bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated triglyceride-glucose (TyG) index predicts impaired islet β-cell function: A hospital-based cross-sectional study
Authors: Chen Zi , Wen Jie 
Published: September 2022

ObjectiveTo explore the relationship between the TyG index and the insulin secretion function of pancreatic β-cells, and to determine the possibility of the TyG index in predicting β-cell dysfunction and the development of diabetes.MethodsA cross-sectional study was performed among 914 participants who took their annual health checkups at the Third Xiangya Hospital. The early- and late-phase pancreatic β-cell secretion was assessed based on the results of the oral glucose tolerance test (OGTT). In addition to anthropometric parameters and laboratory parameters, information about health-related habits and disease histories was obtained from the National Physical Examination Questionnaire. Partial correlation analysis was used to study the relationship between the TyG index and pancreatic β-cell function. The receiver operating characteristic (ROC) curve was used to calculate the cut-off points of the TyG index in predicting β-cell dysfunction. According to the OGTT results and medical history, the participants were categorized into three groups: the normal glucose tolerance group (NGT, n=276), the impaired glucose regulation group (IGT, n=323), and the diabetes group (DM, n=315). The correlation between the TyG index and β-cell function among the three groups and the association between the TyG index and glucose metabolic conditions were further explored.ResultsThe TyG index was negatively correlated with the indexes that reflect the early and late secretory function of β-cells, not only in the NGT group but also in the IGT and DM group. The minimum cut-off values for the TyG index to identify the risk of early- and late-phase β-cell dysfunction are 9.08 and 9.2 respectively. The TyG indexes of the IGT and DM group were higher than that of the NGT group, and with the growth of the TyG index, the risk of prediabetes and diabetes increased significantly.ConclusionIncreased TyG index is associated with impaired β-cell function regardless of the glucose metabolic conditions. The TyG index is an alternative indicator for predicting β-cell dysfunction.
Investigation on distribution of electro-thermal coupling fields influenced by HVDC bushing insulation properties
Authors: Teng Chenyuan , Ding Yichao , Zhang Youbing , Zhang Yunxiao , Huang Meng , Zhan Zhenyu 
Published: September 2022

Bushing is an indispensable component in high voltage direct current (HVDC) transmission project. As the main insulating material possesses poor thermal conductivity and negative temperature coefficient (NTC) electrical resistivity, HVDC bushing suffers from the distortion of electro-thermal-coupled fields. Therefore, it is urgent to reveal the influence of electrical resistivity-temperature characteristic and thermal conductivity on the DC electric field distribution within bushing insulation, guiding the design and application advanced insulating materials. Here, the simulation of temperature and DC electric field distribution within a 400 kV bushing are carried out. The results show that the optimization of NTC effect and thermal conductivity of an insulating material is able to obtain a more uniform electric field distribution through homogenizing the electric resistivity distribution within bushing insulation. The activation energy of the insulating material has a similar variation trend with the maximum electric field within bushing insulation, which has a potential to represent the temperature dependence of electrical resistivity of insulating materials. It also shows that the reduction of DC electric field by increasing the thermal conductivity has a saturation feature. As a result, the suppression of the NTC effect should be considered together to obtain a smaller electric field within HVDC bushing. The research study provides a new idea to regulate the DC electric field distribution, which is beneficial to the design of advanced insulating materials.
A new CCCH-type zinc finger-related lncRNA signature predicts the prognosis of clear cell renal cell carcinoma patients
Authors: Shen Cheng , Chen Zhan , Jiang Jie , Zhang Yong , Xu Wei , Peng Rui , Zuo Wenjing , Jiang Qian , Fan Yihui , Fang Xingxing , Zheng Bing 
Published: September 2022

