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arXiv 2020年

作者： Matsouaka, Roland A. Atem, Folefac D. Department of Biostatistics and Bioinformatics & Program for Comparative Effectiveness Methodology Duke Clinical Research Institute Duke University DurhamNC United States Department of Biostatistics and Data Science University of Texas Health Science Center at Houston HoustonTX United States

In a longitudinal study, measures of key variables might be incomplete or partially recorded due to drop-out, loss to follow-up, or early termination of the study occurring before the advent of the event of interest. In this paper, we focus primarily on the implementation of a regression model with a randomly censored predictor. We examine, particularly, the use of inverse probability weighting methods in a generalized linear model (GLM), when the predictor of interest is right-censored, to adjust for censoring. To improve the performance of the complete-case analysis and prevent selection bias, we consider three different weighting schemes: inverse censoring probability weights, Kaplan-Meier weights, and Cox proportional hazards weights. We use Monte Carlo simulation studies to evaluate and compare the empirical properties of different weighting estimation methods. Finally, we apply these methods to the Framingham Heart Study data as an illustrative example to estimate the relationship between age of onset of a clinically diagnosed cardiovascular event and low-density lipoprotein (LDL) among cigarette smokers. Copyright © 2020, The Authors. All rights reserved.

关键词： Monte Carlo methods

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Universal mechanical response of metallic glasses during strain-rate-dependent uniaxial compression

arXiv

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arXiv 2022年

作者： Jin, Weiwei Datye, Amit Schwarz, Udo D. Shattuck, Mark D. O'Hern, Corey S. Department of Mechanical Engineering and Materials Science Yale University New HavenCT06520 United States Department of Chemical and Environmental Engineering Yale University New HavenCT06520 United States Benjamin Levich Institute Physics Department The City College of New York New YorkNY10031 United States Department of Physics Yale University New HavenCT06520 United States Department of Applied Physics Yale University New HavenCT06520 United States Graduate Program in Computational Biology and Bioinformatics Yale University New HavenCT06520 United States

Experimental data on the compressive strength σmax versus strain rate Ε eng for metallic glasses undergoing uniaxial compression shows significantly different behavior for different alloys. For some metallic glasses, σmax decreases with increasing Ε eng, for others, σmax increases with increasing Ε eng, and for others σmax versus Ε eng is nonmonotonic. Using numerical simulations of metallic glasses undergoing uniaxial compression at nonzero strain rate and temperature, we show that they obey a universal relation for the compressive strength versus temperature, which determines their mechanical response. At low Ε eng, increasing strain rate leads to increases in temperature and decreases in σmax∗, whereas at high Ε eng, increasing strain rate leads to decreases in temperature and increases in σmax∗. This non-monotonic behavior of σmax∗ versus temperature causes the nonmonotonic behavior of σmax∗ versus Ε eng. Variations in the internal dissipation change the characteristic strain rate at which the nonmonotonic behavior occurs. These results are general for a wide range of metallic glasses with different atomic interactions, damping coefficients, and chemical compositions. © 2022, CC BY.

关键词： Strain rate

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Robust statistical inference for the matched net benefit and the matched win ratio using prioritized composite endpoints

arXiv

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arXiv 2020年

作者： Matsouaka, Roland A. Coles, Adrian Lilly Research Laboratories Eli Lilly and Company IndianapolisIN United States Program for Comparative Effectiveness Methodology Duke Clinical Research Institute Duke University DurhamNC United States Department of Biostatistics and Bioinformatics Duke University DurhamNC United States

