bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Value of Serum Neurofilament Light Chain for Disease Activity and Worsening in Patients With Relapsing Multiple Sclerosis: Results From the Phase 3 ASCLEPIOS I and II Trials
Authors: Ziemssen Tjalf , Arnold Douglas L. , Alvarez Enrique , Cross Anne H. , Willi Roman , Li Bingbing , Kukkaro Petra , Kropshofer Harald , Ramanathan Krishnan , Merschhemke Martin , Kieseier Bernd , Su Wendy , Häring Dieter A. , Hauser Stephen L. , Kappos Ludwig , Kuhle Jens 
Published: March 2022

ObjectiveThis study aims to confirm the prognostic value of baseline serum neurofilament light chain (sNfL) for on-study disease activity and worsening in patients with relapsing MS (RMS).BackgroundPrevious post-hoc studies suggested that sNfL could be a prognostic biomarker in RMS. In the phase 3 ASCLEPIOS I/II trials in which ofatumumab demonstrated better efficacy outcomes than teriflunomide, treatment with ofatumumab also led to significantly reduced sNfL levels compared to teriflunomide treatment.Design/MethodsIn this study, we report protocol-planned analyses from the pooled ASCLEPIOS I/II trials (N=1882). Per protocol, patients were stratified by median baseline sNfL levels (9.3 pg/ml) into high (&gt;median) and low (≤median) categories to prognosticate: annualized rate of new/enlarging T2 (neT2) lesions in year 1 and 2, annualized relapse rate, annual percentage change in whole brain (WB) and regional brain volume [thalamus, white matter (WM), cortical gray matter (cGM)], and disability outcomes. Similar analyses were performed for the recently diagnosed (within 3 years), treatment-naive patients (no prior disease-modifying therapy) subgroup.ResultsHigh versus low sNfL at baseline was prognostic of increased on-study T2 lesion formation at year 1 (relative increase: ofatumumab +158%; teriflunomide +69%, both p&lt;0.001), which persisted in year 2 (+65%, p=0.124; +46%, p=0.003); of higher annual percentage change of WB volume (ofatumumab, −0.32% vs. −0.24%, p=0.044, and teriflunomide, −0.43% vs. −0.29%, p=0.002), thalamic volume (−0.56% vs. −0.31%, p=0.047 and −0.94% vs. −0.49%, p&lt;0.001), and WM volume (−0.30% vs. −0.19%, p=0.083 and −0.38% vs. −0.18%, p=0.003) but not of cGM volume (−0.39% vs. −0.32%, p=0.337 and −0.49% vs. −0.46%, p=0.563). A single sNfL assessment at baseline was not prognostic for on-study relapses or disability worsening. Results were similar in the subgroup of recently diagnosed, treatment-naive patients.ConclusionThis study confirms that baseline sNfL levels are prognostic of future on-study lesion formation and whole brain and regional atrophy in all RMS patients, including recently diagnosed, treatment-naive patients.
Potential Involvement of Complement Activation in Kidney Vascular Lesions of Arterionephrosclerosis
Authors: Chen Xuejing , Wang Yu , Yu Xiaojuan , Wang Suxia , Zhao Minghui 
Published: March 2022

