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A genetic variant in the immune-related gene ERAP1 affects colorectal cancer prognosis

Chinese Medical Journal 2024年第4期137卷 431-440页

作者： Danyi Zou Yimin Cai Meng Jin Ming Zhang Yizhuo Liu Shuoni Chen Shuhui Yang Heng Zhang Xu Zhu Chaoqun Huang Ying Zhu Xiaoping Miao Yongchang Wei Xiaojun Yang Jianbo Tian department of Clinical Laboratory Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China department of Epidemiology and biostatistics School of Public HealthTaiKang Center for Life and Medical SciencesWuhan UniversityWuhanHubei 430071China department of Gastrointestinal Oncology Zhongnan Hospital of Wuhan UniversityWuhanHubei 430071China department of Oncology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China department of Gastrointestinal Surgery Renmin Hospital of Wuhan UniversityWuhanHubei 430071China department of Gastrointestinal Surgery Zhongnan Hospital of Wuhan UniversityWuhan UniversityWuhanHubei 430071China department of Epidemiology and biostatistics School of Public HealthTongji Medical CollegeHuazhong University of Sciences and TechnologyWuhanHubei 430030China Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical UniversityNanjingJiangsu 211166China

Background:Findings on the association of genetic factors and colorectal cancer(CRC)survival are limited and inconsistent,and revealing the mechanism underlying their prognostic roles is of great *** study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible ***:We first systematically performed expression quantitative trait locus(eQTL)analysis using The Cancer Genome Atlas(TCGA)***,the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets(TCGA and GSE39582 dataset from the Gene Expression Omnibus database).The seven most potentially functional eQTL single nucleotide polymorphisms(SNPs)associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis *** regulatory mechanism of the survival-related SNP was further confirmed by functional ***:The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1(ERAP1)was significantly associated with the prognosis of CRC(additive model,hazard ratio[HR]:1.43,95%confidence interval[CI]:1.08-1.88,P=0.012).The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3(TCF3)and subsequently reduce the expression of *** results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival ***:The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene *** Registration:***00454519(https://***/)

关键词： Colorectal cancer Prognosis Genetic variation Quantitative trait loci TCF3 rs71630754 Single nucleotide polymorphisms

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Cautionary Remarks When Testing Agreement between Two Raters for Continuous Scale Measurements: A Tutorial in Clinical Epidemiology with Implementation Using R

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Open Journal of Epidemiology 2024年第1期14卷 56-74页

作者： Mohamed M. Shoukri department of Epidemiology and biostatistics Schulich School of Medicine and Dentistry University of Western Ontario London Canada

Background: When continuous scale measurements are available, agreements between two measuring devices are assessed both graphically and analytically. In clinical investigations, Bland and Altman proposed plotting subject-wise differences between raters against subject-wise averages. In order to scientifically assess agreement, Bartko recommended combining the graphical approach with the statistical analytic procedure suggested by Bradley and Blackwood. The advantage of using this approach is that it enables significance testing and sample size estimation. We noted that the direct use of the results of the regression is misleading and we provide a correction in this regard. Methods: Graphical and linear models are used to assess agreements for continuous scale measurements. We demonstrate that software linear regression results should not be readily used and we provided correct analytic procedures. The degrees of freedom of the F-statistics are incorrectly reported, and we propose methods to overcome this problem by introducing the correct analytic form of the F statistic. Methods for sample size estimation using R-functions are also given. Results: We believe that the tutorial and the R-codes are useful tools for testing and estimating agreement between two rating protocols for continuous scale measurements. The interested reader may use the codes and apply them to their available data when the issue of agreement between two raters is the subject of interest.