As alternatives to the time-to-first-event analysis of composite endpoints, the net benefit (NB) and the win ratio (WR)—which assess treatment effects using prioritized component outcomes based on clinical importance— have been proposed. However, statistical inference of NB and WR relies on a large-sample assumptions, which can lead to an invalid test statistic and inadequate, unsatisfactory confidence intervals, especially when the sample size is small or the proportion of wins is near 0 or 1. In this paper, we develop a systematic approach to address these limitations in a paired-sample design. We first introduce a new test statistic under the null hypothesis of no treatment difference. Then, we present the formula to calculate the sample size. Finally, we develop the confidence interval estimations of these two estimators. To estimate the confidence intervals, we use the method of variance estimates recovery (MOVER), that combines two separate individual-proportion confidence intervals into a hybrid interval for the estimand of interest. We assess the performance of the proposed test statistic and MOVER confidence interval estimations through simulation studies. We demonstrate that the MOVER confidence intervals are as good as the large-sample confidence intervals when the sample is large and when the proportions of wins is bounded away from 0 and 1. Moreover, the MOVER intervals outperform their competitors when the sample is small or the proportions are at or near the boundaries 0 and 1. We illustrate the method (and its competitors) using three examples from randomized clinical studies. © 2020, CC0.

关键词： Statistical tests

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Noninvasive assessment of hydroquinidine effect in Brugada syndrome (QUIET BrS)

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Heart Rhythm 2025年

作者： Isbister, Julia C. Strocchi, Marina Riedy, Matthew Yeates, Laura Gray, Belinda Singer, Emma S. Bagnall, Richard D. Ingles, Jodie Raju, Hariharan Semsarian, Christopher Niederer, Steven A. Sy, Raymond W. Faculty of Medicine and Health University of Sydney Sydney NSW Australia Department of Cardiology Royal Prince Alfred Hospital Sydney NSW Australia National Heart and Lung Institute Imperial College London London United Kingdom School of Biomedical Engineering and Imaging Sciences King's College London London United Kingdom Medtronic Australasia Sydney NSW Australia Agnes Ginges Centre for Molecular Cardiology at Centenary Institute The University of Sydney Sydney NSW Australia Genomics and Inherited Disease Program Garvan Institute of Medical Research University of New South Wales Sydney NSW Australia Bioinformatics and Molecular Genetics Group at Centenary Institute The University of Sydney Sydney NSW Australia Faculty of Medicine Health and Human Sciences Macquarie University Sydney NSW Australia The Alan Turing Institute London United Kingdom

Background: Hydroquinidine reduces arrhythmic events in patients with Brugada syndrome (BrS). The mechanism by which it exerts antiarrhythmic benefit and its electrophysiological effects on BrS substrate remain incompletely understood. Objective: This study aimed to determine the effect of hydroquinidine on ventricular depolarization and repolarization in patients with BrS in vivo. Methods: Twelve patients with BrS underwent electrocardiography (standard, high-lead, and signal averaged) and electrocardiographic imaging at baseline and “on-treatment” with hydroquinidine 300 mg twice daily. ST-segment elevation, activation time, repolarization time, and activation-recovery interval (ARI) were computed for the ventricles and right ventricular outflow tract (RVOT). Serum hydroquinidine levels were determined, and adverse drug events were captured through a medication survey. Results: Hydroquinidine increased repolarization time (301.1 ± 24.1 ms vs 348.8 ± 28.3 ms;P<.001), repolarization gradients (1.1 ± 0.4 ms/mm vs 1.6 ± 0.4 ms/mm;P<0.001), and ARI (241.3 ± 18.1 ms vs 284.8 ± 21.5 ms;P<.001) in the RVOT, with a greater change in the RVOT than in the rest of the ventricles. In contrast, activation parameters did not change significantly on-treatment with hydroquinidine, although there was a subtle increase in ST-segment elevation over the RVOT (1.5 ± 0.7 mV vs 1.8 ± 0.8 mV;P<.001). Hydroquinidine levels did not correlate with electrophysiological changes or occurrence of adverse drug reactions. One patient developed frequent nonsustained ventricular tachycardia on-treatment with hydroquinidine. Conclusion: Hydroquinidine primarily affects ventricular repolarization and action potential duration (indicated by ARI) in patients with BrS and demonstrates regional variation with more significant changes in the RVOT. © 2024 Heart Rhythm Society

关键词： Activation-recovery interval Brugada syndrome Electrocardiographic imaging Hydroquinidine Noninvasive Ventricular activation Ventricular repolarization

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Prediction of Drug Classes with a Deep Neural Network using Drug Targets and Chemical Structure Data

Prediction of Drug Classes with a Deep Neural Network using ...

