bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational tumor stroma reaction evaluation led to novel prognosis-associated fibrosis and molecular signature discoveries in high-grade serous ovarian carcinoma
Authors: Jiang Jun , Tekin Burak , Yuan Lin , Armasu Sebastian , Winham Stacey J. , Goode Ellen L. , Liu Hongfang , Huang Yajue , Guo Ruifeng , Wang Chen 
Published: September 2022

BackgroundAs one of the key criteria to differentiate benign vs. malignant tumors in ovarian and other solid cancers, tumor-stroma reaction (TSR) is long observed by pathologists and has been found correlated with patient prognosis. However, paucity of study aims to overcome subjective bias or automate TSR evaluation for enabling association analysis to a large cohort.Materials and methodsServing as positive and negative sets of TSR studies, H&amp;E slides of primary tumors of high-grade serous ovarian carcinoma (HGSOC) (n = 291) and serous borderline ovarian tumor (SBOT) (n = 15) were digitally scanned. Three pathologist-defined quantification criteria were used to characterize the extents of TSR. Scores for each criterion were annotated (0/1/2 as none-low/intermediate/high) in the training set consisting of 18,265 H&amp;E patches. Serial of deep learning (DL) models were trained to identify tumor vs. stroma regions and predict TSR scores. After cross-validation and independent validations, the trained models were generalized to the entire HGSOC cohort and correlated with clinical characteristics. In a subset of cases tumor transcriptomes were available, gene- and pathway-level association studies were conducted with TSR scores.ResultsThe trained models accurately identified the tumor stroma tissue regions and predicted TSR scores. Within tumor stroma interface region, TSR fibrosis scores were strongly associated with patient prognosis. Cancer signaling aberrations associated 14 KEGG pathways were also found positively correlated with TSR-fibrosis score.ConclusionWith the aid of DL, TSR evaluation could be generalized to large cohort to enable prognostic association analysis and facilitate discovering novel gene and pathways associated with disease progress.
Integrative bioinformatics analysis to identify the effects of circadian rhythm on Crohn’s disease
Authors: Liu Dan , Chen Yin-Yun , Li Qing-qing , Xu Ming , Liao Jiang-Tao , Wang Ben 
Published: September 2022

Background: Crohn’s disease (CD) is a multifactorial inflammatory bowel disease characterized by complex aberrant autoimmune disorders. Currently, the involvement of the circadian rhythm in the pathogenesis of CD is unknown.Methods: Bulk and single-cell RNA-seq data and associated clinical data from patients with CD were downloaded from the Gene Expression Omnibus (GEO). Single-sample gene set enrichment analysis was performed to calculate the enrichment score (ES) of circadian rhythm-related genes. Differential expression analysis was used to identify differentially expressed genes. Functional enrichment analysis was used to explore potential disease mechanisms. CIBERSORT was used to estimate immune cell abundance. Single-cell RNA-seq data were analyzed using the R package “Seurat.”Results: The ES of circadian rhythm-related genes was lower in the CD tissue than in the normal tissue. Ubiquitin-specific protease 2 (USP2), a circadian rhythm-related gene, was identified as a potential modulator of CD pathogenesis. USP2 expression was reduced in CD and was associated with disease severity. Moreover, the analysis of bulk RNA-seq and single-cell RNA-seq data showed that monocyte and neutrophil abundance was elevated in CD and was negatively correlated with USP2 expression. It should be noted that USP2 expression in acinar cells was negatively correlated with monocyte and neutrophil abundance. Functional enrichment analysis revealed several canonical pathways to be enriched in CD, including the interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, cytokine–cytokine receptor interaction, toll-like receptor signaling pathway, and nod-like receptor signaling pathway.Conclusion: Aberrant expression of circadian rhythm-related genes is correlated with CD pathogenesis. USP2 might be related to crosstalk among the different cell types in CD. These findings provide insights into future chronotherapy for CD.
Use of electroencephalogram, gait, and their combined signals for classifying cognitive impairment and normal cognition
Authors: Min Jin-Young , Ha Sang-Won , Lee Kiwon , Min Kyoung-Bok 
Published: September 2022