Background: Clear cell renal cell carcinoma (ccRCC) is the main component of renal cell carcinoma (RCC), and advanced ccRCC frequently indicates a poor prognosis. The significance of the CCCH-type zinc finger (CTZF) gene in cancer has been increasingly demonstrated during the past few years. According to studies, targeted radical therapy for cancer treatment may be a revolutionary therapeutic approach. Both lncRNAs and CCCH-type zinc finger genes are essential in ccRCC. However, the predictive role of long non-coding RNA (lncRNA) associated with the CCCH-type zinc finger gene in ccRCC needs further elucidation. This study aims to predict patient prognosis and investigate the immunological profile of ccRCC patients using CCCH-type zinc finger-associated lncRNAs (CTZFLs).Methods: From the Cancer Genome Atlas database, RNA-seq and corresponding clinical and prognostic data of ccRCC patients were downloaded. Univariate and multivariate Cox regression analyses were conducted to acquire CTZFLs for constructing prediction models. The risk model was verified using receiver operating characteristic curve analysis. The Kaplan-Meier method was used to analyze the overall survival (OS) of high-risk and low-risk groups. Multivariate Cox and stratified analyses were used to assess the prognostic value of the predictive feature in the entire cohort and different subgroups. In addition, the relationship between risk scores, immunological status, and treatment response was studied.Results: We constructed a signature consisting of eight CTZFLs (LINC02100, AC002451.1, DBH-AS1, AC105105.3, AL357140.2, LINC00460, DLGAP1-AS2, AL162377.1). The results demonstrated that the prognosis of ccRCC patients was independently predicted by CTZFLs signature and that the prognosis of high-risk groups was poorer than that of the lower group. CTZFLs markers had the highest diagnostic adequacy compared to single clinicopathologic factors, and their AUC (area under the receiver operating characteristic curve) was 0.806. The overall survival of high-risk groups was shorter than that of low-risk groups when patients were divided into groups based on several clinicopathologic factors. There were substantial differences in immunological function, immune cell score, and immune checkpoint expression between high- and low-risk groups. Additionally, Four agents, including ABT737, WIKI4, afuresertib, and GNE 317, were more sensitive in the high-risk group.Conclusion: The Eight-CTZFLs prognostic signature may be a helpful prognostic indicator and may help with medication selection for clear cell renal cell carcinoma.
Genetic and immune crosstalk between severe burns and blunt trauma: A study of transcriptomic data
Authors: Chen Xiaoming , Wang Kuan , Li Dazhuang , Zhao Mingyue , Huang Biao , Su Wenxing , Yu Daojiang 
Published: September 2022

Background:Severe burns and blunt trauma can lead to multiple organ dysfunction syndrome, the leading cause of death in intensive care units. In addition to infection, the degree of immune inflammatory response also affects prognosis. However, the characteristics and clinical relevance of the common mechanisms of these major diseases are still underexplored.Methods:In the present study, we performed microarray data analysis to identify immune-related differentially expressed genes (DEGs) involved in both disease progression in burns and blunt trauma. Six analyses were subsequently performed, including gene enrichment analysis, protein‐protein interaction (PPI) network construction, immune cell infiltration analysis, core gene identification, co-expression network analysis, and clinical correlation analysis.Results:A total of 117 common immune-related DEGs was selected for subsequent analyses. Functional analysis emphasizes the important role of Th17 cell differentiation, Th1 and Th2 cell differentiation, Cytokine-cytokine receptor interaction and T cell receptor signaling pathway in these two diseases. Finally, eight core DEGs were identified using cytoHubba, including CD8A, IL10, CCL5, CD28, LCK, CCL4, IL2RB, and STAT1. The correlation analysis showed that the identified core DEGs were more or less significantly associated with simultaneous dysregulation of immune cells in blunt trauma and sepsis patients. Of these, the downregulation of CD8A and CD28 had a worse prognosis.Conclusion:Our analysis lays the groundwork for future studies to elucidate molecular mechanisms shared in burns and blunt trauma. The functional roles of identified core immune-related DEGs and dysregulated immune cell subsets warrant further in-depth study.
Identification and characterization of extrachromosomal circular DNA in alcohol induced osteonecrosis of femoral head
Authors: Zhou Tingting , Ma Shiqiang , Zhao Yunchao , Guo Donghui , Wang Hengjun , Kuang Mingjie , Li Xiaoming 
Published: September 2022

