bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk factors Affecting the 1-year Outcomes of Minor Ischemic Stroke: Results from Xi’an Stroke Registry Study of China
Authors: Liu Zhongzhong , Lin Wenjuan , Lu Qingli , Wang Jing , Liu Pei , Lin Xuemei , Wang Fang , Shi Yaling , Wang Qing , Liu Guozheng , Wu Songdi 
Published: July 2020

Abstract
Background: The incidences of stroke recurrence, disability, and all-cause mortality of patients with minor ischemic stroke (MIS) remain problematic. The aim of the present was to identify risk factors associated with adverse outcomes at 1-year after MIS in the Xi’an region of China. Methods: The cohort of this prospective cohort study included MIS patients aged 18–97 years with a National Institutes of Health Stroke Scale (NIHSS) score of ≤ 3 who were treated in any of four hospitals in Xi’an region of China between January and December 2015. The 1-year rates of stroke recurrence, disability, and all-cause mortality were evaluated. Multivariate logistic regression analysis was performed to assess the association between the identified risk factors and clinical outcomes. Results: Among the 1,121 patients included for analysis, the rates of stroke recurrence, disability, and all-cause mortality at 1 year after MIS were 3.4% (38/1121), 9.3% (104/1121), and 3.3% (37/1121), respectively. Multivariate logistic regression analysis identified age, current smoking, and pneumonia as independent risk factors for stroke recurrence. Age, pneumonia, and alkaline phosphatase were independent risk factors for all-cause mortality. Independent risk factors for disability were age, pneumonia, NIHSS score on admission, and leukocyte count. Conclusions: The 1-year outcomes of MIS is not optimistic in the Xi’an region of China. Early identification of risk factors for poor clinical outcomes, attention to high risk populations, and targeted interventions contribute to reducing the risk for poor clinical outcomes of patients at 1 year after onset of MIS.
Identification and Prognostic Analysis of Hub Genes in Bladder Cancer
Authors: Yi Haoran , Liu Lingzi , Song Huajie , Zhu Hengcheng 
Published: July 2020

Abstract
Background:Bladder cancer(BC) is one of the most common tumors worldwide. Its incidence and mortality rate rank first in urological malignancies. Due to the lack of credible predictors, most patients are not timely diagnosed and treated. Moreover, in the past 30 years, the clinical treatment of BC had seen little progress, and the 5-year survival rates of patients were flat.Therefore,identifying novel potential markers or therapeutic targets are urgently required for the diagnosis and prognosis of BC.Methods: The BC gene expression chip data （GSE121711）were downloaded from the GEO database and the BLCA RNA-seq data were downloaded from the TCGA database. The differentially expressed genes (DEGs) were identified by R software using limma package and the edgeR package, and obtained the overlapped DEGs from two databases. Then, the Gene Ontology(GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of overlapped DEGs were performed through DAVID database, and the protein–protein interaction(PPI) network was constructed to screen Hub genes for regulatory protein expression in BC. Expression and prognostic analysis of the hub genes were performed by UALCAN and Kaplan-Meier plotter.Results: A total of 372 overlap DEGs were obtained, of which 93 were up-regulated and 279 were down-regulated. These genes were mainly associated with the function and pathway enrichment such as glycosaminoglycan binding, vasculature development, Cell cycle, Proteoglycans in cancer. The protein-protein interaction network analysis obtained 12 hub genes. Among these hub genes，HMMR，NCAPG2，SMC4, TROAP were closely related to the survival rate of bladder cancer patients revealed that these genes might be the key genes play an important role in the occurrence and progression.Conclusion:Therefore, our current studies demonstrated thatHMMR, NCAPG2, SMC4, TROAP are potential prognostic biomarkers for BC.In the future, these may also become clinical therapeutic targets.
Health Assessment Questionnaire-Disability Index (HAQ-DI) use in modelling disease progression in diffuse cutaneous systemic sclerosis: an analysis from the EUSTAR database
Authors: Allanore Yannick , Bozzi Sylvie , Terlinden Augustin , Huscher Doerte , Amand Caroline , Soubrane Christina , Siegert Elise , Czirjak Laszlo , Carreira Patricia E , Hachulla Eric , Zanatta Elisabetta , Li Mengtao , Airò Palo , Mendoza Fabian A , Rosato Edoardo , Distler Oliver 
Published: July 2020

