bluuebunny/crossref_metadata_2025_split huggingface dataset:
Number of CAG repeats and mortality in middle aged and older men
Authors: Heald Adrian , Cook Michael J. , Antonio Leen , Tournoy Jos , Ghaffari Parisa , Mannan Fahmida , Fachim Helene , Vanderschueren Dirk , Laing Ian , Hackett Geoff , Casanueva Felipe F. , Huhtaniemi Ilpo T. , Maggi Mario , Rastrelli Giulia , Slowikowska‐Hilczer Jolanta , Wu Fred , O'Neill Terence W. 
Published: September 2023

AbstractDesignThe androgen receptor (AR) mediates peripheral effects of testosterone. Previous data suggests an association between the number of CAG repeats in exon‐1 of the AR gene and AR transcriptional activity. The aim of this analysis was to determine the association between the number of AR CAG repeats and all‐cause mortality in men and the influence of testosterone level on the association.Patients and MeasurementsFollow‐up data to 27 January 2018 were available for men aged 40–79 years recruited across six countries of the European Male Aging Study between 2003 and 2005. Cox proportional hazards modelling was used to determine the association between CAG repeat number/mortality. Results were expressed as hazard ratios (HR)/95% confidence intervals (CI).ResultsOne thousand nine hundred and seventy‐seven men were followed up. Mean baseline age was 60 ± 11.1 years. Mean duration of follow‐up was 12.2 years. At follow up 25.1% of men had died. CAG repeat length ranged from 6 to 39, with the highest proportion of CAG repeat number at 21 repeats (16.4%). In a multivariable model, compared to men with 22–23 AR CAG repeats: for men with <22 and >23 AR CAG HR, 95% CI for mortality were, <22 CAG repeats 1.17 (0.93–1.49) and >23 CAG repeats 1.14 (0.88–1.47). In a post‐hoc analysis, the association was significant for men in the lowest tertile of baseline testosterone (<14.2 nmol/L) with >23 CAG repeats: in the adjusted model for <22 and >23 CAG repeats, respectively, 1.49 (0.97–2.27) and 1.68 (1.06–2.67) versus 22–23 repeats.ConclusionsOur European‐wide cohort data overall found no association of androgen receptor CAG repeat number and mortality in men. However, post hoc analysis suggested that an association might be present in men with lower baseline testosterone concentrations, which merits further investigation.
Visual cortex repetitive transcranial magnetic stimulation (rTMS) reversing neurodevelopmental impairments in adolescents with major psychiatric disorders (MPDs): A cross‐species translational study
Authors: Liu Juan , Guo Huiling , Yang Jingyu , Xiao Yao , Cai Aoling , Zhao Tongtong , Womer Fay Y. , Zhao Pengfei , Zheng Junjie , Zhang Xizhe , Wang Jie , Zhu Rongxin , Wang Fei 
Published: September 2023

AbstractAimsNeurodevelopmental impairments are closely linked to the basis of adolescent major psychiatric disorders (MPDs). The visual cortex can regulate neuroplasticity throughout the brain during critical periods of neurodevelopment, which may provide a promising target for neuromodulation therapy. This cross‐species translational study examined the effects of visual cortex repetitive transcranial magnetic stimulation (rTMS) on neurodevelopmental impairments in MPDs.MethodsVisual cortex rTMS was performed in both adolescent methylazoxymethanol acetate (MAM) rats and patients with MPDs. Functional magnetic resonance imaging (fMRI) and brain tissue proteomic data in rats and fMRI and clinical symptom data in patients were analyzed.ResultsThe regional homogeneity (ReHo) analysis of fMRI data revealed an increase in the frontal cortex and a decrease in the posterior cortex in the MAM rats, representing the abnormal neurodevelopmental pattern in MPDs. In regard to the effects of rTMS, similar neuroimaging changes, particularly reduced frontal ReHo, were found both in MAM rats and adolescent patients, suggesting that rTMS may reverse the abnormal neurodevelopmental pattern. Proteomic analysis revealed that rTMS modulated frontal synapse‐associated proteins, which may be the underpinnings of rTMS efficacy. Furthermore, a positive relationship was observed between frontal ReHo and clinical symptoms after rTMS in patients.ConclusionVisual cortex rTMS was proven to be an effective treatment for adolescent MPDs, and the underlying neural and molecular mechanisms were uncovered. Our study provides translational evidence for therapeutics targeting the neurodevelopmental factor in MPDs.
Association of serum occludin levels and perihematomal edema volumes in intracranial hemorrhage patients
Authors: Yuan Shuhua , Ma Qingfeng , Hou Chengbei , Zhao Yue , Liu Ke Jian , Ji Xunming , Qi Zhifeng 
Published: September 2023