关键词： Limits of Agreement Pitman and Morgan Tests Test of Parallelism The Arcsine Variance Stabilizing Transformation Sample Size Estimation

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Diagnostic values of questionnaires of Convergence Insufficiency Symptom Survey and College of Optometrists Vision Development Quality of Life in the screening of convergence insufficiency

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 904-908页

作者： Ling Xiong Qian Chen Ye Wu department of Ophthalmology West China HospitalSichuan University/Laboratory of Optometry and Vision ScienceWest China School of MedicineChengdu 610041Sichuan ProvinceChina department of Clinical Research Management Center of BiostatisticsDesignMeasurement and EvaluationWest China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina

AIM:To compare and analyse the diagnostic efficacy of the College of Optometrists Vision Development Quality of Life Questionnaire(COVD-QOL)and the Convergence Insufficiency Symptom Survey(CISS)in detecting convergence insufficiency and to compare their diagnostic value in clinical ***:Using the diagnostic test method,62 adult patients with convergence insufficiency(age:24.74±3.75y)and 62 normal participants(age:23.61±3.13y)who visited the Optometry Clinic of West China Hospital of Sichuan University from April 2021 to January 2023 were *** subjects completed the CISS and *** analysis of the sensitivity and specificity of the CISS and COVD-QOL and comparison and joint experimental analysis of their diagnostic efficacy were ***:The sensitivity of the CISS and COVD-QOL for convergence insufficiency was 64.5%and 71.0%,respectively,while the specificity was 96.8%and 67.7%,*** to the CISS alone,the combination of the CISS and COVD-QOL demonstrated lower sensitivity and *** areas under the receiver operating characteristic curve of CISS,COVD-QOL and CISS combined with COVD-QOL were 0.806,0.694 and 0.782,***:Considering the low sensitivity of the CISS and the low specificity of the COVD-QOL,it is recommended to supplement these questionnaires with other screening tests for the detection of convergence insufficiency.

关键词： convergence insufficiency symptom survey College of Optometrists Vision Development Quality of Life Questionnaire convergence insufficiency asthenopia

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Omics approaches in asthma research:Challenges and opportunities

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Chinese Medical Journal Pulmonary and Critical Care Medicine 2024年第1期2卷 1-9页

作者： Molin Yue Shiyue Tao Kristina Gaietto Wei Chen department of biostatistics School of Public HealthUniversity of PittsburghPittsburghPA 15224USA Division of Pediatric Pulmonary Medicine UPMC Children’s Hospital of PittsburghUniversity of PittsburghPittsburghPA 15224USA

Asthma,a chronic respiratory disease with a global prevalence of approximately 300 million individuals,presents a significant societal and economic *** multifaceted syndrome exhibits diverse clinical phenotypes and pathogenic endotypes influenced by various *** advent of omics technologies has revolutionized asthma research by delving into the molecular foundation of the disease to unravel its underlying *** technologies are employed to systematically screen for potential biomarkers,encompassing genes,transcripts,methylation sites,proteins,and even the microbiome *** review provides an insightful overview of omics applications in asthma research,with a special emphasis on genetics,transcriptomics,epigenomics,and the *** explore the cutting-edge methods,discoveries,challenges,and potential future directions in the realm of asthma omics *** integrating multi-omics and non-omics data through advanced sta-tistical techniques,we aspire to advance precision medicine in asthma,guiding diagnosis,risk assessment,and personalized treatment strategies for this heterogeneous condition.

关键词： Asthma Genomics Transcriptomics Epigenomics Metagenomics Multi-omics integration

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Transurethral prostate surgery in prostate cancer patients: A population-based comparative analysis of complication and mortality rates

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Asian Journal of Urology 2024年第1期11卷 48-54页

作者： Michele Marchioni Giulia Primiceri Alessandro Veccia Marta Di Nicola Umberto Carbonara Fabio Crocerossa Ugo Falagario Ambra Rizzoli Riccardo Autorino Luigi Schips Laboratory of biostatistics Department of MedicalOral and Biotechnological Sciences“G.d'Annunzio”University of ChietiChietiItaly Urology Unit Department of MedicalOral and Biotechnological Sciences“G.d'Annunzio”University of ChietiChietiItaly Division of Urology VCU HealthRichmondVAUSA

