Browsing by Author "Zhang, Fengyu"

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Open Access
A caution in association of ABO blood group with COVID-19
(Global Clinical and Translational Research, 2020-06-10) Hughes, Claude; Zhang, Fengyu
Open Access
Beyond p-value: the Rigor and Power of Study
(Global Clinical and Translational Research, 2020-01-10) Zhang, Fengyu; Hughes, Claude
There have been a series of recent discussions and debates on the p-value and statistical significance. These discussions, including publications of more than 40 papers in a special issue of the American Statistician, provide an excellent opportunity to think about some technical measures for practical implementation in grant applications and publications. While several factors have been discussed, it may be the rigor of a study that determines the p-value for reporting study results and judging a consistent replication of research. Both p-values and power, which integrate Fisherian and Neyman-Pearson methods, should be used for hypothesis testing. We propose new criteria, which can be implemented without fundamental changes in existing statistics, to reduce false positives and irreplicability of studies that are either inadequately powered or overpowered.
Open Access
Clinical Epidemiology of Coronavirus Disease 2019: Defined on Current Research
(Global Clinical and Translational Research, 2020-07-25) Hughes, Claude; Zhang, Fengyu
Coronavirus disease 2019 (COVID-19) is a new infectious respiratory disease that has caused the ongoing global pandemic. The primary purpose of this article is to describe evolving clinical epidemiology of COVID-19, including 1) infection and testing, 2) clinical spectrum including classification of clinical type, asymptomatic cases, severe cases and comorbidity, and clinical and immunological response, 3) regional variation in clinical presentation, 4) population distribution by age, sex, and occupation, and finally, 5) case-fatality. This content may provide important information on detailed clinical type and presentation of the disease, in which appropriate clinical outcomes can be derived for developing prevention strategies and clinical studies or trials that aim to test potential therapeutics or products for different patient populations.
Open Access
Ecological Analysis of Gastroschisis Incidence Decline in Liaoning, China, 2006-2016
(Global Clinical and Translational Research, 2020-12-30) Li, Ruiping; Zhang, Fengyu; Hughes, Claude; Li, Jianxin
Background: A gastroschisis incidence decline has recently been reported in Liaoning, China, from 2006-2015; we suspect that this decline could be associated with the fall in industrial manufacturing activities. Methods: The outcome variable, gastroschisis incidence, was from a previous publication. The industrial manufacturing activities were measured by relative job participation and production in the primary and secondary economic sectors, and the corresponding data were collected in 14 cities from 2005 to 2015. The general linear model and a random-effect Poisson regression model were performed to assess the association and time-series trend of gastroschisis with the manufacturing activities. Results: The relative job participation in the first economic sector was marginally associated with gastroschisis incidence in 2006 (p=0.070), but more significantly associated (Beta=-0.040; p=0.014) in the cross-sectional and time-series analysis with one-year lag in the outcome variable. Conclusion: The gastroschisis incidence decline in Liaoning is likely due to the reduced job participation in manufacturing and heavy industry, which might be an indication of reduced risk exposure associated with the industrial manufacturing activities.
Open Access
Human genetic risk of treatment with antiviral nucleoside analog drugs that induce lethal mutagenesis: The special case of molnupiravir.
