bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene network in pulmonary tuberculosis based on bioinformatic analysis
Authors: Li Lili , Lv Jian , He Yuan , Wang Zhihua 
Published: February 2020

Abstract
Background: Pulmonary tuberculosis (PTB) is one of the serious infectious diseases worldwide; however, the gene network involved in the host response remain largely unclear. Methods: This study integrated two cohorts profile datasets GSE34608 and GSE83456 to elucidate the potential gene network and signaling pathways in PTB. Differentially expressed genes (DEGs) were obtained for Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis using Metascape database. Protein-Protein Interaction (PPI) network of DEGs was constructed by the online database the Search Tool for the Retrieval of Interacting Genes (STRING). Modules were identified by the plug-in APP Molecular Complex Detection (MCODE) in Cytoscape. GO and KEGG pathway of Module 1 were further analyzed by STRING. Hub genes were selected for further expression validation in dataset GSE19439. The gene expression level was also investigated in the dataset GSE31348 to display the change pattern during the PTB treatment. Results: Totally, 180 shared DEGs were identified from two datasets. Gene function and KEGG pathway enrichment revealed that DEGs mainly enriched in defense response to other organism, response to bacterium, myeloid leukocyte activation, cytokine production, etc. Seven modules were clustered based on PPI network. Module 1 contained 35 genes related to cytokine associated functions, among which 14 genes, including chemokine receptors, interferon-induced proteins and Toll-like receptors, were identified as hub genes. Expression levels of the hub genes were validated with a third dataset GSE19439. The signature of this core gene network showed significant response to Mycobacterium tuberculosis (Mtb) infection, and correlated with the gene network pattern during anti-PTB therapy. Conclusions: Our study unveils the coordination of causal genes during PTB infection, and provides a promising gene panel for PTB diagnosis. As major regulators of the host immune response to Mtb infection, the 14 hub genes are also potential molecular targets for developing PTB drugs.
Molecular epidemiology and clinical characteristics of hepatitis delta virus (HDV) infected patients with elevated transaminases in Shanghai, China
Authors: Wu Shanshan , Zhang Yi , Tang Yuyan , Yao Ting , Lv Mengjiao , Tang Zhenghao , Zang Guoqing , Yu Yongsheng , Chen Xiaohua 
Published: February 2020

Abstract
Background: Patients coinfected with HBV and hepatitis D virus (HDV) have a greater risk of HCC and cirrhosis. The current study was undertaken to assess HDV genotype distribution and determine clinical characteristics of hepatitis delta virus (HDV) among HBsAg positive individuals in Shanghai.Method: This retrospective study involved 225 serum samples from HBsAg positive hospitalized patients from October 2010 to April 2013. HDV-specific RT-nested PCR was used to amplify HDV RNA. HDV genotypes were characterized by Next-generation sequencing (NGS), followed by phylogenetic analyses. HDV/HBV co-infected patients and HBV mono-infected patients were compared clinically and virologically.Results: Out of the 225 HBsAg-positive serum samples with elevated transaminases, HDV-RNA was identified in 11 (4.9%) HBsAg positive patients. The HBV loads in the HDV positive group were significantly lower than the HDV negative HBV-infected patients. The aminotransferase enzymes were significantly higher in HDV/HBV co-infected compared to HDV negative patients (P<0.05). Phylogenetic analyses indicated that HDV-2 genotype being the predominant genotype, other HDV genotypes were not observed. HDV/HBV patients were significantly associated with a rather unfavourable clinical outcomeConclusion： In summary, our study showed that the prevalence of HDV infection in patients with elevated transaminases is not low and the predominance of HDV genotype 2 infection in Shanghai. This finding helps us to better understand the correlation of HDV/HBV co-infection. Moreover, Next-generation sequencing (NGS) technologies provide a rapid, precise method for generating HDV genomes to define infecting genotypes.
Do I Lose Cognitive Function as Fast as my Twin Partner? Analyses Based on Classes of MMSE Trajectories of Twins Aged 80 and older
Authors: Muniz-Terrera Graciela , Robitaille Annie , Goerdten Jantje , Massa Fernando , Johansson Boo 
Published: February 2020