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IEEE International Conference on bioinformatics and Biomedicine (BIBM)

作者： Jeonghee Jo Hyun-Soo Choi Sungroh Yoon Interdisciplinary Program in Bioinformatics Seoul National University Seoul South Korea Seoul National University Seoul South Korea Interdisciplinary Program in Bioinformatics ASRI INMC ISRC Institute of Engineering Research Seoul National University Seoul National University Seoul South Korea

ISBN: (纸本)9781728118680

Drugs are classified according to their biological and chemical reactions, and the systems that they target. Thus, an accurate and efficient prediction method for drug class discovery would reveal key properties of candidate drugs, significantly conserving time and resources in drug repositioning and design. Previous approaches, based on data mining or statistics, required complicated feature construction in advance. Knowing that deep learning can identifying patterns in high-dimensional datasets without elaborate feature selection or engineering, we constructed a model for predicting drug classes using deep neural networks - with biological and chemical structure data. Our proposed model outperforms previous learning-based methods in terms of prediction accuracy.

关键词： chemical engineering computing data mining drugs feature selection learning (artificial intelligence) neural nets Neural network Pharmaceutical Preparations data mining Feature extraction Drug Liberation Drug Repositioning chemical structure Biological Prediction methods

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A transcriptome meta-analysis of ethanol embryonic exposure: Implications in neurodevelopment and neuroinflammatory genes

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Neuroscience Informatics 2022年第3期2卷 100094-100094页

作者： Lord, Vinícius Oliveira Giudicelli, Giovanna Câmara Recamonde-Mendoza, Mariana Vianna, Fernanda Sales Luiz Kowalski, Thayne Woycinck Laboratory of Genomic Medicine Center of Experimental Research Hospital de Clínicas de Porto Alegre (HCPA) Porto Alegre Brazil Centro Universitário CESUCA Cachoeirinha Brazil Post-Graduation Program in Genetics and Molecular Biology Genetics Department Universidade Federal do Rio Grande do Sul (UFRGS) Porto Alegre Brazil Institute of Informatics Universidade Federal do Rio Grande do Sul (UFRGS) Porto Alegre Brazil Bioinformatics Core Hospital de Clínicas de Porto Alegre (HCPA) Porto Alegre Brazil National Institute of Medical Population Genetics (INAGEMP) Porto Alegre Brazil Post-Graduation Program in Medical Sciences Medical College Universidade Federal do Rio Grande do Sul (UFRGS) Porto Alegre Brazil

Fetal Alcohol Spectrum Disorder (FASD) comprises the phenotypes induced by prenatal alcohol exposure. Understanding the molecular mechanisms of FASD is needed since it is a public health problem. This study aimed to evaluate the impact of ethanol in the differential gene expression (DGE) of embryonic cells and fetal tissues by performing a transcriptome meta-analysis in microarrays datasets publicly available. The datasets were obtained in the GEO database and DGE was evaluated, followed by meta-analysis. DGE was also analyzed in a RNA-Seq dataset, although it was not included in the meta-analysis. To filter the main candidate genes, a database and literature review was performed, followed by ontologies enrichment analyses. In the meta-analysis, 1,938 genes were deregulated and 487 were perturbed in the RNA-Seq. Calcium homeostasis and neuroinflammation genes were overrepresented in the meta-analysis and RNA-Seq, respectively. After the database and literature review, DOCK8, FOXG1, IL1RN, and PRKN genes were proposed as new candidates for FASD;they are associated with neurodevelopment and neuroinflammation. BDNF and SLC2A1, previously associated to FASD, were also suggested in meta-analysis as candidate genes. It is known neuroinflammation reduction might help to minimize the alcohol damage. Hence, there is an urgent need to understand FASD molecular mechanisms to help in strategies aimed at preventing ethanol-induced neurologic damage. © 2022 The Authors

关键词： bioinformatics Differential gene expression Fetal alcohol spectrum disorder Microarray Neurophenotypes Ontology Prenatal ethanol exposure Random effect model RNA-Seq

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Deletion of a single CTCF motif at the boundary of a chromatin domain with three FGF genes disrupts gene expression and embryonic development

