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Epigenetic connection between gut microbiota-derived short-chain fatty acids and chromatin histone modification in kidney diseases

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Chinese Medical Journal 2022年第14期135卷 1692-1694页

作者： Lingzhi Li Shenyu Zhao Ting Xiang Han Feng Liang Ma Ping Fu Division of Nephrology Kidney Research InstituteWest China Hospital of Sichuan UniversityChengduSichuan 610041China Department of Cardiovascular Medicine West China Hospital of Sichuan UniversityChengduSichuan 610041China Department of Biostatistics and Data Science School of Public HealthUniversity of Texas Health Science Center at HoustonHoustonTXUSA

Gut microbiota-derived metabolites influence host physiology and pathology,where short-chain fatty acids(SCFAs)are the main class of gut microbiota-derived metabolites.[1]SCFAs are fatty acids containing 1 to 6 carbon atoms,including acetate,propionate,butyrate,and pentanoate,which provide 6%to 10%of the body’s total daily energy and 60%to 70%of the colonic epithelial energy needed.[2]Anaerobic bacteria principally generate the SCFAs[1]in the *** produced,SCFAs are mainly absorbed in the colon(90%–95%),reach circulation,and play roles for distal organs and tissues.[2]

关键词： organs intestine colon

Estimation and Evaluation of the Resource-Constrained Optimal Dynamic Treatment Rule: An Application to HIV Care Retention

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arXiv 2025年

作者： Montoya, Lina M. Geng, Elvin Adhiambo, Harriet F. Petersen, Maya L. School of Data Science and Society Department of Biostatistics University of North Carolina Chapel Hill United States Division of Infectious Diseases Washington University in St. Louis School of Medicine United States Department of Child Family and Population Health Nursing University of Washington United States University of California Berkeley United States

The optimal strategy for deploying a treatment in a population may recommend giving all in the population that treatment. Such a strategy may not be feasible, especially in resource-limited settings. One approach for determining how to allocate a treatment in such settings is the resource-constrained optimal dynamic treatment rule (RC ODTR) SuperLearner algorithm, developed by Luedtke and van der Laan. In this paper, we describe this algorithm, offer various novel approaches for presenting the RC ODTR and its value in terms of benefit and cost, and provide practical guidance on implementing the algorithm (including software). In particular, we apply this method to the Adaptive Strategies for Preventing and Treating Lapses of Retention in HIV care (NCT02338739) trial to determine how to best allocate conditional cash transfers (CCTs) for increasing HIV care adherence given varying constraints on the proportion of people who can receive CCTs in the population, providing one of the few applied illustrations of this method and novel substantive findings. We find that there are clinical and monetary benefits to deploying CCTs to a small percent (e.g., 10%) of the population compared to administering the care standard for all;however, results suggest that these incremental benefits are only due to the loosening of constraints, rather than a presence of treatment effect heterogeneity strong enough to drive a more efficient and effective constrained allocation approach. © 2025, CC BY.

关键词： Constrained optimization

Network security modeling using NetFlow data: Detecting botnet attacks in IP traffic

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arXiv 2021年

作者： Subramaniam, Ganesh Chen, Huan Varadhan, Ravi Archibald, Robert Data Science and AI Research At and T Chief Data Office Department of Biostatistics Johns Hopkins Bloomberg School of Public Health Division of Biostatistics and Bioinformatics Department of Oncology Johns Hopkins University

Cybersecurity, security monitoring of malicious events in IP traffic, is an important field largely unexplored by statisticians. Computer scientists have made significant contributions in this area using statistical anomaly detection and other supervised learning methods to detect specific malicious events. In this research, we investigate the detection of botnet command and control (C&C) hosts in massive IP traffic. We use the NetFlow data, the industry standard for monitoring of IP traffic for exploratory analysis and extracting new features. Using statistical as well as deep learning models, we develop a statistical intrusion detection system (SIDS) to predict traffic traces identified with malicious attacks. Employing interpretative machine learning techniques, botnet traffic signatures are derived. These models successfully detected botnet C&C hosts and compromised devices. The results were validated by matching predictions to existing blacklists of published malicious IP addresses. Copyright © 2021, The Authors. All rights reserved.