Abstract
Background: Aging is associated with an increasing risk of decline in cognitive abilities. The decline is, however, not a homogeneous process. There are substantial differences across individuals although previous investigations have identified individuals with distinct cognitive trajectories. Evidence is accumulating that lifestyle contributes significantly to the classification of individuals into various clusters. How and whether genetically related individuals, like twins, change in a more similar manner is yet not fully understood. Methods: In this study, we fitted growth mixture models to Mini Mental State Exam scores (MMSE) from participants of the Swedish OCTO Twin study of oldest old monozygotic (MZ) and same-sex dizygotic (DZ) twins with the purpose of investigating whether twin pairs can be assigned to the same class of cognitive change. Results: We identified 4 distinct groups (latent classes) whose MMSE trajectories followed various patterns of change over time: a class of stable and high performing individuals, two groups of high performers who declined at different annual rates, and a small group of impaired individuals who declined more rapidly. Notably, our analyses show that few individuals in fact could be assigned to the same class as their co-twin. Conclusions: Our study provides evidence for more substantial impact of environmental, rather than genetic, influences on cognitive change trajectories in later life.
Predictors of physical activity in older adults experiencing an emergency hospital admission: a prospective cohort study
Authors: Hartley Peter , Dewitt Amanda L , Forsyth Faye , Romero-Ortuno Roman , Deaton Christi 
Published: February 2020

Abstract
BackgroundReduced mobility may be responsible for functional decline and acute sarcopenia in older hospitalised patients. The drivers of reduced in-hospital mobility are poorly understood, especially during the early phase of acute hospitalisation. We investigated predictors of in-hospital activity during the first 24 hours of hospital admission in older adults. MethodsThis was a secondary analysis of a prospective repeated measures cohort study. Participants aged 75 years or older were recruited within the first 24 hours of admission. At recruitment, patients underwent a baseline assessment including measurements of pre-morbid functional mobility, cognition, frailty, falls efficacy, co-morbidity, acute illness severity, knee extension strength and grip strength, and consented to wear accelerometers to measure physical activity during the first 7 days (or until discharge if earlier). In-hospital physical activity was defined as the amount of upright time (standing or walking). To examine the predictors of physical activity, we used a best subset analysis including all baseline measures. The optimal model was defined by having the lowest Bayesian information criterion in the best-subset analyses. The model specified a maximum of 5 covariates and used an exhaustive search.ResultsSeventy participants were recruited but eight were excluded from the final analysis due to lack of accelerometer data within the first 24 hours after recruitment. Patients spent a median of 0.50 hours (IQR: 0.21; 1.43) standing or walking. The optimal model selected the following covariates: functional mobility as measured by the de Morton Mobility Index and two measures of illness severity, the National Early Warning Score, and serum C-reactive protein.ConclusionsPhysical activity, particularly in the acute phase of hospitalisation, is very low in older adults. The association between illness severity and physical activity may be explained by symptoms of acute illness being barriers to activity. Interdisciplinary approaches are required to identify early mobilisation opportunities.
Cardiovascular and all-cause mortality attributable to loneliness in older Swedish men and women
Authors: Novak Masuma , waern Margda , Johansson Lena , Zettergren Anna , Ryden Lina , Wetterberg Hanna , Gudmundsson Pia , Skoog Ingmar 
Published: February 2020

Abstract
Background. This study examined whether loneliness predicts cardiovascular- and all-cause mortality in older men and women. Methods. Baseline data from the Gothenburg H70 Birth Cohort Studies, collected during 2000 on 70-year-olds born 1930 and living in Gothenburg were used for analysis (n=524). Mortality data was analyzed until 2012 through Swedish national registers. Results. Perceived loneliness was reported by 17.1% of the men and 30.9% of the women in a face-to-face interview with mental health professional. A total of 142 participants died during the 12-year follow-up period, with 5 334 person-years at risk, corresponding to 26.6 deaths/1000 person-years. Cardiovascular disease accounted for 59.2% of all deaths. The cumulative rates/1000 person-years for cardiovascular mortality were 20.8 (men) and 11.5 (women), and for all-cause mortality 33.8 (men) and 20.5 (women), respectively. In Cox regression models, no significant increased risk of mortality was seen for men with loneliness compared to men without loneliness (cardiovascular mortality HR 1.52, 95% CI 0.78 - 2.96; all-cause HR 1.32, 95% CI 0.77 - 2.28). Increased risk of cardiovascular mortality was observed in women with loneliness compared to those without (HR 2.25 95% CI 1.14 - 4.45), and the risk remained significant in a multivariable-adjusted model (HR 2.42 95% CI 1.04 - 5.65). Conclusions. Loneliness was shown to be an independent predictor of cardiovascular mortality in women. We found no evidence to indicate that loneliness was associated with an increased risk of either cardiovascular- or all-cause mortality in men.
What Lies Beneath: Clinical and Resource-use Characteristics of Institutionalized Older People. A Retrospective, Population-based Cohort Study in Catalonia
Authors: Amblàs-Novellas Jordi , Gonzàlez Sebastià J. Santaeugènia , Vela Emili , Clèries Montse , Contel Joan C. 
Published: February 2020