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Developmental Cell 2025年

作者： Chakraborty, Shreeta Wenzlitschke, Nina Anderson, Matthew J. Eraso, Ariel Baudic, Manon Thompson, Joyce J. Evans, Alicia A. Shatford-Adams, Lilly M. Chari, Raj Awasthi, Parirokh Dale, Ryan K. Lewandoski, Mark Petros, Timothy J. Rocha, Pedro P. Unit on Genome Structure and Regulation National Institute of Child Health and Human Development National Institutes of Health Bethesda 20892 MD United States Genetics of Vertebrate Development Section Cancer and Developmental Biology Laboratory National Cancer Institute National Institutes of Health Frederick 21702 MD United States Bioinformatics and Scientific Programming Core National Institute of Child Health and Human Development National Institutes of Health Bethesda 20892 MD United States Laboratory Animal Sciences Program Frederick National Laboratory for Cancer Research Frederick 21702 MD United States Unit on Cellular and Molecular Neurodevelopment National Institute of Child Health and Human Development National Institutes of Health Bethesda 20892 MD United States National Cancer Institute NIH Bethesda 20892 MD United States

Chromatin domains delimited by CTCF can restrict the range of enhancer action. However, disruption of some domain boundaries results in mild gene dysregulation and phenotypes. We tested whether perturbing a domain with multiple developmental regulators would lead to more severe outcomes. We chose a domain with three FGF ligand genes—Fgf3, Fgf4, and Fgf15—that control different murine developmental processes. Heterozygous deletion of a 23.9-kb boundary defined by four CTCF sites led to ectopic interactions of the FGF genes with enhancers active in the brain and induced FGF expression. This caused orofacial clefts, encephalocele, and fully penetrant perinatal lethality. Loss of the single CTCF motif oriented toward the enhancers—but not the three toward the FGF genes—recapitulated these phenotypes. Our works shows that small sequence variants at particular domain boundaries can have a surprisingly outsized effect and must be considered as potential sources of gene dysregulation in development and disease. © 2025

关键词： CTCF epigenetics FGF gene regulation nuclear organization

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Sharing and seeking information about skin cancer risk and prevention among Hispanic people from Florida and Puerto Rico

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PEC Innovation 2023年 3卷 100232-100232页

作者： Rivera Rivera, Jessica N. Lacson, John Charles A. Kim, Youngchul Roetzheim, Richard G. Sutton, Steven K. Soto-Torres, Brenda Vadaparampil, Susan T. Kanetsky, Peter A. Department of Health and Behavioral Outcomes H. Lee Moffitt Cancer Center and Research Institute Tampa FL United States Health Care Delivery Research MedStar Health Research Institute Washington DC United States Department of Cancer Epidemiology H. Lee Moffitt Cancer Center and Research Institute Tampa FL United States Department of Biostatistics and Bioinformatics H. Lee Moffitt Cancer Center and Research Institute Tampa FL United States Department of Family Medicine Morsani College of Medicine University of South Florida Tampa FL United States Public Health Program Ponce Health Sciences University Ponce PR United States

Objective: To explore factors associated with communication and information-seeking after receipt of skin cancer prevention information among Hispanic individuals. Methods: Multivariable logistic regression was used to analyze existing data on demographics, personal experience, salience, and beliefs variables collected from Hispanic individuals to determine independent associations with sharing and seeking information about skin cancer prevention. Results: Of 578 participants, 53% reported any communication about skin cancer prevention behaviors or skin cancer genetic risk;and 31% and 21% sought additional information about preventive behaviors or genetic risk, respectively. Female sex, greater perceived severity, higher comparative chance of getting skin cancer, and lower health literacy were associated with greater communication, while having no idea of one's own skin cancer risk was related to less communication. Greater health numeracy and higher cancer worry were associated with information-seeking about prevention behaviors and genetic risk. Conclusion: Up to half of participants reported communication or information-seeking, although factors associated with specific activities differed. Future studies should evaluate how to promote communication behaviors in the Hispanic community and how sharing and seeking information influence an individual's network prevention practices. Innovation: Several factors related to communication behaviors among Hispanic people after obtaining skin cancer prevention information were identified. Trial registration: This trial was registered on *** (NCT03509467). © 2023 The Authors

