defects, whereas one or more components of the non-canonical WNT signaling pathway mediating planar cell polarity and convergent extension were affected in others. We further show that the recombinant mutant TET1 protein was capable of entering the nucleus and affected the expression of endogenous Grhl2 in IMCD-3 (inner medullary collecting duct) cells. These results indicate that TET1 is an epigenetic determinant for regulating genes that are crucial to closure of the anterior neural tube and its mutation has implications to craniofacial development, as presented by the tuft mouse.</AbstractText
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25542879
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25774497
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26063602
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Arterial spin-labeling perfusion MRI stratifies progression-free survival and correlates with epidermal growth factor receptor status in glioblastoma.
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Increased perfusion in normal appearing white matter in high inflammatory multiple sclerosis patients.
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Ethanol-related alterations in gene expression patterns in the developing murine hippocampus.
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Glioblastoma is a common primary brain tumor with a poor but variable prognosis. Our aim was to investigate the feasibility of MR perfusion imaging by using arterial spin-labeling for determining the prognosis of patients with glioblastoma.</AbstractText Pseudocontinuous arterial spin-labeling with 3D background-suppressed gradient and spin-echo was acquired before surgery on 53 patients subsequently diagnosed with glioblastoma. The calculated CBF color maps were visually evaluated by 3 independent readers blinded to patient history. Pathologic and survival data were correlated with CBF map findings. Arterial spin-labeling values in tumor tissue were also quantified by using manual fixed-size ROIs.</AbstractText Two perfusion patterns were characterized by visual evaluation of CBF maps on the basis of either the presence (pattern 1) or absence (pattern 2) of substantial hyperperfused tumor tissue. Evaluation of the perfusion patterns was highly concordant among the 3 readers (κ = 0.898, P < .001). Pattern 1 (versus pattern 2) was associated with significantly shorter progression-free survival by Kaplan-Meier analysis (median progression-free survival of 182 days versus 485 days, P < .01) and trended with shorter overall survival (P = .079). There was a significant association between pattern 1 and epidermal growth factor receptor variant III expression (P < .01).</AbstractText Qualitative evaluation of arterial spin-labeling CBF maps can be used to stratify survival and predict epidermal growth factor receptor variant III expression in patients with glioblastoma.</AbstractText
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Although cerebral perfusion alterations have long been acknowledged in multiple sclerosis (MS), the relationship between measurable perfusion changes and the status of highly active MS has not been examined. We hypothesized that alteration of perfusion can be detected in normal appearing white matter and is increased in high inflammatory patients.</AbstractText Thirty-three patients with relapsing-remitting MS underwent four monthly 3T MRI scans including dynamic susceptibility contrast perfusion-weighted MRI. Cerebral blood flow (CBF) and cerebral blood volume (CBV) were measured in normal appearing white matter. Patients were stratified in a high- and low-inflammatory group according to the number of new contrast enhancing lesions.</AbstractText Thirteen patients were classified as high-inflammatory. Compared to low-inflammatory patients, the high-inflammatory group demonstrated significantly higher CBV (p = 0.001) and CBF (p = 0.014) values. A mixed model analysis to assess independent variables associated with CBV and CBF revealed that white matter lesion load and atrophy measurements had no significant influence on CBF and CBV.</AbstractText This work provides evidence that high inflammatory lesion load is associated with increased CBV and CBF, underlining the role of global modified microcirculation prior to leakage of the blood-brain barrier in the pathophysiology of MS. Perfusion changes might therefore be sensitive to active inflammation apart from lesion development without local blood-brain barrier breakdown, and could be utilized to further assess the metabolic aspect of current inflammation.</AbstractText
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It is well known that consuming alcohol prior to and during pregnancy can cause harm to the developing fetus. Fetal alcohol spectrum disorder is a term commonly used to describe a range of disabilities that may arise from prenatal alcohol exposure such as fetal alcohol syndrome, partial fetal alcohol syndrome, alcohol-related neurodevelopmental disorders, and alcohol-related birth defects. Here, we report that maternal binge alcohol consumption alters several important genes that are involved in nervous system development in the mouse hippocampus at embryonic day 18. Microarray analysis revealed that Nova1, Ntng1, Gal, Neurog2, Neurod2, and Fezf2 gene expressions are altered in the fetal hippocampus. Pathway analysis also revealed the association of the calcium signaling pathway in addition to other pathways with the differentially expressed genes during early brain development. Alteration of such important genes and dynamics of the signaling pathways may cause neurodevelopmental disorders. Our findings offer insight into the molecular mechanism involved in neurodevelopmental disorders associated with alcohol-related defects.</AbstractText
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Arterial spin-labeling perfusion MRI stratifies progression-free survival and correlates with epidermal growth factor receptor status in glioblastoma. Glioblastoma is a common primary brain tumor with a poor but variable prognosis. Our aim was to investigate the feasibility of MR perfusion imaging by using arterial spin-labeling for determining the prognosis of patients with glioblastoma.</AbstractText Pseudocontinuous arterial spin-labeling with 3D background-suppressed gradient and spin-echo was acquired before surgery on 53 patients subsequently diagnosed with glioblastoma. The calculated CBF color maps were visually evaluated by 3 independent readers blinded to patient history. Pathologic and survival data were correlated with CBF map findings. Arterial spin-labeling values in tumor tissue were also quantified by using manual fixed-size ROIs.</AbstractText Two perfusion patterns were characterized by visual evaluation of CBF maps on the basis of either the presence (pattern 1) or absence (pattern 2) of substantial hyperperfused tumor tissue. Evaluation of the perfusion patterns was highly concordant among the 3 readers (κ = 0.898, P < .001). Pattern 1 (versus pattern 2) was associated with significantly shorter progression-free survival by Kaplan-Meier analysis (median progression-free survival of 182 days versus 485 days, P < .01) and trended with shorter overall survival (P = .079). There was a significant association between pattern 1 and epidermal growth factor receptor variant III expression (P < .01).</AbstractText Qualitative evaluation of arterial spin-labeling CBF maps can be used to stratify survival and predict epidermal growth factor receptor variant III expression in patients with glioblastoma.</AbstractText
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Increased perfusion in normal appearing white matter in high inflammatory multiple sclerosis patients. Although cerebral perfusion alterations have long been acknowledged in multiple sclerosis (MS), the relationship between measurable perfusion changes and the status of highly active MS has not been examined. We hypothesized that alteration of perfusion can be detected in normal appearing white matter and is increased in high inflammatory patients.</AbstractText Thirty-three patients with relapsing-remitting MS underwent four monthly 3T MRI scans including dynamic susceptibility contrast perfusion-weighted MRI. Cerebral blood flow (CBF) and cerebral blood volume (CBV) were measured in normal appearing white matter. Patients were stratified in a high- and low-inflammatory group according to the number of new contrast enhancing lesions.</AbstractText Thirteen patients were classified as high-inflammatory. Compared to low-inflammatory patients, the high-inflammatory group demonstrated significantly higher CBV (p = 0.001) and CBF (p = 0.014) values. A mixed model analysis to assess independent variables associated with CBV and CBF revealed that white matter lesion load and atrophy measurements had no significant influence on CBF and CBV.</AbstractText This work provides evidence that high inflammatory lesion load is associated with increased CBV and CBF, underlining the role of global modified microcirculation prior to leakage of the blood-brain barrier in the pathophysiology of MS. Perfusion changes might therefore be sensitive to active inflammation apart from lesion development without local blood-brain barrier breakdown, and could be utilized to further assess the metabolic aspect of current inflammation.</AbstractText
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Ethanol-related alterations in gene expression patterns in the developing murine hippocampus. It is well known that consuming alcohol prior to and during pregnancy can cause harm to the developing fetus. Fetal alcohol spectrum disorder is a term commonly used to describe a range of disabilities that may arise from prenatal alcohol exposure such as fetal alcohol syndrome, partial fetal alcohol syndrome, alcohol-related neurodevelopmental disorders, and alcohol-related birth defects. Here, we report that maternal binge alcohol consumption alters several important genes that are involved in nervous system development in the mouse hippocampus at embryonic day 18. Microarray analysis revealed that Nova1, Ntng1, Gal, Neurog2, Neurod2, and Fezf2 gene expressions are altered in the fetal hippocampus. Pathway analysis also revealed the association of the calcium signaling pathway in addition to other pathways with the differentially expressed genes during early brain development. Alteration of such important genes and dynamics of the signaling pathways may cause neurodevelopmental disorders. Our findings offer insight into the molecular mechanism involved in neurodevelopmental disorders associated with alcohol-related defects.</AbstractText
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40442130
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28687313
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40499554
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Phonation differentiation by non-contact laryngeal magnetomyography.
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Two different mirror neuron networks: The sensorimotor (hand) and limbic (face) pathways.
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Biocide mixture (CMIT/MIT) induces neurotoxicity through the upregulation of the MAPKs signaling pathways.
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Phonation is important for our daily communication and requires the activation of internal and external laryngeal muscles, which can be recorded by electromyography (EMG) using surface or needle electrodes. Here we present a new noncontact method, laryngeal magnetomyography. As a proof-of-concept, we investigated the feasibility of differentiating various vocalization conditions using laryngeal MMG in two healthy subjects using optically pumped magnetometers (OPM). We recorded magnetic muscle activity of the larynx and neighboring cervical muscles using a 3 × 5 array of OPMs. Subjects vocalized an /a/ in three different conditions: loud high pitch, loud low pitch, and soft high pitch, in 90 s blocks. After removing cardiac artifacts, MMG signals were in the range of 1.5 pT with significant amplitude differences between conditions. In both subjects, Linear Discriminant Analysis (LDA) was able to significantly classify vocalization conditions based on the spatial pattern of MMG activities. In sum, we show that laryngeal MMG allows contactless differentiation of phonations based on myomagnetic signals. Our results set the stage for future studies to explore this method for clinical diagnostics and therapy. Functional, contactless muscle recordings during vocalization enable new applications for miniaturized quantum sensors, e.g. in linguistic studies and speech rehabilitation.</AbstractText
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The vast majority of functional studies investigating mirror neurons (MNs) explored their properties in relation to hand actions, and very few investigated how MNs respond to mouth actions or communicative gestures. Since hand and mouth MNs were recorded in two partially overlapping sectors of the ventral precentral cortex of the macaque monkey, there is a general assumption that they share a same neuroanatomical network, with the parietal cortex as a main source of visual information. In the current review, we challenge this perspective and describe the connectivity pattern of mouth MN sector. The mouth MNs F5/opercular region is connected with premotor, parietal areas mostly related to the somatosensory and motor representation of the face/mouth, and with area PrCO, involved in processing gustatory and somatosensory intraoral input. Unlike hand MNs, mouth MNs do not receive their visual input from parietal regions. Such information related to face/communicative behaviors could come from the ventrolateral prefrontal cortex. Further strong connections derive from limbic structures involved in encoding emotional facial expressions and motivational/reward processing. These brain structures include the anterior cingulate cortex, the anterior and mid-dorsal insula, orbitofrontal cortex and the basolateral amygdala. The mirror mechanism is therefore composed and supported by at least two different anatomical pathways: one is concerned with sensorimotor transformation in relation to reaching and hand grasping within the traditional parietal-premotor circuits; the second one is linked to the mouth/face motor control and is connected with limbic structures, involved in communication/emotions and reward processing.</AbstractText
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The biocides 5-chloro-2-methyl-2h-isothiazolin-3-one and 2-methyl-2h-isothiazolin-3-one (CMIT/MIT) are widely used and can be found in many different types of water-soluble consumer products, such as shampoo, dentifrice, and germicide. Recent reports have suggested that it may be harmful to the skin and lungs. Although not known to be linked to pathogenic cellular and molecular pathways, it is a recognized risk factor for endangering public health. Therefore, the aim of this study was to examine the impact of CMIT/MIT (in 3:1 ratio) in SH-SY5Y human neuroblastoma cells. SHSY-5Y cells were exposed to different concentration (0, 12.5, 25, and 50 μM) of CMIT/MIT for 24 h. Cellular proliferation was considerably reduced in the MTT assay after CMIT/MIT exposure. In addition, the results showed an increase in lactate dehydrogenase (LDH) release and lipid peroxidation and a decrease in physiological antioxidant defense. We also observed an activation of Nrf-2/HO-1 signaling pathway by Western blot and qRT-PCR. Exposure to CMIT/MIT (in 3:1 ratio) also increased the release of proinflammatory cytokines, such as IL-1β, IL-6, and TNF-α. Furthermore, in SHSY-5Y, CMIT/MIT (in 3:1 ratio) raised the levels of phosphorylated ERK1/2, phosphorylated p38, and phosphorylated JNK1/2 proteins. The activation of these pathways was strongly connected with the cell cycle-related genes p53 and p21 and the activation of apoptotic cascade. These results imply that the Nrf-2/HO-1, p38-JNK1/2-ERK1/2, and Bax/Bcl-2 signaling pathways are responsible for inducing cellular damage and accelerating neuronal aging in response to CMIT/MIT (in 3:1 ratio) exposure.<b
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Phonation differentiation by non-contact laryngeal magnetomyography. Phonation is important for our daily communication and requires the activation of internal and external laryngeal muscles, which can be recorded by electromyography (EMG) using surface or needle electrodes. Here we present a new noncontact method, laryngeal magnetomyography. As a proof-of-concept, we investigated the feasibility of differentiating various vocalization conditions using laryngeal MMG in two healthy subjects using optically pumped magnetometers (OPM). We recorded magnetic muscle activity of the larynx and neighboring cervical muscles using a 3 × 5 array of OPMs. Subjects vocalized an /a/ in three different conditions: loud high pitch, loud low pitch, and soft high pitch, in 90 s blocks. After removing cardiac artifacts, MMG signals were in the range of 1.5 pT with significant amplitude differences between conditions. In both subjects, Linear Discriminant Analysis (LDA) was able to significantly classify vocalization conditions based on the spatial pattern of MMG activities. In sum, we show that laryngeal MMG allows contactless differentiation of phonations based on myomagnetic signals. Our results set the stage for future studies to explore this method for clinical diagnostics and therapy. Functional, contactless muscle recordings during vocalization enable new applications for miniaturized quantum sensors, e.g. in linguistic studies and speech rehabilitation.</AbstractText
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Two different mirror neuron networks: The sensorimotor (hand) and limbic (face) pathways. The vast majority of functional studies investigating mirror neurons (MNs) explored their properties in relation to hand actions, and very few investigated how MNs respond to mouth actions or communicative gestures. Since hand and mouth MNs were recorded in two partially overlapping sectors of the ventral precentral cortex of the macaque monkey, there is a general assumption that they share a same neuroanatomical network, with the parietal cortex as a main source of visual information. In the current review, we challenge this perspective and describe the connectivity pattern of mouth MN sector. The mouth MNs F5/opercular region is connected with premotor, parietal areas mostly related to the somatosensory and motor representation of the face/mouth, and with area PrCO, involved in processing gustatory and somatosensory intraoral input. Unlike hand MNs, mouth MNs do not receive their visual input from parietal regions. Such information related to face/communicative behaviors could come from the ventrolateral prefrontal cortex. Further strong connections derive from limbic structures involved in encoding emotional facial expressions and motivational/reward processing. These brain structures include the anterior cingulate cortex, the anterior and mid-dorsal insula, orbitofrontal cortex and the basolateral amygdala. The mirror mechanism is therefore composed and supported by at least two different anatomical pathways: one is concerned with sensorimotor transformation in relation to reaching and hand grasping within the traditional parietal-premotor circuits; the second one is linked to the mouth/face motor control and is connected with limbic structures, involved in communication/emotions and reward processing.</AbstractText
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Biocide mixture (CMIT/MIT) induces neurotoxicity through the upregulation of the MAPKs signaling pathways. The biocides 5-chloro-2-methyl-2h-isothiazolin-3-one and 2-methyl-2h-isothiazolin-3-one (CMIT/MIT) are widely used and can be found in many different types of water-soluble consumer products, such as shampoo, dentifrice, and germicide. Recent reports have suggested that it may be harmful to the skin and lungs. Although not known to be linked to pathogenic cellular and molecular pathways, it is a recognized risk factor for endangering public health. Therefore, the aim of this study was to examine the impact of CMIT/MIT (in 3:1 ratio) in SH-SY5Y human neuroblastoma cells. SHSY-5Y cells were exposed to different concentration (0, 12.5, 25, and 50 μM) of CMIT/MIT for 24 h. Cellular proliferation was considerably reduced in the MTT assay after CMIT/MIT exposure. In addition, the results showed an increase in lactate dehydrogenase (LDH) release and lipid peroxidation and a decrease in physiological antioxidant defense. We also observed an activation of Nrf-2/HO-1 signaling pathway by Western blot and qRT-PCR. Exposure to CMIT/MIT (in 3:1 ratio) also increased the release of proinflammatory cytokines, such as IL-1β, IL-6, and TNF-α. Furthermore, in SHSY-5Y, CMIT/MIT (in 3:1 ratio) raised the levels of phosphorylated ERK1/2, phosphorylated p38, and phosphorylated JNK1/2 proteins. The activation of these pathways was strongly connected with the cell cycle-related genes p53 and p21 and the activation of apoptotic cascade. These results imply that the Nrf-2/HO-1, p38-JNK1/2-ERK1/2, and Bax/Bcl-2 signaling pathways are responsible for inducing cellular damage and accelerating neuronal aging in response to CMIT/MIT (in 3:1 ratio) exposure.<b
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40473593
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32978287
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40744206
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Dim light at night induces depression-like behaviors during the postpartum period through circadian rhythm related pathways in mice.
