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Intelligent Pharmacy 2025年

作者： Joyner David Anaya Miranda Maricela Rojas Canchala Carlos Alberto Gómez Mercado CES University Faculty of Medicine Graduate Program in Epidemiology and Biostatistics Medellín Colombia Federal University of Grande Dourados Faculty of Health Sciences Graduate Program in Health Sciences Dourados MS Brazil

INTRODUCTION Adverse drug reactions (ADRs) in Antiretroviral Treatment (ART) are influenced by multiple potentiators related to the patient, the disease, the drug, the environment and medical treatment, these ADRs are highly prevalent and are identified as an important risk factor that predisposes patients to ADRs. It was considered necessary to determine the demographic, social, and clinical factors associated with ADRs from antiretrovirals in HIV-positive patients, who were treated by the specialized comprehensive care program in a primary health care model. METHODOLOGY Observational, cross-sectional, analytical, and retrospective study with a population of patients on antiretroviral therapy in a primary care program. The outcome evaluated was adverse drug reactions vs. sociodemographic, pharmacological and clinical factors. For the statistical analysis, univariate, bivariate and multivariate analyses were performed, where a multiple binary logistic regression was used for explanatory purposes. RESULTS A total of 5406 records of patients with antiretroviral therapy were analyzed, the prevalence of ADR was 16.68%, the multivariate analysis showed that the variables that increase the probability of ADR are age, education, area of residence, pharmacological group, HDL cholesterol levels, adherence, persistence, change of two or more times of ARV and treatment time. CONCLUSION Antiretrovirals, as well as the risk factors that are mainly associated with the occurrence of ADRs in this study, contribute to health professionals at all levels to anticipate, identify and minimize ADR, as well as to understand the need for close follow-up and monitoring to avoid the occurrence of serious ADRs.

关键词： Human immunodeficiency virus (HIV) Drug-Related Adverse Reactions and Side Effects (ADRs) Antiretroviral therapy (ART)

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DOWNS SYNDROME - VARIATION OF LEUKEMIA OCCURRENCE IN INSTITUTIONALIZED POPULATIONS

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JOURNAL OF CHRONIC DISEASES 1968年第4期21卷 247-+页

作者： JACKSON, EW TURNER, JH KLAUBER, MR NORRIS, FD Epidemiology Section Cancer Field Research Program State of California Department of Public Health Berkeley California USA Biostatistics (Human Genetics) Graduate School of Public Health University of Pittsburgh Pittsburgh Pennsylvania USA

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Development and validation of a risk prediction model for premenopausal breast cancer in 19 cohorts

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Breast cancer research : BCR 2025年第1期27卷 67-67页