Objective:Prostate cancer(PCa)patients might experience lower urinary tract symptoms as those diagnosed with benign prostatic hyperplasia(BPH).Some of them might be treated for their lower urinary tract symptoms instead of *** aimed to test the effect of PCa versus BPH on surgical outcomes after transurethral prostate surgery,namely complication and mortality ***:Within the American College of Surgeons National Surgical Quality Improvement Program database(2011-2016),we identified patients who underwent transurethral resection of the prostate,photoselective vaporization,or laser *** were stratified according to postoperative diagnosis(PCa ***).Univariable and multivariable logistic regression models evaluated the predictors of perioperative morbidity and mortality.A formal test of interaction between diagnosis and surgical technique used was ***:Overall,34542 patients were *** all,2008(5.8%)had a diagnosis of *** multivariable logistic regression model failed to show statistically significant higher rates of postoperative complications in PCa patients(odds ratio:0.9,95%confidence interval:0.7-1.1;p=0.252).Moreover,similar rates of perioperative mortality(p=0.255),major acute cardiovascular events(p=0.581),transfusions(p=0.933),and length of stay of more than or equal to 30 days(p=0.174)were ***,all tests failed to show an interaction between post-operative diagnosis and surgical technique ***:Patients diagnosed with PCa do not experience higher perioperative morbidity or mortality after transurethral prostate surgery when compared to their BPH ***,the diagnosis seems to not influence surgical technique outcomes.

关键词： Prostatecancer Transurethral surgery of the prostate Prostate surgery Population-based analysis Benign prostatic hyperplasia Lasersurgery

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Genetic landscape and clinical significance of cuproptosis-related genes in liver hepatocellular carcinoma

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Genes & Diseases 2024年第2期11卷 516-519页

作者： Dingtao Hu Yichuan Wang Xu Shen Tiantian Mao Xijun Liang Tengjiao Wang Weifeng Shen Yugang Zhuang Jin Ding Clinical Cancer Institute Center for Translational MedicineNaval Medical UniversityShanghai 200433China department of Emergency Shanghai Tenth People's HospitalTongji UniversitySchool of MedicineShanghai 200072China bioinformatics Analysis Laboratory Center for Translational MedicineNaval Medical UniversityShanghai 200433China The department of Hepatic Surgery Eastern Hepatobiliary Surgery HospitalNaval Medical UniversityShanghai 200433China

Recently,Peter et al reported a novel form of cell death(cuproptosis)that was different from other known death mechanisms.1 They found that accumulation of copper ions could induce destabilization of Fe-S cluster proteins and aggregation of mitochondrial lipoylated proteins,ultimately resulting in cuproptosis.1 of note,ten genes were identified as cuproptosis-related genes(CRGs)in copper ion-induced cell death,including PDHB,PDHA1,DLAT,DLD,LIPT1,LIAS,FDX1,CDKN2A,GLS,and MTF1.1 Since dysregulation of copper metabolism is involved in many cancers,cuproptosis and CRGs may play vital roles in cancer development and treatment.1.2 Herein,our pancancer analysis revealed the coordinated upregulation of 9 of 10 CRGs in human liver hepatocellular carcinoma(LIHC)across 33 solid tumors(Fig.S1A;Fig.1A),suggesting the distinct role of CRGs in *** then explored the genetic landscape,biological function,and clinical significance of CRGs in LIHC,and validated our bioinformatic findings by in vitro experiments and clinical *** detailed methods were described in the supplementary material.