BackgroundComplement dysregulation has been implicated in the pathogenesis of malignant nephrosclerosis with typical pathological manifestation as thrombotic microangiopathy (TMA) in recent studies. The aim of the present study was to evaluate the potential role of complement activation in arterionephrosclerosis, the major pathological change in benign hypertensive nephrosclerosis.MethodsPatients with biopsy-proven arterionephrosclerosis from 2010 to 2018 in our center were retrospectively enrolled in the present study. The clinical data were retrieved from the medical chart record. The pathological changes of renal biopsy were semiquantitatively evaluated. The ratio of inner-/outer-luminal diameter of the arterioles was calculated to evaluate the degree of arteriosclerosis. Immunohistochemical staining of CD34 and CD68 was adopted to evaluate peritubular capillary (PTC) density and macrophage infiltration, respectively. Complement components, including C3d, C4d, C1q, and C5b-9, were detected by immunohistochemical staining in paraffin-embedded sections. IgM and albumin were detected by immunofluorescence staining in frozen renal tissues.ResultsFifty-two patients were enrolled. The mean age was 45.0 ± 12.7 years, with 39 (75%) males. The median duration of hypertension was 66 months (IQR: 24–138 months). A total of 950 arterioles were evaluated, with a mean ratio of the inner/outer luminal diameter of 0.43 ± 0.05. The ratio of the inner-/outer-luminal diameter correlated with eGFR (r = 0.341, p = 0.013), sclerotic/ischemic glomerular lesions (r = –0.364, p = 0.008) and PTC density (r = 0.426, p = 0.002). Seventy-four percent (703/950) of the evaluated arterioles had C3d deposition with various patterns and intensities. The percentage of C3d-positive arterioles ranged from 63.6 to 100.0% in each specimen. The ratio of the inner/outer luminal diameter of arterioles correlated with the intensity of C3d deposition (r = –0.174, p = 0.001). Infiltration of macrophages was observed around C3d-positive arterioles. The percentage of C3d-positive arterioles was correlated with macrophage infiltration in each specimen (r = 0.330, p = 0.018). Occasional C4d-positive staining on arterioles was observed with no deposition of C1q or C5b-9 in arterionephrosclerosis specimens.ConclusionOur findings provide evidence for potential complement activation in the pathogenesis of vascular lesions in arterionephrosclerosis.
Association Between Urinary Protein-to-Creatinine Ratio and Chronic Kidney Disease Progression: A Secondary Analysis of a Prospective Cohort Study
Authors: Qin Xun , Hu Haofei , Cen Ji , Wang Xiaoyu , Wan Qijun , Wei Zhe 
Published: March 2022

ObjectiveStudies on the association between urinary protein-to-creatinine ratio (UPCR) and chronic kidney disease (CKD) progression are limited. This study aimed to investigate the relationship between UPCR and CKD progression in a Japanese population.MethodsThe present research was a secondary analysis of a prospective cohort study. Eight hundred and ninety-six subjects from the research of CKD-ROUTE in Japan were included. All the patients were new visitors or first referred to the participating centers of nephrology between October 2010 and December 2011. The target-independent variable was UPCR measured at baseline. The dependent variable was CKD progression and the estimated glomerular filtration rate (eGFR) changes during follow-up. We used Cox proportional hazards regression to investigate the association between UPCR and CKD progression risk. To address UPCR and CKD progression's non-linearity, a multivariate Cox proportional hazards regression analysis with cubic spline functions model and smooth curve fitting (penalized spline method) were conducted. We further used a generalized linear mixed model to explore the relationship between UPCR and the changes of eGFR.ResultThe mean age of the included patients was 67.2 ± 13.4 years old. Two hundred and thirty-four people occurred CKD progression during follow-up. The present study showed that UPCR was independently associated with CKD progression in the multivariate analysis [HR = 1.164, 95% CI (1.116, 1.215)]. The non-linear relationship between UPCR and CKD progression was explored in a dose-dependent manner, with an obvious inflection point of 1.699. Furthermore, our findings indicated that the tendency of the effect sizes on both the left and right sides of the inflection point was not consistent [left HR: 4.377, 95% CI (2.956, 6.483); right HR: 1.100, 95% CI (1.049–1.153)]. Using the linear mixed-effects regression model, we found that UPCR was an independent predictor of the longitudinal changes in eGFR (p &lt; 0.001 for the interaction term with time).ConclusionThis study demonstrates a nonlinear positive relationship between UPCR and CKD progression in the Japanese population. UPCR is also an independent predictor of the longitudinal changes in eGFR.
Potential Blood DNA Methylation Biomarker Genes for Diagnosis of Liver Fibrosis in Patients With Biopsy-Proven Non-alcoholic Fatty Liver Disease
Authors: Sun Qing-Feng , Tang Liang-Jie , Wang Ming-Jie , Zhu Pei-Wu , Li Yang-Yang , Ma Hong-Lei , Huang Ou-Yang , Hong Liang , Li Gang , Byrne Christopher D. , Targher Giovanni , Liu Wen-Yue , Lu Yan , Ding Ji-Guang , Zheng Ming-Hua 
Published: March 2022