作者： Brantley, Kristen D. Jones, Michael E. Tamimi, Rulla M. Rosner, Bernard A. Kraft, Peter Nichols, Hazel B. Adami, Hans-Olov Aizpurua, Amaia de Gonzalez, Amy Berrington Blot, William J. Braaten, Tonje Chen, Yu DeHart, Jessica Clague Dossus, Laure Elias, Sjoerd Fortner, Renée T Garcia-Closas, Montserrat Gram, Inger T. Håkansson, Niclas Hankinson, Susan E. Kitahara, Cari M. Koh, Woon-Puay Linet, Martha S. MacInnis, Robert J. Masala, Giovanna Mellemkjær, Lene Milne, Roger L. Muller, David C. Park, Hannah Lui Ruddy, Kathryn J. Sandin, Sven Shu, Xiao-Ou Tin Tin, Sandar Truong, Thérèse Vachon, Celine M. Vatten, Lars J. Visvanathan, Kala Weiderpass, Elisabete Willett, Walter Wolk, Alicja Yuan, Jian-Min Zheng, Wei Sandler, Dale P. Schoemaker, Minouk J. Swerdlow, Anthony J. Eliassen, A Heather Department of Epidemiology Harvard T.H. Chan School of Public Health Boston MA United States Department of Medical Oncology Dana-Farber Cancer Institute Boston 02115 MA United States Division of Genetics and Epidemiology Institute of Cancer Research London United Kingdom Department of Population Health Sciences Weill Cornell Medicine New York NY USA Department of Medicine Channing Division of Network Medicine Brigham and Women's Hospital Boston MA United States Department of Biostatistics Harvard T.H. Chan School of Public Health Boston MA United States Division of Cancer Epidemiology and Genetics Transdivisional Research Program National Cancer Institute National Institutes of Health Bethesda MD United States University of North Carolina Gillings School of Global Public Health Chapel Hill NC United States Epidemiology Branch National Institute of Environmental Health Sciences Research Triangle Park Durham NC United States Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden Clinical Effectiveness Research Group Institute of Health and Society University of Oslo Oslo Norway Ministry of Health of the Basque Government Sub Directorate for Public Health and Addictions of Gipuzkoa San Sebastian Spain Biogipuzkoa Health Research Institute Epidemiology of Chronic and Communicable Diseases Group San Sebastián Spain Clinical Cancer Epidemiology Institute of Cancer Research Sutton London UK Department of Medicine Division of Epidemiology Vanderbilt Epidemiology Center Vanderbilt-Ingram Cancer Center Vanderbilt University Medical Center Nashville TN United States Department of Community Medicine UiT The Arctic University of Norway Tromsø Norway Department of Population Health Division of Epidemiology NYU Grossman School of Medicine New York NY USA School of Community and Global Health Claremont Graduate University Claremont CA United States Nutrition and Metabolism Branch International Agency for Research On

BACKGROUND: Incidence of premenopausal breast cancer (BC) has risen in recent years, though most existing BC prediction models are not generalizable to young women due to underrepresentation of this age group in model development. METHODS: Using questionnaire-based data from 19 prospective studies harmonized within the Premenopausal Breast Cancer Collaborative Group (PBCCG), representing 783,830 women, we developed a premenopausal BC risk prediction model. The data were split into training (2/3) and validation (1/3) datasets with equal distribution of cohorts in each. In the training dataset variables were chosen from known and hypothesized risk factors: age, age at menarche, age at first birth, parity, breastfeeding, height, BMI, young adulthood BMI, recent weight change, alcohol consumption, first-degree family history of BC, and personal history of benign breast disease (BBD). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox proportional hazards regression using age as time scale, stratified by cohort. Given that complete information on all risk factors was not available in all cohorts, coefficients were estimated separately in groups of cohorts with the same available covariate information, adjusted to account for the correlation between missing and non-missing variables and meta-analyzed. Absolute risk of BC (in situ or invasive) within 5 years, was determined using country-, age-, and birth cohort-specific incidence rates. Discrimination (area under the curve, AUC) and calibration (Expected/Observed, E/O) were evaluated in the validation dataset. We compared our model with a literature-based model for women < 50 years (iCARE-Lit). RESULTS: Selected model risk factors were age at menarche, parity, height, current and young adulthood BMI, family history of BC, and personal BBD history. Predicted absolute 5-year risk ranged from 0% to 5.7%. The model overestimated risk on average [E/O risk = 1.18 (1.14-1.23)], with underestimation of ris

关键词： Premenopausal breast cancer Risk prediction model Young-onset breast cancer

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A genetic variant associated with aquaporin 3 expression is correlated to in-hospital death in COVID-19 patients with extracellular hyperosmolality

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Physiological genomics 2025年第6期57卷 385-390页