(Environmental and molecular mutagenesis, 2022-01) Waters, Michael D; Warren, Stafford; Hughes, Claude; Lewis, Philip; Zhang, Fengyu
This review considers antiviral nucleoside analog drugs, including ribavirin, favipiravir, and molnupiravir, which induce genome error catastrophe in SARS-CoV or SARS-CoV-2 via lethal mutagenesis as a mode of action. In vitro data indicate that molnupiravir may be 100 times more potent as an antiviral agent than ribavirin or favipiravir. Molnupiravir has recently demonstrated efficacy in a phase 3 clinical trial. Because of its anticipated global use, its relative potency, and the reported in vitro "host" cell mutagenicity of its active principle, β-d-N4-hydroxycytidine, we have reviewed the development of molnupiravir and its genotoxicity safety evaluation, as well as the genotoxicity profiles of three congeners, that is, ribavirin, favipiravir, and 5-(2-chloroethyl)-2'-deoxyuridine. We consider the potential genetic risks of molnupiravir on the basis of all available information and focus on the need for additional human genotoxicity data and follow-up in patients treated with molnupiravir and similar drugs. Such human data are especially relevant for antiviral NAs that have the potential of permanently modifying the genomes of treated patients and/or causing human teratogenicity or embryotoxicity. We conclude that the results of preclinical genotoxicity studies and phase 1 human clinical safety, tolerability, and pharmacokinetics are critical components of drug safety assessments and sentinels of unanticipated adverse health effects. We provide our rationale for performing more thorough genotoxicity testing prior to and within phase 1 clinical trials, including human PIG-A and error corrected next generation sequencing (duplex sequencing) studies in DNA and mitochondrial DNA of patients treated with antiviral NAs that induce genome error catastrophe via lethal mutagenesis.
Open Access
Interactions between life stress factors and carrying the APOE4 allele adversely impact self-reported health in old adults.
(The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2011-10) Zeng, Yi; Hughes, Claude L; Lewis, Megan A; Li, Jianxin; Zhang, Fengyu
Based on the multiple logistic regression analysis of data from a random sample of 1,023 old adults collected in Taiwan in 2000, we found that interactions between carrying the APOE4 allele and one of four life stress factors (relocated mainlander, living in a crowded household with six or more persons, living in an earthquake-damaged house, and monthly financial difficulty) significantly increased the odds ratio of poor self-reported health. Correlations between carrying the APOE4 allele and the life stress factors were ruled out by statistical tests. These life stress factors had a substantially larger adverse impact on self-reported health in APOE4 allele carriers than in noncarriers. This study provides evidence that interaction between carrying APOE4 allele and chronic life stressors has significant impacts on self-reported health while controlling for various sociodemographic and health behavior factors. Further studies with richer biomarkers are warranted for deeper understanding of the biological mechanisms.
Open Access
Interactions between social/ behavioral factors and ADRB2 genotypes may be associated with health at advanced ages in China.
(BMC Geriatr, 2013-09-09) Zeng, Yi; Cheng, Lingguo; Zhao, Ling; Tan, Qihua; Feng, Qiushi; Chen, Huashuai; Shen, Ke; Li, Jianxin; Zhang, Fengyu; Cao, Huiqing; Gregory, Simon G; Yang, Ze; Gu, Jun; Tao, Wei; Tian, Xiao-Li; Hauser, Elizabeth R
BACKGROUND: Existing literature indicates that ADRB2 gene is associated with health and longevity, but none of previous studies investigated associations of carrying the ADRB2 minor alleles and interactions between ADRB2 genotypes and social/behavioral factors(GxE) with health outcomes at advanced ages. This study intends to fill in this research gap. METHOD: We conducted an exploratory analysis, using longitudinal survey phenotype/genotype data from 877 oldest-old aged 90+. To estimate association of GxE interactions with health outcome, adjusted for the potential correlation between genotypes and social/behavioral factors and various other potentially confounding factors, we develop and test an innovative three-step procedure which combines logistic regression and structural equation methods. RESULTS: Interaction between regular exercise and carrying rs1042718 minor allele is significantly and positively associated with good cognitive function; interaction between regular exercise and carrying rs1042718 or rs1042719 minor allele is significantly and positively associated with self-reported good health; and interaction between social-leisure activities and carrying rs1042719 minor allele is significantly and positively associated with self-reported good health. Carrying rs1042718 or rs1042719 minor alleles is significantly and negatively associated with negative emotion, but the ADRB2 SNPs are not significantly associated with cognitive function and self-reported health. Our structural equation analysis found that, adjusted for the confounding effects of correlation of the ADRB2 SNPs with negative emotion, interaction between negative emotion and carrying rs1042718 or rs1042719 minor allele is significantly and negatively associated with cognitive function. The positive association of regular exercise and social-leisure activities with cognitive function and self-reported health, and negative association of negative emotion with cognitive function, were much stronger among carriers of rs1042718 or rs1042719 alleles, compared to the non-carriers. CONCLUSIONS: The results indicate significant positive associations of interactions between social/behavioral factors and the ADRB2 genotypes with health outcomes of cognitive function and self-reported health, and negative associations of carrying rs1042718 or rs1042719 minor alleles with negative emotion, at advanced ages in China. Our findings are exploratory rather than causal conclusions. This study implies that near-future health promotion programs considering individuals' genetic profiles, with appropriate protection of privacy/confidentiality, would yield increased benefits and reduced costs to the programs and their participants.
