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The pathogenic mechanism of syndactyly type V identified in aHoxd13Q50R knock-in mice

Bone research 2024年第2期12卷 349-360页

作者： Han Wang Xiumin Chen Xiaolu Meng Yixuan Cao Shirui Han Keqiang Liu Ximeng Zhao Xiuli Zhao Xue Zhang McKusick-Zhang Center for Genetic Medicine State Key Laboratory of Complex Severe and Rare DiseasesDepartment of Medical GeneticsInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100005China department of Orthopedics State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China

Syndactyly type V (SDTY5) is an autosomal dominant extremity malformation characterized by fusion of the fourth and fifthmetacarpals. In the previous publication, we first identified a heterozygous missense mutation Q50R in homeobox domain (HD) ofHOXD13 in a large Chinese family with SDTY5. In order to substantiate the pathogenicity of the variant and elucidate the underlyingpathogenic mechanism causing limb malformation, transcription-activator-like effector nucleases (TALEN) was employed togenerate a Hoxd13Q50R mutant mouse. The mutant mice exhibited obvious limb malformations including slight brachydactyly andpartial syndactyly between digits 2-4 in the heterozygotes, and severe syndactyly, brachydactyly and polydactyly in *** on BMP2 and SHH/GREM1/AER-FGF epithelial mesenchymal (e-m) feedback, a crucial signal pathway for limbdevelopment, we found the ectopically expressed Shh, Grem1 and Fgf8 and down-regulated Bmp2 in the embryonic limb bud atE10.5 to E12.5. A transcriptome sequencing analysis was conducted on limb buds (LBs) at E11.5, revealing 31 genes that exhibitednotable disparities in mRNA level between the Hoxd13Q50R homozygotes and the wild-type. These genes are known to be involvedin various processes such as limb development, cell proliferation, migration, and apoptosis. Our findings indicate that the ectopicexpression of Shh and Fgf8, in conjunction with the down-regulation of Bmp2, results in a failure of patterning along both theanterior-posterior and proximal-distal axes, as well as a decrease in interdigital programmed cell death (PCD). This cascadeultimately leads to the development of syndactyly and brachydactyly in heterozygous mice, and severe limb malformations inhomozygous mice. These findings suggest that abnormal expression of SHH, FGF8, and BMP2 induced by HOXD13Q50R may beresponsible for the manifestation of human SDTY5.

关键词： BMP2 mechanism finding

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What are the pathways between poverty and malaria in sub-Saharan Africa?A systematic review of mediation studies

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Infectious Diseases of Poverty 2023年第3期12卷 13-30页

作者： Solomon T.Wafula Theresa Habermann Mara Anna Franke Jürgen May Dewi Ismajani Puradiredja Eva Lorenz Johanna Brinkel department of Infectious Disease Epidemiology Bernhard Nocht Institute for Tropical MedicineHamburgGermany department of Disease Control and Environmental health School of Public HealthMakerere UniversityKampalaUganda Charité Global health Charité Universitätsmedizin BerlinBerlinGermany German Center for Infection research(DZIF) Partner Site Hamburg-Borstel-Lubeck-RiemsHamburgGermany department of Tropical Medicine University Medical Center Hamburg-Eppendorf(UKE)HamburgGermany Institute of Medical Biostatistics Epidemiology and InformaticsUniversity Centre of the Johannes Gutenberg UniversityMainzGermany

