bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated analysis of the proteome and transcriptome in human ischemic cardiomyopathy
Authors: Zhang Kai , Qin Xianyu , Wu Min , Wen Pengju , Wu Yueheng , Zhuang Jian 
Published: November 2020

Abstract
Background: Ischemic cardiomyopathy (ICM) is the primary cause of heart failure, which leads to an unacceptable rate of mortality and morbidity. The molecular mechanisms involved in ICM remains incompletely understood. This study aimed to investigate the molecular mechanisms of ICM by integrated proteome and transcriptome analyses.Methods and Results: Data independent acquisition (DIA) mass spectrometry and RNA-seq technologies were performed in left ventricular species from 5 ICM patients and 5 unused non-failing donors. A total of 546 differentially expressed proteins (DEPs) and 1080 mRNAs (DEGs) were identified in ICM compared with control, which were mainly involved in inflammatory/immune response, response to stress (such as hypoxia and reactive oxidative species), oxidative stress, and ECM (extracellular matrix) organization. Moreover, though the low correlation between transcriptome and proteome, 41 key genes were identified, which showed the same expression directions at mRNA and protein levels. Among them, HSP90AA1 occupied a central position in the PPI network. Furthermore, a differentially expressed lncRNA-mRNA-protein network was constructed, which consisted of 13, 11, and 11 differentially expressed lncRNAs, mRNAs, and proteins, respectively, and the expression of this network were validated by qRT-PCR.Conclusion: This identified some key genes and a lncRNA-mRNA-protein regulatory network involved in ICM, which should provide a framework for an in-depth interrogation into the complex molecular mechanisms of ICM.
Identification of a novel metabolism‑related prognostic signature in hepatocellular carcinoma through bioinformatics analysis and validation through experimental studies
Authors: Wang Zhihao , Embaye Kidane Siele , Yang Qing , Qin Lingzhi Qin , Zhang Chao , Liu Liwei , Zhan Xiaoqian , Zhang Fengdi , Wang Xi , Qin Shenghui 
Published: November 2020

Abstract
BackgroundGiven that metabolic reprogramming has been recognized as an essential hallmark of cancer cells, this study sought to investigate the potential prognostic values of metabolism-related genes(MRGs) for hepatocellular carcinoma (HCC) diagnosis and treatment.MethodsThe metabolism-related genes sequencing data of HCC samples with clinical information were obtained from the International Cancer Genome Consortium(ICGC) and The Cancer Genome Atlas (TCGA). The differentially expressed MRGs were identified by Wilcoxon rank sum test. Then, univariate Cox regression analysis were performed to identify metabolism-related DEGs that related to overall survival(OS) . A novel metabolism-related prognostic signature was developed using the least absolute shrinkage and selection operator (Lasso) and multivariate Cox regression analyses . Furthermore, the signature was validated in the TCGA dataset. Finally, the expression levels of hub genes were validated in cell lines by Western blotting (WB) and quantitative real-timePCR (qRT-PCR).ResultsA total of 178 differentially expressed MRGs were detected between the ICGA dataset and the TCGA dataset. We found that 17 MRGs were most significantly associated with OS by using the univariate Cox proportional hazards regression analysis in HCC. Then, the Lasso and multivariate Cox regression analyses were applied to construct the novel metabolism-relevant prognostic signature, which consisted of six MRGs. The prognostic value of this prognostic model was further successfully validated in the TCGA dataset. Further analysis indicated that this signature could be an independent prognostic indicator after adjusting to other clinical factors. Six MRGs (FLVCR1, MOGAT2, SLC5A11, RRM2, COX7B2, and SCN4A) showed high prognostic performance in predicting HCC outcomes. Finally, hub genes were chosen for validation and the expression of FLVCR1, SLC5A11, and RRM2 were significantly increased in human hepatocellular carcinoma cell lines when compared to normal human hepatic cell line, which were in agreement with the results of differential expression analysis.ConclusionsIn summary, our data provided evidence that the metabolism-based signature could serve as a reliable prognostic and predictive tool for overall survival in patients with HCC.
Prognostic value of immune-related genes and comparative analysis of immune cell infiltration in lung adenocarcinoma of different genders
Authors: Fan Tao , Li Chunxiang , He Jie 
Published: November 2020