作者： Marks-Hultström, Michael Marks, Amanda M. Butler-Laporte, Guillaume Yoshiji, Satoshi Lu, Tianyuan Morrison, Dave R. Nakanishi, Tomoko Chen, Yiheng Forgetta, Vincenzo Farjoun, Yossi Frithiof, Robert Lipcsey, Miklos Zeberg, Hugo Richards, J Brent Division of Anaesthesiology and Intensive Care Medicine Department of Surgical Sciences Uppsala University Uppsala Sweden Division of Integrative Physiology Department of Medical Cell Biology Uppsala University Uppsala Sweden Department of Epidemiology Biostatistics and Occupational Health McGill University Montréal Québec Canada Lady Davis Institute of Medical Research Jewish General Hospital McGill University Montréal Québec Canada Department of Immunology Genetics Pathology Uppsala University Uppsala Sweden Department of Human Genetics McGill University Montréal Québec Canada Kyoto-McGill International Collaborative Program in Genomic Medicine Graduate School of Medicine Kyoto University Kyoto Japan Japan Society for the Promotion of Science Tokyo Japan Prime Sciences Montréal Québec Canada Broad Institute of Harvard and MIT Cambridge MA United States Fulcrum Genomics Boulder CO United States Hedenstierna Laboratory Department of Surgical Sciences Uppsala University Uppsala Sweden Department of Evolutionary Genetics Max Planck Institute for Evolutionary Anthropology Leipzig Germany Department of Physiology and Pharmacology Karolinska Institutet Stockholm Sweden Department of Twin Research King's College London London United Kingdom

Hyperosmolality is increasingly recognized as a factor contributing to severe COVID-19. Recently, a genetic variant near the aquaporin 3 (AQP3) water channel was associated with severe COVID-19 [rs60840586:G;odds ratio (OR): 1.07, P = 2.5 × 10-9]. The variant is known to increase gene expression of AQP3 in several organs, including the lung [normalized expression scores (NES) = 0.33, P = 4.1 × 10-20] in GTEx. In this study, we investigated 576 patients in the Biobanque Quebecoise de la COVID-19 (BQC-19) with both genetic and clinical data available. We estimated plasma osmolality using the formula: eOSM = 2 × [Na+] + 2 × [K+] + [Urea] + [Glucose]. Using a logistic regression of mortality against eOSM, genotype at rs60840586, sex, age, and the first 10 genetic principal components, we confirm that hyperosmolality is associated with COVID-19 mortality (OR = 2.06 [95% CI = 1.62-2.65], P = 9.13 × 10-9). Interestingly, we found that the risk of death linked to hyperosmolality is influenced by the AQP3 variant rs60840586:G genotype (OR = 1.95 [95% CI = 1.22-3.28], P = 0.0075). However, the rs60840586 genotype did not independently affect mortality in this cohort. These findings suggest that the body's ability to regulate and accommodate hyperosmolality may be disrupted by overexpression of AQP3, potentially worsening outcomes in COVID-19. Given the role of AQP3 in water transport and homeostasis, further defining the functionality of its variants may provide key insights into COVID-19 severity and guide clinical management strategies, particularly in critically ill patients with *** & NOTEWORTHY A genetic variant near water channel AQP3, linked to severe COVID-19, amplifies the risk of death in patients with elevated plasma osmolality. In patients hospitalized with COVID-19, we show that although the variant does not affect systemic osmolality directly, it interacts with hyperosmolality to increase mortality risk. These findings highlight a potential mecha

关键词： COVID-19 personalized medicine risk factors water balance

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Distinguishing genetic correlation from causation across 52 diseases and complex traits (vol 50, pg 1728, 2018)

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NATURE GENETICS 2018年第12期50卷 1753-1753页

作者： O'Connor, Luke J. Price, Alkes L. Department of Epidemiology Harvard T.H. Chan School of Public Health Boston MA USA Program in Bioinformatics and Integrative Genomics Harvard Graduate School of Arts and Sciences Cambridge MA USA Department of Biostatistics Harvard T.H. Chan School of Public Health Boston MA USA Program in Medical and Population Genetics Broad Institute Cambridge MA USA