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It Is All in the Right Amygdala: Increased Synaptic Plasticity and Perineuronal Nets in Male, But Not Female, Juvenile Rat Pups after Exposure to Early-Life Stress.
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Differences in Aortic Remodeling in Patients with Type Ia and Type V Endoleak who Undergo Salvage with F/BEVAR.
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Growing evidence suggests that dim light at night (dLAN) may disrupt circadian rhythms and provoke symptoms of anxiety and depression. Due to the inconvenience of pregnancy and caring for infants, there is a high prevalence of dLAN exposure among pregnant and postpartum women. However, the role and circadian mechanism of dLAN on depression, and anxiety during the postpartum period remain unclear. Pregnant mice were housed in either a light-dark cycle (LD; 12 h of 200 lux:12 h of 0 lux) or a light-dLAN cycle (dLAN; 12 h of 200 lux:12 h of 5 lux) during the gestational and postpartum periods. Depression- and anxiety-related symptoms were assessed by the open field test, sucrose preference test, and forced swim test. Hippocampal transcript profiles were examined using multi-timepoint transcriptome analysis to assess the effects of dLAN exposure. Our findings showed that dLAN significantly increased depression-like behaviors, such as decreased sugar preference and increased immobility time, and decreased levels of brain serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) during the postpartum period. In addition, dLAN reduced the amplitude of circadian rest-activity behaviors and nighttime activity levels, and these disruptions were significantly related to depression-like behaviors and low levels of 5-HT. Moreover, dLAN disrupted the expressions of hippocampal circadian genes particularly Per1 in postpartum mice. These findings reveal that dLAN induces depression-like behaviors in postpartum mice, with disruptions in circadian rest-activity rhythms and rhythmic gene expression likely mediating the adverse effects of dLAN on these behaviors.</AbstractText
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Early-life stress (ELS) is associated with increased vulnerability to mental disorders. The basolateral amygdala (BLA) plays a critical role in fear conditioning and is extremely sensitive to ELS. Using a naturalistic rodent model of ELS, the limited bedding paradigm (LB) between postnatal days 1-10, we previously documented that LB male, but not female preweaning rat pups display increased BLA neuron spine density paralleled with enhanced evoked synaptic responses and altered BLA functional connectivity. Since ELS effects are often sexually dimorphic and amygdala processes exhibit hemispheric asymmetry, we investigated changes in synaptic plasticity and neuronal excitability of BLA neurons <i
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Aneurysm sac growth following endovascular aortic aneurysm repair (EVAR) is multifactorial. A specific cause of growth (eg type 1a endoleak, (EL1a)) may be present or a specific cause may be absent (no observed endoleak resulting in "endotension" or type 5 endoleak (EL5)). Salvage of EL1a with fenestrated/branched EVAR (F/BEVAR) to obtain supraceliac seal is a viable strategy to achieve sac stability or regression. In patients with EL5, it remains unknown whether F/BEVAR leads to similar sac stability or regression. We sought to determine the incidence rate of sac stability or regression following F/BEVAR for EL1a compared to EL5.</AbstractText Prospective databases from two complex aortic centers were retrospectively queried to identify all patients who underwent F/BEVAR for failed EVAR (2015-2024). Patients were categorized to have either EL1a or EL5 based on preoperative CT scan. Pre-, intra-, and post-operative variables were compared between the groups. The primary composite outcome, sac stability (≤5mm change) or regression (>5mm decrease), was calculated using Kaplan-Meier method.</AbstractText A total of 102 patients (75 with EL1, 27 with EL5), with a mean age of 78±6.6 years and large aneurysms (71±16.2mm) were studied; no significant intergroup preoperative characteristic differences were observed. F/BEVAR repairs incorporated 3.8±0.5 target arteries per patient. Fluoroscopy dose, contrast volume, procedure time, blood loss, and technical success were similar between groups. Postoperative complication rates (EL1a: n=15, 20% vs EL5: n=4, 15%; p=.77) and 30-day mortality (EL1a: n=1, 1% vs EL5: n=2, 7%; p=.17) were similar. The cumulative incidence of sac stability or regression at 4-years was 92% [95% CI: 83-97%] for EL1a vs 81% [95% CI: 61-94%] for EL5 (log-rank p=.03) (Figure 1). On multivariable analysis, the hazard ratio for sac stability or regression was 1.72 [95% CI 1.02-2.89;p=.04] for EL1a compared to EL5.</AbstractText Sac stability or regression can be achieved in most patients with EL1a or EL5 who undergo endovascular salvage with F/BEVAR. However, those treated for EL5 are less likely to achieve sac stability or regression. Additional data are needed to better understand fundamental differences in these subsets of failed EVAR patients and to better guide appropriate salvage therapy.</AbstractText
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Dim light at night induces depression-like behaviors during the postpartum period through circadian rhythm related pathways in mice. Growing evidence suggests that dim light at night (dLAN) may disrupt circadian rhythms and provoke symptoms of anxiety and depression. Due to the inconvenience of pregnancy and caring for infants, there is a high prevalence of dLAN exposure among pregnant and postpartum women. However, the role and circadian mechanism of dLAN on depression, and anxiety during the postpartum period remain unclear. Pregnant mice were housed in either a light-dark cycle (LD; 12 h of 200 lux:12 h of 0 lux) or a light-dLAN cycle (dLAN; 12 h of 200 lux:12 h of 5 lux) during the gestational and postpartum periods. Depression- and anxiety-related symptoms were assessed by the open field test, sucrose preference test, and forced swim test. Hippocampal transcript profiles were examined using multi-timepoint transcriptome analysis to assess the effects of dLAN exposure. Our findings showed that dLAN significantly increased depression-like behaviors, such as decreased sugar preference and increased immobility time, and decreased levels of brain serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) during the postpartum period. In addition, dLAN reduced the amplitude of circadian rest-activity behaviors and nighttime activity levels, and these disruptions were significantly related to depression-like behaviors and low levels of 5-HT. Moreover, dLAN disrupted the expressions of hippocampal circadian genes particularly Per1 in postpartum mice. These findings reveal that dLAN induces depression-like behaviors in postpartum mice, with disruptions in circadian rest-activity rhythms and rhythmic gene expression likely mediating the adverse effects of dLAN on these behaviors.</AbstractText
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It Is All in the Right Amygdala: Increased Synaptic Plasticity and Perineuronal Nets in Male, But Not Female, Juvenile Rat Pups after Exposure to Early-Life Stress. Early-life stress (ELS) is associated with increased vulnerability to mental disorders. The basolateral amygdala (BLA) plays a critical role in fear conditioning and is extremely sensitive to ELS. Using a naturalistic rodent model of ELS, the limited bedding paradigm (LB) between postnatal days 1-10, we previously documented that LB male, but not female preweaning rat pups display increased BLA neuron spine density paralleled with enhanced evoked synaptic responses and altered BLA functional connectivity. Since ELS effects are often sexually dimorphic and amygdala processes exhibit hemispheric asymmetry, we investigated changes in synaptic plasticity and neuronal excitability of BLA neurons <i
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Differences in Aortic Remodeling in Patients with Type Ia and Type V Endoleak who Undergo Salvage with F/BEVAR. Aneurysm sac growth following endovascular aortic aneurysm repair (EVAR) is multifactorial. A specific cause of growth (eg type 1a endoleak, (EL1a)) may be present or a specific cause may be absent (no observed endoleak resulting in "endotension" or type 5 endoleak (EL5)). Salvage of EL1a with fenestrated/branched EVAR (F/BEVAR) to obtain supraceliac seal is a viable strategy to achieve sac stability or regression. In patients with EL5, it remains unknown whether F/BEVAR leads to similar sac stability or regression. We sought to determine the incidence rate of sac stability or regression following F/BEVAR for EL1a compared to EL5.</AbstractText Prospective databases from two complex aortic centers were retrospectively queried to identify all patients who underwent F/BEVAR for failed EVAR (2015-2024). Patients were categorized to have either EL1a or EL5 based on preoperative CT scan. Pre-, intra-, and post-operative variables were compared between the groups. The primary composite outcome, sac stability (≤5mm change) or regression (>5mm decrease), was calculated using Kaplan-Meier method.</AbstractText A total of 102 patients (75 with EL1, 27 with EL5), with a mean age of 78±6.6 years and large aneurysms (71±16.2mm) were studied; no significant intergroup preoperative characteristic differences were observed. F/BEVAR repairs incorporated 3.8±0.5 target arteries per patient. Fluoroscopy dose, contrast volume, procedure time, blood loss, and technical success were similar between groups. Postoperative complication rates (EL1a: n=15, 20% vs EL5: n=4, 15%; p=.77) and 30-day mortality (EL1a: n=1, 1% vs EL5: n=2, 7%; p=.17) were similar. The cumulative incidence of sac stability or regression at 4-years was 92% [95% CI: 83-97%] for EL1a vs 81% [95% CI: 61-94%] for EL5 (log-rank p=.03) (Figure 1). On multivariable analysis, the hazard ratio for sac stability or regression was 1.72 [95% CI 1.02-2.89;p=.04] for EL1a compared to EL5.</AbstractText Sac stability or regression can be achieved in most patients with EL1a or EL5 who undergo endovascular salvage with F/BEVAR. However, those treated for EL5 are less likely to achieve sac stability or regression. Additional data are needed to better understand fundamental differences in these subsets of failed EVAR patients and to better guide appropriate salvage therapy.</AbstractText
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25447284
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32069324
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24274862
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Generation and analysis of lentivirus expressing a 2A peptide-linked bicistronic fluorescent construct.
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Novel role of SARM1 mediated axonal degeneration in the pathogenesis of rabies.
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Obesity-associated nonalcoholic fatty liver disease.
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This weeklong protocol for making and testing lentivirus has been used in the Advanced Topics in Molecular Neuroscience (ATMN) lecture and laboratory course at Cold Spring Harbor Laboratory (CSHL) for nearly a decade. Lentiviruses are derived from HIV-1 and are ideal vehicles for the delivery of multiple genes of interest into target cells. In this protocol, 2A peptide-linked sequences are used to create a bicistronic lentiviral construct containing a ubiquitous promoter (chick β actin with a cytomegalovirus [CMV] early enhancer) driving dual expression of two fluorescent proteins (FP): H2B-Cerulean (a nuclear-localized blue FP) and Dendra2 (a photoactivatable green FP that converts to red after exposure to UV light). Polymerase chain reaction (PCR) amplification of the bicistronic insert is followed by subcloning into a lentiviral vector and transfection into a packaging cell line. The resulting viral supernatants can be used to prepare concentrated stocks and infect cells for imaging via epifluorescent and confocal microscopy.</AbstractText
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Neurotropic viral infections continue to pose a serious threat to human and animal wellbeing. Host responses combatting the invading virus in these infections often cause irreversible damage to the nervous system, resulting in poor prognosis. Rabies is the most lethal neurotropic virus, which specifically infects neurons and spreads through the host nervous system by retrograde axonal transport. The key pathogenic mechanisms associated with rabies infection and axonal transmission in neurons remains unclear. Here we studied the pathogenesis of different field isolates of lyssavirus including rabies using ex-vivo model systems generated with mouse primary neurons derived from the peripheral and central nervous systems. In this study, we show that neurons activate selective and compartmentalized degeneration of their axons and dendrites in response to infection with different field strains of lyssavirus. We further show that this axonal degeneration is mediated by the loss of NAD and calpain-mediated digestion of key structural proteins such as MAP2 and neurofilament. We then analysed the role of SARM1 gene in rabies infection, which has been shown to mediate axonal self-destruction during injury. We show that SARM1 is required for the accelerated execution of rabies induced axonal degeneration and the deletion of SARM1 gene significantly delayed axonal degeneration in rabies infected neurons. Using a microfluidic-based ex-vivo neuronal model, we show that SARM1-mediated axonal degeneration impedes the spread of rabies virus among interconnected neurons. However, this neuronal defense mechanism also results in the pathological loss of axons and dendrites. This study therefore identifies a potential host-directed mechanism behind neurological dysfunction in rabies infection. This study also implicates a novel role of SARM1 mediated axonal degeneration in neurotropic viral infection.</AbstractText
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Obesity is strongly associated with the prevalence of nonalcoholic fatty liver disease (NAFLD) in adult and pediatric populations. Nutrition, physical activity, and behavioral modifications are critical components of the treatment regimen for all obese patients with NAFLD. Bariatric surgeries that affect or restrict the flow of food through the gastrointestinal tract may improve liver histology in morbidly obese patients with nonalcoholic steatohepatitis (NASH), although randomized clinical trials and quasi-randomized clinical studies are lacking. Early detection of NASH and hepatic fibrosis using noninvasive biochemical and imaging markers that may replace liver biopsy is the current challenge.</AbstractText
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Generation and analysis of lentivirus expressing a 2A peptide-linked bicistronic fluorescent construct. This weeklong protocol for making and testing lentivirus has been used in the Advanced Topics in Molecular Neuroscience (ATMN) lecture and laboratory course at Cold Spring Harbor Laboratory (CSHL) for nearly a decade. Lentiviruses are derived from HIV-1 and are ideal vehicles for the delivery of multiple genes of interest into target cells. In this protocol, 2A peptide-linked sequences are used to create a bicistronic lentiviral construct containing a ubiquitous promoter (chick β actin with a cytomegalovirus [CMV] early enhancer) driving dual expression of two fluorescent proteins (FP): H2B-Cerulean (a nuclear-localized blue FP) and Dendra2 (a photoactivatable green FP that converts to red after exposure to UV light). Polymerase chain reaction (PCR) amplification of the bicistronic insert is followed by subcloning into a lentiviral vector and transfection into a packaging cell line. The resulting viral supernatants can be used to prepare concentrated stocks and infect cells for imaging via epifluorescent and confocal microscopy.</AbstractText
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Novel role of SARM1 mediated axonal degeneration in the pathogenesis of rabies. Neurotropic viral infections continue to pose a serious threat to human and animal wellbeing. Host responses combatting the invading virus in these infections often cause irreversible damage to the nervous system, resulting in poor prognosis. Rabies is the most lethal neurotropic virus, which specifically infects neurons and spreads through the host nervous system by retrograde axonal transport. The key pathogenic mechanisms associated with rabies infection and axonal transmission in neurons remains unclear. Here we studied the pathogenesis of different field isolates of lyssavirus including rabies using ex-vivo model systems generated with mouse primary neurons derived from the peripheral and central nervous systems. In this study, we show that neurons activate selective and compartmentalized degeneration of their axons and dendrites in response to infection with different field strains of lyssavirus. We further show that this axonal degeneration is mediated by the loss of NAD and calpain-mediated digestion of key structural proteins such as MAP2 and neurofilament. We then analysed the role of SARM1 gene in rabies infection, which has been shown to mediate axonal self-destruction during injury. We show that SARM1 is required for the accelerated execution of rabies induced axonal degeneration and the deletion of SARM1 gene significantly delayed axonal degeneration in rabies infected neurons. Using a microfluidic-based ex-vivo neuronal model, we show that SARM1-mediated axonal degeneration impedes the spread of rabies virus among interconnected neurons. However, this neuronal defense mechanism also results in the pathological loss of axons and dendrites. This study therefore identifies a potential host-directed mechanism behind neurological dysfunction in rabies infection. This study also implicates a novel role of SARM1 mediated axonal degeneration in neurotropic viral infection.</AbstractText
|
Obesity-associated nonalcoholic fatty liver disease. Obesity is strongly associated with the prevalence of nonalcoholic fatty liver disease (NAFLD) in adult and pediatric populations. Nutrition, physical activity, and behavioral modifications are critical components of the treatment regimen for all obese patients with NAFLD. Bariatric surgeries that affect or restrict the flow of food through the gastrointestinal tract may improve liver histology in morbidly obese patients with nonalcoholic steatohepatitis (NASH), although randomized clinical trials and quasi-randomized clinical studies are lacking. Early detection of NASH and hepatic fibrosis using noninvasive biochemical and imaging markers that may replace liver biopsy is the current challenge.</AbstractText
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34649566
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26635544
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33639448
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Investigation of anti-osteoporosis mechanisms of Rehmanniae Radix Preparata based on network pharmacology and experimental verification.