Abstract
BackgroundPlanning population care in a specific health care setting requires deep knowledge of the clinical characteristics of the target care recipients, which tend to be country specific. Our area virtually lacks any descriptive, far-reaching publications about institutionalized older people (IOP). We aimed to investigate the demographic and clinical characteristics of institutionalized older people (IOP) ≥65 years old and compare them with those of the rest of the population of the same age.MethodsRetrospective analysis (total cohort approach) of clinical and resource-use characteristics of IOP and non-IOP older than 65 years in Catalonia (North-East Spain). Variables analysed included age and sex, diagnoses, morbidity burden—using Adjusted Morbidity Groups (GMA)—, mortality, use of resources, and medications taken. All data were obtained from the administrative database of the local healthcare system.ResultsThis study included 93,038, 78,458, 68,545 and 67,456 IOP from 2011, 2013, 2015 and 2017, respectively. In this interval, an increase in mean age (82.02 vs. 85.95 years), in women (68.64% vs. 72.11%) and in annual mortality (11.74% vs. 20.46%) was observed. Compared with non-IOP (p<0.001 in all comparisons), IOP showed a higher annual mortality (20.46% vs. 3.13%), a larger number of chronic diseases (specially dementia: 46.47% vs. 4.58%), higher multimorbidity (15.2% vs. 4.2% with GMA of maximum complexity), and annual admissions to acute care (47.6% vs. 27.7%) and skilled nursing facilities (27.8% vs. 7.4%), mean length of hospital stay (10.0 vs. 7.2 days) and mean of medications taken (11.7 vs. 8.0). ConclusionsThere is a growing gap between the clinical and demographic characteristics of age-matched IOP and non-IOP, which overlaps with a higher mortality rate of IOP. The profile of resources utilization of IOP compared with non-IOP strongly suggests a deficiency of preventive actions and stresses the need to rethink the care model for IOP from a social and health care perspective.
Efficacy and biomarker analysis of nivolumab plus gemcitabine and cisplatin in patients with unresectable or metastatic biliary tract cancers: results from a phase II study
Authors: Feng Kaichao , Liu Yang , Zhao Yongtian , Yang Qingming , Dong Liang , Liu Jiejie , Li Xiang , Zhao Zhikun , Mei Qian , Han Weidong 
Published: February 2020

Abstract

Background: The prognosis of patients with unresectable or metastatic biliary tract cancer (BTC) is unacceptable low. This study aimed to determine the efficacy, safety and predicting biomarkers of immune checkpoint inhibitor nivolumab in combination with chemotherapy in advanced BTCs.Methods: In this open-label, single-arm, phase Ⅱ trial, chemo-immunology combination therapy consisting of gemcitabine 1000mg/m2, cisplatin 75mg/m2 plus nivolumab 3mg/kg was administered every 3 weeks for up to 6 cycles. Maintenance treatment with gemcitabine plus nivolumab was administered to patients achieving disease control following the combination therapy. The primary outcome was objective response rate (ORR). Secondary outcomes included safety, disease control rate (DCR), progression free survival (PFS) and overall survival (OS). The exploratory objectives were to assess biomarkers for predicting clinical response and prognosis.Results: 32 patients with a median age of 60 (range 27-69) years were enrolled. As of September 31, 2019, the median follow-up was 12.8 (95% CI, 10.8-14.8) months. 27 response-evaluable patients received a median of 4 (IQR, 3-6) cycles combination therapy, of which 15 (55.6%) patients achieved objective response, including 5 (18.6%)with complete response (CR), and the DCR was 92.6%. 2 of 6 patients in cohort A who were refractory to gemcitabine or cisplatin-based chemotherapy achieved 1 CR and 1 partial response. 13 of 21 chemotherapy-naive patients (61.9%) in cohort B achieved objective response. The median PFS of all patients in cohort A+B was 6.1 months. The median OS was 8.5 months with 33.3% 12-month OS rate. The most frequent grade 3 or higher adverse events were thrombocytopenia (56%), and neutropenia (22%). Fitness might be a biomarker for predicting clinical response. On-therapy change of serum sFASL, MCP-1 and IFN-γ were correlated with prognosis.Conclusions: Nivolumab in combination with gemcitabine and cisplatin offer promising efficacy and manageable safety profile for patients with advanced BTCs.
Tobacco exposure as a major modifier of oncologic outcomes in Human PapillomaVirus (HPV) associated oropharyngeal squamous cell carcinoma
Authors: Elhalawani Hesham , Mo Abdallah S.R. , Elgohari Baher , Lin Timothy A. , Sikora Andrew G. , Lai Stephen Y. , Phan Jack , Morrison William H. , Gunn G. Brandon , Rosenthal David I. , Garden Adam S. , Fuller Clifton D. , Sandulache Vlad C. 
Published: February 2020