Abstract
Background

Lung adenocarcinoma (LUAD) is one of the most important subtypes of lung cancer. Compared with male LUAD patients, female patients have a higher incidence, but better long-term survival rate, with unknown reasons. In this study, we aimed to explore the effect of gender on immune cell infiltration of LUAD tumor microenvironment (TME), and tried to clarify the reasons for the different clinical characteristics of male and female LUAD patients, by conducting a comparative analysis of the TME in female and male LUAD patients.
Methods

We calculated immune and stromal scores of LUAD patients samples from The Cancer Genome Atlas (TCGA) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted to reveal biological processes of intersecting genes. Cox regression analysis and protein-protein interaction (PPI) network analysis were conducted to screen immune-related prognostic genes in female (CCR2, LCP2, and PTPRC) and male (BTK and CCR2) patients. Kaplan-Meier survival analysis was used to evaluate prognostic value of identified genes. Mann-Whitney test was used to compare various indicators of male patients and female patients. The main result was subsequently validated in 420 cases from GSE72094.
Results

304 and 368 intersecting genes were identified in female and male patients respectively. The immune score is ranged from − 943.17 to 3229.35 among female patients with LUAD and from − 541.75 to 3441.78 among male patients with LUAD. The stromal score is ranged from − 1790.23 to 2097.27 among female patients and from − 1786.94 to 1722.70 among male patients. The immune and stromal scores of women were higher than those of men (P < 0.05). CCR2, LCP2 and PTPRC were identified as the most important immune-related prognostic genes in women. BTK and CCR2 were identified as the most important immune-related prognostic genes in men. Female patients had a higher proportion of memory B cells than that of male patients, while the percentage of T cells CD4 naïve and resting NK cells was lower in female patients (P < 0.05).
Conclusions

This study compared the differences in TIICs in the TME of male and female LUAD patients, and identified prognosis-related genes for patients of different genders.
Overexpressed WDR3 Induces the Activation of Hippo Pathway by Interacting with GATA4 in Pancreatic Cancer
Authors: Su Wenjie , Zhu Shikai , Chen Kai , Yang Hongji , Tian Mingwu , Fu Qiang , Shi Ganggang , Feng Shijian , Ren Dianyun , Jin Xin , Yang Chong 
Published: November 2020

Abstract
Background: WD repeat domain 3 (WDR3) is involved in a variety of cellular processes including gene regulation, cell cycle progression, signal transduction and apoptosis. However, the biological role of WDR3 in pancreatic cancer and the associated mechanism remains unclear. We seek to explore the immune-independent functions and relevant mechanism for WDR3 in pancreatic cancer.Methods: The GEPIA web tool was searched, and IHC assays were conducted to determine the mRNA and protein expression levels of WDR3 in pancreatic cancer patients. MTS, colony formation, and transwell assays were conducted to determine the biological role of WDR3 in human cancer. Western blot analysis, RT-qPCR, and immunohistochemistry were used to detect the expression of specific genes. An immunoprecipitation assay was used to explore protein-protein interactions.Results: Our study proved that overexpressed WDR3 was correlated with poor survival in pancreatic cancer and that WDR3 silencing significantly inhibited the proliferation, invasion and tumor growth of pancreatic cancer. Furthermore, WDR3 activated the Hippo signaling pathway by inducing yes association protein 1 (YAP1) expression, and the combination of WDR3 silencing and administration of the YAP1 inhibitor TED-347 had a synergistic inhibitory effect on the progression of pancreatic cancer. Finally, the upregulation of YAP1 expression induced by WDR3 was dependent on an interaction with GATA binding protein 4 (GATA4), the transcription factor of YAP1, in pancreatic cancer cells.Conclusions: We identified a novel mechanism by which WDR3 plays a critical role in promoting pancreatic cancer progression by activating the Hippo signaling pathway through an interaction with GATA4. Therefore, WDR3 is potentially a therapeutic target for pancreatic cancer treatment.
Gut Microbiome of the Amazon Master of the Grasses Harbors Unprecedented Enzymatic Strategies for Plant Glycans Breakdown
Authors: Cabral Lucelia , Persinoti Gabriela F , Paixao Douglas A , Martins Marcele P , Chinaglia Mariana , Domingues Mariane N , Morais Mariana AB , Sforca Mauricio L , Pirolla Renan A. S. , Generoso Wesley C , Santos Clelton A , Maciel Lucas F , terrapon Nicolas , Lombard Vincent , Henrissat Bernard , Murakami Mario 
Published: November 2020