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The Structural Connectivity Pattern of the Default Mode Network and Its Association with Memory and Anxiety.
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Barbed suture Extrusion and Exposure in palatoplasty for OSA: What does it mean?
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Rehmanniae Radix Preparata (RRP) can effectively improve the symptoms of osteoporosis, but its molecular mechanism for treating osteoporosis is still unclear. The objective of this study is to investigate the anti-osteoporosis mechanisms of RRP through network pharmacology.</AbstractText The overlapping targets of RRP and osteoporosis were screened out using online platforms. A visual network diagram of PPI was constructed and analyzed by Cytoscape 3.7.2 software. Molecular docking was used to evaluate the binding activity of ligands and receptors, and some key genes were verified through pharmacological experiments.</AbstractText According to topological analysis results, AKT1, MAPK1, ESR1, and SRC are critical genes for RRP to treat osteoporosis, and they have high binding activity with stigmasterol and sitosterol. The main signal pathways of RRP in the treatment of osteoporosis, including the estrogen signaling pathway, HIF-1 signal pathway, MAPK signal pathway, PI3K-Akt signal pathway. Results of animal experiments showed that RRP could significantly increase the expression levels of Akt1, MAPK1, ESR1, and SRC1 mRNA in bone tissue to increase bone density.</AbstractText This study explained the coordination between multiple components and multiple targets of RRP in the treatment of osteoporosis and provided new ideas for its clinical application and experimental research.</AbstractText
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The default mode network (DMN) is one of the most widely studied resting state functional networks. The structural basis for the DMN is of particular interest and has been studied by several researchers using diffusion tensor imaging (DTI). Most of these previous studies focused on a few regions or white matter tracts of the DMN so that the global structural connectivity pattern and network properties of the DMN remain unclear. Moreover, evidences indicate that the DMN is involved in both memory and emotion, but how the DMN regulates memory and anxiety from the perspective of the whole DMN structural network remains unknown. We used multimodal neuroimaging methods to investigate the structural connectivity pattern of the DMN and the association of its network properties with memory and anxiety in 205 young healthy subjects with age ranging from 18 to 29 years old. The Group ICA method was used to extract the DMN component from functional magnetic resonance imaging (fMRI) data and a probabilistic fiber tractography technique based on DTI data was applied to construct the global structural connectivity pattern of the DMN. Then we used the graph theory method to analyze the DMN structural network and found that memory quotient (MQ) score was significantly positively correlated with the global and local efficiency of the DMN whereas anxiety was found to be negatively correlated with the efficiency. The strong structural connectivity between multiple brain regions within DMN may reflect that the DMN has certain structural basis. Meanwhile, the results we found that the network efficiency of the DMN were related to memory and anxiety measures, indicated that the DMN may play a role in the memory and anxiety.</AbstractText
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Analyze Extrusion&Exposion (E&E), its implications in the functional, anatomical results and subjective discomfort in OSA patients treated with Barbed Reposition Pharyngoplasty (BRP).</AbstractText 488 patients treated with BRP or multilevel TORS. Stratafix wire was used in 230 patients, V-Loc in 258. E&E, timing and localization evaluated at follow-up. Polygraphy used to assess the impact of E&E on functional results, PPOPS questionnaire used for subjective discomfort.</AbstractText E&E in the entire group was 18,4%, with significant difference between Stratafix and V-Loc wire (p = 0,002), but not between BRP alone and multilevel surgery (p = 0,68). 28,9% of extrusion happened within the first seven days, 76,7% between seven days and two months, 5,5% after two months. Symptomatic clinical profile has been seen in 62,2%, asymptomatic one in 37,8% of patients. 35,5% of E&E were localized in tonsillar bed, 46,7% in soft palate and 20% in other sites. Mean delta-AHI of E&E patients was -15,87 ± 16.82 compared with one of those who did not have E&E was -16.34 ± 22,77 (p = 0,38). Mean PPOPS of 183 patients analyzed was 12,32 ± 4,96. Mean PPOPS of extruded group was 12,94 ± 4,68 and 11,92 ± 5,11 in not extruded one (p = 0,166).</AbstractText E&E are suture-type sensitive (V-Loc > Stratafix), reported more frequent when BRP is performed alone than BRP-TORS with no statistical significance. 76,7% of the E&E occur after patient discharge and within 2 months. About half of the E&E were localized in soft palate. There is no need to fear Extrusion&Exposition because it does not affect in a negative way subjective and PSG outcome.</AbstractText
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Investigation of anti-osteoporosis mechanisms of Rehmanniae Radix Preparata based on network pharmacology and experimental verification. Rehmanniae Radix Preparata (RRP) can effectively improve the symptoms of osteoporosis, but its molecular mechanism for treating osteoporosis is still unclear. The objective of this study is to investigate the anti-osteoporosis mechanisms of RRP through network pharmacology.</AbstractText The overlapping targets of RRP and osteoporosis were screened out using online platforms. A visual network diagram of PPI was constructed and analyzed by Cytoscape 3.7.2 software. Molecular docking was used to evaluate the binding activity of ligands and receptors, and some key genes were verified through pharmacological experiments.</AbstractText According to topological analysis results, AKT1, MAPK1, ESR1, and SRC are critical genes for RRP to treat osteoporosis, and they have high binding activity with stigmasterol and sitosterol. The main signal pathways of RRP in the treatment of osteoporosis, including the estrogen signaling pathway, HIF-1 signal pathway, MAPK signal pathway, PI3K-Akt signal pathway. Results of animal experiments showed that RRP could significantly increase the expression levels of Akt1, MAPK1, ESR1, and SRC1 mRNA in bone tissue to increase bone density.</AbstractText This study explained the coordination between multiple components and multiple targets of RRP in the treatment of osteoporosis and provided new ideas for its clinical application and experimental research.</AbstractText
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The Structural Connectivity Pattern of the Default Mode Network and Its Association with Memory and Anxiety. The default mode network (DMN) is one of the most widely studied resting state functional networks. The structural basis for the DMN is of particular interest and has been studied by several researchers using diffusion tensor imaging (DTI). Most of these previous studies focused on a few regions or white matter tracts of the DMN so that the global structural connectivity pattern and network properties of the DMN remain unclear. Moreover, evidences indicate that the DMN is involved in both memory and emotion, but how the DMN regulates memory and anxiety from the perspective of the whole DMN structural network remains unknown. We used multimodal neuroimaging methods to investigate the structural connectivity pattern of the DMN and the association of its network properties with memory and anxiety in 205 young healthy subjects with age ranging from 18 to 29 years old. The Group ICA method was used to extract the DMN component from functional magnetic resonance imaging (fMRI) data and a probabilistic fiber tractography technique based on DTI data was applied to construct the global structural connectivity pattern of the DMN. Then we used the graph theory method to analyze the DMN structural network and found that memory quotient (MQ) score was significantly positively correlated with the global and local efficiency of the DMN whereas anxiety was found to be negatively correlated with the efficiency. The strong structural connectivity between multiple brain regions within DMN may reflect that the DMN has certain structural basis. Meanwhile, the results we found that the network efficiency of the DMN were related to memory and anxiety measures, indicated that the DMN may play a role in the memory and anxiety.</AbstractText
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Barbed suture Extrusion and Exposure in palatoplasty for OSA: What does it mean? Analyze Extrusion&Exposion (E&E), its implications in the functional, anatomical results and subjective discomfort in OSA patients treated with Barbed Reposition Pharyngoplasty (BRP).</AbstractText 488 patients treated with BRP or multilevel TORS. Stratafix wire was used in 230 patients, V-Loc in 258. E&E, timing and localization evaluated at follow-up. Polygraphy used to assess the impact of E&E on functional results, PPOPS questionnaire used for subjective discomfort.</AbstractText E&E in the entire group was 18,4%, with significant difference between Stratafix and V-Loc wire (p = 0,002), but not between BRP alone and multilevel surgery (p = 0,68). 28,9% of extrusion happened within the first seven days, 76,7% between seven days and two months, 5,5% after two months. Symptomatic clinical profile has been seen in 62,2%, asymptomatic one in 37,8% of patients. 35,5% of E&E were localized in tonsillar bed, 46,7% in soft palate and 20% in other sites. Mean delta-AHI of E&E patients was -15,87 ± 16.82 compared with one of those who did not have E&E was -16.34 ± 22,77 (p = 0,38). Mean PPOPS of 183 patients analyzed was 12,32 ± 4,96. Mean PPOPS of extruded group was 12,94 ± 4,68 and 11,92 ± 5,11 in not extruded one (p = 0,166).</AbstractText E&E are suture-type sensitive (V-Loc > Stratafix), reported more frequent when BRP is performed alone than BRP-TORS with no statistical significance. 76,7% of the E&E occur after patient discharge and within 2 months. About half of the E&E were localized in soft palate. There is no need to fear Extrusion&Exposition because it does not affect in a negative way subjective and PSG outcome.</AbstractText
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19760239
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17242272
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19944588
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Retrospective analysis of patients for development of nephrogenic systemic fibrosis following conventional angiography using gadolinium-based contrast agents.
|
Gadodiamide-associated nephrogenic systemic fibrosis: why radiologists should be concerned.
|
Dosimetric study and verification of total body irradiation using helical tomotherapy and its comparison to extended SSD technique.
|
The purpose was to retrospectively review the data of 27 patients with renal insufficiency who underwent conventional angiography with gadolinium-based contrast agents (GDBCA) as alternative contrast agents and assess the occurrence of nephrogenic systemic fibrosis (NSF) together with associated potential risk factors.</AbstractText This HIPAA-compliant study had institutional review board approval, and informed consent was waived. Statistical analysis was performed for all available laboratory and clinical data, including dermatology reports. Type and amount of the GDBCA used were recorded for angiography and additional MRI studies, if applicable. Serum creatinine levels (SCr) pre- and post-angiography were recorded, and estimated glomerular filtration rates (eGFR) were calculated.</AbstractText Ten female and 17 male patients who underwent angiography with GDBCA were included. The mean amount of GDBCA administered was 44 +/- 15.5 ml (range 15-60 ml) or 0.24 + 0.12 mmol/kg (range 0.1-0.53 mmol/kg). At the time of angiography all patients had renal insufficiency (eGFR <60 ml/min/1.73 m(2)). Mean eGFR pre-angiography was 26 ml/min/1.73 m(2) and 33 ml/min/1.73 m(2) post-angiography. The mean follow-up period covers 28 months, range 1-84 months. Additional MRI studies with GDBCA administration were performed in 15 patients. One patient with typical skin lesions had developed biopsy-confirmed NSF.</AbstractText Conventional arterial angiography with GDBCA may play a role in the development of NSF in patients with renal insufficiency. Alternative contrast agents, such as CO(2) angiography or rather the use of low doses of iodinated contrast agents, should be considered in these patients.</AbstractText
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Nephrogenic systemic fibrosis (NSF) is a rare multisystemic fibrosing disorder that principally affects the skin but may affect other organs of patients with renal insufficiency. The purpose of our study was to identify any common risk factors and determine whether i.v. gadodiamide is associated with the development of NSF.</AbstractText A retrospective chart review was performed for all 12 patients diagnosed with NSF at our institution between 2000 and 2006 to identify the clinical manifestations, timing, and dose of gadodiamide administration; dialysis records; concurrent medications; comorbid conditions and surgeries; laboratory findings; imaging findings; and clinical outcome. A review of the dialysis and MR records between 2000 and 2006 showed 559 MRI examinations on 168 dialysis patients (including 301 contrast-enhanced examinations).</AbstractText NSF was diagnosed by clinical findings and tissue diagnosis. All 12 patients had renal insufficiency--eight with dialysis-dependent chronic renal insufficiency and four with acute hepatorenal syndrome. All 12 patients developed skin fibrosis within 2-11 weeks after gadodiamide administration. The odds ratio for development of NSF after gadodiamide exposure was 22.3. No other common event or exposure could be found. Four patients had abnormal scintigraphic bone scans with skin and muscle uptake and lower-extremity MRI finding of edema in the muscles, intermuscular fascia, and skin. Despite the fact that 10 patients were dialyzed within 2 days of gadodiamide administration, this did not prevent the development of NSF.</AbstractText Development of NSF was strongly associated with gadodiamide administration in the setting of either acute hepatorenal syndrome or dialysis-dependent chronic renal insufficiency.</AbstractText
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The American College of Radiology practice guideline for total body irradiation (TBI) requires a back-up treatment delivery system. This study investigates the development of helical tomotherapy (HT) for delivering TBI and compares it with conventional extended source-to-surface distance (X-SSD) technique. Four patients' head-to-thigh computed tomographic images were used in this study, with the target defined as the body volume without the left and right lungs. HT treatment plans with the standard TBI prescription (1.2 Gy/fx, 10 fractions) were generated and verified on phantoms. To compare HT plans with X-SSD treatment, the dose distribution of X-SSD technique was simulated using the Eclipse software. The average dose received by 90% of the target volume was 12.3 Gy (range, 12.2-12.4 Gy) for HT plans and 10.3 Gy (range, 10.08-10.58 Gy) for X-SSD plans (p < 0.001). The left and right lung median doses were 5.44 Gy and 5.40 Gy, respectively, for HT plans and 8.34 Gy and 8.95 Gy, respectively, for X-SSD treatment. The treatment planning time was comparable between the two methods. The beam delivery time of HT treatment was longer than X-SSD treatment. In conclusion, HT-based TBI plans have better dose coverage to the target and better dose sparing to the lungs compared with X-SSD technique, which applies dose compensators, lung blocks, and electron boosts. This study demonstrates that HT is possible for delivering TBI. Clinical validation of the feasibility of this approach would be of interest in the future.</AbstractText
|
Retrospective analysis of patients for development of nephrogenic systemic fibrosis following conventional angiography using gadolinium-based contrast agents. The purpose was to retrospectively review the data of 27 patients with renal insufficiency who underwent conventional angiography with gadolinium-based contrast agents (GDBCA) as alternative contrast agents and assess the occurrence of nephrogenic systemic fibrosis (NSF) together with associated potential risk factors.</AbstractText This HIPAA-compliant study had institutional review board approval, and informed consent was waived. Statistical analysis was performed for all available laboratory and clinical data, including dermatology reports. Type and amount of the GDBCA used were recorded for angiography and additional MRI studies, if applicable. Serum creatinine levels (SCr) pre- and post-angiography were recorded, and estimated glomerular filtration rates (eGFR) were calculated.</AbstractText Ten female and 17 male patients who underwent angiography with GDBCA were included. The mean amount of GDBCA administered was 44 +/- 15.5 ml (range 15-60 ml) or 0.24 + 0.12 mmol/kg (range 0.1-0.53 mmol/kg). At the time of angiography all patients had renal insufficiency (eGFR <60 ml/min/1.73 m(2)). Mean eGFR pre-angiography was 26 ml/min/1.73 m(2) and 33 ml/min/1.73 m(2) post-angiography. The mean follow-up period covers 28 months, range 1-84 months. Additional MRI studies with GDBCA administration were performed in 15 patients. One patient with typical skin lesions had developed biopsy-confirmed NSF.</AbstractText Conventional arterial angiography with GDBCA may play a role in the development of NSF in patients with renal insufficiency. Alternative contrast agents, such as CO(2) angiography or rather the use of low doses of iodinated contrast agents, should be considered in these patients.</AbstractText
|
Gadodiamide-associated nephrogenic systemic fibrosis: why radiologists should be concerned. Nephrogenic systemic fibrosis (NSF) is a rare multisystemic fibrosing disorder that principally affects the skin but may affect other organs of patients with renal insufficiency. The purpose of our study was to identify any common risk factors and determine whether i.v. gadodiamide is associated with the development of NSF.</AbstractText A retrospective chart review was performed for all 12 patients diagnosed with NSF at our institution between 2000 and 2006 to identify the clinical manifestations, timing, and dose of gadodiamide administration; dialysis records; concurrent medications; comorbid conditions and surgeries; laboratory findings; imaging findings; and clinical outcome. A review of the dialysis and MR records between 2000 and 2006 showed 559 MRI examinations on 168 dialysis patients (including 301 contrast-enhanced examinations).</AbstractText NSF was diagnosed by clinical findings and tissue diagnosis. All 12 patients had renal insufficiency--eight with dialysis-dependent chronic renal insufficiency and four with acute hepatorenal syndrome. All 12 patients developed skin fibrosis within 2-11 weeks after gadodiamide administration. The odds ratio for development of NSF after gadodiamide exposure was 22.3. No other common event or exposure could be found. Four patients had abnormal scintigraphic bone scans with skin and muscle uptake and lower-extremity MRI finding of edema in the muscles, intermuscular fascia, and skin. Despite the fact that 10 patients were dialyzed within 2 days of gadodiamide administration, this did not prevent the development of NSF.</AbstractText Development of NSF was strongly associated with gadodiamide administration in the setting of either acute hepatorenal syndrome or dialysis-dependent chronic renal insufficiency.</AbstractText
|
Dosimetric study and verification of total body irradiation using helical tomotherapy and its comparison to extended SSD technique. The American College of Radiology practice guideline for total body irradiation (TBI) requires a back-up treatment delivery system. This study investigates the development of helical tomotherapy (HT) for delivering TBI and compares it with conventional extended source-to-surface distance (X-SSD) technique. Four patients' head-to-thigh computed tomographic images were used in this study, with the target defined as the body volume without the left and right lungs. HT treatment plans with the standard TBI prescription (1.2 Gy/fx, 10 fractions) were generated and verified on phantoms. To compare HT plans with X-SSD treatment, the dose distribution of X-SSD technique was simulated using the Eclipse software. The average dose received by 90% of the target volume was 12.3 Gy (range, 12.2-12.4 Gy) for HT plans and 10.3 Gy (range, 10.08-10.58 Gy) for X-SSD plans (p < 0.001). The left and right lung median doses were 5.44 Gy and 5.40 Gy, respectively, for HT plans and 8.34 Gy and 8.95 Gy, respectively, for X-SSD treatment. The treatment planning time was comparable between the two methods. The beam delivery time of HT treatment was longer than X-SSD treatment. In conclusion, HT-based TBI plans have better dose coverage to the target and better dose sparing to the lungs compared with X-SSD technique, which applies dose compensators, lung blocks, and electron boosts. This study demonstrates that HT is possible for delivering TBI. Clinical validation of the feasibility of this approach would be of interest in the future.</AbstractText
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24925857
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24552746
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23580443
|
In vivo chemical exchange saturation transfer imaging of creatine (CrCEST) in skeletal muscle at 3T.
