bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amino acid torsion angles enable prediction of protein fold classification
Authors: Tian Kun , Zhao Xin , Wan Xiaogeng , Yau Stephen 
Published: January 2020

Abstract
Background Protein structure can provide insights that help biologists to predict and understand protein functions and interactions. However, the number of known protein structures has not kept pace with the number of protein sequences determined by high-throughput sequencing. Current techniques used to determine the structure of proteins, such as X-ray crystallography and Nuclear Magnetic Resonance (NMR) spectroscopy, are complex and may require a lot of time to analyze the experimental results, especially for large protein molecules. The limitations of these methods have motivated us to create a new approach for protein structure prediction.Results Here we describe a new approach that uses integration and analysis of torsion angle information from the Protein Data Bank to enable prediction of protein structures from amino acid sequences. Our prediction model performed well in comparison with previous methods when applied to the structural classification of two CATH datasets with more than 5000 protein domains. This new prediction model performs well with an average of 92.5% accuracy for structure classification, which is higher than the previous research. We also used our model to predict four known protein structures with a single amino acid sequence, while many other existing methods could only obtain one possible structure for a given sequence.Conclusions The results show that our method provides a new effective and reliable tool for protein structure prediction research.
Comprehensive Analysis of LncRNAs Role in Tumorigenesis of Colon Adenocarcinoma
Authors: Poursheikhani Arash , Abbaszadegan Mohammad Reza , Nokhandani Negin , Kerachian Mohammad Amin 
Published: January 2020

Abstract
Background Colon adenocarcinoma (COAD) is one of the most common gastrointestinal cancers globally. Molecular aberrations of tumor suppressors and/or oncogenes are the main contributors to its tumorigenesis. However, the exact underlying mechanisms of COAD pathogenesis are not clear yet. Thus, there is an urgent need to indicate promising potential diagnostic and prognostic biomarkers in COAD patients. In the current study, level 3 RNA-seq and miR-seq data and corresponding clinical data of colon adenocarcinoma (COAD) were retrieved from the TCGA database.The “limma” package in R software was utilized to indicate the differentially expressed genes. For in silico functional analysis, GO and KEGG signaling pathways were conducted. PPI network was constructed based on the STRING online database by Cytoscape 3.7.2. A ceRNA network was also constructed by “GDCRNATools” package in R software. Kaplan-Meier survival analysis (log-rank test) was used to indicate the relation between RNA expressions with patient’s survival time.Results The differential expression data demonstrated that 1512 mRNAs, 188 lncRNAs, and 329 miRNAs were differentially expressed in COAD. The GO and KEGG pathway analysis indicated that the differentially expressed mRNAs were primarily enriched in canonical processes in cancer. The PPI network showed that the PPARGC1A, ADAMTS5, PTGS2, FGFR2, TBX1, TWIST1, KIT, BDNF and MET proteins were the critical hubs. The Kaplan-Meier analysis revealed that 128 mRNAs, 15 lncRNAs, and 39 miRNAs were associated with overall survival time in the patients. The ceRNA network data demonstrated that three lncRNA including MAGI2-AS3, NEAT1, and SNHG3 genes were involved in the development of COAD.Conclusions Altogether, we integrated differentially expressed mRNAs, lncRNAs, and miRNAs in COAD bioinformatically. Our data suggested promising lncRNAs in the diagnosis and prognosis of patients with COAD.
Whole transcriptome analysis of human lung tissue to identify COPD-associated gene
Authors: Li Qiuyu , Zhu Yizhang , Zhou Aiyuan , Yin Yuxin 
Published: January 2020

Abstract
Identification of the dysfunctional genes in human lung from patients with Chronic obstructive pulmonary disease (COPD) will help up to understand the pathology of this disease. Here, using transcriptomic data of lung tissue for 91 COPD cases and 182 matched healthy controls from the Genotype-Tissue Expression (GTEx) database. Employing a stringent model controlling for known covariates and hidden confounders, we identified 1,359 significant differentially expressed genes (DEG) with 707 upregulated and 602 downregulated respectively. We evaluated the identified DEGs in an independent microarray cohort of 219 COPD and 108 controls, demonstrating the robustness of our result. Functional annotation of COPD-associated genes highlighted the activation of complement cascade, dysregulation of inflammatory response and extracellular matrix organization in the COPD patients. In addition, we identified several novel key-hub genes involved in the COPD pathogenesis using a network analysis method. In summary, our study represents the comprehensive analysis of gene expression on COPD with the largest sample size providing great resource for the molecular research in the COPD community.
Value of biomarkers in the diagnosis of community-acquired pneumonia with concomitant chronic heart failure: a prospective observation study.
Authors: Rachina Svetlana , Bobylev Andrey , Avdeev Sergey , Kozlov Roman , Lazarev Pavel , Mladov Vladimir , Khruleva Yulia 
Published: January 2020