Abstract
BackgroundPlant biomass is a promising feedstock to replace fossil-based products including fuels, chemicals and materials. However, the high resistance of plant biomass to either physicochemical or biological deconstruction has been hampering its broad industrial utilization and, consequently, the transition to a sustainable bioeconomy. The gut system from herbivores are formidable bioreactors in nature for lignocellulose breakdown and the diverse ecological niches where herbivores are found have led to the rise of a myriad of molecular strategies to cope with the sheer complexity of plant polysaccharides. This study illuminates how the unexplored microbiota of the largest living rodent, capybara, found in Pantanal wetlands and the Amazon basin, can efficiently depolymerize and utilize lignocellulosic biomass. ResultsHere, we have elucidated the gut microbial structure and composition of the semiaquatic herbivorous capybara through multi-omics approaches. Metabolic reconstruction of this microbiota showed that cellulose degradation is chiefly performed by Fibrobacter bacteria, whereas hemicelluloses and pectins are processed by a broad arsenal of Carbohydrate-Active enZymes (CAZymes) organized in polysaccharide utilization loci (PULs) identified in multiple metagenome-assembled genomes from the phylum Bacteroidetes. Furthermore, metabolomics analysis showed short chain fatty acids as major fermentation products, which are key markers of digestion performance of plant polysaccharides. Exploring the genomic dark matter of this gut microbial community, two novel CAZymes families were unveiled including a glycoside hydrolase family of β-galactosidases and a carbohydrate-binding module family involved in xylan binding that establishes an unprecedented three-dimensional fold among associated modules to CAZymes. ConclusionsOur results unveil how the capybara gut microbiota orchestrates the depolymerization and utilization of dietary plant polysaccharides, representing an untapped reservoir of new and intricate enzymatic strategies to overcome the recalcitrance of plant polysaccharides, a central challenge toward a circular and sustainable economy.
Vairimorpha Ceranae Alters Honey Bee Microbiota Composition and Sustain the Survival of Adult Honey Bees
Authors: Zhang Yakun , Su Meiling , Wang Lon , Huang Shaokang , Su Songkun , HUANG WEI-FONE 
Published: November 2020

Abstract
Background: Vairimorpha (Nosema) ceranae is the most common eukaryotic gut pathogen in honey bees, Apis mellifera. Infection is typically chronic but may result in mortality. Additional factors may be involved in mortality, including the honey bee gut microbiota. Previous studies of V. ceranae and gut microbiota identified positive associations between core bacteria and V. ceranae infection. These possibly synergistic or mutualistic associations are often disregarded because some core bacteria act as probiotic symbionts. Methods: To clarify the effects caused by the positive associations, we added isomaltooligosaccharide (IMO), a prebiotic also found in honey, to alter the interactions between V. ceranae and gut bacteria. Mortality and sugar consumption of the caged bees were monitored. Infection intensities and gut bacteria were examed after 12 days post inoculation, the plateau phase of infection. The gut bacteria were evaluated using both qPCR and 16S rDNA sequencing.Results: We confirmed that V. ceranae infections alone significantly enhance several core bacterial populations, including Bifidobacterium spp., Snodgrassella alvi, and Gilliamella apicola in the honey bee hindgut microbiota. Moreover, the qPCR results suggested that V. ceranae infected bees had significantly higher bacterial microbiota populations. In addition to the enhanced core bacteria, Commensalibacter and Bartonella were significantly increased in the fecal microbiome. Infected bees fed IMO had significantly higher V. ceranae spore counts but lower mortality; however, infected bees fed IMO did not have significant changes in gut bacteria populations compared to those fed only sucrose, but feeding IMO further reduced the fecal microbiome alpha-diversity. Conclusions: The microbiota alterations caused by infection were similar to the microbiota differences found between summer bees and winter bees, the latter of which have longer lifespans, and feeding IMO increased this similarity. Our results indicated that the interactions between gut bacteria and V. ceranae not only enhanced both the pathogen and bacteria populations but also sustained the host survival. This mutualistic interaction potentially enhances disease transmission and avoids social immune responses of the honey bee hosts.
Development of a Rapid, Efficient, Intelligent and Cost-Saving Tool to Diagnose Pasteurella Multocida by Using Whole Genome Sequence and Genotypes of Pasteurella Multocida From Different Hosts
Authors: Peng Zhong , Liu Junyang , Liang Wan , Wang Fei , Wang Li , Hua Lin , Wang Xiangru , Tan Chen , Zhou Rui , Chen Huanchun , Wilson Brenda A. , Wang Jia , Wu Bin 
Published: November 2020