|
Investigation of outer cortical magnetisation transfer ratio abnormalities in multiple sclerosis clinical subgroups.
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Measurement of interscapular brown adipose tissue of mice in differentially housed temperatures by chemical-shift-encoded water-fat MRI.
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To characterize the chemical exchange saturation transfer (CEST)-based technique to measure free creatine (Cr), a key component of muscle energy metabolism, distribution in skeletal muscle with high spatial resolution before and after exercise at 3T.</AbstractText CrCEST saturation parameters were empirically optimized for 3T. CEST, T2 , magnetization transfer ratio (MTR), and (31) P magnetic resonance spectroscopy (MRS) acquisitions of the lower leg were performed before and after mild plantar flexion exercise on a 3T whole-body MR scanner on six healthy volunteers.</AbstractText The feasibility of imaging Cr changes in skeletal muscle following plantar flexion exercise using CrCEST was demonstrated at 3T. This technique exhibited good spatial resolution and was able to differentiate differences in muscle use among subjects. The CrCEST results were compared with (31) P MRS results, showing good agreement in the Cr and PCr recovery kinetics. A relationship of 0.45% CrCESTasym /mM Cr was observed across all subjects.</AbstractText It is demonstrated that the CrCEST technique could be applied at 3T to measure dynamic changes in creatine in muscle in vivo. The widespread availability and clinical applicability of 3T scanners has the potential to clinically advance this method.</AbstractText
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Pathological abnormalities including demyelination and neuronal loss are reported in the outer cortex in multiple sclerosis (MS).</AbstractText We investigated for in vivo evidence of outer cortical abnormalities by measuring the magnetisation transfer ratio (MTR) in MS patients of different subgroups.</AbstractText Forty-four relapsing-remitting (RR) (mean age 41.9 years, median Expanded Disability Status Scale (EDSS) 2.0), 25 secondary progressive (SP) (54.1 years, EDSS 6.5) and 19 primary progressive (PP) (53.1 years, EDSS 6.0) MS patients and 35 healthy control subjects (mean age 39.2 years) were studied. Three-dimensional (3D) 1×1×1mm(3) T1-weighted images and MTR data were acquired. The cortex was segmented, then subdivided into outer and inner bands, and MTR values were calculated for each band.</AbstractText In a pairwise analysis, mean outer cortical MTR was lower than mean inner cortical MTR in all MS groups and controls (p<0.001). Compared with controls, outer cortical MTR was decreased in SPMS (p<0.001) and RRMS (p<0.01), but not PPMS. Outer cortical MTR was lower in SPMS than PPMS (p<0.01) and RRMS (p<0.01).</AbstractText Lower outer than inner cortical MTR in healthy controls may reflect differences in myelin content. The lowest outer cortical MTR was seen in SPMS and is consistent with more extensive outer cortical (including subpial) pathology, such as demyelination and neuronal loss, as observed in post-mortem studies of SPMS patients.</AbstractText
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To determine differences in fat-signal fraction (FF) from chemical-shift-encoded water-fat MRI of interscapular BAT in mice housed at different ambient temperatures (Ta ).</AbstractText C57BL/6J male mice (8 weeks old) were singly housed at 16°C, 23°C, or 30°C (n = 16/group) for 4 weeks. Measures included food intake, body weight (both measured weekly) and body composition (at baseline, 2, and 4 weeks post-thermal exposure); chemical-shift-encoded water-fat MRI was performed on a 9.4 Tesla Bruker magnet with respiratory gating and anesthesia at 4 weeks post-thermal exposure.</AbstractText A significant inverse relationship between food intake and Ta was evidenced (P < 0.0001). Lean mass was similar among groups, while total fat mass was significantly different among groups ([mean ± SE]: 30°C = 5.10 ± 0.19 g; 23°C = 4.18 ± 0.16 g; 16°C = 3.48 ± 0.54 g; P < 0.0001). Mean BAT-FF was positively related to Ta (means: 30°C = 79.4%; 23°C = 61.8%; 16°C = 50.9%; P < 0.0001).</AbstractText These cross-sectional results demonstrate that MRI measurement of FF within the interscapular BAT in mice reflects recent functional status of the tissue, with a lower Ta leading to a significantly reduced BAT-FF, indicative of the tissue's involvement in thermogenesis.</AbstractText
|
In vivo chemical exchange saturation transfer imaging of creatine (CrCEST) in skeletal muscle at 3T. To characterize the chemical exchange saturation transfer (CEST)-based technique to measure free creatine (Cr), a key component of muscle energy metabolism, distribution in skeletal muscle with high spatial resolution before and after exercise at 3T.</AbstractText CrCEST saturation parameters were empirically optimized for 3T. CEST, T2 , magnetization transfer ratio (MTR), and (31) P magnetic resonance spectroscopy (MRS) acquisitions of the lower leg were performed before and after mild plantar flexion exercise on a 3T whole-body MR scanner on six healthy volunteers.</AbstractText The feasibility of imaging Cr changes in skeletal muscle following plantar flexion exercise using CrCEST was demonstrated at 3T. This technique exhibited good spatial resolution and was able to differentiate differences in muscle use among subjects. The CrCEST results were compared with (31) P MRS results, showing good agreement in the Cr and PCr recovery kinetics. A relationship of 0.45% CrCESTasym /mM Cr was observed across all subjects.</AbstractText It is demonstrated that the CrCEST technique could be applied at 3T to measure dynamic changes in creatine in muscle in vivo. The widespread availability and clinical applicability of 3T scanners has the potential to clinically advance this method.</AbstractText
|
Investigation of outer cortical magnetisation transfer ratio abnormalities in multiple sclerosis clinical subgroups. Pathological abnormalities including demyelination and neuronal loss are reported in the outer cortex in multiple sclerosis (MS).</AbstractText We investigated for in vivo evidence of outer cortical abnormalities by measuring the magnetisation transfer ratio (MTR) in MS patients of different subgroups.</AbstractText Forty-four relapsing-remitting (RR) (mean age 41.9 years, median Expanded Disability Status Scale (EDSS) 2.0), 25 secondary progressive (SP) (54.1 years, EDSS 6.5) and 19 primary progressive (PP) (53.1 years, EDSS 6.0) MS patients and 35 healthy control subjects (mean age 39.2 years) were studied. Three-dimensional (3D) 1×1×1mm(3) T1-weighted images and MTR data were acquired. The cortex was segmented, then subdivided into outer and inner bands, and MTR values were calculated for each band.</AbstractText In a pairwise analysis, mean outer cortical MTR was lower than mean inner cortical MTR in all MS groups and controls (p<0.001). Compared with controls, outer cortical MTR was decreased in SPMS (p<0.001) and RRMS (p<0.01), but not PPMS. Outer cortical MTR was lower in SPMS than PPMS (p<0.01) and RRMS (p<0.01).</AbstractText Lower outer than inner cortical MTR in healthy controls may reflect differences in myelin content. The lowest outer cortical MTR was seen in SPMS and is consistent with more extensive outer cortical (including subpial) pathology, such as demyelination and neuronal loss, as observed in post-mortem studies of SPMS patients.</AbstractText
|
Measurement of interscapular brown adipose tissue of mice in differentially housed temperatures by chemical-shift-encoded water-fat MRI. To determine differences in fat-signal fraction (FF) from chemical-shift-encoded water-fat MRI of interscapular BAT in mice housed at different ambient temperatures (Ta ).</AbstractText C57BL/6J male mice (8 weeks old) were singly housed at 16°C, 23°C, or 30°C (n = 16/group) for 4 weeks. Measures included food intake, body weight (both measured weekly) and body composition (at baseline, 2, and 4 weeks post-thermal exposure); chemical-shift-encoded water-fat MRI was performed on a 9.4 Tesla Bruker magnet with respiratory gating and anesthesia at 4 weeks post-thermal exposure.</AbstractText A significant inverse relationship between food intake and Ta was evidenced (P < 0.0001). Lean mass was similar among groups, while total fat mass was significantly different among groups ([mean ± SE]: 30°C = 5.10 ± 0.19 g; 23°C = 4.18 ± 0.16 g; 16°C = 3.48 ± 0.54 g; P < 0.0001). Mean BAT-FF was positively related to Ta (means: 30°C = 79.4%; 23°C = 61.8%; 16°C = 50.9%; P < 0.0001).</AbstractText These cross-sectional results demonstrate that MRI measurement of FF within the interscapular BAT in mice reflects recent functional status of the tissue, with a lower Ta leading to a significantly reduced BAT-FF, indicative of the tissue's involvement in thermogenesis.</AbstractText
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24629508
|
18545998
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24630569
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Safety aspects of gadofosveset in clinical practice--analysis of acute and long-term complications.
|
Preclinical investigation to compare different gadolinium-based contrast agents regarding their propensity to release gadolinium in vivo and to trigger nephrogenic systemic fibrosis-like lesions.
|
A rare case of internal jugular vein aneurysm with massive hemorrhage in neurofibromatosis type 1.
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The purpose of this retrospective study was to systematically search for acute adverse reactions and long-term complications in all patients that had been administered gadofosveset at our hospital.</AbstractText We identified 67 gadofosveset administrations during 2006-2009 in 62 patients from 8 to 84years of age. Radiological information system (RIS) and clinical patient records were analyzed for suspected acute adverse reactions and long-term complications including nephrogenic systemic fibrosis (NSF). The gadofosveset doses ranged between 0.024 and 0.060mmol/kg bodyweight with a mean dose of 0.031-mmol/kg bodyweight. Follow-up time of the patients ranged from less than 1year up to 4years with a mean follow-up time of 2.1years.</AbstractText No acute adverse events or technical failures related to the contrast medium were recorded in the RIS. No dermatological and nephrological diseases related to the gadofosveset administration were found in the clinical patient records. Four patients died during follow-up without any apparent relation to the gadofosveset exposure.</AbstractText Based on our clinical material we conclude that gadofosveset is safe for a mixed patient population with no acute adverse events or any indications of long-term complications during the follow-up time up to four years.</AbstractText
|
Recent reports suggest that nephrogenic systemic fibrosis (NSF) is associated with the administration of gadolinium (Gd)-based contrast agents (GBCAs) and in particular with the stability of the Gd-complex. The aim of this investigation was to compare GBCAs and their potential to trigger NSF. Forty-two healthy male rats received repeated intravenous injections of six different GBCAs at high doses to simulate the exposure seen in patients with severe renal dysfunction. Histopathological and immunohistochemical analysis of the skin was performed, and the concentrations of Gd, zinc and copper were measured in several tissues by inductive coupled plasma atomic emission spectroscopy. Macroscopic and histological skin changes similar to those seen in NSF patients were only observed in rats receiving Omniscan. In addition, very high concentrations of Gd were observed in the animals treated with Omniscan, and, to a lesser extent, in animals treated with OptiMARK. Significantly lower levels of Gd were found after the treatment with ionic linear agents and even less after the treatment with macrocyclic agents. The data in this investigation strongly suggest that the stability of the Gd-complex is a key factor for the development of NSF-like symptoms in this experimental setting.</AbstractText
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Neurofibromatosis Type 1 (NF1) is a relatively common autosomal dominant disorder. Vascular involvement is a well-recognized manifestation of NF1, but venous aneurysm associated with NF1 is extremely rare. We present a case of an NF1 patient with a left internal jugular vein aneurysm with massive hemorrhage occurring during surgery. Due to the extreme fragility of both the aneurismal wall and the surrounding tissue, the patient developed severe intraoperative bleeding. Pathological examination confirmed aneurismal wall infiltration of the neurofibromatosis. Physicians should be aware that hemorrhagic complication in NF1 can occur and be fatal.</AbstractText
|
Safety aspects of gadofosveset in clinical practice--analysis of acute and long-term complications. The purpose of this retrospective study was to systematically search for acute adverse reactions and long-term complications in all patients that had been administered gadofosveset at our hospital.</AbstractText We identified 67 gadofosveset administrations during 2006-2009 in 62 patients from 8 to 84years of age. Radiological information system (RIS) and clinical patient records were analyzed for suspected acute adverse reactions and long-term complications including nephrogenic systemic fibrosis (NSF). The gadofosveset doses ranged between 0.024 and 0.060mmol/kg bodyweight with a mean dose of 0.031-mmol/kg bodyweight. Follow-up time of the patients ranged from less than 1year up to 4years with a mean follow-up time of 2.1years.</AbstractText No acute adverse events or technical failures related to the contrast medium were recorded in the RIS. No dermatological and nephrological diseases related to the gadofosveset administration were found in the clinical patient records. Four patients died during follow-up without any apparent relation to the gadofosveset exposure.</AbstractText Based on our clinical material we conclude that gadofosveset is safe for a mixed patient population with no acute adverse events or any indications of long-term complications during the follow-up time up to four years.</AbstractText
|
Preclinical investigation to compare different gadolinium-based contrast agents regarding their propensity to release gadolinium in vivo and to trigger nephrogenic systemic fibrosis-like lesions. Recent reports suggest that nephrogenic systemic fibrosis (NSF) is associated with the administration of gadolinium (Gd)-based contrast agents (GBCAs) and in particular with the stability of the Gd-complex. The aim of this investigation was to compare GBCAs and their potential to trigger NSF. Forty-two healthy male rats received repeated intravenous injections of six different GBCAs at high doses to simulate the exposure seen in patients with severe renal dysfunction. Histopathological and immunohistochemical analysis of the skin was performed, and the concentrations of Gd, zinc and copper were measured in several tissues by inductive coupled plasma atomic emission spectroscopy. Macroscopic and histological skin changes similar to those seen in NSF patients were only observed in rats receiving Omniscan. In addition, very high concentrations of Gd were observed in the animals treated with Omniscan, and, to a lesser extent, in animals treated with OptiMARK. Significantly lower levels of Gd were found after the treatment with ionic linear agents and even less after the treatment with macrocyclic agents. The data in this investigation strongly suggest that the stability of the Gd-complex is a key factor for the development of NSF-like symptoms in this experimental setting.</AbstractText
|
A rare case of internal jugular vein aneurysm with massive hemorrhage in neurofibromatosis type 1. Neurofibromatosis Type 1 (NF1) is a relatively common autosomal dominant disorder. Vascular involvement is a well-recognized manifestation of NF1, but venous aneurysm associated with NF1 is extremely rare. We present a case of an NF1 patient with a left internal jugular vein aneurysm with massive hemorrhage occurring during surgery. Due to the extreme fragility of both the aneurismal wall and the surrounding tissue, the patient developed severe intraoperative bleeding. Pathological examination confirmed aneurismal wall infiltration of the neurofibromatosis. Physicians should be aware that hemorrhagic complication in NF1 can occur and be fatal.</AbstractText
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14608603
|
8698883
|
14501495
|
Architectonics and cortical connections of the upper bank of the superior temporal sulcus in the rhesus monkey: an analysis in the tangential plane.
|
Quantitative MRI of the temporal lobe, amygdala, and hippocampus in normal human development: ages 4-18 years.