Abstract
Background

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) in the US is rapidly increasing, driven largely by the epidemic of human papillomavirus (HPV)-mediated OPSCC. Although survival for patients with HPV mediated OPSCC (HPV+ OPSCC) is generally better than that of patients with non-viral HPV+ OPSCC, the improvement is not uniform. We hypothesized that tobacco exposure remains a critical modifier of survival for HPV+ OPSCC patients.

Methods

We conducted a retrospective analysis of 611 OPSCC patients with concordant p16 and HPV testing treated at a single institute (2002-2013). Survival analysis was performed using Kaplan-Meier analysis and Cox regression. Recursive partitioning analysis (RPA) was used to define tobacco exposure associated with survival (p<0.05).

Results

Tobacco exposure impacted overall survival (OS) for HPV+ patients on univariate and multivariate analysis (p=0.002, p=0.003 respectively). RPA identified 30 pack-years (PY) as a threshold at which survival became significantly worse in HPV+ patients. OS and disease-free survival (DFS) for HPV+ >30 PY patients didn’t differ significantly from HPV- group (p= 0.72, p= 0.27, respectively). HPV+ >30 PY patients had substantially lower 5-year OS when compared to their ≤30 PYs counterparts: 78.4% vs 91.6%; p= 0.03, 76% vs 88.3%; p= 0.07, and 52.3% vs 74%; p= 0.05, for stages I, II, and III (AJCC 8th Edition Manual), respectively.

Conclusions

Tobacco exposure can eliminate the survival benefit associated with HPV+ status in OPSCC patients. Until this effect can be clearly quantified using prospective datasets, de-escalation of treatment for HPV+OPSCC smokers should be avoided.
Diagnostic and prognostic performance of circulating levels of the Epstein-Barr virus microRNAs BART 7-3p and BART 13-3p in nasopharyngeal carcinoma
Authors: Lu Tianzhu , Guo Qiaojuan , Lin Keyu , Chen Honglin , Chen Yixin , Xu Yuanji , Lin Cheng , Su Ying , Chen Yan , Chen Mengyuan , Zheng Yuhong , Ye Yunbin , Lin Shaojun , Zong Jingfeng , Pan Jianji 
Published: February 2020

Abstract
Background Nasopharyngeal carcinoma (NPC) is closely associated with Epstein-Barr virus (EBV) infection. EBV BamHI A rightward transcripts (BART) encode microRNAs (EBV-miR-BARTs) abnormally highly expressed and play an essential role in NPC. Our previous study indicated that circulating EBV-miR-BARTs was potentially severed as a biomarker of NPC. This study aims to investigate the diagnostic and prognostic performance of miR-BART7-3p and miR-BART13-3p. Methods Plasma levels of EBV DNA, miR-BART7-3p, and miR-BART13-3p were examined by quantitative PCR in 483 treatment-naïve NPC patients and 243 controls without NPC. The prognostic performance was examined by comparing plasma levels with rates of distant metastasis during follow-up. Results Plasma EBV DNA was detected in 93.7% of NPC subjects vs. 8.6% of controls. The microRNAs BART7-3p and miR-BART13-3p were detected in 96.1% and 97.9% of NPC subjects vs. 3.39% and 3.3% of controls. The area under the receiver operating characteristic curve for diagnosing NPC was 0.926 for EBV DNA, 0.964 for miR-BART7-3p, 0.973 for miR-BART13-3p, and 0.997 for all three indices. Among 465 NPC patients without distant metastasis, the above-median miR-BART7-3p and EBV-DNA were independent risk for shorter distant metastasis-free survival (DMFS) (HR=2.94, 95%CI: 1.44-5.97, p=0.003; HR=2.27, 95%CI:1.26-4.10, p=0.006) in multivariate Cox regression. In the 245 patients who received radiotherapy, EBV DNA, miR-BART7-3p, and miR-BART13-3p were detectable immediately afterward in, respectively, 28.6%, 17.6%, and 54.7% of patients. Four-year DMFS rate was lower in patients with detectable miR-BART7-3p (73.0% vs. 89.7%, p<0.001), miR-BART13-3p (61.4% vs. 90.0%, p<0.001), and EBV-DNA (82.7% vs. 89.5%, p=0.035) after radiotherapy. In multivariate Cox regression, detectable miR-BART7-3p and EBV-DNA were independent risks for shorter DMFS (HR=4.13, 95%CI: 1.89-9.01, p<0.001; HR = 2.14, 95%CI: 1.04-4.42, p=0.039). Four-years DMFS rate was 92.0% in subjects (n=156) with neither detectable miR-BART7-3p nor EBV-DNA after radiotherapy, 80.0% in subjects (n=65) with either detectable miR-BART7-3p or EBV-DNA after radiotherapy, and 52.9% in subjects (n=24) with both detectable miR-BART7-3p and EBV-DNA after radiotherapy (p<0.001). Conclusions Circulating levels of miR-BART7-3p and miR-BART13-3p show excellent diagnostic performance for NPC. The combination of plasma levels of miR-BART7-3p and EBV DNA at diagnosis and after radiotherapy may help stratify patients by risk of poor DMFS.
Molecular Determinant s Elucidate the Selectivity in Abscisic acid Receptor and HAB1 Protein Interactions
Authors: Yang Jing-Fang , Yin Chun-Yan , Wang Di , Jia Chen-Yang , Hao Ge-Fei , Yang Guang-Fu 
Published: February 2020