Open Access
Interpretation of the Environmental Impact on Autism Spectrum Disorder
(Global Clinical and Translational Research, 2019-09-30) Zhang, Fengyu; Hughes, Claude
Comments on Maternal exposure to triclosan constitutes a yet unrecognized risk factor for autism spectrum disorders. Cell Res. 2019. https://www.nature.com/articles/s41422-019-0220-1, PMID:31462724
Open Access
New Journal Launch: Global Clinical and Translational Research
(Global Clinical and Translational Research, 2019-03-30) Hughes, Claude; Zhang, Fengyu
We are proud to announce the launch of Global Clinical and Translational Research, a new journal that aims to promote clinical and translational research in the genomic era from a global perspective. The journal will (1) provide a unified platform of research communication for basic scientists, medical doctors, other clinical health professionals, social scientists and social workers to share the most recent advances in all areas of clinical and translational sciences; (2) introduce new techniques and methodology such as genomics-based techniques and approaches to design and perform a new generation of clinical research; (3) foster collaborative clinical research from a global perspective.
Open Access
Prenatal Environment and Perinatal Factors Associated with Autism Spectrum Disorder
(Global Clinical and Translational Research, 2019-09-30) Ou, Jianjun; Shen, Yidong; Li, Yamin; Xu, Guanglei; Liu, Huaqing; He, Yiqun; Guo, Hui; Wu, Renrong; Hughes, Claude; Xia, Kun; Zhao, Jingping; Zhang, Fengyu
Background: Both genetic and epidemiological studies have indicated that environmental factors play an essential role in the development of autism spectrum disorder (ASD). We conducted this study to identify maternal exposure to environmental factors, in particular during the fetal development or perinatal period, associated with ASD. Methods: Two independent samples of children with ASD and typical developed (TD) were from distinct regions in China. Multiple logistic regression analysis was performed to identify factors associated with ASD in each sample and then in the combined sample. Results: Five factors were consistently associated with ASD in both samples. In the combined sample, maternal chemical exposure (odds ratio [OR] =4.50; 95% CI: 2.38-8.52), use of medication (OR = 3.19; 95% CI: 2.19-4.65), maternal infection (OR = 2.68; 95% CI: 1.99-3.61), threatened abortion (OR = 2.37; 95% CI: 1.61-3.50), and induced abortion before having the child (OR = 2.07; 95% CI: 1.65-2.60) showed strong associations with ASD; moreover, five factors explained 10-15% of the variation in the risk of ASD. A significant interaction between maternal infection and the use of medication during pregnancy was consistently detected in both independent and combined samples together. Conclusion: Two novel risk factors of maternal chemical exposure and induced abortion may have important implications for understanding the etiology of ASD, particularly in China. Prospective studies are needed to validate these findings, and necessary interventions are recommended to reduce the risk of ASD. KEYWORDS Autism spectrum disorder, chemical exposure, induced abortion, maternal infection
Open Access
Reply to Comments on "Beyond P-value: the Rigor and Power of Study"
(Global Clinical and Translational Research, 2020-01-10) Zhang, Fengyu; Hughes, Claude
We received commentaries that included comments on our paper. Here we provide replies to the comments in the order received. To avoid confusion, we made a revision in the Table 1 to assure that level of significance and power at specified effect size are used appropriately.
Open Access
Reporting standards for clinical and translational research
(Global Clinical and Translational Research, 2019-04-16) Hughes, Claude; Zhang, Fengyu