Alcohol-induced osteonecrosis of the femoral head (AIONFH) is a complicated refractory bone disease seen in the clinic. The pathogenesis of AIONFH is still controversial. Extrachromosomal circular DNA (eccDNA) elements have been indicated ubiquitously exist in eukaryotic genomes. However, the characteristics and biological functions of eccDNAs remain unclear in AIONFH. In this study, eccDNAs from AIONFH samples (n = 7) and fracture of femoral neck samples as a control (n = 7) were purified by removing linear DNA and rolling circle amplification. High-throughput sequencing and bioinformatics analysis were performed to study the characterization and biofunction of eccDNAs. We identified more than 600,000 unique eccDNAs. The number of detected eccDNAs in AIONFH was less than that in the control, and eccDNA formation may be related to transcription or other characteristics of coding genes. The eccDNA lengths are mainly distributed between 0.1 kb and 1 kb, with a major peak in 0.358 kb. The bioinformatic analysis showed that 25 significant genes were detected, including MAP3K1, ADCY1, CACNA1S, and MACF1, which contributed to regulating bone formation. GO and KEGG analyses suggested that the related genes derived from exons mainly affected metabolic processes and signal transduction, and bone metabolism-related pathways, such as the MAPK pathway and TGF-β pathway, were enriched. EccDNAs in AIONFH are common and may play an important role in pathogenesis by regulating bone metabolism.
Development and verification of a prognostic model for colon cancer on pyroptosis-related genes
Authors: Wu Zizhen , Wang Bo , Ye Yingjiang , Wang Shan , Jiang Kewei 
Published: September 2022

Background: Recently, the role of pyroptosis in cancer has attracted people’s attention, but its function in colon cancer remains unclear. This study aimed to construct a pyroptosis-related model that can effectively predict the prognosis of patients with colon cancer and explore the potential functions of pyroptosis-related genes.Methods: We identified 40 differentially expressed PRGs between colon cancer and normal colon tissues. The model was established using the least absolute shrinkage and selection operator (LASSO) Cox regression method, and the patients were divided into high- and low-risk groups. Finally, we verified its biological function in vitro based on three PRGs and demonstrated discrepant expression of PRGs within colon cancer and non-tumor tissues at the protein level with immunohistochemistry.Results: A pyroptosis-related prognosis model was constructed, which divided 446 patients with colon cancer into high- and low-risk groups. Kaplan–Meier analysis results showed that the survival of patients with colon cancer in the high-risk group was worse than that in the low-risk group. Finally, we also confirmed that this score is an independent prognostic factor for colon cancer progression.Conclusion: In summary, the model established by three PRGs was a reliable indicator for predicting prognosis, suggesting that pyroptosis might be a noteworthy therapeutic target in CC.
Ecological niche modelling as a tool to identify candidate indigenous chicken ecotypes of Tigray (Ethiopia)
Authors: Gebru Gebreslassie , Belay Gurja , Vallejo-Trujillo Adriana , Dessie Tadelle , Gheyas Almas , Hanotte Olivier 
Published: September 2022

The Tigray region is an ancient entry route for the domestic chickens into Africa. The oldest African chicken bones were found in this region at Mezber, a pre-Aksumite rural farming settlement. They were dated to around 800–400 BCE. Since then, the farming communities of the region have integrated chicken into their livelihoods. The region is also recognised for its high chicken-to-human population ratio and diverse and complex geography, ranging from 500 to 4,000 m above sea level (m.a.s.l.). More than 15 agro-ecological zones have been described. Following exotic chicken introductions, the proportion of indigenous chicken is now 70% only in the region. It calls for the characterisation of indigenous Tigrayan chicken ecotypes and their habitats. This study reports an Ecological Niche Modelling using MaxEnt to characterise the habitats of 16 indigenous village chicken populations of Tigray. A total of 34 ecological and landscape variables: climatic (22), soil (eight), vegetation, and land cover (four), were included. We applied Principal Component Analysis correlation, and MaxentVariableSelection procedures to select the most contributing and uncorrelated variables. The selected variables were three climatic (bio5 = maximum temperature of the warmest month, bio8 = mean temperature of the wettest quarter, bio13 = precipitation of the wettest month), three vegetation and land cover (grassland, forest land, and cultivated land proportional areas), and one soil (clay content). Following our analysis, we identified four main chicken agro-ecologies defining four candidates indigenous Tigrayan chicken ecotypes. The study provides baseline information for phenotypic and genetic characterisation as well as conservation interventions of indigenous Tigrayan chickens.
Genetic susceptibility loci for Chlamydia trachomatis endometrial infection influence expression of genes involved in T cell function, tryptophan metabolism and epithelial integrity
Authors: Zhong Wujuan , Kollipara Avinash , Liu Yutong , Wang Yuhan , O’Connell Catherine M. , Poston Taylor B. , Yount Kacy , Wiesenfeld Harold C. , Hillier Sharon L. , Li Yun , Darville Toni , Zheng Xiaojing 
Published: September 2022