BackgroundEarly identification of people at risk for cognitive decline is an important step in delaying the occurrence of cognitive impairment. This study investigated whether multimodal signals assessed using electroencephalogram (EEG) and gait kinematic parameters could be used to identify individuals at risk of cognitive impairment.MethodsThe survey was conducted at the Veterans Medical Research Institute in the Veterans Health Service Medical Center. A total of 220 individuals volunteered for this study and provided informed consent at enrollment. A cap-type wireless EEG device was used for EEG recording, with a linked-ear references based on a standard international 10/20 system. Three-dimensional motion capture equipment was used to collect kinematic gait parameters. Mild cognitive impairment (MCI) was evaluated by Seoul Neuropsychological Screening Battery-Core (SNSB-C).ResultsThe mean age of the study participants was 73.5 years, and 54.7% were male. We found that specific EEG and gait parameters were significantly associated with cognitive status. Individuals with decreases in high-frequency EEG activity in high beta (25–30 Hz) and gamma (30–40 Hz) bands increased the odds ratio of MCI. There was an association between the pelvic obliquity angle and cognitive status, assessed by MCI or SNSB-C scores. Results from the ROC analysis revealed that multimodal signals combining high beta or gamma and pelvic obliquity improved the ability to discriminate MCI individuals from normal controls.ConclusionThese findings support prior work on the association between cognitive status and EEG or gait, and offer new insights into the applicability of multimodal signals to distinguish cognitive impairment.
Frailty and hearing loss: From association to causation
Authors: Liu Yun , Qian Peiyi , Guo Shuli , Liu Shuangyan , Wang Dahui , Yang Lei 
Published: September 2022

BackgroundObservational studies suggest that frailty is associated with hearing loss (HL) but with inconsistent results. This study aims to examine such association and to assess its causality.Materials and methodsThe cross-sectional data from the National Health and Nutrition Examination Survey (NHANES). Multivariate logistic regression models were used to assess the association between HL and frailty index (FI). Genetic variants associated with the FI and HL were obtained from a large genome-wide association study (GWAS) meta-analysis and UK Biobank GWAS. The inverse variance weighting (IVW) method was used to estimate causal effects. Sensitivity analyses were performed to further validate the robustness of results.ResultsIn this cross-sectional analysis, results support the possibility that frailty may be associated with a higher risk of developing HL, with self-reported [odds ratio (OR) = 2.813; 95% CI, 2.386, 3.317; p &lt; 0.001], speech frequency HL (OR = 1.975; 95% CI, 1.679–2.323; p &lt; 0.001), and high frequency HL (OR = 1.748; 95% CI, 1.459–2.094; p &lt; 0.001). In the adjusted model, frail participants remained at high risk of HL. Mendelian randomization (MR) studies showed a bidirectional causal association between genetically predicted FI and risk of HL (FI for exposure: OR = 1.051; 95% CI, 1.020–1.083; p = 0.001; HL for exposure: OR = 1.527; 95% CI, 1.227–1.901; p &lt; 0.001).ConclusionOur observational study found that inter-individual differences in frailty were associated with the risk of developing HL. Genetic evidence suggests a potential bidirectional causal association between FI and HL. Furthermore, the potential mechanisms of this association require investigation.
Effects of Wu Qin Xi exercise on reactive inhibition in Parkinson’s disease: A randomized controlled clinical trial
Authors: Wang Zhen , Pi Yanling , Tan Xiaoyin , Wang Zhen , Chen Robert , Liu Yu , Guo Wei , Zhang Jian 
Published: September 2022

ObjectiveMotor symptom in patients with Parkinson’s disease (PD) are related to reduced motor inhibitory ability (proactive and reactive inhibition). Although exercise has been shown to improve this ability, its effects on different levels of motor inhibition have not been determined.Materials and methodsSixty patients with PD aged 55–75 years were allocated randomly to 24-week exercise interventions [Wu Qin Xi exercise (WQX) and stretching exercise (SE)]. The stop signal task and questionnaires were administered pre and post interventions. Twenty-five age-matched healthy controls were recruited to obtain reference values for inhibition.ResultsCompared to healthy controls, patients with PD showed motor inhibition deficits in reactive inhibition, but not in proactive inhibition. Post-intervention, the WQX group showed significant improvement in reactive inhibition compared to the SE group. In both the WQX and SE groups, movement speed was improved post-intervention, accompanied by reduction in negative emotions, stable improvement of sleep quality, and high self-reported satisfaction levels.ConclusionThis study demonstrated that Wu Qin Xi exercise can improve the reactive inhibition of patients with PD. Our results provide theoretical support for the formulation of reasonable and effective exercise prescriptions for PD rehabilitation.Clinical trial registration[http://www.chictr.org.cn], identifier [ChiCTR2000038517].
A quantitative meta-analysis of vitamin C in the pathophysiology of Alzheimer’s disease
Authors: Hamid Maryam , Mansoor Sumaiya , Amber Sanila , Zahid Saadia 
Published: September 2022