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RingTag: ring-shaped tagging for myocardial centerline assessment.
|
Area TPO in the upper bank of the superior temporal sulcus (STS) of macaque monkeys is thought to correspond to the superior temporal polysensory (STP) cortex, but has been shown to have neurochemical/connectional subdivisions. To examine directly the relationship between chemoarchitecture and cortical connections of area TPO, the upper bank of the STS was sectioned tangential to the cortical surface. Three subdivisions of area TPO (TPOr, TPOi, and TPOc) were examined with cytochrome oxidase (CO) histochemistry and neurofilament protein (NF) immunoreactivity and architectonic patterns were compared with connections on the same or adjacent sections. Area TPOc, which may partly overlap with the location of the medial superior temporal area MST, exhibited regular patchy staining for CO in layers III/IV and a complementary pattern in the NF stain. Area TPOr, but not TPOi, also had a patchy pattern of complementary staining in CO and neurofilament similar to TPOc, although not as distinct. Tracer injections within cortex including the frontal eye fields (areas 46 and 8) labeled areas TPOc, TPOi, and TPOr. The caudal inferior parietal lobule (IPL) projected to all three areas. The projections from prearcuate and posterior parietal cortices showed both overlap and nonoverlap with each other within TPOc, TPOi, and TPOr. Projections were to all neurochemical components within the subdivisions of TPO. The findings support the parcellation of area TPO into three subdivisions and extend findings of chemoarchitectonic modules within high-order association cortices.</AbstractText
|
The volume of the temporal lobe, superior temporal gyrus, amygdala, and hippocampus was quantified from magnetic images of the brains of 99 healthy children and adolescents aged 4-18 years. Variability in volume was high for all structures examined. When adjusted for a 9% larger total cerebral volume in males, there were no significant volume differences between sexes. However, sex-specific maturational changes were noted in the volumes of medial temporal structures, with the left amygdala increasing significantly only in males and with the right hippocampus increasing significantly only in females. Right-greater-than-left laterality effects were found for temporal lobe, superior temporal gyrus, amygdala, and hippocampal volumes. These results are consistent with previous preclinical and human studies that have indicated hormonal responsivity of these structures and extend quantitative morphologic findings from the adult literature. In addition to highlighting the need for large samples and sex-matched controls in pediatric neuroimaging studies, the information from this understudied age group may be of use in evaluating developmental hypotheses of neuropsychiatric disorders.</AbstractText
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Although endocardial ejection indexes lead to overestimation of contractility in hypertrophied hearts, circumferential fiber shortening at the mid wall (cFS) is less affected by wall thickness. In this study magnetic resonance tagging is exploited to assess directly cFS in normal and hypertrophied hearts.</AbstractText A novel tagging procedure generates freely definable, convex ring saturation bands. Data acquisition during the cardiac cycle is achieved with a fast, single breath-hold echo-planar imaging measurement that is combined with a slice-following approach and a navigator-guided breath-holding technique to improve reproducibility of breath hold positions.</AbstractText The procedure is able to create variably shaped convex saturation structures on the myocardium that can be tracked automatically throughout the cardiac cycle. Circumferential shortening at the endocardial border (FSendo) obtained in 6 healthy volunteers and in 6 patients with hypertensive cardiomyopathy suggested hypercontractility of hypertrophied hearts (30.7 +/- 4.1% vs. 43.9 +/- 4.4% respectively; P < 0.002), whereas shortening at the level of the myofibers assessed as cFS was not different (17.2 +/- 1.4% vs. 18.1 +/- 2.8% respectively; P = 0.49).</AbstractText The presented approach allows for assessment of midwall myocardial mechanics and may become a useful tool to study contractile function in hypertrophied hearts.</AbstractText
|
Architectonics and cortical connections of the upper bank of the superior temporal sulcus in the rhesus monkey: an analysis in the tangential plane. Area TPO in the upper bank of the superior temporal sulcus (STS) of macaque monkeys is thought to correspond to the superior temporal polysensory (STP) cortex, but has been shown to have neurochemical/connectional subdivisions. To examine directly the relationship between chemoarchitecture and cortical connections of area TPO, the upper bank of the STS was sectioned tangential to the cortical surface. Three subdivisions of area TPO (TPOr, TPOi, and TPOc) were examined with cytochrome oxidase (CO) histochemistry and neurofilament protein (NF) immunoreactivity and architectonic patterns were compared with connections on the same or adjacent sections. Area TPOc, which may partly overlap with the location of the medial superior temporal area MST, exhibited regular patchy staining for CO in layers III/IV and a complementary pattern in the NF stain. Area TPOr, but not TPOi, also had a patchy pattern of complementary staining in CO and neurofilament similar to TPOc, although not as distinct. Tracer injections within cortex including the frontal eye fields (areas 46 and 8) labeled areas TPOc, TPOi, and TPOr. The caudal inferior parietal lobule (IPL) projected to all three areas. The projections from prearcuate and posterior parietal cortices showed both overlap and nonoverlap with each other within TPOc, TPOi, and TPOr. Projections were to all neurochemical components within the subdivisions of TPO. The findings support the parcellation of area TPO into three subdivisions and extend findings of chemoarchitectonic modules within high-order association cortices.</AbstractText
|
Quantitative MRI of the temporal lobe, amygdala, and hippocampus in normal human development: ages 4-18 years. The volume of the temporal lobe, superior temporal gyrus, amygdala, and hippocampus was quantified from magnetic images of the brains of 99 healthy children and adolescents aged 4-18 years. Variability in volume was high for all structures examined. When adjusted for a 9% larger total cerebral volume in males, there were no significant volume differences between sexes. However, sex-specific maturational changes were noted in the volumes of medial temporal structures, with the left amygdala increasing significantly only in males and with the right hippocampus increasing significantly only in females. Right-greater-than-left laterality effects were found for temporal lobe, superior temporal gyrus, amygdala, and hippocampal volumes. These results are consistent with previous preclinical and human studies that have indicated hormonal responsivity of these structures and extend quantitative morphologic findings from the adult literature. In addition to highlighting the need for large samples and sex-matched controls in pediatric neuroimaging studies, the information from this understudied age group may be of use in evaluating developmental hypotheses of neuropsychiatric disorders.</AbstractText
|
RingTag: ring-shaped tagging for myocardial centerline assessment. Although endocardial ejection indexes lead to overestimation of contractility in hypertrophied hearts, circumferential fiber shortening at the mid wall (cFS) is less affected by wall thickness. In this study magnetic resonance tagging is exploited to assess directly cFS in normal and hypertrophied hearts.</AbstractText A novel tagging procedure generates freely definable, convex ring saturation bands. Data acquisition during the cardiac cycle is achieved with a fast, single breath-hold echo-planar imaging measurement that is combined with a slice-following approach and a navigator-guided breath-holding technique to improve reproducibility of breath hold positions.</AbstractText The procedure is able to create variably shaped convex saturation structures on the myocardium that can be tracked automatically throughout the cardiac cycle. Circumferential shortening at the endocardial border (FSendo) obtained in 6 healthy volunteers and in 6 patients with hypertensive cardiomyopathy suggested hypercontractility of hypertrophied hearts (30.7 +/- 4.1% vs. 43.9 +/- 4.4% respectively; P < 0.002), whereas shortening at the level of the myofibers assessed as cFS was not different (17.2 +/- 1.4% vs. 18.1 +/- 2.8% respectively; P = 0.49).</AbstractText The presented approach allows for assessment of midwall myocardial mechanics and may become a useful tool to study contractile function in hypertrophied hearts.</AbstractText
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34775274
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19818908
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34211877
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Is rushing always faster than strolling? A reaction time study on the processing of sentences containing manner of motion verbs.
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Another kind of 'BOLD Response': answering multiple-choice questions via online decoded single-trial brain signals.
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Fremantle Back Awareness Questionnaire in Chronic Low Back Pain (Frebaq-I): Translation and Validation in the Indian Population.
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In the context of the embodied cognition debate, an effect of motion verb associated speed information has previously been detected using eye-tracking, functional magnetic resonance imaging (fMRI), and reaction times (RT). The latter, for instance, was implemented by Wender and Weber (1982), who observed that participants were faster in detecting motion in sentences associated with fast motion compared to sentences associated with slow motion after having formed mental images of the sentences' content. It remains open whether the reported effects of speed are associated with automatic lexical-semantic retrieval processes or whether they reflect higher top-down cognitive processes. To answer this question, the paradigm by Wender and Weber (1982) was adopted and further elaborated in the present study. In Experiment 1 visualization instructions were eliminated. Additionally, the stimulus material was manipulated in regards to the agent of the described movement (human vs. object motion) in order to determine the representation's modality (visual vs. motoric). In Experiment 2, the task to detect motion was replaced by the task to judge sensicality. The results suggest that the prompt to perform mental imagery is not a precondition for the engagement of modal representations in this speed of motion paradigm and that the involved representations' modality is visual rather than motoric. However, the modal representations' involvement is dependent on the task. They thus do not seem to be part of the invariant semantic representation of manner of motion verbs.</AbstractText
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The term 'locked-in'syndrome (LIS) describes a medical condition in which persons concerned are severely paralyzed and at the same time fully conscious and awake. The resulting anarthria makes it impossible for these patients to naturally communicate, which results in diagnostic as well as serious practical and ethical problems. Therefore, developing alternative, muscle-independent communication means is of prime importance. Such communication means can be realized via brain-computer interfaces (BCIs) circumventing the muscular system by using brain signals associated with preserved cognitive, sensory, and emotional brain functions. Primarily, BCIs based on electrophysiological measures have been developed and applied with remarkable success. Recently, also blood flow-based neuroimaging methods, such as functional magnetic resonance imaging (fMRI) and functional near-infrared spectroscopy (fNIRS), have been explored in this context. After reviewing recent literature on the development of especially hemodynamically based BCIs, we introduce a highly reliable and easy-to-apply communication procedure that enables untrained participants to motor-independently and relatively effortlessly answer multiple-choice questions based on intentionally generated single-trial fMRI signals that can be decoded online. Our technique takes advantage of the participants' capability to voluntarily influence certain spatio-temporal aspects of the blood oxygenation level-dependent (BOLD) signal: source location (by using different mental tasks), signal onset and offset. We show that healthy participants are capable of hemodynamically encoding at least four distinct information units on a single-trial level without extensive pretraining and with little effort. Moreover, real-time data analysis based on simple multi-filter correlations allows for automated answer decoding with a high accuracy (94.9%) demonstrating the robustness of the presented method. Following our 'proof of concept', the next step will involve clinical trials with LIS patients, undertaken in close collaboration with their relatives and caretakers in order to elaborate individually tailored communication protocols. As our procedure can be easily transferred to MRI-equipped clinical sites, it may constitute a simple and effective possibility for online detection of residual consciousness and for LIS patients to communicate basic thoughts and needs in case no other alternative communication means are available (yet)--especially in the acute phase of the LIS. Future research may focus on further increasing the efficiency and accuracy of fMRI-based BCIs by implementing sophisticated data analysis methods (e.g., multivariate and independent component analysis) and neurofeedback training techniques. Finally, the presented BCI approach could be transferred to portable fNIRS systems as only this would enable hemodynamically based communication in daily life situations.</AbstractText
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The Fremantle Back Awareness Questionnaire (FreBAQ) has been found to possess adequate psychometric properties in low back pain (LBP) patients worldwide. The aim of this study was to translate the questionnaire into a classical Indian language (Odiya) and validate in the Indian population (FreBAQ-I).</AbstractText The English edition of the FreBAQ was transformed into Indian classical language (Odiya). One hundred adult patients with chronic LBP were recruited for psychometric evaluation using Rasch analysis. Demographic parameters, clinical characteristics like pain, Oswestry Disability Index, and Beck's depression inventory were assessed along with responses to the study questionnaire.</AbstractText The FreBAQ-I correlated well with intensity of pain (<i Patients with greater disturbed body perception are addressed adequately by the questionnaire. All nine items are essential and adequate, which makes the survey complete, although item 2 was found to be endorsed more often. Overall, the FreBAQ-I has suitable psychometric properties in Indian populations with chronic LBP.</AbstractText
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Is rushing always faster than strolling? A reaction time study on the processing of sentences containing manner of motion verbs. In the context of the embodied cognition debate, an effect of motion verb associated speed information has previously been detected using eye-tracking, functional magnetic resonance imaging (fMRI), and reaction times (RT). The latter, for instance, was implemented by Wender and Weber (1982), who observed that participants were faster in detecting motion in sentences associated with fast motion compared to sentences associated with slow motion after having formed mental images of the sentences' content. It remains open whether the reported effects of speed are associated with automatic lexical-semantic retrieval processes or whether they reflect higher top-down cognitive processes. To answer this question, the paradigm by Wender and Weber (1982) was adopted and further elaborated in the present study. In Experiment 1 visualization instructions were eliminated. Additionally, the stimulus material was manipulated in regards to the agent of the described movement (human vs. object motion) in order to determine the representation's modality (visual vs. motoric). In Experiment 2, the task to detect motion was replaced by the task to judge sensicality. The results suggest that the prompt to perform mental imagery is not a precondition for the engagement of modal representations in this speed of motion paradigm and that the involved representations' modality is visual rather than motoric. However, the modal representations' involvement is dependent on the task. They thus do not seem to be part of the invariant semantic representation of manner of motion verbs.</AbstractText
|
Another kind of 'BOLD Response': answering multiple-choice questions via online decoded single-trial brain signals. The term 'locked-in'syndrome (LIS) describes a medical condition in which persons concerned are severely paralyzed and at the same time fully conscious and awake. The resulting anarthria makes it impossible for these patients to naturally communicate, which results in diagnostic as well as serious practical and ethical problems. Therefore, developing alternative, muscle-independent communication means is of prime importance. Such communication means can be realized via brain-computer interfaces (BCIs) circumventing the muscular system by using brain signals associated with preserved cognitive, sensory, and emotional brain functions. Primarily, BCIs based on electrophysiological measures have been developed and applied with remarkable success. Recently, also blood flow-based neuroimaging methods, such as functional magnetic resonance imaging (fMRI) and functional near-infrared spectroscopy (fNIRS), have been explored in this context. After reviewing recent literature on the development of especially hemodynamically based BCIs, we introduce a highly reliable and easy-to-apply communication procedure that enables untrained participants to motor-independently and relatively effortlessly answer multiple-choice questions based on intentionally generated single-trial fMRI signals that can be decoded online. Our technique takes advantage of the participants' capability to voluntarily influence certain spatio-temporal aspects of the blood oxygenation level-dependent (BOLD) signal: source location (by using different mental tasks), signal onset and offset. We show that healthy participants are capable of hemodynamically encoding at least four distinct information units on a single-trial level without extensive pretraining and with little effort. Moreover, real-time data analysis based on simple multi-filter correlations allows for automated answer decoding with a high accuracy (94.9%) demonstrating the robustness of the presented method. Following our 'proof of concept', the next step will involve clinical trials with LIS patients, undertaken in close collaboration with their relatives and caretakers in order to elaborate individually tailored communication protocols. As our procedure can be easily transferred to MRI-equipped clinical sites, it may constitute a simple and effective possibility for online detection of residual consciousness and for LIS patients to communicate basic thoughts and needs in case no other alternative communication means are available (yet)--especially in the acute phase of the LIS. Future research may focus on further increasing the efficiency and accuracy of fMRI-based BCIs by implementing sophisticated data analysis methods (e.g., multivariate and independent component analysis) and neurofeedback training techniques. Finally, the presented BCI approach could be transferred to portable fNIRS systems as only this would enable hemodynamically based communication in daily life situations.</AbstractText
|
Fremantle Back Awareness Questionnaire in Chronic Low Back Pain (Frebaq-I): Translation and Validation in the Indian Population. The Fremantle Back Awareness Questionnaire (FreBAQ) has been found to possess adequate psychometric properties in low back pain (LBP) patients worldwide. The aim of this study was to translate the questionnaire into a classical Indian language (Odiya) and validate in the Indian population (FreBAQ-I).</AbstractText The English edition of the FreBAQ was transformed into Indian classical language (Odiya). One hundred adult patients with chronic LBP were recruited for psychometric evaluation using Rasch analysis. Demographic parameters, clinical characteristics like pain, Oswestry Disability Index, and Beck's depression inventory were assessed along with responses to the study questionnaire.</AbstractText The FreBAQ-I correlated well with intensity of pain (<i Patients with greater disturbed body perception are addressed adequately by the questionnaire. All nine items are essential and adequate, which makes the survey complete, although item 2 was found to be endorsed more often. Overall, the FreBAQ-I has suitable psychometric properties in Indian populations with chronic LBP.</AbstractText
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28381492
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23198894
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28881588
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Dynamic population codes of multiplexed stimulus features in primate area MT.