Abstract
Background The diagnosis of community-acquired pneumonia (CAP) in patients with chronic heart failure (CHF) is associated with objective difficulties due to similar clinical presentation. We aimed to evaluate the utility of serum biomarkers - С-reactive protein (CRP), procalcitonin (PCT), tumour necrosis factor α (TNFα), interleukin-6 (IL-6) and brain natriuretic peptide (BNP) in diagnosis of CAP in the presence of СHF.Methods Prospective observational study included patients with previously diagnosed CHF and suspected non-severe CAP. Participants underwent routine procedures and chest multispiral computed tomography (MSCT); serum levels of biomarkers (CRP, PCT, TNFα, IL-6) and BNP were measured. All patients were divided into group 1 with confirmed CAP and group 2 with excluded CAP according to MSCT findings. Standard statistical tools were applied, p-value <0.05 in two-tailed tests was considered statistically significant. The value of biomarkers was determined using logistic regression, their discriminatory efficacy was assessed by analyzing Receiver Operation Characteristic (ROC) curves.Results Altogether 35 with CAP (median age 78 (64-82) years, female 24/35 (68.6%)) and 35 - without CAP (median age 77 (71-82) years, female 22/35 (62.9%)) were enrolled. There were no differences between groups in baseline characteristics, with the exception of body temperature. We found significantly higher levels of CRP 50.0 (35.5-98.5) mg/L, PCT 0.10 (0.05-0.54) ng/mL and IL-6 46.1 (21.4-150.3) pg/mL in group 1 as compared to group 2 - 15.0 (9.5-25.0) mg/L, 0.05 (0.05-0.05) ng/mL and 13,6 (9,5; 25,0) pg/mL, respectively. AUC (95% CI) was the highest for CRP – 0.91 (0.83-0.98), followed by PCT – 0.81 (0.72-0.90) and IL-6 – 0.81 (0.71-0.91). CRP value of 28.5 mg/L had optimal sensitivity and specificity ratio (85.7/91.4%).Conclusion The measurement of serum CRP, PCT, IL-6 levels can be useful for diagnostics of CAP in patients with concomitant CHF. CRP had the optimal diagnostic utility in this population. Key words: community-acquired pneumonia, chronic heart failure, inflammatory biomarkers
Prevalence and risk factors of asymptomatic Neisseria gonorrhoeae and Chlamydia trachomatis infections in Shenzhen, China.
Authors: Chang Shu-Xia , Chen Kang-Kang , Liu Xiao-Ting , Zhang Hao-Yuan , Wu Meng-Man , Zhang Chun-Lai , Ye Jian-Bin , Cai yumao , Yang Wei 
Published: January 2020