ObjectivesIdentify genetic loci of enhanced susceptibility to Chlamydial trachomatis (Ct) upper genital tract infection in women.MethodsWe performed an integrated analysis of DNA genotypes and blood-derived mRNA profiles from 200 Ct-exposed women to identify expression quantitative trait loci (eQTL) and determine their association with endometrial chlamydial infection using a mediation test. We further evaluated the effect of a lead eQTL on the expression of CD151 by immune cells from women with genotypes associated with low and high whole blood expression of CD151, respectively.ResultsWe identified cis-eQTLs modulating mRNA expression of 81 genes (eGenes) associated with altered risk of ascending infection. In women with endometrial infection, eGenes involved in proinflammatory signaling were upregulated. Downregulated eGenes included genes involved in T cell functions pivotal for chlamydial control. eGenes encoding molecules linked to metabolism of tryptophan, an essential chlamydial nutrient, and formation of epithelial tight junctions were also downregulated in women with endometrial infection. A lead eSNP rs10902226 was identified regulating CD151, a tetrospanin molecule important for immune cell adhesion and migration and T cell proliferation. Further in vitro experiments showed that women with a CC genotype at rs10902226 had reduced rates of endometrial infection with increased CD151 expression in whole blood and T cells when compared to women with a GG genotype.ConclusionsWe discovered genetic variants associated with altered risk for Ct ascension. A lead eSNP for CD151 is a candidate genetic marker for enhanced CD4 T cell function and reduced susceptibility.
Genetic factors underlying tacrolimus intolerance after liver transplantation
Authors: Liu Yuan , Wang Rui , Wen Peizhen , An Wenbin , Zheng Jinxin , Zhang Tao , Zhang Pengshan , Wang Haoyu , Zou Fan , Pan Hui , Fan Junwei , Peng Zhihai 
Published: September 2022

BackgroundTacrolimus (FK506) is the cornerstone of immunosuppression after liver transplantation (LT), however, clinically, switching from FK506 to cyclosporine (SFTC) is common in LT patients with tacrolimus intolerance. The aim of this study was to investigate the genetic risk of patients with tacrolimus intolerance.MethodsA total of 114 LT patients were enrolled in this retrospective study. SNPs were genotyped using Infinium Human Exome-12 v1.2 BeadChip, and genome-wide gene expression levels were profiled using Agilent G4112F array.ResultsSFTC was a potential risk factor of dyslipidemia (OR=4.774[1.122-20.311], p = 0.034) and insulin resistance (IR) (OR=6.25[1.451-26.916], p = 0.014), but did not affect the survival of LT patients. Differential expression analysis showed donor CYP3A5, CYP2C9, CFTR, and GSTP1, four important pharmacogenetic genes were significantly up-regulated in the tacrolimus intolerance group. Twelve SNPs of these four genes were screened to investigate the effects on tacrolimus intolerance. Regression analysis showed donor rs4646450 (OR=3.23 [1.22-8.60] per each A allele, p = 0.01), donor rs6977165 (OR=6.44 [1.09-37.87] per each C allele, p = 0.02), and donor rs776746 (OR=3.31 [1.25-8.81] per each A allele, p = 0.01) were independent risk factors of tacrolimus intolerance.ConclusionsThese results suggested that SFTC was a potential risk factor for dyslipidemia and IR after LT. Besides, rs4646450, rs6977165, and rs776746 of CYP3A5 might be the underlying genetic risks of tacrolimus intolerance. This might help transplant surgeons make earlier clinical decisions about the use of immunosuppression.
Elevated serum C1q is an independent predictor of high residual platelet reactivity in CAD patients receiving clopidogrel therapy
Authors: Zhao Zehao , Ma Meishi , Huang Xin , Sun Tienan , Han Kangning , Yang Shiwei , Zhou Yujie 
Published: September 2022