Background Malaria remains a major burden in sub-Saharan Africa(SSA).While an association between poverty and malaria has been demonstrated,a clearer understanding of explicit mechanisms through which socioeconomic position(SEP)influences malaria risk is needed to guide the design of more comprehensive interventions for malaria risk *** systematic review provides an overview of the current evidence on the mediators of socioeconomic disparities in malaria in *** We searched PubMed and Web of Science for randomised controlled trials,cohort,case-control and cross-sectional studies published in English between January 1,2000 to May 31,*** studies were identified following reviews of reference lists of the studies *** included studies that either(1)conducted a formal mediation analysis of risk factors on the causal pathway between SEP and malaria infections or(2)adjusted for these potential mediators as confounders on the association between SEP and malaria using standard regression *** least two independent reviewers appraised the studies,conducted data extraction,and assessed risk of bias.A systematic overview is presented for the included *** We identified 41 articles from 20 countries in SSA for inclusion in the final *** these,30 studies used cross-sectional design,and 26 found socioeconomic inequalities in malaria *** formal mediation analyses showed limited evidence of mediation of food security,housing quality,and previous antimalarial ***,education,insecticide-treated nets,and nutrition were highlighted in the remaining studies as being protective against malaria independent of SEP,suggesting potential for ***,methodological limitations included the use of cross-sectional data,insufficient confounder adjustment,heterogeneity in measuring both SEP and malaria,and generally low or moderate-quality *** studies considered exposure mediator interactions or considered iden

关键词： Malaria Mediation Socioeconomic disparity Sub-Saharan Africa

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Determinants of mortality among seniors acutely readmitted for heart failure: racial disparities and clinical correlations

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Journal of Geriatric Cardiology 2022年第9期19卷 719-724页

作者： Tuoyo O Mene-Afejuku Gini P Jeyashanmugaraja Mahfuz Hoq Olatunde Ola Amit J Shah department of Cardiology Tower Health SystemReading HospitalPAUSA Yale New Haven health System Bridgeport hospitalCTUSA Mayo Clinic health System La CrosseWIUSA department of Cardiology Emory UniversityAtlantaGAUSA

Heart failure(HF)is a devastating condi-tion characterized by a high rate of mor-tality.[1]About 6.2 million individuals are grappling with the burden of HF in the United States(U.S).[2]Of this over 6 million individuals af-fected with HF,a higher proportion is made up of people older than 65 years.[3,4]More than 50%of pa-tients hospitalized due HF are older than 75 years.[5]Seniors do not just account for the greater propor-tion of individuals affected by HF but also have a worse outcome compared to younger individuals with HF.[6−14]In the light of the above,we aim to address racial disparities as they affect seniors with HF in terms of mortality in addition to other potential prognostic indices.

关键词： admitted mortality clinical

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Immunization coverage,knowledge,satisfaction,and associated factors of non-National Immunization Program vaccines among migrant and left-behind families in China:evidence from Zhejiang and Henan provinces

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Infectious Diseases of Poverty 2023年第5期12卷 69-80页

作者： Yaguan Zhou Duanhui Li Yuan Cao Fenhua Lai Yu Wang Qian Long Zifan Zhang Chuanbo An Xiaolin Xu School of Public health The Second Afliated HospitalZhejiang University School of MedicineYuhangtang Road 866Hangzhou 310058ZhejiangChina The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province HangzhouZhejiangChina Songxian Center for Disease Control and Prevention LuoyangHenanChina department of Immunoprophylaxis Xiaoshan Center for Disease Control and PreventionHangzhouZhejiangChina Global health research Center Division of Social SciencesDuke Kunshan UniversityKunshanJiangsuChina Global health research Center Duke Kunshan UniversityKunshanJiangsuChina School of Public health Faculty of MedicineThe University of QueenslandBrisbaneAustralia