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Decoding attended information in short-term memory: an EEG study.
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Experimental study of brachial plexus and vessel compression: evaluation of combined central and peripheral electrodiagnostic approach.
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The middle-temporal area (MT) of primate visual cortex is critical in the analysis of visual motion. Single-unit studies suggest that the response dynamics of neurons within area MT depend on stimulus features, but how these dynamics emerge at the population level, and how feature representations interact, is not clear. Here, we used multivariate classification analysis to study how stimulus features are represented in the spiking activity of populations of neurons in area MT of marmoset monkey. Using representational similarity analysis we distinguished the emerging representations of moving grating and dot field stimuli. We show that representations of stimulus orientation, spatial frequency, and speed are evident near the onset of the population response, while the representation of stimulus direction is slower to emerge and sustained throughout the stimulus-evoked response. We further found a spatiotemporal asymmetry in the emergence of direction representations. Representations for high spatial frequencies and low temporal frequencies are initially orientation dependent, while those for high temporal frequencies and low spatial frequencies are more sensitive to motion direction. Our analyses reveal a complex interplay of feature representations in area MT population response that may explain the stimulus-dependent dynamics of motion vision.<b
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For decades it has been assumed that sustained, elevated neural activity--the so-called active trace--is the neural correlate of the short-term retention of information. However, a recent fMRI study has suggested that this activity may be more related to attention than to retention. Specifically, a multivariate pattern analysis failed to find evidence that information that was outside the focus of attention, but nonetheless in STM, was retained in an active state. Here, we replicate and extend this finding by querying the neural signatures of attended versus unattended information within STM with electroencephalograpy (EEG), a method sensitive to oscillatory neural activity to which the previous fMRI study was insensitive. We demonstrate that in the delay-period EEG activity, there is information only about memory items that are also in the focus of attention. Information about items outside the focus of attention is not detectable. This result converges with the fMRI findings to suggest that, contrary to conventional wisdom, an active memory trace may be unnecessary for the short-term retention of information.</AbstractText
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We sought to investigate the reliability of a new electrodiagnostic method for identifying Electrodiagnosis of Brachial Plexus & Vessel Compression Syndrome (BPVCS) in rats that involves the application of transcranial electrical stimulation motor evoked potentials (TES-MEPs) combined with peripheral nerve stimulation compound muscle action potentials (PNS-CMAPs).</AbstractText The latencies of the TES-MEP and PNS-CMAP were initially elongated in the 8-week group. The amplitudes of TES-MEP and PNS-CMAP were initially attenuated in the 16-week group. The isolateral amplitude ratio of the TES-MEP to the PNS-CMAP was apparently decreased, and spontaneous activities emerged at 16 weeks postoperatively.</AbstractText Superior and inferior trunk models of BPVCS were created in 72 male Sprague Dawley (SD) rats that were divided into six experimental groups. The latencies, amplitudes and isolateral amplitude ratios of the TES-MEPs and PNS-CMAPs were recorded at different postoperative intervals.</AbstractText Electrophysiological and histological examinations of the rats' compressed brachial plexus nerves were utilized to establish preliminary electrodiagnostic criteria for BPVCS.</AbstractText
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Dynamic population codes of multiplexed stimulus features in primate area MT. The middle-temporal area (MT) of primate visual cortex is critical in the analysis of visual motion. Single-unit studies suggest that the response dynamics of neurons within area MT depend on stimulus features, but how these dynamics emerge at the population level, and how feature representations interact, is not clear. Here, we used multivariate classification analysis to study how stimulus features are represented in the spiking activity of populations of neurons in area MT of marmoset monkey. Using representational similarity analysis we distinguished the emerging representations of moving grating and dot field stimuli. We show that representations of stimulus orientation, spatial frequency, and speed are evident near the onset of the population response, while the representation of stimulus direction is slower to emerge and sustained throughout the stimulus-evoked response. We further found a spatiotemporal asymmetry in the emergence of direction representations. Representations for high spatial frequencies and low temporal frequencies are initially orientation dependent, while those for high temporal frequencies and low spatial frequencies are more sensitive to motion direction. Our analyses reveal a complex interplay of feature representations in area MT population response that may explain the stimulus-dependent dynamics of motion vision.<b
|
Decoding attended information in short-term memory: an EEG study. For decades it has been assumed that sustained, elevated neural activity--the so-called active trace--is the neural correlate of the short-term retention of information. However, a recent fMRI study has suggested that this activity may be more related to attention than to retention. Specifically, a multivariate pattern analysis failed to find evidence that information that was outside the focus of attention, but nonetheless in STM, was retained in an active state. Here, we replicate and extend this finding by querying the neural signatures of attended versus unattended information within STM with electroencephalograpy (EEG), a method sensitive to oscillatory neural activity to which the previous fMRI study was insensitive. We demonstrate that in the delay-period EEG activity, there is information only about memory items that are also in the focus of attention. Information about items outside the focus of attention is not detectable. This result converges with the fMRI findings to suggest that, contrary to conventional wisdom, an active memory trace may be unnecessary for the short-term retention of information.</AbstractText
|
Experimental study of brachial plexus and vessel compression: evaluation of combined central and peripheral electrodiagnostic approach. We sought to investigate the reliability of a new electrodiagnostic method for identifying Electrodiagnosis of Brachial Plexus & Vessel Compression Syndrome (BPVCS) in rats that involves the application of transcranial electrical stimulation motor evoked potentials (TES-MEPs) combined with peripheral nerve stimulation compound muscle action potentials (PNS-CMAPs).</AbstractText The latencies of the TES-MEP and PNS-CMAP were initially elongated in the 8-week group. The amplitudes of TES-MEP and PNS-CMAP were initially attenuated in the 16-week group. The isolateral amplitude ratio of the TES-MEP to the PNS-CMAP was apparently decreased, and spontaneous activities emerged at 16 weeks postoperatively.</AbstractText Superior and inferior trunk models of BPVCS were created in 72 male Sprague Dawley (SD) rats that were divided into six experimental groups. The latencies, amplitudes and isolateral amplitude ratios of the TES-MEPs and PNS-CMAPs were recorded at different postoperative intervals.</AbstractText Electrophysiological and histological examinations of the rats' compressed brachial plexus nerves were utilized to establish preliminary electrodiagnostic criteria for BPVCS.</AbstractText
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33965527
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24593982
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34056948
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The neural basis of counting sequences.
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Characterizing the dynamics of mental representations: the temporal generalization method.
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B and T Lymphocyte Densities Remain Stable With Age in Human Cortex.
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Sequence processing is critical for complex behavior, and counting sequences hold a unique place underlying human numerical development. Despite this, the neural bases of counting sequences remain unstudied. We hypothesized that counting sequences in adults would involve representations in sensory, order, magnitude, and linguistic codes that implicate regions in auditory, supplementary motor, posterior parietal, and inferior frontal areas, respectively. In an fMRI scanner, participants heard four-number sequences in a 2 × 2 × 2 design. The sequences were adjacent or not (e.g., 5, 6, 7, 8 vs. 5, 6, 7, 9), ordered or not (e.g., 5, 6, 7, 8 vs. 8, 5, 7, 6), and were spoken by a voice of consistent or variable identity. Then, neural substrates of counting sequences were identified by testing for the effect of consecutiveness (ordered nonadjacent versus ordered adjacent, e.g., 5, 6, 7, 9 > 5, 6, 7, 8) in the hypothesized brain regions. Violations to consecutiveness elicited brain activity in the right inferior frontal gyrus (IFG) and the supplementary motor area (SMA). In contrast, no such activation was observed in the auditory cortex, despite violations in voice identity recruiting strong activity in that region. Also, no activation was observed in the inferior parietal lobule, despite a robust effect of orderedness observed in that brain region. These findings indicate that listening to counting sequences do not automatically elicit sensory or magnitude codes but suggest that the precise increments in the sequence are tracked by the mechanism for processing ordered associations in the SMA and by the mechanism for binding individual lexical items into a cohesive whole in the IFG.</AbstractText
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Parsing a cognitive task into a sequence of operations is a central problem in cognitive neuroscience. We argue that a major advance is now possible owing to the application of pattern classifiers to time-resolved recordings of brain activity [electroencephalography (EEG), magnetoencephalography (MEG), or intracranial recordings]. By testing at which moment a specific mental content becomes decodable in brain activity, we can characterize the time course of cognitive codes. Most importantly, the manner in which the trained classifiers generalize across time, and from one experimental condition to another, sheds light on the temporal organization of information-processing stages. A repertoire of canonical dynamical patterns is observed across various experiments and brain regions. This method thus provides a novel way to understand how mental representations are manipulated and transformed.</AbstractText
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One hallmark of human aging is increased brain inflammation represented by glial activation. With age, there is also diminished function of the adaptive immune system, and modest decreases in circulating B- and T-lymphocytes. Lymphocytes traffic through the human brain and reside there in small numbers, but it is unknown how this changes with age. Thus we investigated whether B- and T-lymphocyte numbers change with age in the normal human brain. We examined 16 human subjects in a pilot study and then 40 human subjects from a single brain bank, ranging in age from 44-96 years old, using rigorous criteria for defining neuropathological changes due to age alone. We immunostained post-mortem cortical tissue for B- and T-lymphocytes using antibodies to CD20 and CD3, respectively. We quantified cell density and made a qualitative assessment of cell location in cortical brain sections, and reviewed prior studies. We report that density and location of both B- and T-lymphocytes do not change with age in the normal human cortex. Solitary B-lymphocytes were found equally in intravascular, perivascular, and parenchymal locations, while T-lymphocytes appeared primarily in perivascular clusters. Thus, any change in number or location of lymphocytes in an aging brain may indicate disease rather than normal aging.</AbstractText
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The neural basis of counting sequences. Sequence processing is critical for complex behavior, and counting sequences hold a unique place underlying human numerical development. Despite this, the neural bases of counting sequences remain unstudied. We hypothesized that counting sequences in adults would involve representations in sensory, order, magnitude, and linguistic codes that implicate regions in auditory, supplementary motor, posterior parietal, and inferior frontal areas, respectively. In an fMRI scanner, participants heard four-number sequences in a 2 × 2 × 2 design. The sequences were adjacent or not (e.g., 5, 6, 7, 8 vs. 5, 6, 7, 9), ordered or not (e.g., 5, 6, 7, 8 vs. 8, 5, 7, 6), and were spoken by a voice of consistent or variable identity. Then, neural substrates of counting sequences were identified by testing for the effect of consecutiveness (ordered nonadjacent versus ordered adjacent, e.g., 5, 6, 7, 9 > 5, 6, 7, 8) in the hypothesized brain regions. Violations to consecutiveness elicited brain activity in the right inferior frontal gyrus (IFG) and the supplementary motor area (SMA). In contrast, no such activation was observed in the auditory cortex, despite violations in voice identity recruiting strong activity in that region. Also, no activation was observed in the inferior parietal lobule, despite a robust effect of orderedness observed in that brain region. These findings indicate that listening to counting sequences do not automatically elicit sensory or magnitude codes but suggest that the precise increments in the sequence are tracked by the mechanism for processing ordered associations in the SMA and by the mechanism for binding individual lexical items into a cohesive whole in the IFG.</AbstractText
|
Characterizing the dynamics of mental representations: the temporal generalization method. Parsing a cognitive task into a sequence of operations is a central problem in cognitive neuroscience. We argue that a major advance is now possible owing to the application of pattern classifiers to time-resolved recordings of brain activity [electroencephalography (EEG), magnetoencephalography (MEG), or intracranial recordings]. By testing at which moment a specific mental content becomes decodable in brain activity, we can characterize the time course of cognitive codes. Most importantly, the manner in which the trained classifiers generalize across time, and from one experimental condition to another, sheds light on the temporal organization of information-processing stages. A repertoire of canonical dynamical patterns is observed across various experiments and brain regions. This method thus provides a novel way to understand how mental representations are manipulated and transformed.</AbstractText
|
B and T Lymphocyte Densities Remain Stable With Age in Human Cortex. One hallmark of human aging is increased brain inflammation represented by glial activation. With age, there is also diminished function of the adaptive immune system, and modest decreases in circulating B- and T-lymphocytes. Lymphocytes traffic through the human brain and reside there in small numbers, but it is unknown how this changes with age. Thus we investigated whether B- and T-lymphocyte numbers change with age in the normal human brain. We examined 16 human subjects in a pilot study and then 40 human subjects from a single brain bank, ranging in age from 44-96 years old, using rigorous criteria for defining neuropathological changes due to age alone. We immunostained post-mortem cortical tissue for B- and T-lymphocytes using antibodies to CD20 and CD3, respectively. We quantified cell density and made a qualitative assessment of cell location in cortical brain sections, and reviewed prior studies. We report that density and location of both B- and T-lymphocytes do not change with age in the normal human cortex. Solitary B-lymphocytes were found equally in intravascular, perivascular, and parenchymal locations, while T-lymphocytes appeared primarily in perivascular clusters. Thus, any change in number or location of lymphocytes in an aging brain may indicate disease rather than normal aging.</AbstractText
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38969907
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30169972
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39534810
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Synchronous citizen science with dogs.
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Using Tools to Help Us Think: Actual but Also Believed Reliability Modulates Cognitive Offloading.
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Comparative Efficacy and Safety of Novel Antiplatelets and Standard Therapy in Patients With Coronary Artery Disease.