关键词： Network security

Impact of selection bias on polygenic risk score estimates in healthcare settings

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Psychological Medicine 2023年第6期89卷 7435-7445页

作者： Lee, Younga Heather Thaweethai, Tanayott Sheu, Yi-Han Feng, Yen-Chen Anne Karlson, Elizabeth W. Ge, Tian Kraft, Peter Smoller, Jordan W. Psychiatric and Neurodevelopmental Genetics Unit Center for Genomic Medicine Massachusetts General Hospital Boston MA United States Stanley Center for Psychiatric Research Broad Institute of MIT and Harvard Cambridge MA United States Harvard Medical School Boston MA United States Biostatistics Center Massachusetts General Hospital Boston MA United States Analytic and Translational Genetics Unit Center for Genomic Medicine Massachusetts General Hospital Boston MA United States Division of Biostatistics and Data Science Institute of Epidemiology and Preventive Medicine National Taiwan University Taipei Taiwan Division of Rheumatology Immunity and Inflammation Department of Medicine Brigham and Women's Hospital Boston MA United States Center for Precision Psychiatry Massachusetts General Hospital Boston MA United States Department of Epidemiology Harvard T. H. Chan School of Public Health Boston MA United States Department of Biostatistics Harvard T. H. Chan School of Public Health Boston MA United States

Background Hospital-based biobanks are being increasingly considered as a resource for translating polygenic risk scores (PRS) into clinical practice. However, since these biobanks originate from patient populations, there is a possibility of bias in polygenic risk estimation due to overrepresentation of patients with higher frequency of healthcare interactions. Methods PRS for schizophrenia, bipolar disorder, and depression were calculated using summary statistics from the largest available genomic studies for a sample of 24 153 European ancestry participants in the Mass General Brigham (MGB) Biobank. To correct for selection bias, we fitted logistic regression models with inverse probability (IP) weights, which were estimated using 1839 sociodemographic, clinical, and healthcare utilization features extracted from electronic health records of 1 546 440 non-Hispanic White patients eligible to participate in the Biobank study at their first visit to the MGB-affiliated hospitals. Results Case prevalence of bipolar disorder among participants in the top decile of bipolar disorder PRS was 10.0% (95% CI 8.8-11.2%) in the unweighted analysis but only 6.2% (5.0-7.5%) when selection bias was accounted for using IP weights. Similarly, case prevalence of depression among those in the top decile of depression PRS was reduced from 33.5% (31.7-35.4%) to 28.9% (25.8-31.9%) after IP weighting. Conclusions Non-random selection of participants into volunteer biobanks may induce clinically relevant selection bias that could impact implementation of PRS in research and clinical settings. As efforts to integrate PRS in medical practice expand, recognition and mitigation of these biases should be considered and may need to be optimized in a context-specific manner. © The Author(s), 2023. Published by Cambridge University Press.

关键词： biobank causal inference inverse probability weighting polygenic risk score selection bias

TENSOR-BASED HOMOGENEOUS POLYNOMIAL DYNAMICAL SYSTEM ANALYSIS FROM data∗

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arXiv 2025年

作者： Mao, Xin Dong, Anqi He, Ziqin Mei, Yidan Mei, Shenghan Chen, Can School of Data Science and Society University of North Carolina at Chapel Hill Chapel HillNC27599 United States Division of Decision and Control Systems Department of Mathematics KTH Royal Institute of Technology StockholmSE-100 44 Sweden Department of Mathematics University of North Carolina at Chapel Hill Chapel HillNC27599 United States School of Data Science and Society Department of Mathematics Department of Biostatistics University of North Carolina at Chapel Hill Chapel HillNC27599 United States