Background Migrant and left-behind families are vulnerable in health services utilization,but little is known about their disparities in immunization of non-National Immunization Program(NIP)*** study aims to evaluate the immunization coverage,knowledge,satisfaction,and associated factors of non-NIP vaccines among local and migrant families in the urban areas and non-left-behind and left-behind families in the rural areas of *** A cross-sectional survey was conducted in urban areas of Zhejiang and rural areas of Henan in China.A total of 1648 caregivers of children aged 1-6 years were interviewed face-to-face by a pre-designed online questionnaire,and their families were grouped into four types:local urban,migrant,non-left-behind,and ***-NIP vaccines includedHemophilus influenza b(Hib)vaccine,varicella vaccine,rotavirus vaccine,enterovirus 71 vaccine(EV71)and 13-valent pneumonia vaccine(PCV13).Log-binomial regression models were used to calculate prevalence ratios(PRs)and 95%confidence intervals(CIs)for the difference on immunization coverage of children,and knowledge and satisfaction of caregivers among *** network models were conducted to explore the interplay of immunization coverage,knowledge,and *** regression models with odds ratios(ORs)and 95%CIs were used to estimate the associated factors of non-NIP *** The immunization coverage of all non-NIP vaccines and knowledge of all items of local urban families was the highest,followed by migrant,non-left-behind and left-behind *** with local urban children,thePRs(95%CIs)for getting all vaccinated were 0.65(0.52-0.81),0.29(0.22-0.37)and 0.14(0.09-0.21)among migrant children,non-left-behind children and left-behind children,*** coverage-knowledge-satisfaction network model showed the core node was the satisfaction of vaccination ***-NIP vaccination was associated with characteristics of both children and car

关键词： Non-National Immunization Program vaccines Migrant family Left-behind family Immunization coverage Immunization knowledge Immunization satisfaction China

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Mechanisms of hepatocellular carcinoma progression

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World Journal of Gastroenterology 2019年第19期25卷 2279-2293页

作者： Olorunseun O Ogunwobi Trisheena Harricharran Jeannette Huaman Anna Galuza Oluwatoyin Odumuwagun Yin Tan Grace X Ma Minhhuyen T Nguyen department of Biological Sciences Hunter College of The City University of New York The Graduate Center departments of Biology and Biochemistry The City University of New York Joan and Sanford I. Weill department of Medicine Weill Cornell Medicine Cornell University Hunter College Center for Cancer health disparities research (CCHDR) Center for Asian health School of Medicine Temple University department of Medicine Fox Chase Cancer Center

Hepatocellular carcinoma(HCC) is the most common primary malignancy of the liver. It is the second leading cause of cancer-related deaths worldwide, with a very poor prognosis. In the United States, there has been only minimal improvement in the prognosis for HCC patients over the past 15 years. Details of the molecular mechanisms and other mechanisms of HCC progression remain unclear. Consequently, there is an urgent need for better understanding of these mechanisms. HCC is often diagnosed at advanced stages, and most patients will therefore need systemic therapy, with sorafenib being the most common at the present time. However, sorafenib therapy only minimally enhances patient survival. This review provides a summary of some of the known mechanisms that either cause HCC or contribute to its progression. Included in this review are the roles of viral hepatitis, non-viral hepatitis, chronic alcohol intake, genetic predisposition and congenital abnormalities, toxic exposures, and autoimmune diseases of the liver. Well-established molecular mechanisms of HCC progression such as epithelial-mesenchymal transition, tumor-stromal interactions and the tumor microenvironment, cancer stem cells, and senescence bypass are also discussed. Additionally, we discuss the roles of circulating tumor cells,immunomodulation, and neural regulation as potential new mechanisms of HCC progression. A better understanding of these mechanisms could have implications for the development of novel and more effective therapeutic and prognostic strategies, which are critically needed.

关键词： Hepatocellular carcinoma Viral/non-viral hepatitis Alcohol consumption Epithelial-mesenchymal transition Tumor-stromal interactions Tumor microenvironment Cancer stem cells Circulating tumor cells Immunomodulation Neural regulation

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Evolution in disparity of PM_(2.5)pollution in China

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Eco-Environment & health 2023年第4期2卷 257-263页