Background and objectiveThis pilot study aimed to identify potential blood DNA methylation (BDM) biomarker genes for the diagnosis of liver fibrosis in non-alcoholic fatty liver disease (NAFLD).MethodsWe included a total of 16 NAFLD patients with significant (SLF, liver fibrosis stage ≥ 2) and 16 patients with non-significant liver fibrosis (NSLF, fibrosis stages 0–1). The association between BDM and liver fibrosis was analyzed. Genes were selected based on a stepwise-filtering with CpG islands containing significant differentially methylated probes.ResultsThe two groups of patients were distinguishable through both t-distributed stochastic neighbor embedding (t-SNE) analysis and unsupervised hierarchical clustering analysis based on their BDM status. BDM levels were significantly higher in the NSLF group than in the SLF group. The methylation levels in the island and shelf regions were also significantly higher in the NSLF group, as well as the methylation levels in the first exon, 3′-untranslated region, body, ExonBnd, non-intergenic region, transcription start site (TSS)1500, and TSS200 regions (all p &lt; 0.05). BDM status was associated with greater histological liver fibrosis, but not with age, sex, or other histological features of NAFLD (p &lt; 0.05). The methylation levels of the hypomethylated CpG island region of CISTR, IFT140, and RGS14 genes were increased in the NSLF group compared to the SLF group (all p &lt; 0.05).ConclusionBDM may stratify NAFLD patients with significant and non-significant liver fibrosis. The CISTR, IFT140, and RGS14 genes are potential novel candidate BDM biomarkers for liver fibrosis and these pilot data suggest further work on BDM biomarkers is warranted.
Identification of Zinc-Binding Inhibitors of Matrix Metalloproteinase-9 to Prevent Cancer Through Deep Learning and Molecular Dynamics Simulation Approach
Authors: Mathpal Shalini , Sharma Priyanka , Joshi Tushar , Pande Veena , Mahmud Shafi , Jeong Mi-Kyung , Obaidullah Ahmad J. , Chandra Subhash , Kim Bonglee 
Published: March 2022

The overexpression of matrix metalloproteinase-9 (MMP-9) is associated with tumor development and angiogenesis, and hence, it has been considered an attractive drug target for anticancer therapy. To assist in drug design endeavors for MMP-9 targets, an in silico study was presented to investigate whether our compounds inhibit MMP-9 by binding to the catalytic domain, similar to their inhibitor or not. For that, in the initial stage, a deep-learning algorithm was used for the predictive modeling of the CHEMBL321 dataset of MMP-9 inhibitors. Several regression models were built and evaluated based on R2, MAE MSE, RMSE, and Loss. The best model was utilized to screen the drug bank database containing 9,102 compounds to seek novel compounds as MMP-9 inhibitors. Then top high score compounds were selected for molecular docking based on the comparison between the score of the reference molecule. Furthermore, molecules having the highest docking scores were selected, and interaction mechanisms with respect to S1 pocket and catalytic zinc ion of these compounds were also discussed. Those compounds, involving binding to the catalytic zinc ion and the S1 pocket of MMP-9, were considered preferentially for molecular dynamics studies (100 ns) and an MM-PBSA (last 30 ns) analysis. Based on the results, we proposed several novel compounds as potential candidates for MMP-9 inhibition and investigated their binding properties with MMP-9. The findings suggested that these compounds may be useful in the design and development of MMP-9 inhibitors in the future.
Anti-platelet Therapy Is Associated With Lower Risk of Dementia in Patients With Cerebral Small Vessel Disease
Authors: Pan Dong , Rong Xiaoming , Li Honghong , Deng Zhenhong , Wang Jia , Liu Xiaohuan , He Lei , Xu Yongteng , Tang Yamei 
Published: March 2022