Abstract
The abscisic acid (ABA), as a pivotal plant hormone, plays a key role in controlling the life cycle and adapting to the environmental stresses. The receptors of ABA are the Pyrabactin Resistance /Pyrabactin Resistance -Like/Regulatory Component of ABA Receptors (PYR/PYL/RCAR, PYLs for simplicity), which regulate the Protein Phosphatase 2Cs (PP2Cs) in the signal pathway. As an important ABA mimicking ligand, Pyrabactin shows the activation function to parts of members of PYLs, such as PYR1 and PYL1. Due to the antagonism of Pyrabactin to PYL2, it was used as a probe to discover a part of ABA receptors. Since then, many researchers have been trying to find out the determinants of the selective regulation of PYLs and PP2Cs interaction. However, the roles of residues on the selective regulation of PYR1/PYL2 and PP2Cs interaction induced by Pyrabactin are still ambiguous. This research investigated the selective activation mechanism of Pyrabactin through the sequence alignment, molecular docking, molecular dynamics simulation, and binding free energy calculation. Furthermore, the electrostatic and hydrophobic interaction differences induced by Pyrabactin and agonists were compared. The results indicate that Leu137/Val114, Ser85/Ser89, and Gly86/Gly90 from the pocket and gate of PYR1/PYL2 are the vital residues for the selective activation of Pyrabactin. Meanwhile, the electrostatic interaction between PP2Cs and PYLs complexed with agonists was improved. This mechanism provides strong support for the design of selective agonists and antagonists.
SYBA: Bayesian estimation of synthetic accessibility of organic compounds
Authors: Voršilák Milan , Kolář Michal , Čmelo Ivan , Svozil Daniel 
Published: February 2020

Abstract
SYBA (SYnthetic Bayesian Accessibility) is a fragment based method for the rapid classification of organic compounds as easy- (ES) or hard-to-synthesize (HS). SYBA is based on the Bayesian analysis of the frequency of molecular fragments in the database of ES and HS molecules. It was trained on ES molecules available in the ZINC15 database and on HS molecules generated by the Nonpher methodology. SYBA was compared with a random forest, that was utilized as a baseline method, as well as with other two methods for synthetic accessibility assessment: SAScore and SCScore. When used with their suggested thresholds, SYBA improves over random forest classification, albeit marginally, and outperforms SAScore and SCScore. However, with thresholds optimized by the analysis of ROC curves, SAScore improves considerably and yields similar results as SYBA. Because SYBA is based merely on fragment contributions, it can be used for the analysis of the contribution of individual molecular parts to compound synthetic accessibility. Though SYBA was developed to quickly assess compound synthetic accessibility, its underlying Bayesian framework is a general approach that can be applied to any binary classification problem. Therefore, SYBA can be easily re-trained to classify compounds by other physico-chemical or biological properties. SYBA is publicly available at https://github.com/lich-uct/syba under the GNU General Public License.