Abstract
Objective The aim of this study was to investigate the prevalence and proportion of laboratory-confirmed urethral Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections that were asymptomatic among individuals presenting to different clinics in Shenzhen and the risk factors related to STI infections in this population.Methods In a cross-sectional study, 8,309 eligible individuals were invited to participate in a questionnaire interview, and urine specimens were collected for identification of CT and NG infections. Corresponding outcomes were analyzed by Chi-square test and multivariate logistic regression.Results Among 7070 participants who completed the questionnaire and provided the urine specimen, 2871 were asymptomatic and included in our analyses: 1120 (39.0%) males and 1751 (61.0%) females. The prevalence of NG and CT was 0.9% and 6.2% among males reporting no symptoms, and 0.4% and 7.9% among females reporting no symptoms, respectively. The proportion of asymptomatic urethral CT among males with urethral CT was 28.3%; for females, it was 34.2%. For asymptomatic males with urethral NG/CT, 3 independent risk factors were identified: (1) males under the age of 30 (OR, 1.75; 95% CI, 1.07-2.84); (2) being employed in the commercial service work (2.69; 1.33-5.45); and (3) being recruited through the urological department (2.18; 1.24-3.83). For asymptomatic females with urethral NG/CT, 2 independent risk factors were identified: (1) females under the age of 30 (OR, 1.80; 95% CI, 1.25-2.58); and (2) being recruited through the dermatological department (2.83; 1.46-5.46).Conclusion A substantial prevalence of asymptomatic CT infections was found among males and females presenting to clinics in Shenzhen. The significant correlation between asymptomatic CT infection and these risk factors could help identify high-risk populations and guide screening.
Controversial T1G3 bladder cancer is the key to revealing the changes in the biological functions of bladder cancer cells
Authors: Pan Shen , Zhan Yunhong , Chen Xiaonan , Wu Bin , Liu Bitian 
Published: January 2020

Abstract
Background T1G3 shows a higher chance of recurrence and progression among early bladder cancer types and the available treatment option is controversial. High recurrence and progression are the problems that need to be explored and solved. Changes in the internal signals of bladder cancer cells and differential genes may be the root cause of these problems. Methods GSE120736, GSE19915, GSE19423, GSE32548 and GSE37815 datasets were obtained from Gene Expression Omnibus (GEO ) to identify differentially expressed genes (DEGs). Bladder cancer transcript data from The Cancer Genome Atlas (TCGA) were clustered into different cell-specific gene sets according to weighted gene co-expression network analysis (WGCNA). Multiple sets of databases were used for gene expression comparison, functional enrichment, and protein interaction analysis, including The Human Protein Atlas, Cancer Dependency Map, Metascape, Gene set enrichment analysis, and DisNor. Results DEGs were obtained through GEO data comparison and intersection. After WGCNA was proven to recognise cell-specific gene sets, candidate DEGs were selected and shown to be specifically expressed in cancer cells. Candidate DEGs were related to mitosis and cell cycle. Further, 12 functional candidate markers were identified from the sequencing data of 30 bladder cancer cell lines. These genes were all up-regulated and previously shown to be closely related to bladder cancer progression. Conclusions Twelve functional genes with specific differential expression in bladder cancer cells were identified. WGCNA can identify the relatively specific expression sets of different cells in bladder cancer with greater tumour heterogeneity, which provides new perspectives for future cancer research.
Gender and key population disparities in tuberculosis programs in Cambodia: a situational assessment of the national response
Authors: Yi Siyan , Teo Alvin Kuo Jing , Sok Say , Tuot Sovannary , Tieng Sivanna , Khun Kim Eam , Choub Sok Chamreun , Pheng Sok Heng , Mao Tan Eang 
Published: January 2020

Abstract
Background Globally, the successes in tuberculosis (TB) programs are hampered by the challenges in new case identification, particularly in key and vulnerable populations. Identification of gaps in the programs in response to gender and key population sensitivity is crucial in reaching the un-identified cases. This study aims to define TB key populations, assess gender- and key population-specific issues, and identify successes and gaps in the national TB response in Cambodia.Methods This national assessment was conducted in 2018 through a consultative workshop and a validation workshop with representatives of multi-stakeholder groups, a desk review of documents from all levels of the national health system, and 19 in-depth interviews and 30 focus group discussions with policymakers, service providers, and representatives of key populations. Content analysis was conducted for qualitative interviews.Results We identified seven TB key populations to be prioritized for the national TB programs in Cambodia. Key themes that inhibit access to TB services included the lack of knowledge and awareness, distance to TB clinics, lack of time and financial means, and other systemic barriers such as inconsistencies in policy and guideline implementation at different levels of the health system and lack of financial and human resources required for effective program implementation. We did not find any indications of discriminatory practices against women and key populations. In general, community participation in the national TB response was encouraging. However, there were significant gaps in data and reporting system at all levels, which are required to understand the burden of TB and risk behaviors in genders and key populations.Conclusions Disparities in gender and key populations are well-recognized in Cambodia. Barriers to TB services faced by key populations ought to be addressed through consistent engagements with different stakeholders. Data availability is vital for enhancing the understanding of gender and key population gaps, and the existing data should be duly utilized. Mechanisms to ensure equality and inclusivity are necessary to end TB in Cambodia.
Impact of elastic ankle exoskeleton stiffness on neuromechanics and energetics of human walking across multiple speeds
Authors: Nuckols Richard W. , Sawicki Gregory S. 
Published: January 2020