IntroductionCerebral small vessel disease (CSVD) is common among older people and it could lead to dementia. Whether anti-platelet therapy (APT) could retard the cognitive decline of CSVD is unclear. The aim of the study was to evaluate, in newly diagnosed CSVD patients without dementia, the association between the APT and dementia during follow-up.MethodsWe conducted a nested case-control study within a CSVD cohort. Dementia cases, such as vascular dementia (VaD), Alzheimer’s disease (AD), and unspecified dementia (UD), were individually matched (1:1) to controls by age, sex, and follow-up time. Conditional logistic regression models were used to estimate the odds ratios (ORs) between APT and dementia.ResultsOf 9,991 patients in a cohort screened from January 2009 to December 2019 and followed-up until November 2020, 131 dementia cases were finally included and successfully matched to 131 controls. Among 262 patients with CSVD, the mean [standard deviation (SD)] age was 73.9 (7.9) years and 126 (48.1%) were men. The median [interquartile range (IQR)] follow-up periods were 4.73 (2.70–6.57) years in the control group and 2.94 (1.34–4.89) years in the case group. According to MRI at baseline, the case group showed higher CSVD burden in lacune(s) (p = 0.001), moderate-to-severe white matter hyperintensities (WMHs) (p = 0.015), enlarged perivascular spaces (EPVSs) in basal ganglia (p = 0.005), and brain atrophy (p &lt; 0.001). The APT was associated with the lower overall dementia risk and the matched OR was statistically significant (aOR 0.15, 95% CI 0.05–0.45, p = 0.001), and clopidogrel showed protective effects on overall dementia (aOR 0.30, 95% CI 0.14–0.62, p = 0.001).ConclusionAmong newly diagnosed CSVD patients without dementia, APT was associated with a lower risk of dementia and clopidogrel might be an appropriate candidate in preventing dementia.
Abnormal Default Mode Network Homogeneity in Major Depressive Disorder With Gastrointestinal Symptoms at Rest
Authors: Yan Meiqi , Chen Jindong , Liu Feng , Li Huabing , Zhao Jingping , Guo Wenbin 
Published: March 2022

BackgroundGastrointestinal (GI) symptoms are prominent in many patients with major depressive disorder (MDD). However, it remains unclear whether MDD patients with GI symptoms have brain imaging alterations in the default mode network (DMN) regions.MethodsA total of 35 MDD patients with GI symptoms, 17 MDD patients without GI symptoms, and 28 healthy controls (HCs) were recruited. All participants underwent resting-state functional magnetic resonance imaging scans. Network homogeneity (NH) and support vector machine (SVM) methods were used to analyze the imaging data.ResultsGastrointestinal group showed higher 17-item Hamilton Rating Scale for Depression total scores and factor scores than the non-GI group. Compared with the non-GI group and HCs, the GI group showed decreased NH in the right middle temporal gyrus (MTG) and increased NH in the right precuneus (PCu). The SVM results showed that a combination of NH values of the right PCu and the right MTG exhibited the highest accuracy of 88.46% (46/52) to discriminate MDD patients with GI symptoms from those without GI symptoms.ConclusionMajor depressive disorder patients with GI symptoms have more severe depressive symptoms than those without GI symptoms. Distinctive NH patterns in the DMN exist in MDD patients with GI symptoms, which can be applied as a potential brain imaging marker to discriminate MDD patients with GI symptoms from those without GI symptoms.
Systemic-Immune-Inflammation Index as a Promising Biomarker for Predicting Perioperative Ischemic Stroke in Older Patients Who Underwent Non-cardiac Surgery
Authors: Zhang Faqiang , Niu Mu , Wang Long , Liu Yanhong , Shi Likai , Cao Jiangbei , Mi Weidong , Ma Yulong , Liu Jing 
Published: March 2022

ObjectiveThis study aimed to investigate the clinical prognostic values of the preoperative systemic-immune-inflammation index (SII) in older patients undergoing non-cardiac surgery, using perioperative ischemic stroke as the primary outcome.MethodsThis retrospective cohort study included older patients who underwent non-cardiac surgery between January 2008 and August 2019. The patients were divided into SII &lt; 583 and SII ≥ 583 group according to the optimal SII cut-off value. The outcome of interest was ischemic stroke within 30 days after surgery. Primary, sensitivity, and subgroup analyses were performed to confirm that preoperative SII qualifies as a promising, independent prognostic indicator. Propensity score matching (PSM) analysis was further applied to address the potential residual confounding effect of covariates to examine the robustness of our results.ResultsAmong the 40,670 included patients with a median age of 70 years (interquartile range: 67, 74), 237 (0.58%) experienced an ischemic stroke within 30 days after surgery. SII ≥ 583 was associated with an increased risk of perioperative ischemic stroke in multivariate regression analysis [odds ratio (OR), 1.843; 95% confidence interval (CI), 1.369–2.480; P &lt; 0.001]. After PSM adjustment, all covariates were well balanced between the two groups. The correlation between the SII and perioperative ischemic stroke remained significantly robust (OR: 2.195; 95% CI: 1.574–3.106; P &lt; 0.001) in the PSM analysis.ConclusionPreoperative SII, which includes neutrophil, platelet, and lymphocyte counts obtained from routine blood analysis, was a potential prognostic biomarker for predicting perioperative ischemic stroke after non-cardiac surgery in older patients. An elevated SII, based on an optimal cut-off value of 583, was an independent risk factor for perioperative ischemic stroke.
The Application of the Omaha System in Community Rehabilitation Nursing for Patients With Stroke and Previous Falls
Authors: Fang Xiaoqun , Jia Shulei , Wang Qiuyan , Liu Huifang , Zhou Yumei , Zhang Lingling , Dai Tanghua , Luo Hui , Peng Hui , Yuan Jun , Zhou Huyan 
Published: March 2022