Abstract
Background: Patients with diffuse cutaneous systemic sclerosis (dcSSc) have a poor prognosis. The importance of monitoring subjective measures of functioning and disability, such as the Health Assessment Questionnaire-Disability Index (HAQ-DI), is important as dcSSc is rated by patients as worse than diabetes or hemodialysis for quality of life impairment. This European Scleroderma Trials and Research (EUSTAR) database analysis was undertaken to examine the importance of impaired functionality in dcSSc prognosis. The primary objectives were to identify predictors of death and HAQ-DI score progression over 1 year. HAQ-DI score, major advanced organ involvement, and death rate were also used to develop a comprehensive model to predict lifetime dcSSc progression.Methods: This was an observational, longitudinal study in patients with dcSSc registered in EUSTAR. Death and HAQ-DI scores were, respectively, analyzed by Cox regression and linear regression analyses in relation to baseline covariates. A Markov model was developed to estimate/predict natural progression of dcSSc over a patient’s lifetime.Results: The analysis included dcSSc patients with (N = 690) and without (N = 4132) HAQ-DI score assessments from the EUSTAR database. Baseline HAQ-DI score, corticosteroid treatment and major advanced organ involvement were predictive of death on multivariable analysis; a 1-point increase in baseline HAQ-DI score multiplied the risk of death by 2.7 (p < 0.001) and multiple advanced major organ involvement multiplied the risk of death by 2.8 (p < 0.05). Multivariable analysis showed that baseline modified Rodnan Skin Score (mRSS) and baseline HAQ-DI score were associated with HAQ-DI score progression at 1 year (p < 0.05), but there was no association between baseline organ involvement and HAQ-DI score progression at 1 year. HAQ-DI score, major advanced organ involvement, and death were successfully used to model long-term disease progression in dcSSc.Conclusions: HAQ-DI score and major advanced organ involvement were comparable predictors of mortality risk in dcSSc. Baseline mRSS and baseline HAQ-DI score were predictive of HAQ-DI score progression at 1 year, indicating a correlation between these endpoints in monitoring disease progression. It is hoped that this EUSTAR analysis may change physician perception about the importance of the HAQ-DI score in dcSSc.
Association Between Growth Differentiation Factor 5 rs143383 Genetic Polymorphism and the Risk of Knee Osteoarthritis Among Caucasian but Not Asian: A Meta-analysis (PROSPERO CRD42020168180)
Authors: lei peng , Jin Song , Lu Jiping , Ouyang Chao , Gou Jiang , Xie Zhongyu , Shen Huiyong , Wang Peng 
Published: July 2020

Abstract
Background. A few months ago, the Bioscience Reports journal showed that Growth Differentiation Factor 5 (GDF5) rs143383 genetic polymorphism increases the susceptibility of knee osteoarthritis (KOA), but previous studies’ results have debates about available data. Considering the availability of more recent data, we focus on clarifying the relationship of KOA and GDF5 rs143383 genetic polymorphism by a meta-analysis of case-control trial data.Methods. The eligible studies from the time of database established to Oct. 2019 were collected from PubMed, Springer, Cochrane library, Web of Science, China National Knowledge Infrastructure (CNKI), Wan Fang library.Odds ratios (OR) and 95% confidence intervals (CI) were used to estimate the association between these polymorphisms and KOA risk. The meta-analysis was completed by STATA 18.0 software. Results. A total of 196 studies were collected, 16 of them including in final meta-analysis (7997 cases and 12684 controls). There was significant association between GDF 5 rs143383 polymorphism and KOA in all genetic models (for Allele model (C versus T): OR = 0.84 (95% CI = 0.76-0.91); dominate model (CC+CT versus TT): OR = 0.80(95% CI = (0.72-0.90); recessive model (CC versus CT+TT): OR= 0.79 (95% CI = 0.68-0.92); heterozygote model (CT versus CC+TT): OR = 0.89 (95% CI=0.80-0.97 ); homozygous model (CC versus TT): OR = 0.71 (95% CI=0.60-0.85). In the subgroup analysis by ethnicity, we obtained the results is no significant among Asians.Conclusion. GDF5 rs143383 genetic polymorphism increases the risk of KOA among Caucasians; CC genotype and C allele are protective factors for the susceptibility of KOA among Caucasians.
Performance of Model Based Multifactor Dimensionality Reduction Methods for Epistasis Detection by Controlling Population Structure
Authors: Abegaz Fentaw , Lishout Francois van , John Jestinah M. Mahachie , Chiachoompu Kridsadakorn , Bhjardwa Archana , Duroux Diane , Gusareva Elena S. , Wei Zhi , Hakonarson Hakon , Steen Kristel Van 
Published: July 2020