Mendelian randomization, a method to infer causal relationships, is confounded by genetic correlations reflecting shared etiology. We developed a model in which a latent causal variable mediates the genetic correlation; trait 1 is partially genetically causal for trait 2 if it is strongly genetically correlated with the latent causal variable, quantified using the genetic causality proportion. We fit this model using mixed fourth moments \({\it{E}}({\it{\alpha }}_1^2{\it{\alpha }}_1{\it{\alpha }}_2)\) and \({\it{E}}\left( {{\it{\alpha }}_2^2{\it{\alpha }}_1{\it{\alpha }}_2} \right)\) of marginal effect sizes for each trait; if trait 1 is causal for trait 2, then SNPs affecting trait 1 (large \({\it{\alpha }}_1^2\)) will have correlated effects on trait 2 (large α₁α₂), but not vice versa. In simulations, our method avoided false positives due to genetic correlations, unlike Mendelian randomization. Across 52 traits (average n = 331,000), we identified 30 causal relationships with high genetic causality proportion estimates. Novel findings included a causal effect of low-density lipoprotein on bone mineral density, consistent with clinical trials of statins in osteoporosis.

关键词： Genetics Genome-wide association studies

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Genome-wide association studies in a large Korean cohort identify quantitative trait loci for 36 traits and illuminate their genetic architectures

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Nature Communications 2025年第1期16卷 1-13页

作者： Yon Ho Jee Alkes L. Price Peter Kraft Ying Wang Alicia R. Martin Keum Ji Jung Ji-Young Lee Heejin Kimm Rui Duan Department of Epidemiology Harvard T.H. Chan School of Public Health Boston MA USA Department of Biostatistics Harvard T.H. Chan School of Public Health Boston MA USA Program in Medical and Population Genetics Broad Institute of MIT and Harvard Cambridge MA USA Trans-Divisional Research Program Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Boston MD USA Analytic and Translational Genetics Unit Massachusetts General Hospital Boston MA USA Stanley Center for Psychiatric Research and Program in Medical and Population Genetics Broad Institute of MIT and Harvard Cambridge MA USA Department of Medicine Harvard Medical School Boston MA USA Institute for Health Promotion Department of Epidemiology and Health Promotion Graduate School of Public Health Yonsei University Seoul Korea

Genome-wide association studies (GWAS) have predominantly focused on European ancestry populations, limiting biological discoveries across diverse populations. Here we report GWAS findings from 153,950 individuals across 36 quantitative traits in the Korean Cancer Prevention Study-II (KCPS2) Biobank. We discovered 301 previously unreported genetic loci in KCPS2, including an association between thyroid-stimulating hormone andCD36. Meta-analysis with the Korean Genome and epidemiology Study, Biobank Japan, Taiwan Biobank, and UK Biobank identified 4588 loci that were not significant in any contributing GWAS. We describe differences in genetic architectures across these East Asian and European samples. We also highlight East Asian specific associations, including a known pleiotropic missense variant inALDH2, which fine-mapping identified as a likely causal variant for multiple traits. Our findings provide insights into the genetic architecture of complex traits in East Asian populations and highlight how broadening the population diversity of GWAS samples can aid discovery.

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GranatumX:A Community-engaging, Modularized, and Flexible Webtool for Single-cell Data Analysis

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Genomics, Proteomics & Bioinformatics 2021年第3期19卷 452-460页

作者： David G.Garmire Xun Zhu Aravind Mantravadi Qianhui Huang Breck Yunits Yu Liu Thomas Wolfgruber Olivier Poirion Tianying Zhao Cédric Arisdakessian Stefan Stanojevic Lana X.Garmire Department of Electrical Engineering&Computer Science University of MichiganAnn ArborMI 48109USA Epidemiology Program University of Hawaii Cancer CenterHonoluluHI 96813USA Department of Biostatistics University of MichiganAnn ArborMI 48109USA Department of Computational Medicine and Bioinformatics University of MichiganAnn ArborMI 48105USA Molecular Biosciences and Bioengineering Graduate Program University of Hawaii at ManoaHonoluluHI 96822USA

We present GranatumX,a next-generation software environment for single-cell RNA sequencing(scRNA-seq)data *** is inspired by the interactive webtool *** enables biologists to access the latest scRNA-seq bioinformatics methods in a web-based graphical *** also offers software developers the opportunity to rapidly promote their own tools with others in customizable *** architecture of GranatumX allows for easy inclusion of plugin modules,named Gboxes,which wrap around bioinformatics tools written in various programming languages and on various *** can be run on the cloud or private servers and generate reproducible *** is a community-engaging,flexible,and evolving software ecosystem for scRNA-seq analysis,connecting developers with bench *** is freely accessible at http://***/granatumx/app.