ObjectiveThis study aimed to explore the use of the Omaha System in rehabilitation and nursing methods and the effects on patients within the community who had experienced stroke and previous falls.MethodsThis study enrolled 42 patients who had experienced stroke and previous falls and had returned to the community after being discharged from the Department of Neurology and Rehabilitation of the Affiliated Hospital of Nanchang University from January to July 2018. The patients were randomly divided into two groups: an experimental group (n = 21) and a control group (n = 21). Patients in the control group received routine community rehabilitation care, and patients in the experimental group received community rehabilitation care on the basis of the Omaha System. Intervention lasted for 1 year. The Omaha outcome score, the ability to perform activities of daily living (ADL) (measured via the Modified Barthel Index [MBI]), and the incidence of falls for each group were compared before and after the intervention.ResultsAfter 1 year of intervention, the Omaha outcome score and MBI of both groups were higher than before; the Omaha outcome score and MBI of the experimental group were higher than those of the control group; the differences were statistically significant (P &lt; 0.05). No fall occurred in either of the two groups.ConclusionThe Omaha System can comprehensively evaluate the health problems of patients, guide nursing intervention, and quantitatively evaluate the effect of nursing intervention; it is therefore worthy of promotion.
Effects of Ordered Grasping Movement on Brain Function in the Performance Virtual Reality Task: A Near-Infrared Spectroscopy Study
Authors: Li Xiangyang , Yin Jiahui , Li Huiyuan , Xu Gongcheng , Huo Congcong , Xie Hui , Li Wenhao , Liu Jizhong , Li Zengyong 
Published: March 2022

ObjectiveVirtual reality (VR) grasping exercise training helps patients participate actively in their recovery and is a critical approach to the rehabilitation of hand dysfunction. This study aimed to explore the effects of active participation and VR grasping on brain function combined with the kinematic information obtained during VR exercises.MethodsThe cerebral oxygenation signals of the prefrontal cortex (LPFC/RPFC), the motor cortex (LMC/RMC), and the occipital cortex (LOC/ROC) were measured by functional near-infrared spectroscopy (fNIRS) in 18 young people during the resting state, grasping movements, and VR grasping movements. The EPPlus plug-in was used to collect the hand motion data during simulated interactive grasping. The wavelet amplitude (WA) of each cerebral cortex and the wavelet phase coherence (WPCO) of each pair of channels were calculated by wavelet analysis. The total difference in acceleration difference of the hand in the VR grasping movements was calculated to acquire kinematic characteristics (KCs). The cortical activation and brain functional connectivity (FC) of each brain region were compared and analyzed, and a significant correlation was found between VR grasping movements and brain region activation.ResultsCompared with the resting state, the WA values of LPFC, RPFC, LMC, RMC, and ROC increased during the grasping movements and the VR grasping movements, these changes were significant in LPFC (p = 0.0093) and LMC (p = 0.0007). The WA values of LMC (p = 0.0057) in the VR grasping movements were significantly higher than those in the grasping movements. The WPCO of the cerebral cortex increased during grasping exercise compared with the resting state. Nevertheless, the number of significant functional connections during VR grasping decreased significantly, and only the WPCO strength between the LPFC and LMC was enhanced. The increased WA of the LPFC, RPFC, LMC, and RMC during VR grasping movements compared with the resting state showed a significant negative correlation with KCs (p &lt; 0.001).ConclusionThe VR grasping movements can improve the activation and FC intensity of the ipsilateral brain region, inhibit the FC of the contralateral brain region, and reduce the quantity of brain resources allocated to the task. Thus, ordered grasping exercises can enhance active participation in rehabilitation and help to improve brain function.