PurposeAlzheimer’s disease (AD) is a multifaceted neurodegenerative disorder with many complex pathways feeding into its pathogenesis and progression. Vitamin C, an essential dietary antioxidant, is vital for proper neurological development and maintenance. This meta-analysis and systematic review attempted to define the relationship between vitamin C plasma levels and AD while highlighting the importance and involvement of vitamin C in the pathogenesis of AD.Materials and methodsPRISMA guidelines were used to obtain studies quantifying the plasma levels of vitamin C in AD and control subjects. The literature was searched in the online databases PubMed, Google Scholar, and Web of Science. A total of 12 studies were included (n = 1,100) and analyzed using Comprehensive Meta-Analysis 3.0.ResultsThe results show that there is a significant decrease in the plasma vitamin C levels of AD patients as compared to healthy controls (pooled SMD with random-effect model: −1.164, with 95%CI: −1.720 to −0.608, Z = −4.102, p = 0.00) with significant heterogeneity (I2 = 93.218). The sensitivity analysis showed directionally similar results. Egger’s regression test (p = 0.11) and visual inspection of the funnel plot showed no publication bias.ConclusionBased on these studies, it can be deduced that the deficiency of vitamin C is involved in disease progression and supplementation is a plausible preventive and treatment strategy. However, clinical studies are warranted to elucidate its exact mechanistic role in AD pathophysiology and prevention.
Research trends and hotspots of exercise for Alzheimer’s disease: A bibliometric analysis
Authors: Chen Binglin , Fu Yujie , Song Ge , Zhong Weiquan , Guo Jiabao 
Published: September 2022

ObjectiveAlzheimer’s disease (AD) is a socially significant neurodegenerative disorder among the elderly worldwide. An increasing number of studies have revealed that as a non-pharmacological intervention, exercise can prevent and treat AD. However, information regarding the research status of this field remains minimal. Therefore, this study aimed to analyze trends and topics in exercise and AD research by using a bibliometric method.MethodsWe systematically searched the Web of Science Core Collection for published papers on exercise and AD. The retrieved data regarding institutions, journals, countries, authors, journal distribution, and keywords were analyzed using CiteSpace software. Meanwhile, the co-occurrence of keywords was constructed.ResultsA total of 1,104 papers were ultimately included in accordance with our specified inclusion criteria. The data showed that the number of published papers on exercise and AD is increasing each year, with papers published in 64 countries/regions and 396 academic journals. The Journal of Alzheimer’s Disease published the most papers (73 publications). Journals are concentrated in the fields of neuroscience and geriatrics gerontology. The University of Kansas and the United States are the major institution and country, respectively. The cited keywords show that oxidative stress, amyloid beta, and physical exercise are the research hotspots in recent years. After analysis, the neuroprotective effect of exercise was identified as the development trend in this field.ConclusionsBased on a bibliometric analysis, the number of publications on exercise and AD has been increasing rapidly, especially in the past 10 years. “Amyloid beta,” “oxidative stress,” and “exercise program” trigger the most interest among researchers in this field. The study of exercise program and mechanism of exercise in AD is still the focus of future research.
Transcranial direct current stimulation for gait recovery following stroke: A systematic review of current literature and beyond
Authors: Corominas-Teruel Xavier , Mozo Rosa María San Segundo , Simó Montserrat Fibla , Colomina Fosch Maria Teresa , Valero-Cabré Antoni 
Published: September 2022