作者： Su Shi Weidong Wang Xinyue Li Chang Xu Jian Lei Yixuan Jiang Lina Zhang Cheng He Tao Xue Renjie Chen Haidong Kan Xia Meng School of Public health Key Laboratory of Public Health Safety of the Ministry of Education and Key Laboratory of Health Technology Assessment of the Ministry of HealthFudan UniversityShanghai 200032China Institute of Epidemiology Helmholtz Zentrum München–German Research Center for Environmental Health(GmbH)Munich D-85764Germany Institute of Reproductive and Child health/Ministry of health Key Laboratory of Reproductive health and department of Epidemiology and Biostatistics School of Public HealthPeking University Health Science CenterBeijing 100191China Shanghai Typhoon Institute/CMA Shanghai Key Laboratory of Meteorology and HealthShanghai 200030China

The spatial disparity of air pollutants is one of the key influential factors for environmental *** quantitatively evaluated the evolution of PM_(2.5)spatial disparity in China during 2013–2020,and investigated the associations between PM_(2.5)spatial disparity and economic *** in PM_(2.5)between more-and less-polluted cities declined over time,suggesting decreased absolute ***,the more polluted cities in 2013 remained so in 2017 and 2020,and vice versa,indicating persistent relative ***_(2.5)pollution levels increased with higher GDP per capita in less-developed areas of China,but such negative effects weakened over time,while economic development tended to promote cleaner air in developed areas of ***,policies to improve air quality and promote economic development simultaneously are needed in China to reduce the disparity of air pollution and promote all people to enjoy environmental equality.

关键词： Fine particulate matter Spatiotemporal disparities Gini coefficient Environmental Kuznets curve

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Colorectal cancer screening:The value of early detection and modern challenges

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World Journal of Gastroenterology 2024年第20期30卷 2726-2730页

作者： Jian Li Zhi-Peng Li Wen-Jie Ruan Wei Wang department of Interventional Oncology Municipal Hospital Affiliated to Taizhou UniversityTaizhou 318000Zhejiang ProvinceChina School of Medicine Taizhou UniversityTaizhou 318000Zhejiang ProvinceChina

The screening of colorectal cancer(CRC)is pivotal for both the prevention and treatment of this disease,significantly improving early-stage tumor detection *** advancement not only boosts survival rates and quality of life for patients but also reduces the costs associated with ***,the adoption of CRC screening methods faces numerous challenges,including the technical limitations of both noninvasive and invasive methods in terms of sensitivity and ***,socioeconomic factors such as regional disparities,economic conditions,and varying levels of awareness affect screening *** coronavirus disease 2019 pandemic further intensified these challenges,leading to reduced screening participation and increased waiting ***,the growing prevalence of early-onset CRC necessitates innovative screening *** response,research into new methodologies,including artificial intelligence-based systems,aims to improve the precision and accessibility of *** measures by governments and health organizations to enhance CRC screening efforts are underway,including increased advocacy,improved service delivery,and international *** role of technological innovation and global health collaboration in advancing CRC screening is *** such as artificial intelligence and gene sequencing are set to revolutionize CRC screening,making a significant impact on the fight against this *** the rise in early-onset CRC,it is crucial for screening strategies to continually evolve,ensuring their effectiveness and applicability.

关键词： Colorectal cancer Early detection Economic implications Noninvasive tests Quality of life Survival rates Therapeutic modalities Technical challenges

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A Bayesian Mixture Model Approach to Disparity Testing

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Applied Mathematics 2024年第3期15卷 214-234页

作者： Gary C. McDonald department of Mathematics and Statistics Oakland University Rochester USA

The topic of this article is one-sided hypothesis testing for disparity, i.e., the mean of one group is larger than that of another when there is uncertainty as to which group a datum is drawn. For each datum, the uncertainty is captured with a given discrete probability distribution over the groups. Such situations arise, for example, in the use of Bayesian imputation methods to assess race and ethnicity disparities with certain insurance, health, and financial data. A widely used method to implement this assessment is the Bayesian Improved Surname Geocoding (BISG) method which assigns a discrete probability over six race/ethnicity groups to an individual given the individual’s surname and address location. Using a Bayesian framework and Markov Chain Monte Carlo sampling from the joint posterior distribution of the group means, the probability of a disparity hypothesis is estimated. Four methods are developed and compared with an illustrative data set. Three of these methods are implemented in an R-code and one method in WinBUGS. These methods are programed for any number of groups between two and six inclusive. All the codes are provided in the appendices.