AbstractBackground and PurposePerihematomal edema (PHE) is one of the severe secondary damages following intracranial hemorrhage (ICH). Studies showed that blood–brain barrier (BBB) injury contributes to the development of PHE. Previous studies showed that occludin protein is a potential biomarker of BBB injury. In the present study, we investigated whether the levels of serum occludin on admission are associated with PHE volumes in ICH patients.MethodsThis cross‐sectional study included 90ICH patients and 32 healthy controls.The volumes of hematoma and PHE were assessed using non‐contrast cranial CT within 30 min of admission. Blood samples were drawn on admission, and the levels of baseline serum occludin were detected using enzyme‐linked immunosorbent assay. Partial correlation analysis and multiple linear regression analysis were performed to evaluate the association between serum occludin levels and PHE volumes in ICH patients.ResultsThe serum occludin levels in ICH patients were much higher than health controls (median 0.27 vs. 0.13 ng/mL, p < 0.001). At admission, 34 ICH patients (37.78%) had experienced a severe PHE (≥30 mL), and their serum occludin levels were higher compared to those with mild PHE (<30 mL) (0.78 vs. 0.21 ng/mL, p < 0.001). The area under the receiver operating characteristics curve (ROC) of serum occludin level in predicting severe PHE was 0.747 (95% confidence interval CI 0.644–0.832, p < 0.001). There was a significant positive correlation between serum occludin levels and PHE volumes (partial correlation r = 0.675, p < 0.001). Multiple linear regression analysis showed that serum occludin levels remained independently associated with the PHE volumes after adjusting other confounding factors.ConclusionThe present study showed that serum occludin levels at admission were independently correlated with PHE volumes in ICH patients, which may provide a biomarker indicating PHE volume change.
Role of TRPV1 in electroacupuncture‐mediated signal to the primary sensory cortex during regulation of the swallowing function
Authors: Yuan Si , Qiu Bo , Liang Ying , Deng Bing , Xu Jing , Tang Xiaorong , Wu Junshang , Zhou Sheng , Li Zeli , Li Hongzhu , Ye Qiuping , Wang Lin , Cui Shuai , Tang Chunzhi , Yi Wei , Yao Lulu , Xu Nenggui 
Published: September 2023

AbstractAimsElectroacupuncture (EA) at the Lianquan (CV23) could alleviate swallowing dysfunction. However, current knowledge of its neural modulation focused on the brain, with little evidence from the periphery. Transient receptor potential channel vanilloid subfamily 1 (TRPV1) is an ion channel predominantly expressed in sensory neurons, and acupuncture can trigger calcium ion (Ca2+) wave propagation through active TRPV1 to deliver signals. The present study aimed to investigate whether TRPV1 mediated the signal of EA to the primary sensory cortex (S1) during regulation of swallowing function.MethodsBlood perfusion was evaluated by laser speckle contrast imaging (LSCI), and neuronal activity was evaluated by fiber calcium recording and c‐Fos staining. The expression of TRPV1 was detected by RNA‐seq analysis, immunofluorescence, and ELISA. In addition, the swallowing function was assessed by in vivo EMG recording and water consumption test.ResultsEA treatment potentiated blood perfusion and neuronal activity in the S1, and this potentiation was absent after injecting lidocaine near CV23. TRPV1 near CV23 was upregulated by EA‐CV23. The blood perfusion at CV23 was decreased in the TRPV1 hypofunction mice, while the blood perfusion and the neuronal activity of the S1 showed no obvious change. These findings were also present in post‐stroke dysphagia (PSD) mice.ConclusionThe TRPV1 at CV23 after EA treatment might play a key role in mediating local blood perfusion but was not involved in transferring EA signals to the central nervous system (CNS). These findings collectively suggested that TRPV1 may be one of the important regulators involved in the mechanism of EA treatment for improving swallowing function in PSD.
Distinct serum GDNF coupling with brain structural and functional changes underlies cognitive status in Parkinson's disease
Authors: Tang Chuanxi , Sun Ruiao , Xue Ke , Wang Mengying , Liang Sijie , Kambey Piniel Alphayo , Shi Mingyu , Wu Changyu , Chen Gang , Gao Dianshuai 
Published: September 2023