BackgroundOver the last decade, transcranial direct current stimulation (tDCS) has set promise contributing to post-stroke gait rehabilitation. Even so, results are still inconsistent due to low sample size, heterogeneity of samples, and tDCS design differences preventing comparability. Nonetheless, updated knowledge in post-stroke neurophysiology and stimulation technologies opens up opportunities to massively improve treatments.ObjectiveThe current systematic review aims to summarize the current state-of-the-art on the effects of tDCS applied to stroke subjects for gait rehabilitation, discuss tDCS strategies factoring individual subject profiles, and highlight new promising strategies.MethodsMEDLINE, SCOPUS, CENTRAL, and CINAHL were searched for stroke randomized clinical trials using tDCS for the recovery of gait before 7 February 2022. In order to provide statistical support to the current review, we analyzed the achieved effect sizes and performed statistical comparisons.ResultsA total of 24 records were finally included in our review, totaling n = 651 subjects. Detailed analyses revealed n = 4 (17%) studies with large effect sizes (≥0.8), n = 6 (25%) studies with medium ones (≥0.5), and n = 6 (25%) studies yielding low effects sizes (≤ 0.2). Statistically significant negative correlations (rho = −0.65, p = 0.04) and differences (p = 0.03) argued in favor of tDCS interventions in the sub-acute phase. Finally, significant differences (p = 0.03) were argued in favor of a bifocal stimulation montage (anodal M1 ipsilesional and cathodal M1 contralesional) with respect to anodal ipsilesional M1.ConclusionOur systematic review highlights the potential of tDCS to contribute to gait recovery following stroke, although also the urgent need to improve current stimulation strategies and subject-customized interventions considering stroke severity, type or time-course, and the use of network-based multifocal stimulation approaches guided by computational biophysical modeling.Systematic review registrationPROSPERO: CRD42021256347.
Effects of regenerative peripheral nerve interface on dorsal root ganglia neurons following peripheral axotomy
Authors: Wang Zheng , Zhang Dong , Yi Xin Zeyu , Zhao Yong , Yu Aixi 
Published: September 2022

BackgroundLong-term delayed reconstruction of injured peripheral nerves always results in poor recovery. One important reason is retrograde cell death among injured sensory neurons of dorsal root ganglia (DRG). A regenerative peripheral nerve interface (RPNI) was capable of generating new synaptogenesis between the proximal nerve stump and free muscle graft. Meanwhile, sensory receptors within the skeletal muscle can also be readily reinnervated by donor sensory axons, which allows the target muscles to become sources of sensory information for function reconstruction. To date, the effect of RPNI on injured sensory neurons is still unclear. Here, we aim to investigate the potential neuroprotective role of RPNI on sensory DRG neurons after sciatic axotomy in adult rats.Materials and methodsThe sciatic nerves of sixty rats were transected. The rats were randomly divided into three groups following this nerve injury: no treatment (control group, n = 20), nerve stump implantation inside a fully innervated muscle (NSM group, n = 20), or nerve stump implantation inside a free muscle graft (RPNI group, n = 20). At 8 weeks post-axotomy, ipsilateral L4 and L5 DRGs were harvested in each group. Toluidine blue staining was employed to quantify the neuronal densities in DRGs. The neuronal apoptosis index was quantified with TUNEL assay. Western blotting was applied to measure the expressions of Bax, Bcl-2, and neurotrophins (NTs) in ipsilateral DRGs.ResultsThere were significantly higher densities of neurons in ipsilateral DRGs of RPNI group than NSM and control groups at 8 weeks post-axotomy (p &lt; 0.01). Meanwhile, neuronal apoptosis index and the expressions of pro-apoptotic Bax within the ipsilateral DRGs were significantly lower in the RPNI group than those in the control and NSM groups (p &lt; 0.05), while the opposite result was observed in the expression of pro-survival Bcl-2. Furthermore, the expressions of NGF, NT-3, BDNF, and GDNF were also upregulated in the ipsilateral DRGs in the RPNI group (p &lt; 0.01).ConclusionThe present results demonstrate that RPNI could prevent neuronal loss after peripheral axotomy. And the neuroprotection effect has a relationship with the upregulation of NTs in DRGs, such as NGF, NT-3, BDNF, and GDNF. These findings provide an effective therapy for neuroprotection in the delayed repair of the peripheral nerve injury.
Disease specific symptoms indices in patients with celiac disease—A hardly recognised entity
Authors: Jabeen Shaista , Khan Azmat Ullah , Ahmed Waqas , Ahmad Mansur-ud-Din , Jafri Saghir Ahmad , Bacha Umar , Ali Amjed , Muzammil Hafiz Shehzad , Alsagaby Suliman A. , Al Abdulmonem Waleed , Abdelgawad Mohamed A. , Riaz Mishal , Mahwish  , Nasir Makia , Zafar Aimen , Tufail Tabussam , Imran Muhammad , Anwar Faridi Tallat , Aslam Maria , Abid Shah Syedda Fatima , Farooq Sana , Awan Tayyaba Niaz , Ur-Rehman Habib 
Published: September 2022