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Citizen science approaches have grown in popularity over the years, partly due to their ability to reach a wider audience and produce more generalizable samples. In dogs, these studies, though, have been limited in their controls over materials or experimental protocols, with guardians typically reporting results without researcher supervision. Over two studies, we explored and validated a synchronous citizen science approach. We had dog guardians act as experimenters while being supervised by a researcher over Zoom. In study 1, we demonstrated that synchronous citizen science produced equivalent levels of performance to in-lab designs in a choice task. Consistent with past in-lab research, dogs selected a treat (vs. an empty plate) in a two-alternative forced-choice task. In study 2, we showed that Zoom methods are also appropriate for studies utilizing looking time measures. We explored dogs' looking behaviors when a bag of treats was placed in an unreachable location, and dogs' guardians were either attentive or inattentive while dogs attempted to retrieve the treats. Consistent with past work, dogs in the attentive condition looked at their guardian for longer periods and had a shorter latency to first look than dogs in the inattentive condition. Overall, we have demonstrated that synchronous citizen science studies with dogs are feasible and produce valid results consistent with those found in a typical lab setting.</AbstractText
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A <i High-tech working environments oftentimes represent distributed cognitive systems. Because cognitive offloading can both support and harm performance, depending on the specific circumstances, it is essential to understand when and why people offload their cognition.</AbstractText We used an extension of the mental rotation paradigm. It allowed participants to rotate stimuli either internally as in the original paradigm or with a rotation knob that afforded rotating stimuli externally on a computer screen. Two parameters were manipulated: the knob's actual reliability (AR) and an instruction altering participants' beliefs about the knob's reliability (believed reliability; BR). We measured cognitive offloading proportion and perceived knob utility.</AbstractText Participants were able to quickly and dynamically adjust their cognitive offloading proportion and subjective utility assessments in response to AR, suggesting a high level of offloading proficiency. However, when BR instructions were presented that falsely described the knob's reliability to be lower than it actually was, participants reduced cognitive offloading substantially.</AbstractText The extent to which people offload their cognition is not based solely on utility maximization; it is additionally affected by possibly erroneous preexisting beliefs.</AbstractText To support users in efficiently operating in a distributed cognitive system, an external resource's utility should be made transparent, and preexisting beliefs should be adjusted prior to interaction.</AbstractText
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Coronary artery disease (CAD) is a significant health concern that has affected approximately 110 million people worldwide. CAD is defined as persistent narrowing of the coronary arteries as a result of atherosclerotic plaque build-up. Acute coronary syndrome (ACS), which encompasses ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina, often results from plaque ruptures. Platelets are crucial for atherogenesis, vascular inflammation, and oxidative stress. Antiplatelet therapy aimed at reducing thrombotic events is vital for ACS treatment. Clinical guidelines advise the use of dual antiplatelet therapy (DAPT) that combines aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) in ACS patients undergoing percutaneous intervention (PCI). This study aimed to assess comprehensively the effectiveness and safety of ticagrelor and prasugrel in comparison to clopidogrel in patients with ACS. An extensive literature search was conducted using PubMed, PubMed Central (PMC), ScienceDirect, and EBSCO databases. The search revealed studies that compared ticagrelor and prasugrel to clopidogrel in ACS patients, and we selected these studies based on specific inclusion and exclusion criteria, which included observational studies, clinical trials, literature reviews, and meta-analyses involving adult ACS patients treated with ticagrelor, prasugrel, or clopidogrel. The efficacy outcomes were defined as major adverse cardiovascular events (MACE) and thrombotic events, whereas the safety outcomes were measured by major and minor bleeding and hemorrhagic stroke. After a rigorous quality assessment to minimize bias, 23 studies were selected for analysis. The findings indicated that novel antiplatelets reduced MACE but increased bleeding complications, with ticagrelor consistently associated with dyspnea. In conclusion, novel P2Y12 inhibitors provide cardiovascular benefits but require careful patient selection and monitoring due to gastrointestinal bleeding (GIB) risks. Future research should standardize bleeding definitions and assess long-term outcomes. Ticagrelor and prasugrel may be more effective and safer than clopidogrel in ACS patients. Given the high risk of GIB, especially among older individuals or those with a past stroke, it is advisable to suggest a lower prasugrel dose without raising the bleeding rates. Since fewer patients use the novel antiplatelet regimen compared to clopidogrel, future clinical trials should include a broader patient population and compare these regimens.</AbstractText
|
Synchronous citizen science with dogs. Citizen science approaches have grown in popularity over the years, partly due to their ability to reach a wider audience and produce more generalizable samples. In dogs, these studies, though, have been limited in their controls over materials or experimental protocols, with guardians typically reporting results without researcher supervision. Over two studies, we explored and validated a synchronous citizen science approach. We had dog guardians act as experimenters while being supervised by a researcher over Zoom. In study 1, we demonstrated that synchronous citizen science produced equivalent levels of performance to in-lab designs in a choice task. Consistent with past in-lab research, dogs selected a treat (vs. an empty plate) in a two-alternative forced-choice task. In study 2, we showed that Zoom methods are also appropriate for studies utilizing looking time measures. We explored dogs' looking behaviors when a bag of treats was placed in an unreachable location, and dogs' guardians were either attentive or inattentive while dogs attempted to retrieve the treats. Consistent with past work, dogs in the attentive condition looked at their guardian for longer periods and had a shorter latency to first look than dogs in the inattentive condition. Overall, we have demonstrated that synchronous citizen science studies with dogs are feasible and produce valid results consistent with those found in a typical lab setting.</AbstractText
|
Using Tools to Help Us Think: Actual but Also Believed Reliability Modulates Cognitive Offloading. A <i High-tech working environments oftentimes represent distributed cognitive systems. Because cognitive offloading can both support and harm performance, depending on the specific circumstances, it is essential to understand when and why people offload their cognition.</AbstractText We used an extension of the mental rotation paradigm. It allowed participants to rotate stimuli either internally as in the original paradigm or with a rotation knob that afforded rotating stimuli externally on a computer screen. Two parameters were manipulated: the knob's actual reliability (AR) and an instruction altering participants' beliefs about the knob's reliability (believed reliability; BR). We measured cognitive offloading proportion and perceived knob utility.</AbstractText Participants were able to quickly and dynamically adjust their cognitive offloading proportion and subjective utility assessments in response to AR, suggesting a high level of offloading proficiency. However, when BR instructions were presented that falsely described the knob's reliability to be lower than it actually was, participants reduced cognitive offloading substantially.</AbstractText The extent to which people offload their cognition is not based solely on utility maximization; it is additionally affected by possibly erroneous preexisting beliefs.</AbstractText To support users in efficiently operating in a distributed cognitive system, an external resource's utility should be made transparent, and preexisting beliefs should be adjusted prior to interaction.</AbstractText
|
Comparative Efficacy and Safety of Novel Antiplatelets and Standard Therapy in Patients With Coronary Artery Disease. Coronary artery disease (CAD) is a significant health concern that has affected approximately 110 million people worldwide. CAD is defined as persistent narrowing of the coronary arteries as a result of atherosclerotic plaque build-up. Acute coronary syndrome (ACS), which encompasses ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina, often results from plaque ruptures. Platelets are crucial for atherogenesis, vascular inflammation, and oxidative stress. Antiplatelet therapy aimed at reducing thrombotic events is vital for ACS treatment. Clinical guidelines advise the use of dual antiplatelet therapy (DAPT) that combines aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) in ACS patients undergoing percutaneous intervention (PCI). This study aimed to assess comprehensively the effectiveness and safety of ticagrelor and prasugrel in comparison to clopidogrel in patients with ACS. An extensive literature search was conducted using PubMed, PubMed Central (PMC), ScienceDirect, and EBSCO databases. The search revealed studies that compared ticagrelor and prasugrel to clopidogrel in ACS patients, and we selected these studies based on specific inclusion and exclusion criteria, which included observational studies, clinical trials, literature reviews, and meta-analyses involving adult ACS patients treated with ticagrelor, prasugrel, or clopidogrel. The efficacy outcomes were defined as major adverse cardiovascular events (MACE) and thrombotic events, whereas the safety outcomes were measured by major and minor bleeding and hemorrhagic stroke. After a rigorous quality assessment to minimize bias, 23 studies were selected for analysis. The findings indicated that novel antiplatelets reduced MACE but increased bleeding complications, with ticagrelor consistently associated with dyspnea. In conclusion, novel P2Y12 inhibitors provide cardiovascular benefits but require careful patient selection and monitoring due to gastrointestinal bleeding (GIB) risks. Future research should standardize bleeding definitions and assess long-term outcomes. Ticagrelor and prasugrel may be more effective and safer than clopidogrel in ACS patients. Given the high risk of GIB, especially among older individuals or those with a past stroke, it is advisable to suggest a lower prasugrel dose without raising the bleeding rates. Since fewer patients use the novel antiplatelet regimen compared to clopidogrel, future clinical trials should include a broader patient population and compare these regimens.</AbstractText
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40571293
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31335641
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37921713
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A Medical Student Curriculum on Functional Medical Disorders.
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Efficacy of a transdiagnostic emotion-focused exposure treatment for chronic pain patients with comorbid anxiety and depression: a randomized controlled trial.
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Treatment of Complete Brachial Plexus Injuries Using Double Free Muscle Transfer.
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Functional medical disorders (FMDs) refer to persistent physical symptoms that cause impairment or disability, but which cannot be explained by routine medical testing. Negative perceptions towards FMDs exist amongst a variety of healthcare professionals, including medical students. The aim of this study was to develop and evaluate a course addressing FMDs for medical students in their first year of clinical training, which was integrated within the formal medical school curriculum.</AbstractText A multidisciplinary team of eight healthcare professionals delivered seven teaching sessions, each two hours in length, over six weeks. The curriculum was delivered via a combination of didactic teaching, small group tutorials and sessions with simulated patients. Pre- and post-course validated questionnaires assessed knowledge of, attitudes towards and confidence around irritable bowel syndrome (IBS). Students undertook a two-station objective structured clinical examination (OSCE), which assessed their ability to take a clinical history from and communicate a diagnosis to simulated patients with IBS and fibromyalgia.</AbstractText Twenty-seven students completed the pre- and post-course surveys, which demonstrated an increase in knowledge of FMDs at course conclusion (88.89% vs. 57.50%, p < 0.001). Students' confidence ratings increased in all (100%) domains relating to FMDs: pathophysiology, symptoms, investigations for diagnosis and communicating a diagnosis (p < 0.001, all analyses). There was a statistically significant improvement in attitude ratings towards FMDs in 11 of 12 (91.7%) questions. All (100%) students passed the OSCE.</AbstractText A course integrated within the formal medical school curriculum may be a helpful way to improve knowledge and reduce stigma around FMDs.</AbstractText
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The comorbidity between chronic pain and emotional problems has proven difficult to address with current treatment options. This study addresses the efficacy of a transdiagnostic emotion-focused exposure treatment ("hybrid") for chronic pain patients with comorbid emotional problems. Adults (n = 115) with chronic musculoskeletal pain and functional and emotional problems were included in a 2-centre, parallel randomized controlled, open-label trial comparing this treatment to an active control condition receiving a guided Internet-delivered pain management treatment based on CBT principles (iCBT). The hybrid treatment (n = 58, 10-16 sessions) integrates exposure in vivo for chronic pain based on the fear-avoidance model with an emotion-regulation approach informed by procedures in Dialectical Behavior Therapy. The iCBT (n = 57; 8 treatment modules) addresses topics such as pain education, coping strategies, relaxation, problem solving, stress, and sleep management using standard CBT techniques. Patient-reported outcomes were assessed before and after treatment as well as at a 9-month primary end point. Across conditions, 78% participants completed post-treatment and 81% follow-up assessment. Intent-to-treat analyses showed that the hybrid had a significantly better post-treatment outcome on pain catastrophizing (d = 0.39) and pain interference (d = 0.63) and significantly better follow-up outcomes on depression (d = 0.43) and pain interference (d = 0.51). There were no differences on anxiety and pain intensity. Observed proportions of clinically significant improvement favoured the hybrid on all but one comparison, but no statistically significant differences were observed. We conclude that the hybrid emotion-focused treatment may be considered an acceptable, credible, and efficacious treatment option for chronic pain patients with comorbid emotional problems.</AbstractText
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The purpose of this study was to examine the surgical outcomes of double free muscle transfer (DFMT) performed in patients with complete brachial plexus injury (BPI).</AbstractText We retrospectively analyzed the outcomes of DFMT for 12 patients with complete BPI who were followed up for more than 2 years after the final muscle transplantation. Their mean age was 29 years (range, 18-41). Three patients underwent contralateral C7 nerve root transfer before the DFMT. The range of motion (ROM) of the shoulder, elbow, and fingers was measured. Patient-reported outcome measures, including Disability of the Shoulder, Arm, and Hand (DASH) scores and visual analog scale (VAS) scores for pain, were also examined.</AbstractText The mean shoulder ROM against gravity was 22° ± 8° in abduction and 33° ± 5° in flexion. Seven patients underwent phrenic nerve (PhN) transfer to the suprascapular nerves, and five exhibited asymptomatic lung impairment on spirography more than 2 years after PhN transfer. The mean elbow ROM against gravity was 111° ± 9° in flexion and -32° ± 7° in extension. All patients obtained elbow flexion >90° against a 0.5-kg weight. All patients obtained touch sensation and two recognized warm and cold sensations in the affected palm. The mean total active motion of the affected fingers was 44° ± 11°. All patients exhibited hook function of the hands. The mean preoperative and postoperative DASH scores were 70.3 ± 13.4 and 51.8 ± 15.9, respectively. The mean pain VAS score was 28 ± 31 at the final follow-up.</AbstractText Double free muscle transfer provided patients with complete brachial plexus palsy with good elbow flexion and hand hook functions.</AbstractText Therapeutic IV.</AbstractText
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A Medical Student Curriculum on Functional Medical Disorders. Functional medical disorders (FMDs) refer to persistent physical symptoms that cause impairment or disability, but which cannot be explained by routine medical testing. Negative perceptions towards FMDs exist amongst a variety of healthcare professionals, including medical students. The aim of this study was to develop and evaluate a course addressing FMDs for medical students in their first year of clinical training, which was integrated within the formal medical school curriculum.</AbstractText A multidisciplinary team of eight healthcare professionals delivered seven teaching sessions, each two hours in length, over six weeks. The curriculum was delivered via a combination of didactic teaching, small group tutorials and sessions with simulated patients. Pre- and post-course validated questionnaires assessed knowledge of, attitudes towards and confidence around irritable bowel syndrome (IBS). Students undertook a two-station objective structured clinical examination (OSCE), which assessed their ability to take a clinical history from and communicate a diagnosis to simulated patients with IBS and fibromyalgia.</AbstractText Twenty-seven students completed the pre- and post-course surveys, which demonstrated an increase in knowledge of FMDs at course conclusion (88.89% vs. 57.50%, p < 0.001). Students' confidence ratings increased in all (100%) domains relating to FMDs: pathophysiology, symptoms, investigations for diagnosis and communicating a diagnosis (p < 0.001, all analyses). There was a statistically significant improvement in attitude ratings towards FMDs in 11 of 12 (91.7%) questions. All (100%) students passed the OSCE.</AbstractText A course integrated within the formal medical school curriculum may be a helpful way to improve knowledge and reduce stigma around FMDs.</AbstractText
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Efficacy of a transdiagnostic emotion-focused exposure treatment for chronic pain patients with comorbid anxiety and depression: a randomized controlled trial. The comorbidity between chronic pain and emotional problems has proven difficult to address with current treatment options. This study addresses the efficacy of a transdiagnostic emotion-focused exposure treatment ("hybrid") for chronic pain patients with comorbid emotional problems. Adults (n = 115) with chronic musculoskeletal pain and functional and emotional problems were included in a 2-centre, parallel randomized controlled, open-label trial comparing this treatment to an active control condition receiving a guided Internet-delivered pain management treatment based on CBT principles (iCBT). The hybrid treatment (n = 58, 10-16 sessions) integrates exposure in vivo for chronic pain based on the fear-avoidance model with an emotion-regulation approach informed by procedures in Dialectical Behavior Therapy. The iCBT (n = 57; 8 treatment modules) addresses topics such as pain education, coping strategies, relaxation, problem solving, stress, and sleep management using standard CBT techniques. Patient-reported outcomes were assessed before and after treatment as well as at a 9-month primary end point. Across conditions, 78% participants completed post-treatment and 81% follow-up assessment. Intent-to-treat analyses showed that the hybrid had a significantly better post-treatment outcome on pain catastrophizing (d = 0.39) and pain interference (d = 0.63) and significantly better follow-up outcomes on depression (d = 0.43) and pain interference (d = 0.51). There were no differences on anxiety and pain intensity. Observed proportions of clinically significant improvement favoured the hybrid on all but one comparison, but no statistically significant differences were observed. We conclude that the hybrid emotion-focused treatment may be considered an acceptable, credible, and efficacious treatment option for chronic pain patients with comorbid emotional problems.</AbstractText
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Treatment of Complete Brachial Plexus Injuries Using Double Free Muscle Transfer. The purpose of this study was to examine the surgical outcomes of double free muscle transfer (DFMT) performed in patients with complete brachial plexus injury (BPI).</AbstractText We retrospectively analyzed the outcomes of DFMT for 12 patients with complete BPI who were followed up for more than 2 years after the final muscle transplantation. Their mean age was 29 years (range, 18-41). Three patients underwent contralateral C7 nerve root transfer before the DFMT. The range of motion (ROM) of the shoulder, elbow, and fingers was measured. Patient-reported outcome measures, including Disability of the Shoulder, Arm, and Hand (DASH) scores and visual analog scale (VAS) scores for pain, were also examined.</AbstractText The mean shoulder ROM against gravity was 22° ± 8° in abduction and 33° ± 5° in flexion. Seven patients underwent phrenic nerve (PhN) transfer to the suprascapular nerves, and five exhibited asymptomatic lung impairment on spirography more than 2 years after PhN transfer. The mean elbow ROM against gravity was 111° ± 9° in flexion and -32° ± 7° in extension. All patients obtained elbow flexion >90° against a 0.5-kg weight. All patients obtained touch sensation and two recognized warm and cold sensations in the affected palm. The mean total active motion of the affected fingers was 44° ± 11°. All patients exhibited hook function of the hands. The mean preoperative and postoperative DASH scores were 70.3 ± 13.4 and 51.8 ± 15.9, respectively. The mean pain VAS score was 28 ± 31 at the final follow-up.</AbstractText Double free muscle transfer provided patients with complete brachial plexus palsy with good elbow flexion and hand hook functions.</AbstractText Therapeutic IV.</AbstractText
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31937413
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25039829
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32457515
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Cone mosaic characteristics in red-green colour deficiency: a comparative study.