AbstractAimAberrations in brain connections are implicated in the pathogenesis of Parkinson's disease (PD). We previously demonstrated that Glial cell‐derived neurotrophic factor (GDNF) reduction is associated with cognition decline. Nonetheless, it is elusive if the pattern of brain topological connectivity differed across PD with divergent serum GDNF levels, and the accompanying profile of cognitive deficits has yet to be determined.MethodsWe collected data on the participants' cognition, demographics, and serum GDNF levels. Participants underwent 3.0T magnetic resonance imaging, and we assessed the degree centrality, brain network topology, and cortical thickness of the healthy control (HC) (n = 25), PD‐high‐GDNF (n = 19), and PD‐low‐GDNF (n = 19) groups using graph‐theoretic measures of resting‐state functional MRI to reveal how much brain connectivity varies and its clinical correlates, as well as to determine factors predicting the cognitive status in PD.ResultsThe results show different network properties between groups. Degree centrality abnormalities were found in the right inferior frontal gyrus and right parietal lobe postcentral gyrus, linked with cognition scores. The two aberrant clusters serve as a potentially powerful signal for determining whether a patient has PD and the patient's cognition level after integrating with GDNF, duration, and dopamine dosage. Moreover, we found a significant positive relationship between the thickness of the left caudal middle frontal lobe and a plethora of cognitive domains. Further discriminant analysis revealed that the cortical thickness of this region could distinguish PD patients from healthy controls. The mental state evaluation will also be more precise when paired with GDNF and duration.ConclusionOur findings reveal that the topological features of brain networks and cortical thickness are altered in PD patients with cognitive deficits. The above change, accompanied by the serum GDNF, may have merit as a diagnosis marker for PD and, arguably, cognition status.
Neurophysiological characterization of stroke recovery: A longitudinal TMS and EEG study
Authors: Ding Qian , Chen Jixiang , Zhang Shunxi , Chen Songbin , Li Xiaotong , Peng Yuan , Chen Yujie , Chen Junhui , Chen Kang , Cai Guiyuan , Xu Guangqing , Lan Yue 
Published: September 2023

AbstractAimsUnderstanding the neural mechanisms underlying stroke recovery is critical to determine effective interventions for stroke rehabilitation. This study aims to systematically explore how recovery mechanisms post‐stroke differ between individuals with different levels of functional integrity of the ipsilesional corticomotor pathway and motor function.MethodsEighty‐one stroke survivors and 15 age‐matched healthy adults participated in this study. We used transcranial magnetic stimulation (TMS), electroencephalography (EEG), and concurrent TMS‐EEG to investigate longitudinal neurophysiological changes post‐stroke, and their relationship with behavioral changes. Subgroup analysis was performed based on the presence of paretic motor evoked potentials and motor function.ResultsFunctional connectivity was increased dramatically in low‐functioning individuals without elicitable motor evoked potentials (MEPs), which showed a positive effect on motor recovery. Functional connectivity was increased gradually in higher‐functioning individuals without elicitable MEP during stroke recovery and influence from the contralesional hemisphere played a key role in motor recovery. In individuals with elicitable MEPs, negative correlations between interhemispheric functional connectivity and motor function suggest that the influence from the contralesional hemisphere may be detrimental to motor recovery.ConclusionOur results demonstrate prominent clinical implications for individualized stroke rehabilitation based on both functional integrity of the ipsilesional corticomotor pathway and motor function.
SERPINA3: A novel inflammatory biomarker associated with cerebral small vessel disease burden in ischemic stroke
Authors: Hu Xiao , Xiao Zhong‐Song , Shen Yi‐Qing , Yang Wen‐Song , Wang Peng , Li Pei‐Zheng , Wang Zi‐Jie , Pu Ming‐Jun , Zhao Li‐Bo , Xie Peng , Li Qi 
Published: September 2023