关键词： Communication Genetic risk Hispanic people Information-seeking MC1R Skin cancer prevention

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Single-molecule localization microscopy reveals the ultrastructural constitution of distal appendages in expanded mammalian centrioles

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Nature communications 2023年第1期14卷 1688页

作者： Ting-Jui Ben Chang Jimmy Ching-Cheng Hsu T Tony Yang Department of Physics National Taiwan University Taipei Taiwan. Department of Electrical Engineering National Taiwan University Taipei Taiwan. Nano Science and Technology Program Taiwan International Graduate Program Academia Sinica and National Taiwan University Taipei Taiwan. Department of Electrical Engineering National Taiwan University Taipei Taiwan. tonyyang@ntu.edu.tw. Graduate Institute of Biomedical Electronics and Bioinformatics National Taiwan University Taipei Taiwan. tonyyang@ntu.edu.tw.

Distal appendages (DAPs) are vital in cilia formation, mediating vesicular and ciliary docking to the plasma membrane during early ciliogenesis. Although numerous DAP proteins arranging a nine-fold symmetry have been studied using superresolution microscopy analyses, the extensive ultrastructural understanding of the DAP structure developing from the centriole wall remains elusive owing to insufficient resolution. Here, we proposed a pragmatic imaging strategy for two-color single-molecule localization microscopy of expanded mammalian DAP. Importantly, our imaging workflow enables us to push the resolution limit of a light microscope well close to a molecular level, thus achieving an unprecedented mapping resolution inside intact cells. Upon this workflow, we unravel the ultra-resolved higher-order protein complexes of the DAP and its associated proteins. Intriguingly, our images show that C2CD3, microtubule triplet, MNR, CEP90, OFD1, and ODF2 jointly constitute a unique molecular configuration at the DAP base. Moreover, our finding suggests that ODF2 plays an auxiliary role in coordinating and maintaining DAP nine-fold symmetry. Together, we develop an organelle-based drift correction protocol and a two-color solution with minimum crosstalk, allowing a robust localization microscopy imaging of expanded DAP structures deep into the gel-specimen composites.

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The complete chloroplast genome ofArtocarpus altilis(Moraceae) and phylogenetic relationships

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Mitochondrial DNA Part B 2021年第8期6卷 2291-2293页

作者： Ueric José Borges de Souza Raíssa Nunes dos Santos Renisson Neponuceno de Araújo Filho Gil Rodrigues dos Santos Renato Almeida Sarmento Fabien De Bellis Fabrício Souza Campos a Laboratory of Bioinformatics & Biotechnology Federal University of Tocantins Gurupi Brazil b Department of Forestry Engineering Federal University of Tocantins Gurupi Brazil c Laboratory of Phytopathology Federal University of Tocantins Gurupi Brazil b Department of Forestry Engineering Federal University of Tocantins Gurupi Brazild Post-Graduate Program in Plant Production Federal University of Tocantins Gurupi Brazil e CIRAD UMR AGAP Institute Montpellier Francef UMR AGAP Institute University of Montpellier CIRAD INRAE L’Institut Agro Montpellier France

The chloroplast (cp) is an essential organelle in higher plants. The genes of the plastome are well suited to infer phylogenetic relationships among taxa. In this study, we report the assembly of the cp genome ofArtocarpus altilisand its phylogeny among species from Moraceae family. The cp genome ofA. altiliswas 160,822 base pair (bp) in length, comprising one large single-copy region of 88,692 bp, one small single-copy region of 19,290 bp, and a pair of inverted repeat regions (IRs) of 26,420 bp. A total of 113 different genes were predicted, including 79 protein-coding genes, 30tRNA genes, and fourrRNA genes. The phylogenetic analysis of 19 species belonging to the Moraceae family confirmed the phylogenetic proximity of the genusArtocarpusandMorusand the genetic similarity ofA. camansiandA. altilis.

关键词： Plastid genome plastome phylogenetic relationships

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