关键词： Bayesian Improved Surname and Geocoding (BISG) Mixture Likelihood Function Posterior Distribution Metropolis-Hastings Algorithms Random Walk Chain Independence Chain Gibbs Sampling WinBUGS

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Metabolic alterations in cancer cells and therapeutic implications

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Chinese Journal of Cancer 2011年第8期30卷 508-525页

作者： Naima Hammoudi Kausar Begam Riaz Ahmed1 Celia Garcia- Prieto Peng Huang department of Molecular Pathology The University of Texas MD Anderson Cancer Center Houston Texas 77030 USA The University of Texas Graduate School of Biomedical Sciences at Houston Houston Texas 77030 USA the department of health disparities research The University of Texas MD Anderson Cancer Center. Houston. Texas 77030. USA.

Cancer metabolism has emerged as an important area of research in recent *** of the metabolic differences between cancer and normal cells and the underlying mechanisms will not only advance our understanding of fundamental cancer cell biology but also provide an important basis for the development of new therapeutic strategies and novel compounds to selectively eliminate cancer cells by targeting their unique *** article reviews several important metabolic alterations in cancer cells,with an emphasis on increased aerobic glycolysis (the Warburg effect) and glutamine addiction,and discusses the mechanisms that may contribute to such metabolic *** addition,metabolic alterations in cancer stem cells,mitochondrial metabolism and its influence on drug sensitivity,and potential therapeutic strategies and agents that target cancer metabolism are also discussed.

关键词：新陈代谢肿瘤细胞治疗细胞生物学药物敏感性正常细胞谷氨酰胺代谢变化

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Unveiling Global Human Trafficking Trends: A Comprehensive Analysis

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Journal of Data Analysis and Information Processing 2024年第1期12卷 49-75页

作者： Somtobe Olisah Clement Odooh Oghenekome Efijemue Echezona Obunadike Jane Onwuchekwa Omoshola Owolabi Saheed Akintayo Callistus Obunadike department of Computer Science Austin Peay State University Clarkesville TN USA department of Data Science Carolina University Winston-Salem NC USA

This paper presents a comprehensive analysis of global human trafficking trends over a twenty-year period, leveraging a robust dataset from the Counter Trafficking Data Collaborative (CTDC). The study unfolds in a systematic manner, beginning with a detailed data collection phase, where ethical and legal standards for data usage and privacy are strictly observed. Following collection, the data undergoes a rigorous preprocessing stage, involving cleaning, integration, transformation, and normalization to ensure accuracy and consistency for analysis. The analytical phase employs time-series analysis to delineate historical trends and utilizes predictive modeling to forecast future trajectories of human trafficking using the advanced analytical capabilities of Power BI. A comparative analysis across regions—Africa, the Americas, Asia, and Europe—is conducted to identify and visualize the distribution of human trafficking, dissecting the data by victim demographics, types of exploitation, and duration of victimization. The findings of this study not only offer a descriptive and predictive outlook on trafficking patterns but also provide insights into the regional nuances that influence these trends. The article underscores the prevalence and persistence of human trafficking, identifies factors contributing to its evolution, and discusses the implications for policy and law enforcement. By integrating a methodological approach with quantitative analysis, this research contributes to the strategic planning and resource allocation for combating human trafficking. It highlights the necessity for continued research and international cooperation to effectively address and mitigate this global issue. The implications of this research are significant, offering actionable insights for policymakers, law enforcement, and advocates in the ongoing battle against human trafficking.

关键词： Human Trafficking Global Trends Data Analysis Victim Demographics Policy Implications Technological Advancements Socioeconomic Factors Forecasting Regional disparities Transnational Crime

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