BackgroundCeliac disease (CD) was considered a rare disease before and was perceivably only limited to children but now affects almost 1–2% of the global population. This abrupt increase in prevalence is due to advancements in diagnostic criteria and medical facilities but still many countries lack the basic data that can assess the severity of this health issue. The present study was conducted with the aim to assess the common but rarely diagnosed condition with the identification of its underlying secondary ailments.Materials and methodsPatients visiting public sector hospitals were recruited and tested for clinical symptoms secondary to gluten-containing foods (wheat and barley, etc.), followed by serological testing for immunoglobulin A, tissue transglutaminase A, and anti-endomysial antibodies. Only seropositive candidates were included in the endoscopic and biopsy examination for the features of villous atrophy and intestinal cell damage. The secondary ailments including anemia, growth retardation, and gastrointestinal symptoms were also documented for the tested positive patients. The modified European Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) criterion was followed throughout the study.ResultsFrom 647 suspected cases from March 2018 to July 2019, 113 were confirmed with CD while 58% were female children and 42% were male children. The majority of them were from a lower class (75%) and 26% of them had a positive family history of CD. A total of 67% of patients with CD were underweight while wasting was observed in 38%, and 80% were stunted as well. Of the positively tested patients with CD, 49% had moderate anemia with 15% having severe anemia. Approximately 33% had hypoalbuminemia as well. The majority of them had a mild to severe range of gastrointestinal symptoms, such as abdominal pain, diarrhea, flatus, eructation, diarrhea, and steatorrhea.ConclusionThe study finding indicates an increased number of patients diagnosed with CD with an excessive sum of secondary ailments, such as anemia, growth failure, growth retardation, malnutrition, and gastrointestinal symptoms.
Astragalus Mongholicus: A review of its anti-fibrosis properties
Authors: Gong Fengying , Qu Rongmei , Li Yongchun , Lv Ying , Dai Jingxing 
Published: September 2022

Background: Fibrosis-related diseases (FRD) include cerebral fibrosis, pulmonary fibrosis, cardiac fibrosis, liver fibrosis, renal fibrosis, peritoneal fibrosis, etc. The effects of fibrosis can be severe, resulting in organ dysfunction, functional decline, and even organ failure, which can cause serious health problems.Aim: Currently, there is no effective modern medicine for anti-fibrosis in the clinics; however, Chinese medicine has a certain beneficial effect on treating such diseases. Astragalus Mongholicus (AM) has rich medicinal value, and its anti-fibrosis effect has been recently investigated. In recent years, more and more experimental studies have been conducted on the intervention of astragaloside IV (AS-IV), astragalus polysaccharide (APS), astragalus flavone, cycloastragalus alcohol, astragalus water extract and other pharmacological components in fibrosis-related diseases, attracting the interest of researchers. We aim to provide ideas for future research by summarizing recent research advances of AM in treating fibrosis-related diseases.Methods: A literature search was conducted from the core collections of electronic databases such as Baidu Literature, Sciencen.com, Google Scholar, PubMed, and Science Direct using the above keywords and the pharmacological and phytochemical details of the plant.Results: AM can be used to intervene in fibrosis-disease progression by regulating inflammation, oxidative stress, the immune system, and metabolism.Conclusion: AS-IV, APS, and astragalus flavone were studied and discussed in detail. These components have high potential anti-fibrosis activity. Overall, this review aims to gain insight into the AM’s role in treating fibro-related diseases.