Abstract
Background: Elastic ankle exoskeletons with springs of intermediate stiffness springs in parallel with the human plantarflexors can reduce the metabolic cost of walking by ~7% at 1.25 m s-1. In a move toward ‘real-world’ application, we examined whether the unpowered approach has metabolic benefit across a range of walking speeds, and if so, whether the optimal exoskeleton stiffness was speed dependent. We hypothesized that there is an ‘optimal’ exoskeleton stiffness for any speed which minimizes the user’s metabolic rate and that the metabolically optimal exoskeleton stiffness will also increase with walking speed. Methods: Eleven participants walked on a level treadmill at 1.25, 1.50, and 1.75 m s-1 while we used a state-of-the-art exoskeleton emulator system to apply bilateral ankle exoskeleton assistance at five controlled rotational stiffnesses (kexo = 0, 50, 100, 150, 250 Nm rad-1). We measured metabolic cost, lower limb joint mechanics, and EMG of muscles crossing the ankle, knee, and hip. Results: We measured significant reductions in metabolic cost at the lowest exoskeleton stiffness (50 Nm rad-1) for assisted walking at both 1.25 (4.2%; p = 0.032) and 1.75 m s-1 (4.7%; p = 0.009). At these speeds, the metabolically optimal ankle exoskeleton stiffness provided peak assistive torques of ~0.20 Nm kg-1 that resulted in reduced biological ankle moment of ~12% and reduced soleus muscle activity of ~10%. We found no spring stiffness that could reduce the metabolic cost of walking at 1.5 m s-1. Across all speeds, the non-weighted sum of soleus and tibialis anterior activation rate explained the change metabolic rate due to exoskeleton assistance (p < .05; R2 > 0.56)). Conclusions: Elastic ankle exoskeletons with low rotational stiffness reduce users’ metabolic cost of walking at slow and fast walking speeds but not at intermediate walking speed. The relationship between the non-weighted sum of soleus and tibialis activation and metabolic cost (R2 > 0.56) indicates that muscle activation may drive metabolic demand. Future work using computer simulations and ultrasound imaging will get ‘under the skin’ and examine the interaction between exoskeleton stiffness and plantarflexor muscle dynamics to better inform stiffness selection in human-machine systems.
Impact of relative dose intensity of FOLFOX adjuvant chemotherapy on risk of death among stage III colon cancer patients
Authors: Zhou Meijiao , Thompson Trevor D. , Lin Hui-Yi , Chen Vivien W. , Karlitz Jordan J. , Fontham Elizabeth T.H. , Theall Katherine P. , Zhang Lu , Pollack Lori A. , Wu Xiao-Cheng 
Published: January 2020

Abstract
Background Clinical trials have indicated high-risk (T4 and/or N2) and low-risk (T1-T3 and N1) stage III colon cancer patients might need different doses of FOLFOX to reserve a similar survival probability. Observational studies have investigated the effect of relative dose intensity (RDI) of FOLFOX on cancer survival for patients with stage III colon cancer, but nonetheless, the studies focused on very specific populations, and none performed stratified analysis by risk profiles. This study aims to identify the optimal RDI of FOLFOX administered for high-risk and low-risk stage III colon cancer patients.Methods Data on 407 eligible patients, diagnosed with stage III colon cancer in 2011 who received FOLFOX, were collected by the eight population-based cancer registries for a CDC National Program of Cancer Registries (NPCR) project focused on Comparative Effectiveness Research. We employed Kaplan-Meier method, cumulative incidence function (CIF), Multivariable Cox model and Fine-Gray competing risks model to explore Optimal Relative Dose Intensity (RDI) defined as the lowest RDI administered without significant differences in either overall or cause-specific death.Results Among the 168 high-risk patients, the optimal RDI cut-off point was 70% where there was no statistically significant difference in overall mortality (HR=1.87; 95% CI: 0.84-4.19) and cause-specific mortality (HR=1.72; 95% CI: 0.61-4.85) when RDI<70% vs. RDI≥70%, adjusting for sociodemographic and clinical covariates. When the RDI cut-off was lower than the optimal one (<55% vs. ≥55%, <60% vs. ≥60%, or <65% vs. ≥65%), the overall and cause-specific mortalities were significantly statistically different between the two groups of each comparison. Among the 239 low-risk patients, none of the evaluated cut-offs were associated with statistically significant differences in overall and cause-specific mortalities between comparison groups. The lowest RDI we assessed was 45%, HR=0.79; 95% CI: 0.23-2.67 for the overall mortality and HR=0.49; 95% CI: 0.05-4.84 for the cause-specific mortality, when RDI<45% vs. RDI≥45%.Conclusions To best utilize health care resources while maintaining efficacy, RDI can be maintained at a minimum of 70% in high-risk stage III colon cancer patients. For low-risk patients, we found that RDI as low as 45% did not impact risk of death.
The Prognostic Value of Risk Score Based on Immunogenenomic Landscape Analysis in Glioma
Authors: Luo Haitao , Huang Kai , Tao Chuming , Wu Mioaojing , Ye Minhua , Lv Shigang , Zhu Xingen 
Published: January 2020