Numerous complex real-world systems, such as those in biological, ecological, and social networks, exhibit higher-order interactions that are often modeled using polynomial dynamical systems or homogeneous polynomial dynamical systems (HPDSs). However, identifying system parameters and analyzing key system-theoretic properties remain challenging due to their inherent nonlinearity and complexity, particularly for large-scale systems. To address these challenges, we develop an innovative computational framework in this article that leverages advanced tensor decomposition techniques, namely tensor train and hierarchical Tucker decompositions, to facilitate efficient identification and analysis of HPDSs that can be equivalently represented by tensors. Specifically, we introduce memory-efficient system identification techniques for directly estimating system parameters represented through tensor decompositions from time-series data. Additionally, we develop necessary and sufficient conditions for determining controllability and observability using the tensor decomposition-based representations of HPDSs, accompanied by detailed complexity analyses that demonstrate significant reductions in computational demands. The effectiveness and efficiency of our framework are validated through numerical *** Codes 15A69, 53A45, 93B05, 93B07, 93B40, 93C15, 93D05 © 2025, CC BY.

关键词： Tensors

Influence of electric field orientation on the effect of ocular current stimulation using full field electroretinogram

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Influence of electric field orientation on the effect of ocu...

作者： Blum, Maren-Christina Leydolph, Lilly Klee, Sascha Institute of Biomedical Engineering and Informatics Faculty of Computer Sciences and Automation Technische Universität Ilmenau Ilmenau Germany Department of General Health Studies Division Biostatistics and Data Science Karl Landsteiner University of Health Sciences Krems an der Donau Austria

Ocular current stimulation (CS) exhibits potential for the treatment of neurodegenerative ocular diseases. For a full field electroretinogram (ffERG) we found no CS effect on the characteristic waves (a-wave, b'-wave, and b-wave). To investigate whether the orientation of the generated electric field has an influence on the CS effect, this study repeated the previous ffERG study with changing one CS electrode position and compared the results of both studies. In the first study 15 (8 m, 27.5 ± 4.5 years) and in the second study 17 (7 m, 22.0 ± 1.9 years) healthy volunteers were stimulated with an anodal, cathodal, and sham direct CS of 800 μA for 5 min in three sessions (randomized, different days). For both studies, a cut-sized ring rubber electrode was placed around the eye. A square rubber electrode was placed for the first study at the ipsilateral temple and for the second study at the visual cortex. Before (ERG 1) and during (ERG 2) the CS, the ffERG was measured. For both studies, the difference between the ERG 1 and ERG 2 measurement (CS effect) for the three characteristic waves was analyzed and compared between the studies. For statistical analysis, the Mann-Whitney U test with Bonferroni correction was applied (α = 0.05). The comparison of the data distribution showed only slight differences between the studies. The Mann-Whitney U test found no significant difference of the CS effect between the studies for all amplitudes and CS groups (p ≥ 0.0055). In the mean, the latency differences were smaller than the time resolution, therefore no statements for latency effects were possible. It can be concluded that the retinal cells generating the ffERG are not affected by ocular CS in either electrode montages tested. © 2021 by Walter de Gruyter Berlin/Boston.

关键词： Rubber

Full-field electroretinography examinations of the human eye with the eye diagnostic device PEP-2000-First results

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Full-field electroretinography examinations of the human eye...

作者： Schieding, Nikola Reuter, Thomas Grundmann, Andreas Walther, Sebastian Klee, Sascha ICM-Institut Chemnitzer Maschinen-und Anlagenbau E.V. Otto-Schmerbach-Str. 19 Chemnitz09117 Germany Department of General Health Studies Division Biostatistics and Data Science Karl Landsteiner University of Health Sciences Krems an der Donau Austria Institute of Biomedical Engineering and Informatics Faculty of Computer Sciences and Automation TU Ilmenau Ilmenau Germany

Full-field electroretinography (full-field ERG) forms the diagnostic basis for numerous pathologies of the eye. For this reason, fast and accurate diagnostics in the field of ophthalmology are essential. Two examination techniques, full-field ERG and pupillometry were combined in a diagnostic device developed by ICM e.V. to reduce the examination process for both examiners and patients. In this paper, the device is examined for the quality of the full-field ERG measurements. A feasibility study with 12 healthy subjects (3 f, 9 m, 36.33 ± 11.94 years) was conducted to evaluate the device. The results showed that the peak times for both light-and dark-adapted measurements were within the range of the researched literature values. However, the amplitudes were markedly lower in both measurements compared to the averaged literature values (dark-adapted about 8.5-fold and light-adapted about 5.5-fold) and are clearly outside the range of values researched. The main reason for this is the use of cup electrodes, which were placed on the skin of the lower eyelid. Nevertheless, plausible and comparable analysis values could be obtained with the eye diagnostic device PEP-2000. Further studies with wire electrodes will be performed. © 2022 by Walter de Gruyter Berlin/Boston.