Abstract
Background: Different typing systems including capsular genotyping, lipopolysaccharide (LPS) genotyping, multilocus sequence typing (MLST), and virulence genotyping based on the detection of different virulence factor-encoding gene (VFG) profiles have been applied to characterize Pasteurella multocida strains from different host species. However, these methods require much time and effort in laboratories. Particularly, relying on one of these methods is difficult to address the biology of P. multocida from host species. Recently, we found that assigning P. multocida strains according to the combination of their capsular, LPS, and MLST genotypes (marked as capsular genotype: LPS genotype: MLST genotype) could help address the biological characteristics of P. multocida circulation in multiple hosts. However, it is still lack of a rapid, efficient, intelligent and cost-saving tool to diagnose P. multocida according to this system. Results: We have developed an intelligent genotyping and host tropism prediction tool PmGT for P. multocida strains according to their whole genome sequences by using machine learning and web 2.0 technologies. By using this tool, the capsular genotypes, LPS genotypes, and MLST genotypes as well as the main VFGs of P. multocida isolates in different host species were determined based on whole genome sequences. The results revealed a closer association between the genotypes and pasteurellosis rather than between genotypes and host species. Finally, we also used PmGT to predict the host species of P. multocida strains with the same capsular: lipopolysaccharide: MLST genotypes. Conclusions: With the advent of high-quality, inexpensive DNA sequencing, this platform represents a more efficient and cost-saving tool for P. multocida diagnosis in both epidemiological studies and clinical settings.
Gut Microbiota Dysbiosis in High-Risk Individuals For Rheumatoid Arthritis Triggers Mucosal Immunity Perturbation and Promotes Arthritis in Mice
Authors: Tong Yanli , Tang Huairong , Li Yanhong , Su Lin Chong , Wu Yuxi , Bozec Aline , Zaiss Mario , Qing Pingying , Zhao Hua , Tan Chunyu , Bai Yunqiang , Zhang Qiuping , Chen Anping , Lin Hui , Zhao Yi , Liu Yi , Luo Yubin , Niu Haitao 
Published: November 2020

Abstract
The authors have requested that this preprint be removed from Research Square.
Anticoagulation Contributes to Antimicrobial Treatment of Lemierre Syndrome: A Case Report
Authors: Ge Jie , Zhou Peipei , Yang Yifei , Xu Tianshu , Yang Xu 
Published: November 2020

Abstract
Background: Lemierre syndrome (LS) is characterized by multisystemic infection beginning in the oropharynx, thrombophlebitis of the internal jugular vein and thrombotic extension to the periphery. It is difficult to establish an evidence-based guideline for management of the disease and the use of anticoagulation therapy remains controversial.Case presentation: A 61-year-old man suffered left neck swelling, odynophagia, and dyspnea. He underwent emergency surgery and received intravenous antimicrobial treatment. The primary infection was controlled on hospital day 5. However, he had a sudden increased WBC and decreased SpO on hospital day 6. Further thoracic CT angiography revealed an intraluminal filling defect in the pulmonary artery on hospital day 8. LS was diagnosed and then anticoagulation therapy was initiated. The WBC count maintained its peak value on hospital days 6-8 before anticoagulation therapy was initiated and decreased instantly after initiation.Conclusions: Our case supported the opinion that anticoagulation therapy contributed to the antiinflammatory effect achieved by the LS treatment.
National Surveillance of Stroke Quality of Care and Outcomes by Applying Post-Stratification Survey Weights on the Get With The Guidelines-Stroke Patient Registry
Authors: Ziaeian Boback , Xu Haolin , Matsouaka Roland A. , Xian Ying , Khan Yosef , Schwamm Lee S. , Smith Eric E. , Fonarow Gregg C. 
Published: November 2020