关键词： Single-cell RNA sequencing Analysis Pipeline Webtool Module

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Age and kidney function are the primary correlates of fasting plasma total homocysteine levels in non-diabetic and diabetic adults. Results from the 1999-2002 National Health and Nutrition Examination Survey

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Nutrition and Metabolism 2005年第1期2卷 1-8页

作者： Duncan, Glen E. Li, Sierra M. Zhou, Xiao-Hua Department of Epidemiology Interdisciplinary Graduate Program in Nutritional Sciences University of Washington Seattle WA 98195 United States Department of Biostatistics University of Washington Seattle WA 98195 United States HSRandD Center of Excellence VA Puget Sound Health Care System Seattle WA 98101 United States

Background: Plasma total homocysteine (tHcy) is commonly elevated in persons with diabetes. This may be due to effects of insulin and/or glucose and/or metabolic control on the metabolism or plasma levels of tHcy. This study examined the effects of fasting plasma glucose status on fasting tHcy levels among adults without diabetes, and diabetes per se among adults with a self-report history of diabetes. Methods: Analysis of data on adults (≥ 20y) who had fasted at least 8 hours, from the National Health and Nutrition Examination Survey (1999-2000 and 2001-2002). Subjects with no selfreport history of diabetes were grouped according to fasting plasma glucose status as normal (< 100 mg/dL = NFG, n = 2,244), impaired (≥ 100 < 126 mg/dL = IFG, n = 1,108), or a provisional diagnosis of diabetes (≥ 126 mg/dL = DFG, n = 133). Subjects with a self-report history of diabetes (n = 275) were examined separately. Results: Fasting tHcy was higher (Ps < 0.01) among non-diabetic subjects with DFG and IFG, compared to NFG (median [95% confidence interval] = 8.6 [8.0-9.2], 8.3 [8.1-8.5], and 7.4 [7.3-7.5] μmol/L, respectively). Diabetic subjects had levels similar to non-diabetic subjects with DFG and IFG (8.3 [7.9-8.6] μmol/L). Age and estimated creatinine clearance were strong correlates of fasting tHcy among non-diabetic subjects (r = 0.38 to 0.44 and r = -0.35 to -0.46, respectively) and diabetic subjects (r = 0.41 and r = -0.46, respectively) (Ps < 0.001), while fasting glucose and glycohemoglobin (HbA_1c) were weaker (but still significant) correlates of tHcy in non-diabetic and diabetic subjects. Fasting glucose status was not a significant independent predictor of fasting tHcy levels in non-diabetic subjects, and HbA_1c was not a significant independent predictor of tHcy in diabetic subjects (Ps > 0.05). Conclusion: Fasting tHcy levels are elevated among non-diabetic adults with elevated fasting glucose levels, compared to persons with normal fasting gluco

关键词： Metabolic Control Glucose Status Provisional Diagnosis Nondiabetic Subject tHcy Level

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Multi-institutional atlas of brain metastases informs spatial modeling for precision imaging and personalized therapy

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Nature Communications 2025年第1期16卷 1-15页