关键词： Ophthalmology

Technical light-field setup for 3D imaging of the human nerve head validated with an eye model

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Technical light-field setup for 3D imaging of the human nerv...

作者： Schramm, Stefan Dietzel, Alexander Blum, Maren-Christina Link, Dietmar Klee, Sascha Institute of Biomedical Engineering and Informatics Faculty of Computer Sciences and Automation Technische Universität Ilmenau Ilmenau Germany Department of General Health Studies Division Biostatistics and Data Science Karl Landsteiner University of Health Sciences Krems an der Donau Austria

With the new technology of 3D light field (LF) imaging, fundus photography can be expanded to provide depth information. This increases the diagnostic possibilities and additionally improves image quality by digitally refocusing. To provide depth information in the human optic nerve head such as in glaucoma diagnostics, a mydriatic fundus camera was upgraded with an LF imager. The aim of the study presented here was the validation of the technical setup and resulting depth estimations with an appropriate eye model. The technical setup consisted of a mydriatic fundus camera (FF450, Carl Zeiss Meditec AG, Jena, Germany) and an LF imager (R12, Raytrix GmbH, Kiel, Germany). The field of view was set to 30°. The eye model (24.65 mm total length) consisted of a two-lens optical system and interchangeable fundus models with papilla excavations from 0.2 to 1 mm in steps of 0.2 mm. They were coated with red acrylic lacquer and vessels were drawn with a thin brush. 15 images were taken for each papilla depth illuminated with green light (wavelength 520 nm ± 20 nm). Papilla depth was measured from the papilla ground to the surrounding flat region. All 15 measurements for each papilla depth were averaged and compared to the printed depth. It was possible to perform 3D fundus imaging in an eye model by means of a novel LF-based optical setup. All LF images could be digitally refocused subsequently. Depth estimation in the eye model was successfully performed over a 30° field of view. The measured virtual depth and the printed model papilla depth is linear correlated. The presented LF setup allowed high-quality 3D one-shot imaging and depth estimation of the optic nerve head in an eye model. © 2021 by Walter de Gruyter Berlin/Boston.

关键词： Optical systems

An Overview and Recent Developments in the Analysis of Multistate Processes

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arXiv 2025年

作者： Gorfine, Malka Cook, Richard J. Andersen, Per Kragh Therneau, Terry M. Joly, Pierre Putter, Hein Perme, Maja Pohar Abrahamowicz, Michal Department of Statistics and Operations Research Tel Aviv University Israel Department of Statistics and Actuarial Science University of Waterloo Canada Section of Biostatistics University of Copenhagen Denmark Division of Biomedical Statistics and Informatics Mayo Clinic New York United States Inserm ISPED Bordeaux Populations Health Research Center University of Bordeaux France Department of Biomedical Data Sciences Leiden University Medical Center Leiden Netherlands Department of Biostatistics and Medical Informatics Medical Faculty University of Ljubljana Slovenia Department of Epidemiology Biostatistics and Occupational Health McGill University MontrealQC Canada

Multistate models offer a powerful framework for studying disease processes and can be used to formulate intensity-based and more descriptive marginal regression models. They also represent a natural foundation for the construction of joint models for disease processes and dynamic marker processes, as well as joint models incorporating random censoring and intermittent observation times. This article reviews the ways multistate models can be formed and fitted to life history data. Recent work on pseudo-values and the incorporation of random effects to model dependence on the process history and between-process heterogeneity are also discussed. The software available to facilitate such analyses is listed. © 2025, CC BY.

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