Abstract
Background: The U.S. lacks a stroke surveillance system. This study develops a method to transform an existing registry into a nationally representative database to evaluate acute ischemic stroke care quality.Methods: Two statistical approaches were used to develop post-stratification weights for the Get With The Guidelines-Stroke registry by anchoring population estimates to the National Inpatient Sample. Post-stratification survey weights were estimated using a raking procedure and Bayesian interpolation methods. Weighting methods were adjusted to limit the dispersion of weights and make reasonable epidemiologic estimates of patient characteristics, quality of hospital care, and clinical outcomes. Standardized differences in national estimates were reported between the two post-stratification methods for anchored and non-anchored patient characteristics to evaluate estimation quality. Primary measures evaluated were patient and hospital characteristics, stroke severity, vital and laboratory measures, disposition, and clinical outcomes at discharge. Results: A total of 1,388,296 acute ischemic strokes occurred between 2012 and 2014. Raking and Bayesian estimates of clinical data not recorded in administrative databases were estimated within 5% to 10% of the margins of expected values. Median weights for the raking method were 1.386 and the weights at the 99th percentile were 6.881 with a maximum weight of 30.775. Median Bayesian weights were 1.329 and the 99th percentile weights were 11.201 with a maximum weight of 515.689. Conclusions: Leveraging existing databases with patient registries to develop post-stratification weights is a reliable approach to estimate acute ischemic stroke epidemiology and monitoring for stroke quality of care nationally. These methods may be applied to other diseases or settings to better monitor population health.
Patient Characteristics and Determinants of CD4 at Diagnosis of HIV in Mexico from 2008 to 2017: A 10-Year Population-Based Study
Authors: Alonso Amilcar Azamar , Bautista-Arredondo Sergio A , Smaill Fiona , Mbuagbaw Lawrence , Costa Andrew P , Tarride Jean-Eric 
Published: November 2020

Abstract
Background: Worldwide, around 37.9 million people are living with HIV, of which 220,000 live in Mexico. In 2007-2012 the Mexican government launched the National HIV program and there was a major change in HIV policies implemented in 2013-2018, when efforts focused on prevention, increase in early diagnosis and timely treatment. Thus, the objectives of this study were to identify the determinants of late HIV diagnosis (i.e. CD4 count less than 200 cells/mm3) in Mexico from 2008 to 2017 and to evaluate the impact of the 2013-2017 National HIV program. Methods: Using patient level data from the SALVAR database, which includes 64% of the population receiving HIV care in Mexico, an adjusted logistic model was conducted. Main study outcomes were HIV late diagnosis which was defined as CD4 count less than 200 cells/mm3 at diagnosis. Results: the study included 106,830 individuals newly diagnosed with HIV and treated in Mexican public health facilities between 2008 and 2017 (mean age: 33 years old, 80% male). HIV late diagnosis decreased from 45% to 43% (P <0.001) between 2008-2012 and 2013-2017 (i.e. before and after the implementation of the 2013-2017 policy). Multivariable logistic regressions indicated that being diagnosed between 2013-2017 (odds ratio [OR]= 0.96 [95% Confidence interval [CI]: [0.93, 0.98]) or in health facilities specialized in HIV (OR=0.64 [95% CI: 0.60, 0.69]) was associated with early diagnosis. Being male, older than 29 years old, diagnosed in Central East, the South region of Mexico or in high-marginalized locality increased the odds of a late diagnosis.Conclusions: The results of this study indicate that the 2013-2017 National HIV program in Mexico has been marginally successful in decreasing the proportion of individuals with late HIV diagnosis in Mexico.