Abstract
Background
In genome-wide association studies the extent and impact of confounding due population structure has been well recognized. Inadequate handling of such confounding is likely to lead to spurious associations, hampering replication and the identification of causal variants. Several strategies have been developed for protecting associations against confounding, the most popular one being based on Principal Component Analysis. In contrast, the extent and impact of confounding due to population structure in gene-gene interaction association epistasis studies is much less investigated and understood. In particular, the role of nonlinear genetic population substructure in epistasis detection is largely under-investigated, especially outside a regression framework.
Methods
In order to identify causal variants in synergy, to improve interpretability and replicability of epistasis results, we introduce three strategies based on model-based multifactor dimensionality reduction approach for structured populations namely: MBMDR-PC, MBMDR-PG and MBMDR-GC.
Results
Simulation results comparing the performance of various approaches show that in the presence of population structure MBMDR-PC and MBMDR-PG consistently better control type I error rate at the nominal level than MBMDR-GC. Moreover, our proposed three methods of population structure correction outperform MDR-SP in terms of statistical power.
Conclusion
We demonstrate through extensive simulation studies the effect of various degrees of genetic population structure and relatedness on epistasis detection and propose appropriate remedial measures based on linear and nonlinear sample genetic similarity.
Circular RNA expression profiles in the development of acute chronic liver failure in hepatitis B virus-infected patients
Authors: Lian Jiangshan , Lin Feiyan , Lu Yinfeng , Hao Shaorui , Yu Jiong , Cai Huan , Zhang Xiaoli , Gu Yuqing , Yang Yida , hu lufeng 
Published: July 2020

Abstract
Hundreds of millions of people worldwide suffer from chronic hepatitis B (CHB), which is thus among the most serious public health problems. CHB can lead to serious acute chronic liver failure (ACLF). Since ACLF has a very high mortality rate, prediction of ACLF risk is a critical issue in clinical practice. To investigate the development of ACLF from CHB, circular RNA (circRNA), a novel type of endogenous non-coding RNA, was examined in healthy control (HC) subjects and CHB and ACLF patients using high-throughput RNA sequencing technology. Differentially expressed circRNAs were selected and analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses, circRNA-miRNA co-expression networks, and statistical analyses.The results showed that a total of 21,101 circRNAs were identified in HC, CHB and ACLF subjects. Compared with the HCs, 4 up-regulated and 14 down-regulated circRNAs were identified in ACLF subjects, which exhibited a consistent trend of change in the three groups. GO analysis revealed that regulation of lymphocyte activation and macrophage tolerance induction were the most important biological processes in ACLF progression. KEGG pathway analysis revealed that primary immunodeficiency and NOD-like receptor signaling pathways were the most enriched terms. The circRNA-miRNA co-expression network and statistical analyses showed that circRNA_07734, circRNA_08533, and circRNA_16083 were the most important circRNAs in the process of ACLF. In conclusions, immune dysfunction and immunodeficiency may be critical in the development of ACLF, which results in aberrant expression of circRNAs, especially circRNA_07734, circRNA_08533, and circRNA_16083.
Accelerating R&amp;D for Emerging Infectious Diseases: Lessons Learnt From Ebola
Authors: Li Chao , Chen Jingyi , Ma Jiyan , Huang Yangmu 
Published: July 2020