AbstractBackground and ObjectiveInflammation has emerged as a prominent risk factor for cerebral small vessel disease (CSVD). However, the specific association between various inflammatory biomarkers and the development of CSVD remains unclear. Serine proteinase inhibitor A3 (SERPINA3), Matrix metalloproteinase‐9 (MMP‐9), Tissue inhibitor metalloproteinase‐1 (TIMP‐1), Monocyte Chemoattractant Protein‐1 (MCP‐1) are several inflammatory biomarkers that are potentially involved in the development of CSVD. In this present study, we aimed to investigate the relationship between candidate molecules and CSVD features.MethodThe concentration of each biomarker was measured in 79 acute ischemic stroke patients admitted within 72 h after symptom onset. The associations between blood levels of inflammatory markers and CSVD score were investigated, as well as each CSVD feature, including white matter hyperintensities (WMH), lacunes, and enlarged perivascular spaces (EPVS).ResultsThe mean age was 69.0 ± 11.8 years, and 65.8% of participants were male. Higher SERPINA3 level (>78.90 ng/mL) was significantly associated with larger WMH volume and higher scores on Fazekas's scale in all three models. Multiple regression analyses revealed the linear association between absolute WMH burden and SERPINA3 level, especially in model 3 (β = 0.14; 95% confidence interval [CI], 0.04–0.24p ). Restricted cubic spline regression demonstrated a dose–response relationship between SERPINA3 level and larger WMH volume (p nonlineariy = 0.0366 and 0.0378 in model 2 and mode 3, respectively). Using a receiving operating characteristic (ROC) curve, plasma SERPINA3 level of 64.15 ng/mL distinguished WMH >7.8 mL with the highest sensitivity and specificity (75.92% and 60%, respectively, area under curve [AUC] = 0.668, p = 0.0102). No statistically significant relationship has been found between other candidate biomarkers and CSVD features.ConclusionIn summary, among four inflammatory biomarkers that we investigated, SERPINA3 level at baseline was associated with WMH severity, which revealed a novel biomarker for CSVD and validated its relationship with inflammation and endothelial dysfunction.
Dynamic Motion and Human Agents Facilitate Visual Nonadjacent Dependency Learning
Authors: Lu Helen Shiyang , Mintz Toben H. 
Published: September 2023

AbstractMany events that humans and other species experience contain regularities in which certain elements within an event predict certain others. While some of these regularities involve tracking the co‐occurrences between temporally adjacent stimuli, others involve tracking the co‐occurrences between temporally distant stimuli (i.e., nonadjacent dependencies, NADs). Prior research shows robust learning of adjacent dependencies in humans and other species, whereas learning NADs is more difficult, and often requires support from properties of the stimulus to help learners notice the NADs. Here, we report on seven experiments that examined NAD learning from various types of visual stimuli, exploring the effects of dynamic motion on adults' NAD learning from visual sequences involving human and nonhuman agents. We tested adults' NAD learning from visual sequences of human actions, object transformations, static images of human postures, and static images of an object in different postures. We found that dynamic motion aids the acquisition of NADs. We also found that learning NADs in sequences involving human agents is more robust compared to sequences involving nonhuman objects. We propose that dynamic motion and human agents both independently result in richer representations that provide a stronger signal for NAD learning.
Age‐Related Differences in Moral Judgment: The Role of Probability Judgments
Authors: Margoni Francesco , Geipel Janet , Hadjichristidis Constantinos , Bakiaj Richard , Surian Luca 
Published: September 2023

AbstractResearch suggests that moral evaluations change during adulthood. Older adults (75+) tend to judge accidentally harmful acts more severely than younger adults do, and this age‐related difference is in part due to the greater negligence older adults attribute to the accidental harmdoers. Across two studies (N = 254), we find support for this claim and report the novel discovery that older adults’ increased attribution of negligence, in turn, is associated with a higher perceived likelihood that the accident would occur. We propose that, because older adults perceive accidents as more likely than younger adults do, they condemn the agents and their actions more and even infer that the agents’ omission to exercise due care is intentional. These findings refine our understanding of the cognitive processes underpinning moral judgment in older adulthood and highlight the role of subjective probability judgments in negligence attribution.
Two Computational Approaches to Visual Analogy: Task‐Specific Models Versus Domain‐General Mapping
Authors: Ichien Nicholas , Liu Qing , Fu Shuhao , Holyoak Keith J. , Yuille Alan L. , Lu Hongjing 
Published: September 2023