关键词： clinical metabolism hepatocellular

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Using Pearson’s System of Curves to Approximate the Distributions of the Difference between Two Correlated Estimates of Signal-to-Noise Ratios: The Cases of Bivariate Normal and Bivariate Lognormal Distributions

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Open Journal of Statistics 2024年第3期14卷 207-227页

作者： Mohamed M. Shoukri department of Epidemiology and biostatistics Schulich School of Medicine and Dentistry University of Western Ontario London Ontario Canada

Background: The signal-to-noise ratio (SNR) is recognized as an index of measurements reproducibility. We derive the maximum likelihood estimators of SNR and discuss confidence interval construction on the difference between two correlated SNRs when the readings are from bivariate normal and bivariate lognormal distribution. We use the Pearsons system of curves to approximate the difference between the two estimates and use the bootstrap methods to validate the approximate distributions of the statistic of interest. Methods: The paper uses the delta method to find the first four central moments, and hence the skewness and kurtosis which are important in the determination of the parameters of the Pearsons distribution. Results: The approach is illustrated in two examples;one from veterinary microbiology and food safety data and the other on data from clinical medicine. We derived the four central moments of the target statistics, together with the bootstrap method to evaluate the parameters of Pearsons distribution. The fitted Pearsons curves of Types I and II were recommended based on the available data. The R-codes are also provided to be readily used by the readers.

关键词： Signal-to-Noise Ratio Bivariate Distributions Bootstrap Methods Delta Method Pearson System of Curves

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Reduced clinical severity during 2022 Shanghai Spring epidemic of SARS-CoV-2 omicron BA.2 variant infection——an integrated account of virus pathogenicity and vaccination effectiveness

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National Science Review 2024年第4期11卷 24-27页

作者： Xingyue Wu Yao Chen Kangli Cao Yao Shen Xueling Wu Yilin Yang Zhongshu Kuang Qingrun Li Zhenzhen Lu Yichen Jia Mian Shao Guorong Gu Xiangwei Wang Ye Yao Ying Wang Shaodie Chen Zhigao Yu Wei Wei Longfei Ding Lulu Lan Tianwen Gu Xiangyu Long Jian Sun Lingyu Xing Jiayuan Shen Yi Han Yue Luo Sucheng Mu Mengna Lin Xiaoyan Zhang Rong Zeng Jianqing Xu Guoping Zhao Lihong Huang Zhenju Song department of Emergency Medicine Clinical Center for Bio-Therapy Department of Biostatistics and Department of UrologyShanghai Key Laboratory of Lung Inflammation and Injury Zhongshan Hospital Fudan University department of Respiratory and Critical Care Medicine Shanghai Pudong Hospital Fudan University department of Pulmonology Renji Hospital Shanghai Jiao Tong University School of Medicine Key Laboratory of Systems Biology Center for Excellence in Molecular Cell Science Shanghai Institute of Biochemistry and Cell Biology Chinese Academy of Sciences Shanghai Public Health Clinical Center Fudan University department of biostatistics School of Public Health Key Laboratory of Public Health Safety of Ministry of Education and Shanghai Institute of Infectious Disease and Biosecurity School of Public Health Fudan University Shanghai Institute of Immunology Department of Immunology and Microbiology Shanghai Institute of Virology Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of EducationSchool of Medicine Shanghai Jiao Tong University State Key Laboratory of Genetic Engineering Fudan Microbiome CenterSchool of Life Sciences Fudan University Bio-Med Big Data Center Shanghai Institute of Nutrition and Health Chinese Academy of Sciences

The emergence of SARS-Co V-2 variant of concern omicron BA.2 led to high infection incidence rates as well as reduced severity of COVID-19 during the Shanghai Spring epidemic of 2022 [1]. We assessed the role of viral pathogenicity and the effectiveness of inactivated vaccines in a retrospective observational study including 10 258 confirmed COVID-19cases identified between April and June of 2022, from four COVID-19 designated hospitals located in two areas of Shanghai, namely the West Bund and the East Bund, where the populations’ demographic characteristics varied significantly (Table S1, Fig. S1).