Abstract
Objective: The R&D explosion for Ebola virus disease (EVD) during the 2014-2016 outbreak led to the successful development of high-quality vaccines performed by China and the U.S. This study aims to compare the R&D activities of Ebola-related medical products in two countries, as a way to present the influential factors of R&D for emerging infectious disease (EID) and to provide suggestions for timely and efficient R&D response to the COVID-19 pandemic.Methods: In this comparative study, R&D activities were analyzed in terms of research funding, scientific research outputs, R&D timeline, and government incentive and coordinated mechanisms. Quantitative analysis was performed using data retrieved from national websites, clinical trial registries and databases.Qualitative semi-structured interviews were conducted to explore perspectives of fifteen key informants from EID field, especially of those involved in Ebola product development. Findings: The funding gap between China and the U.S. was significant before 2014 and narrowed after the Ebola outbreak. Both research teams started basic studies prior to the Ebola outbreak; however, the U.S. got FDA approval for clinical trials 5 months earlier than China. The underlying gap reveals the lack of participation and support by private sectors, the stagnant transformation platform, and the inadequate government incentives in China. Conclusion: R&D pre-planning and resource deployment mechanisms are crucial for EID preparedness and response. Funding should be allocated to support diversified R&D institutions for coping with the risks. Building private and public collaboration, and strengthening government support for clinical trials may accelerate the translation of basic research.
Identification ACTA2 and KDR as Key Proteins for Prognosis of PD-1/PD-L1 Blockade Therapy in Melanoma
Authors: Wang Yuchen , Li Zhaojun , Zhang Zhihui , Chen Xiaoguang 
Published: July 2020

Abstract
Background: Programmed cell death protein 1 (PD-1) /programmed cell death ligand 1 (PD-L1) blockade is an important therapeutic strategy for melanoma, despite its low clinical response. It is important to identify genes and pathways that may reflect the clinical outcomes of this therapy in patients. Methods: In this study, we analyzed clinical dataset GSE96619, which contains clinical information from five melanoma patients before and after anti-PD-1 therapy (five pairs of data). Two of the five patients responded to the anti-PD-1 treatment, whereas the other three patients did not respond to the treatment. We used MetaboAnalyst to identify differentially expressed genes (DEGs). The significant GO terms and KEGG pathway enrichment analysis of the identified DEGs were performed by using DAVID. The STRING v10 online tool was used to construct and visualize the PPI network. Validation the expression of hub genes in the B16F10 subcutaneous xenograft model Results: We identified 704 DEGs using these five pairs of data, and then the number of DEGs was narrowed down to 286 in patients who responded to treatment. Next, we performed KEGG pathway enrichment and constructed a DEG-associated protein-protein interaction network. Smooth muscle actin 2 (ACTA2) and tyrosine kinase growth factor receptor (KDR) were identified as the hub genes, which were significantly downregulated in the tumor tissue of the two patients who responded to treatment. To confirm our analysis, we demonstrated similar expression tendency to the clinical data for the two hub genes in a B16F10 subcutaneous xenograft model. Conclusions: This study demonstrates that ACTA2 and KDR are valuable responsive markers for PD-1/PD-L1 blockade therapy.
The Change of Soluble Programmed Cell Death-Ligand 1 (sPD-L1) in Glioma Patients Receiving Radiotherapy and Its Impact on Clinical Outcome
Authors: Ding Xing-chen , Wang Liang-liang , Zhu Yu-fang , Yang Jia , Yu Jin-ming , Hu Man 
Published: July 2020

Abstract
Background: It has been proved that the levels of soluble programmed death-ligand 1 (sPD-L1) are associated with prognosis in extracranial malignancies. However, the expression of sPD-L1 in glioma patients receiving radiotherapy (RT) still remains unclear.The purpose of this study is to evaluate the concentration of sPD-L1in the plasma of glioma patients before and after RT, and to explore its relationship with clinical outcomes.Methods: Between October 2017 and September 2018, the glioma patients treated with RT (30 ± 10 Gy, 2 Gy/f) were enrolled and the blood samples were collected before and after RT. We quantified the sPD-L1 levels by enzyme-linked immunosorbent assay (ELISA). The isocitrate dehydrogenase-1 (IDH-1) promoter status and Ki-67 expression were evaluated by immunohistochemistry. The murine models of glioma were used to address whether circulating sPD-L1 molecules are directly targeted by the anti-PD-L1 antibody. The associations between sPD-L1 and clinical features were assessed with Pearson or Spearman correlation. The progression-free survival (PFS) and overall survival (OS) were determined by Kaplan-Meier method.Results: Sixty glioma patients were included, with the median age 52-year-old. The proportion of grade I, II, III, IV were 6.7%, 23.3%, 28.4% and 41.6%, respectively. The baseline sPD-L1 levels were significantly associated with tumor grades, IDH-1 mutation status and Ki-67 expression. Using 14.35 pg/mL as the cutoff, significantly worse PFS and OS were both observed in patients with higher baseline level of sPD-L1 (P = 0.027, 0.008, respectively). RT significantly increased the mean level of sPD-L1 (P < 0.001). Further analysis showed that increased level of sPD-L1 in IDH-1 mutation patients was higher than that in wide-type ones. Furthermore, the murine models of glioma indicate that sPD-L1 can be blocked by anti-PD-L1 antibody. Conclusion: This study reported that sPD-L1 might be a potential biomarker to predict the outcome in glioma receiving RT. The elevated level of sPD-L1 after RT suggested that the strategy of combination with immune checkpoint inhibitors and RT might be promising for glioma, especially for patients with IDH-1 mutation.
Temporal and Spatial Characteristics Endogenous Hormone Regulation During Male Cone Development of Dacrydium pectinatum
Authors: Lu Wenju , Li Zhaoji , Song Xiqiang , Wang Jian , Ren Mingxun , Yang Donghua , Huo Shaojie , Zhao Ying , Liang Haiying 
Published: July 2020