AbstractAdvances in artificial intelligence have raised a basic question about human intelligence: Is human reasoning best emulated by applying task‐specific knowledge acquired from a wealth of prior experience, or is it based on the domain‐general manipulation and comparison of mental representations? We address this question for the case of visual analogical reasoning. Using realistic images of familiar three‐dimensional objects (cars and their parts), we systematically manipulated viewpoints, part relations, and entity properties in visual analogy problems. We compared human performance to that of two recent deep learning models (Siamese Network and Relation Network) that were directly trained to solve these problems and to apply their task‐specific knowledge to analogical reasoning. We also developed a new model using part‐based comparison (PCM) by applying a domain‐general mapping procedure to learned representations of cars and their component parts. Across four‐term analogies (Experiment 1) and open‐ended analogies (Experiment 2), the domain‐general PCM model, but not the task‐specific deep learning models, generated performance similar in key aspects to that of human reasoners. These findings provide evidence that human‐like analogical reasoning is unlikely to be achieved by applying deep learning with big data to a specific type of analogy problem. Rather, humans do (and machines might) achieve analogical reasoning by learning representations that encode structural information useful for multiple tasks, coupled with efficient computation of relational similarity.
Physiologically based absorption modeling to predict the bioequivalence of two cilostazol formulations
Authors: Wang Lu , Zhao Pengfei , Luo Ting , Yang Dandan , Jiang Qianqian , Chen Jinliang , Lou Honggang , Ruan Zourong , Jiang Bo 
Published: September 2023

AbstractIn vivo pharmacokinetic simulations and virtual bioequivalence (BE) evaluation of cilostazol have not yet been described for humans. Here, we successfully developed a physiologically based absorption model to simulate plasma concentrations of cilostazol. In addition, virtual population simulations integrating dissolution of 0.3% sodium dodecyl sulfate water media were executed to evaluate the BE of test and reference formulations. Simulation results show that test and reference formulations were bioequivalent among 28 subjects, but not nine subjects, consistent with clinical studies. The model proved to be an important tool to show potential BE for cilostazol. This finding may facilitate understanding of the potential risks during the development of generic products.
Rural E‐commerce and County Economic Development in China
Authors: Qin Qiuxia , Guo Hongdong , Shi Xinjie , Chen Kevin 
Published: September 2023

AbstractWith the proliferation of information and communication technology in rural areas, rural e‐commerce has gradually become a new economic phenomenon in China. Using the national rural e‐commerce comprehensive demonstration policy as a quasi‐natural experiment, this study examines the causal linkage between rural e‐commerce and county‐level economic development in China. Its findings, which draw on county‐level panel data from 2011 to 2018, indicate that the policy had a positive effect on the county‐level economy in China, resulting in an overall increase in county GDP by 3.5 percent (0.7 percent annually). Our analysis further shows that the impact of the policy differed along the region and human capital dimensions. Further analysis reveals that industrial structure and nonagricultural employment were the main channels for the policy to exert a county‐level economic impact. Infrastructure improvement in China also plays an important role. The findings emphasize the importance of advancing e‐commerce in rural areas to stimulate county‐level economic development.
Increasing Wages, Factor Substitution, and Cropping Pattern Changes in China
Authors: Yan Zhoufu , Zhang Shurui , Wu Fangwei , Gong Binlei 
Published: September 2023

AbstractThis article analyzed the influence of increasing wages on cropping patterns from theoretical and empirical perspectives. The results showed that the increasing labor cost provided a significant incentive to adjust the grain cropping pattern, which increased the production of the three major cereal grains but reduced the production of other grain crops. Increasing wages had a significant negative impact on cash crops. More labor‐intensive cash crops experienced a larger negative impact in the context of increasing wages. The increase in labor costs also had a negative impact on the proportion of vegetables produced, which was more evident in northern China. A further mechanism test indicated that factor substitution was a significant reason for cropping pattern changes; this illustrated the substitution of labor by machinery not only between grain crops and cash crops but also among different cash crops.