作者： Barrios, Jorge Porter, Evan Capaldi, Dante P. I. Upadhaya, Taman Chen, William C. Perks, Julian R. Apte, Aditya Aristophanous, Michalis LoCastro, Eve Hsu, Dylan Stone, Payton H. Villanueva-Meyer, Javier E. Valdes, Gilmer Jiang, Fei Maddalena, Michael Ballangrud, Ase Prezelski, Kayla Lin, Hui Sun, Jinger Y. Aldin, Muhtada A. K. Chau, Oi Wai Ziemer, Benjamin Seaberg, Maasa Sneed, Penny K. Nakamura, Jean L. Boreta, Lauren C. Fogh, Shannon E. Raleigh, David R. Chew, Jessica Vasudevan, Harish Cha, Soonmee Hess, Christopher Fragoso, Ruben Shultz, David B. Pike, Luke Hervey-Jumper, Shawn L. Tsang, Derek S. Theodosopoulos, Philip Cooke, Daniel Benedict, Stanley H. Sheng, Ke Seuntjens, Jan Coolens, Catherine Deasy, Joe Braunstein, Steve Morin, Olivier Department of Radiation Oncology University of California San Francisco San Francisco CA United States Department of Radiation Oncology University of California Davis Health Sacramento CA United States Department of Radiation Oncology Memorial Sloan Kettering New York NY United States Department of Medical Physics Memorial Sloan Kettering New York NY United States Department of Radiology and Biomedical Imaging University of California San Francisco San Francisco CA United States Department of Neurological Surgery University of California San Francisco San Francisco CA United States Department of Epidemiology and Biostatistics University of California San Francisco San Francisco CA United States Moffit Cancer Center Tampa FL United States Radiation Medicine Program Princess Margaret Cancer Centre University Health Network Toronto ON Canada Department of Medical Biophysics University of Toronto Toronto ON Canada UCSF/UC Berkeley Graduate Program in Bioengineering San Francisco CA United States Department of Pathology University of California San Francisco San Francisco CA United States

Brain metastases are a frequent and debilitating manifestation of advanced cancer. Here, we collect and analyze neuroimaging of 3,065 cancer patients with 13,067 brain metastases, representing an extensive collection for research. We find that metastases predominantly localize to high perfusion areas near the grey-white matter junction, but also identify notable differences depending on the primary cancer histology as well as brain regions which do not conform to this relationship. Lung and breast cancers, in contrast to melanoma, frequently metastasize to the cerebellum, hinting at biological pathways of spread. Additionally, the deep brain structures are relatively spared from metastasis, regardless of primary cancer type. Leveraging this data, we propose a probabilistic brain metastasis risk model to enhance the therapeutic ratio of whole-brain radiotherapy by targeting high risk areas while preserving cortical and subcortical brain regions of functional significance and low metastasis risk, potentially reducing the cognitive side effects of therapy. © The Author(s) 2025.

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Prevention Science 2001年第3期2卷 145-163页

作者： Wills, Thomas A. Cleary, Sean Filer, Marnie Shinar, Ori Mariani, John Spera, Karen Ferkauf Graduate School of Psychology Yeshiva University Bronx NY United States Department of Epidemiology and Social Medicine Albert Einstein College of Medicine of Yeshiva University Bronx NY United States Department of Epidemiology and Biostatistics George Washington University Medical Center Washington DC United States Psychology Department Mercy College Dobbs Ferry NY United States Health Psychology Training Program Ferkauf Graduate School of Psychology Albert Einstein College of Medicine Bronx NY 10461 1300 Morris Park Avenue United States

We tested a theoretical model of early-onset substance (tobacco, alcohol, and marijuana) use. A sample of 1,810 public school students was surveyed in sixth grade (M age 11.5 years) and seventh grade. Temperament dimensions were related to substance use, and structural modeling analyses showed indirect effects through self-control constructs. Good self-control had a path to higher academic competence and had direct effects to less peer use and less adolescent substance use;poor self-control had a path to more adolescent life events and more deviant peer affiliations. Academic competence and life events had indirect effects to adolescent substance use, through peer affiliations. Findings from self-report data were corroborated by independent teacher ratings. Effects were also noted for family variables and demographic characteristics. Implications of epigenetic theory for prevention research are discussed. © 2001 Society for Prevention Research.

关键词： Early onset Epigenetic theory Self-control Substance use Temperament

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