Abstract
Background: Dacrydiumpectinatum de Laubenfels is a perennial gymnosperm dominant in tropical montane rain forests. Due to severe damages by excessive deforestation, typhoons, and other external forces, the population of the species has been significantly reduced. Furthermore, natural regeneration is poor. In order to better understand the reproductive process in D. pectinatum, we examined the morphological and anatomical changes during the development of male cone and analyzed the endogenous hormone dynamics.Results: Our study indicates that D. pectinatum male buds become distinguishable in April in tropical montane rain forests, while microspore sac forms in September and pollen mother cell forms and divides in December. Pollen grains mature and disperse in the following February. A mature male cone averages 8.5 mm in length. Level of GA, IAA, ABA and JA and their ratios fluctuated during late August to late November when sporogenous tissues were actively differentiated.Conclusions: The differentiation of sporogenous tissues is accompanied by variations in levels of endogenous hormones (GA, ABA, IAA, and JA) and their balances. The new insights about the cone development in D. pectinatum lay the foundation for future cone induction with hormones and study of factors contributing to the species’ low rate of seed germination.
Association between body mass index and fragility fracture in postmenopausal women: a cross-sectional study using Korean National Health and Nutrition Examination Survey 2008-2009 (KNHANES IV)
Authors: Kim Jihan , Lee Sami , Kim Sung Soo , Lee Jong-Pyo , Kim Jong Sung , Jung Jin Gyu , Yoon Seok Jun , Kim Kyu Pil , Park Chan-Keol , Kim Yong-Hwan 
Published: July 2020

Abstract
Background: The present study examined the relationship between body mass index (BMI) and the risk for fragility fractures in postmenopausal Korean women. Method: Among subjects who participated in the 4th National Health and Nutrition Examination Survey (2008-2009), 2114 women ≥ 40 years of age were included. BMI was based on standards set by the Korean Society for the Study of Obesity, as follows: <18.5 kg/m2, underweight; 18.5 ≤ to <25 kg/m2, normal weight; and ≥25 kg/m2, obese. Subjects were also divided into three groups according to the location of fragility fracture: spine, hip, or wrist. Results: The mean (± SD) rate of fragility fracture was significantly different among the three groups: 5.9±2.9% (underweight), 1.1±0.3% (normal weight), and 3.0±0.7% (obese) (p=0.001). After correcting for age, family history, and treatment history of osteoporosis and rheumatoid arthritis, smoking and drinking status, and level of exercise, multivariable regression analysis revealed that the odds ratio for fragility fracture in the underweight group was 5.51 (95% confidence interval [CI] 1.88–16.13) and 3.19 (95% CI 1.51–6.74) in the obese group. After subdividing fragility fractures into vertebral and non-vertebral, the odds ratio for vertebral fracture in the underweight group was 6.05 (95% CI 1.61–22.68) times higher than that in the normal weight group; in the obese group, the non-vertebral fracture odds ratio was 3.73 (95% CI 1.33–10.44) times higher. Analysis of non-vertebral fractures in the obese group revealed an odds ratio for fracture 8.29 (95% CI 1.04–66.37) times higher for hip fracture and 3.73 (95% CI 1.21–11.43) times higher for wrist fracture. Conclusions: Obesity and underweight increased the risk for fragility fractures in postmenopausal Korean women. As such, it is important for this patient population to maintain bone health through proper weight management, sufficient exercise, and regular examination of bone density.