关键词： REPLICATION

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Prioritization of risk genes in colorectal cancer by integrative analysis of multi-omics data and gene networks

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Science China(Life Sciences) 2024年第1期67卷 132-148页

作者： Ming Zhang Xiaoyang Wang Nan Yang Xu Zhu Zequn Lu Yimin Cai Bin Li Ying Zhu Xiangpan Li Yongchang Wei Shaokai Zhang Jianbo Tian Xiaoping Miao department of Epidemiology and biostatistics School of Public HealthDepartment of Gastrointestinal OncologyZhongnan Hospital of Wuhan UniversityDepartment of Radiation OncologyRenmin Hospital of Wuhan UniversityTaiKang Center for Life and Medical SciencesWuhan UniversityWuhan 430071China Research Center of Public Health Renmin hospital of Wuhan UniversityWuhan UniversityWuhan 430060China department of Cancer Epidemiology The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalHenan Engineering Research Center of Cancer Prevention and ControlHenan International Joint Laboratory of Cancer PreventionZhengzhou 450008China department of Gastrointestinal Surgery Renmin Hospital of Wuhan UniversityWuhan 430060China department of Radiation Oncology Renmin Hospital of Wuhan UniversityWuhan 430060China department of Gastrointestinal Oncology Hubei Cancer Clinical Study CenterZhongnan Hospital of Wuhan UniversityWuhan 430062China department of Epidemiology and biostatistics School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430073China Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical UniversityNanjing 211166China

Genome-wide association studies(GWASs)have identified over 140 colorectal cancer(CRC)-associated loci;however,target genes at the majority of loci and underlying molecular mechanisms are poorly ***,we utilized a Bayesian approach,integrative risk gene selector(iRIGS),to prioritize risk genes at CRC GWAS loci by integrating multi-omics *** a result,a total of 105 high-confidence risk genes(HRGs)were identified,which exhibited strong gene dependencies for CRC and enrichment in the biological processes implicated in *** the 105 HRGs,CEBPB,located at the 20q13.13 locus,acted as a transcription factor playing critical roles in *** subsequent assays indicated the tumor promoter function of CEBPB that facilitated CRC cell proliferation by regulating multiple oncogenic pathways such as MAPK,PI3K-Akt,and Ras ***,by integrating a fine-mapping analysis and three independent case-control studies in Chinese populations consisting of 8,039 cases and 12,775 controls,we elucidated that rs1810503,a putative functional variant regulating CEBPB,was associated with CRC risk(OR=0.90,95%CI=0.86–0.93,P=1.07×10^(−7)).The association between rs1810503 and CRC risk was further validated in three additional multi-ancestry populations consisting of 24,254 cases and 58,741 ***,the rs1810503 A to T allele change weakened the enhancer activity in an allele-specific manner to decrease CEBPB expression via longrange promoter-enhancer interactions,mediated by the transcription factor,REST,and thus decreased CRC *** summary,our study provides a genetic resource and a generalizable strategy for CRC etiology investigation,and highlights the biological implications of CEBPB in CRC tumorigenesis,shedding new light on the etiology of CRC.

关键词： susceptibility genes gene screening models multi-omics GWAS CEBPB long-range promoter-enhancer interactions

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Translational bioinformatics: Past, Present, and Future

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Genomics, Proteomics & bioinformatics 2016年第1期14卷 31-41页

作者： Jessica D.Tenenbaum department of biostatistics and bioinformatics Duke University School of Medicine

Though a relatively young discipline, translational bioinformatics （TBI） has become a key component of biomedical research in the era of precision medicine. Development of high-throughput technologies and electronic health records has caused a paradigm shift in both healthcare and biomedical research. Novel tools and methods are required to convert increasingly voluminous datasets into information and actionable knowledge. This review provides a definition and contex- tualization of the term TBI, describes the discipline＇s brief history and past accomplishments, as well as current loci, and concludes with predictions of future directions in the field.

关键词： Translational bioinformatics Biomarkers Genomics Precision medicine Personalized medicine

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