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Is screening for congenital colour vision deficiency in school students worthwhile? A review.
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Barriers and facilitators to optimising inpatient bladder management after spinal cord injury.
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To compare photoreceptor cone characteristics using adaptive optics (AO) technology between congenital colour blind patients and healthy age-matched controls.</AbstractText Cross-sectional.</AbstractText 21 eyes (21 cases) with congenital red-green colour blindness and 21 eyes of age-matched controls (21 controls), all having a best-corrected visual acuity of 20/20 and normal ophthalmological examination, were recruited.</AbstractText Colour vision testing was done using the Farnsworth-Munsell 100-Hue test and Nagel anomaloscope. Imaging of fovea was done using rtx1 AO retinal camera with a sampling window size of 4° × 4°. Peak cone density, intercone spacing, cone regularity, and cone dispersion were determined using AOdetect Mosaic software.</AbstractText Overall, mean cone characteristics at 2° off fixation in cases and controls, respectively, were density 26 587 ± 1328/26 448 ± 687 cells/mm<sup Cone photoreceptor characteristics are anatomically well preserved in young colour-deficient individuals except cone dispersion.</AbstractText
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This review analyses the literature on screening for congenital colour vision deficiency in school students, which predominantly uses the Ishihara test. The review was framed with respect to the established Wilson and Jungner criteria for screening programs. These criteria relate to the characteristics of the condition concerned, the performance of the screening test, the existence of treatment options and the performance of screening programs. The literature reviewed suggests that congenital colour vision deficiency has not been shown to increase risk of road traffic crashes and is not a preclusion to driver licensing in most developed countries. The occurrence of congenital colour vision deficiency has been used to limit entry into certain occupations; however, the value of screening school students with regard to occupational preclusion is questionable. Stronger evidence exists indicating no association between congenital colour vision deficiency and level of educational achievement. Studies showing any association between congenital colour vision deficiency and other health and lifestyle impacts were rare. The most commonly used screening test (using Ishihara pseudoisochromatic plates) performs well with respect to detecting red-green colour vision deficiencies. Finally, the only interventions we identified for congenital colour vision deficiency were management ones around the availability of specific tinted lenses and computer programs to aid colour perception in certain tasks. Given this picture, the weight of evidence appears to be in favour of not adopting (or discontinuing) routine colour vision screening programs for school students; however, it may be worthwhile for a career advisor to refer school students to an optometrist or ophthalmologist for colour vision screening, upon expression of interest in an occupation where normal colour vision is either particularly desirable or is a regulatory requirement.</AbstractText
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Qualitative survey.</AbstractText Examine clinicians' perspectives on adherence to published evidence-based guidelines and clinician-perceived barriers, and facilitators to optimising inpatient bladder management within one Spinal Cord Injury (SCI) service.</AbstractText Surgical Hospital (acute care) and SCI Unit (sub-acute, rehabilitation) in Western Australia (WA).</AbstractText Clinicians reviewed an 'Evidence Matrix' summarising published clinical practice guidelines and recommendations for SCI bladder management. Focus groups examined the extent to which current practice adhered to recommendations and identified perceived barriers and facilitators to optimal management. Data were analysed thematically using a deductive approach.</AbstractText Current management closely mirrors published recommendations. Key facilitators included long-standing prioritisation of rapid progression from urethral indwelling (IDC) to a 6 hourly intermittent catheterisation (IC) protocol; regular competency audits of catheterisation technique; and a Spinal Urology Clinical Nurse Consultant (CNC) position. Barriers included limited resources/staffing; restricted access to Neuro-urology consultation; inter-disciplinary communication gaps; and delays in determining and implementing long-term bladder management.</AbstractText Inpatient SCI bladder care in WA closely emulates published evidence, although adherence at other sites may reveal different practices. Bladder management was found to have been facilitated by a strong culture of practice led by Neuro-urologists, informed by evidence and embraced by Senior Clinicians. Further reduction in duration of initial IDC, provision of early and ongoing Neuro-urology consultations as part of standard care, increased interdisciplinary communication and dedicated SCI Urology theatre lists would further optimise management.</AbstractText
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Cone mosaic characteristics in red-green colour deficiency: a comparative study. To compare photoreceptor cone characteristics using adaptive optics (AO) technology between congenital colour blind patients and healthy age-matched controls.</AbstractText Cross-sectional.</AbstractText 21 eyes (21 cases) with congenital red-green colour blindness and 21 eyes of age-matched controls (21 controls), all having a best-corrected visual acuity of 20/20 and normal ophthalmological examination, were recruited.</AbstractText Colour vision testing was done using the Farnsworth-Munsell 100-Hue test and Nagel anomaloscope. Imaging of fovea was done using rtx1 AO retinal camera with a sampling window size of 4° × 4°. Peak cone density, intercone spacing, cone regularity, and cone dispersion were determined using AOdetect Mosaic software.</AbstractText Overall, mean cone characteristics at 2° off fixation in cases and controls, respectively, were density 26 587 ± 1328/26 448 ± 687 cells/mm<sup Cone photoreceptor characteristics are anatomically well preserved in young colour-deficient individuals except cone dispersion.</AbstractText
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Is screening for congenital colour vision deficiency in school students worthwhile? A review. This review analyses the literature on screening for congenital colour vision deficiency in school students, which predominantly uses the Ishihara test. The review was framed with respect to the established Wilson and Jungner criteria for screening programs. These criteria relate to the characteristics of the condition concerned, the performance of the screening test, the existence of treatment options and the performance of screening programs. The literature reviewed suggests that congenital colour vision deficiency has not been shown to increase risk of road traffic crashes and is not a preclusion to driver licensing in most developed countries. The occurrence of congenital colour vision deficiency has been used to limit entry into certain occupations; however, the value of screening school students with regard to occupational preclusion is questionable. Stronger evidence exists indicating no association between congenital colour vision deficiency and level of educational achievement. Studies showing any association between congenital colour vision deficiency and other health and lifestyle impacts were rare. The most commonly used screening test (using Ishihara pseudoisochromatic plates) performs well with respect to detecting red-green colour vision deficiencies. Finally, the only interventions we identified for congenital colour vision deficiency were management ones around the availability of specific tinted lenses and computer programs to aid colour perception in certain tasks. Given this picture, the weight of evidence appears to be in favour of not adopting (or discontinuing) routine colour vision screening programs for school students; however, it may be worthwhile for a career advisor to refer school students to an optometrist or ophthalmologist for colour vision screening, upon expression of interest in an occupation where normal colour vision is either particularly desirable or is a regulatory requirement.</AbstractText
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Barriers and facilitators to optimising inpatient bladder management after spinal cord injury. Qualitative survey.</AbstractText Examine clinicians' perspectives on adherence to published evidence-based guidelines and clinician-perceived barriers, and facilitators to optimising inpatient bladder management within one Spinal Cord Injury (SCI) service.</AbstractText Surgical Hospital (acute care) and SCI Unit (sub-acute, rehabilitation) in Western Australia (WA).</AbstractText Clinicians reviewed an 'Evidence Matrix' summarising published clinical practice guidelines and recommendations for SCI bladder management. Focus groups examined the extent to which current practice adhered to recommendations and identified perceived barriers and facilitators to optimal management. Data were analysed thematically using a deductive approach.</AbstractText Current management closely mirrors published recommendations. Key facilitators included long-standing prioritisation of rapid progression from urethral indwelling (IDC) to a 6 hourly intermittent catheterisation (IC) protocol; regular competency audits of catheterisation technique; and a Spinal Urology Clinical Nurse Consultant (CNC) position. Barriers included limited resources/staffing; restricted access to Neuro-urology consultation; inter-disciplinary communication gaps; and delays in determining and implementing long-term bladder management.</AbstractText Inpatient SCI bladder care in WA closely emulates published evidence, although adherence at other sites may reveal different practices. Bladder management was found to have been facilitated by a strong culture of practice led by Neuro-urologists, informed by evidence and embraced by Senior Clinicians. Further reduction in duration of initial IDC, provision of early and ongoing Neuro-urology consultations as part of standard care, increased interdisciplinary communication and dedicated SCI Urology theatre lists would further optimise management.</AbstractText
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25037846
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12961051
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24657659
|
Agnosia for mirror stimuli: a new case report with a small parietal lesion.
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Visually guided grasping produces fMRI activation in dorsal but not ventral stream brain areas.
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GABAergic signaling facilitates breast cancer metastasis by promoting ERK1/2-dependent phosphorylation.
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Only seven cases of agnosia for mirror stimuli have been reported, always with an extensive lesion. We report a new case of an agnosia for mirror stimuli due to a circumscribed lesion. An extensive battery of neuropsychological tests and a new experimental procedure to assess visual object mirror and orientation discrimination were assessed 10 days after the onset of clinical symptoms, and 5 years later. The performances of our patient were compared with those of four healthy control subjects matched for age. This test revealed an agnosia for mirror stimuli. Brain imaging showed a small right occipitoparietal hematoma, encompassing the extrastriate cortex adjoining the inferior parietal lobe. This new case suggests that: (i) agnosia for mirror stimuli can persist for 5 years after onset and (ii) the posterior part of the right intraparietal sulcus could be critical in the cognitive process of mirror stimuli discrimination.</AbstractText
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Although both reaching and grasping require transporting the hand to the object location, only grasping also requires processing of object shape, size and orientation to preshape the hand. Behavioural and neuropsychological evidence suggests that the object processing required for grasping relies on different neural substrates from those mediating object recognition. Specifically, whereas object recognition is believed to rely on structures in the ventral (occipitotemporal) stream, object grasping appears to rely on structures in the dorsal (occipitoparietal) stream. We used functional magnetic resonance imaging (fMRI) to determine whether grasping (compared to reaching) produced activation in dorsal areas, ventral areas, or both. We found greater activity for grasping than reaching in several regions, including anterior intraparietal (AIP) cortex. We also performed a standard object perception localizer (comparing intact vs. scrambled 2D object images) in the same subjects to identify the lateral occipital complex (LOC), a ventral stream area believed to play a critical role in object recognition. Although LOC was activated by the objects presented on both grasping and reaching trials, there was no greater activity for grasping compared to reaching. These results suggest that dorsal areas, including AIP, but not ventral areas such as LOC, play a fundamental role in computing object properties during grasping.</AbstractText
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The present study aims to determine the role of γ-aminobutyric acid (GABA) signaling molecules in breast cancer metastasis. Our results reveal that GABAergic system exists in breast cancer cells. Both the GABA synthetic enzyme. (GAD65/67) and GABAB receptor are expressed in 4T1 mouse breast cancer cells, MCF-7 human breast cancer cells and human breast cancer tissue. Baclofen, a GABABR agonist, significantly promoted 4T1 cells invasion and migration in vitro and metastasis in vivo, an event that was attenuated by GABABR antagonist CGP55845. Baclofen-induced breast cancer metastasis was mediated by ERK1/2 pathway.</AbstractText
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Agnosia for mirror stimuli: a new case report with a small parietal lesion. Only seven cases of agnosia for mirror stimuli have been reported, always with an extensive lesion. We report a new case of an agnosia for mirror stimuli due to a circumscribed lesion. An extensive battery of neuropsychological tests and a new experimental procedure to assess visual object mirror and orientation discrimination were assessed 10 days after the onset of clinical symptoms, and 5 years later. The performances of our patient were compared with those of four healthy control subjects matched for age. This test revealed an agnosia for mirror stimuli. Brain imaging showed a small right occipitoparietal hematoma, encompassing the extrastriate cortex adjoining the inferior parietal lobe. This new case suggests that: (i) agnosia for mirror stimuli can persist for 5 years after onset and (ii) the posterior part of the right intraparietal sulcus could be critical in the cognitive process of mirror stimuli discrimination.</AbstractText
|
Visually guided grasping produces fMRI activation in dorsal but not ventral stream brain areas. Although both reaching and grasping require transporting the hand to the object location, only grasping also requires processing of object shape, size and orientation to preshape the hand. Behavioural and neuropsychological evidence suggests that the object processing required for grasping relies on different neural substrates from those mediating object recognition. Specifically, whereas object recognition is believed to rely on structures in the ventral (occipitotemporal) stream, object grasping appears to rely on structures in the dorsal (occipitoparietal) stream. We used functional magnetic resonance imaging (fMRI) to determine whether grasping (compared to reaching) produced activation in dorsal areas, ventral areas, or both. We found greater activity for grasping than reaching in several regions, including anterior intraparietal (AIP) cortex. We also performed a standard object perception localizer (comparing intact vs. scrambled 2D object images) in the same subjects to identify the lateral occipital complex (LOC), a ventral stream area believed to play a critical role in object recognition. Although LOC was activated by the objects presented on both grasping and reaching trials, there was no greater activity for grasping compared to reaching. These results suggest that dorsal areas, including AIP, but not ventral areas such as LOC, play a fundamental role in computing object properties during grasping.</AbstractText
|
GABAergic signaling facilitates breast cancer metastasis by promoting ERK1/2-dependent phosphorylation. The present study aims to determine the role of γ-aminobutyric acid (GABA) signaling molecules in breast cancer metastasis. Our results reveal that GABAergic system exists in breast cancer cells. Both the GABA synthetic enzyme. (GAD65/67) and GABAB receptor are expressed in 4T1 mouse breast cancer cells, MCF-7 human breast cancer cells and human breast cancer tissue. Baclofen, a GABABR agonist, significantly promoted 4T1 cells invasion and migration in vitro and metastasis in vivo, an event that was attenuated by GABABR antagonist CGP55845. Baclofen-induced breast cancer metastasis was mediated by ERK1/2 pathway.</AbstractText
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