Abstract
Background: Glioma is a lethal intracranial tumor, and inflammation plays an important role in the initiation and development of glioma. Hence, there is an urgent need to conduct a bioinformatics analysis of immune-related genes (IRGs) for glioma. The present study aims to explore the association of the risk score with clinical outcomes and predict the prognosis with glioma. Methods: In The Cancer Genome Atlas (TCGA) database, 462 low grade glioma (LGG) samples and 166 glioblastoma (GBM) samples were reviewed, and IRGs correlated with the prognosis were selected by performing a survival analysis and establishing a Cox regression model. The potential molecular mechanism of these IRGs were also explored with assistance of computational biology. The risk score based on seven survival-associated IRGs was determined with the help of the multivariable Cox analysis, the patients were divided into two subgroups according to their risk score. Results: It was found that these differentially expressed IRGs were involved with the cytokine-cytokine receptor through functional enrichment analysis. The risk score based on the seven IRGs (SSTR5、CXCL10、CCL13、SAA1、CCL21、CCL27 and HTR1A) performed well in predicting patient’s the overall survival (OS), and correlated with age, 1p/19q codeletion status, IDH status, and WHO grades, both in the training (TCGA) datasets and the validation ((Chinese Glioma Genome Atlas) CGGA) datasets. The risk score also could reflect infiltration through several types of immune cells. Conclusions: This present study screened some IRGs associated with the patient’s clinical characteristic and prognosis, connect to the immune repertoire, demonstrated the importance of the risk score as a promising biomarker for estimating the clinical prognosis of glioma.
Correlation between detergent activity and anti-herpes simplex virus-2 activity of commercially available vaginal gels
Authors: Szőllősi Andrea , Raffai Tímea , Bogdanov Anita , Endrész Valéria , Párducz László , Somogyvári Ferenc , Janovák László , Burián Katalin , Virok Dezső Peter 
Published: January 2020

Abstract
Objective Herpes simplex virus-2 (HSV-2) infections are almost exclusively sexually transmitted. The presence of vaginal gels during the sexual activity may have a significant positive or negative impact on the viral transmission. Therefore we investigated three off-the-shelf vaginal lubricants and one pH restoring gel to evaluate their impact on HSV-2 growth. Results HeLa cells were infected with untreated virions and virions incubated with the particular gels. The accumulation of viral genomes was monitored by quantitative PCR (qPCR) method at 24 hours post infection. Two of the tested gels had no significant effect on HSV-2 growth at the maximum applied concentration, while two had a strong inhibitory effect (~ 98% growth reduction). The growth inhibitory effect was observed at various multiplicity of infection (MOI 0.4-6.4) and the two inhibitory gels were also capable of inhibiting the HSV-2 induced cytopathic effect on HeLa cells. The surface tension decreasing activity - a sign of detergent activity - was strongly correlated with the anti-HSV-2 activity of the gels (R2: 0.88). Our results indicate that off-the-shelf vaginal gels have a markedly different anti-HSV-2 activity that may influence HSV-2 transmission.