BackgroundInflammation increases the risk of thrombosis in coronary artery disease (CAD) patients and affects the antiplatelet efficacy of clopidogrel. C1q interacts with platelets to activate platelets and induce thrombosis by participating in and regulating the inflammatory response. Whether C1q affects adenosine diphosphate (ADP)-induced platelet reactivity during clopidogrel therapy was unclear and our study aimed to explore the issue.MethodWe enrolled 1,334 CAD patients receiving clopidogrel therapy and evaluated the association between C1q level and high residual platelet reactivity (HRPR) using logistic regression and restricted cubic spline (RCS). HRPR was defined as ADP-induced maximum amplitude (MAADP) &gt; 47 mm plus ADP-induced platelet aggregation (ADPi) &lt; 50%.ResultsA total of 516 patients (38.7%) performed HRPR. The frequency of HRPR increases with the increase in C1q level (26.3%, 38.4%, 43.2%, and 46.7% for the 1st to 4th quartile of C1q). The result of multivariate logistic regression demonstrated elevated C1q as an independent predictor for HRPR (2ndquartile: OR = 1.722, 95% CI 1.215–2.440; 3rdquartile: OR = 2.015, 95% CI 1.413–2.874; 4thquartile: OR = 2.362, 95% CI 1.631–3.421, compared to the 1st quartile). RCS depicted the nonlinear relationship between C1q and HRPR risk (pfor non-linear &lt; 0.05).ConclusionThe current research is the first to explore the association of C1q and ADP-induced platelet reactivity and to demonstrate elevated C1q as an independent risk factor for HRPR in CAD patients during clopidogrel therapy.
The human myocardium harbors a population of naive B-cells with a distinctive gene expression signature conserved across species
Authors: Bermea Kevin C. , Kostelecky Nicolas , Rousseau Sylvie T. , Lin Chieh-Yu , Adamo Luigi 
Published: September 2022

IntroductionCardiac immunology studies in murine models have identified a sizeable population of myocardial B-cells and have shown that its modulation represents a promising strategy to develop novel therapies for heart failure. However, scarce data on B-cells in the human heart leaves unclear whether findings in rodents are relevant to human biology.MethodsWe performed immunohistochemical stains to characterize the amount and distribution of B-cells in human hearts, analyzing both fresh and post-mortem tissue. To gain insight into the biology of human myocardial B-cells we analyzed publicly-available spatial transcriptomics and single-cell sequencing datasets of myocardial and peripheral blood mononuclear cells (PBMCs). We validated these findings on primary B-cells sorted from the heart and peripheral blood of left ventricular assistive device recipients. To identify biological pathways upregulated in myocardial B-cells across species, we compared differential gene expression in myocardial vs peripheral blood B-cells across the studied human datasets and published rodent datasets.ResultsIn healthy human heart samples, we found B-cells at a ratio of 1:8 compared to T-cells (2.41 ± 0.45 vs 19.36 ± 4.43, p-value &lt;0.001). Myocardial B-cells were more abundant in the interstitium compared with the intravascular space (p-value=0.011), and also more abundant in the myocardium vs. epicardium (p-value=0.048). Single-cell gene expression analysis showed that the human myocardium harbored mostly naive B-cells with a gene expression profile distinct from that of PBMC B-cells. Cross-comparison of differentially-expressed genes in myocardial vs. PBMC B-cells across human and rodent datasets identified 703 genes with consistent differential gene expression across species (binomial p-value=2.9e-48). KEGG pathway analysis highlighted “B-cell receptor signaling pathway,” “Antigen processing and presentation,” and “Cytokine-cytokine receptor interaction” among the top pathways upregulated in cardiac B-cells (FDR &lt;0.001) conserved between species.ConclusionsLike the murine heart, the human heart harbors naive B-cells that are both intravascular and extravascular. Human myocardial B-cells are fewer and more evenly distributed between these two compartments than rodent myocardial B-cells. However, analysis of single-gene expression data indicates that the biological function of myocardial B-cells is conserved across species.