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The spatial zonation of the murine placental vasculature is specified by epigenetic mechanisms

Developmental Cell 2025年第10期60卷 1467-1482.e8页

作者： Gehrs, Stephanie Jakab, Moritz Gutjahr, Ewgenija Gu, Zuguang Weichenhan, Dieter Mallm, Jan-Philipp Mogler, Carolin Schlesner, Matthias Plass, Christoph Schlereth, Katharina Augustin, Hellmut G. Division of Vascular Oncology and Metastasis German Cancer Research Center (DKFZ) Heidelberg 69120 Germany European Center for Angioscience (ECAS) Medical Faculty Mannheim Heidelberg University Mannheim 68167 Germany Faculty of Biosciences Heidelberg University Heidelberg 69120 Germany Institute of Pathology University Clinic Heidelberg Heidelberg 69120 Germany Computational Oncology Group Molecular Precision Oncology Program National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ) Heidelberg 69120 Germany Division of Cancer Epigenomics German Cancer Research Center (DKFZ) Heidelberg 69120 Germany Division of Chromatin Networks German Cancer Research Center (DKFZ) and Bioquant Heidelberg 69120 Germany Institute of Pathology TUM School of Medicine Technical University of Munich Munich 80333 Germany Biomedical Informatics Data Mining and Data Analytics Faculty of Applied Computer Science and Medical Faculty University of Augsburg Augsburg 86159 Germany

The labyrinthian fetoplacental capillary network is vital for proper nourishment of the developing embryo. Dysfunction of the maternal-fetal circulation is a primary cause of placental insufficiency. Here, we show that the spatial zonation of the murine placental labyrinth vasculature is controlled by flow-regulated epigenetic mechanisms. Spatiotemporal transcriptomic profiling identified a gradual change in the expression of epigenetic enzymes, including the de novo DNA methyltransferase 3a (DNMT3A). Loss of Dnmt3a resulted in DNA hypomethylation and perturbation of zonated placental gene expression. The resulting global DNA hypomethylation impaired the angiogenic capacity of endothelial cells. Global or endothelium-predominant deletion of Dnmt3a resulted in impaired placental vascularization and fetal growth retardation (FGR). Human placental endothelial gene expression profiling associated preeclampsia with reduced DNMT3A expression. Collectively, our study identified DMNT3A as critical methylome-regulator of placental endothelial gene expression and function with clinical implications for placental dysfunction, as it occurs during preeclampsia or FGR. © 2024 The Authors

关键词： angiogenesis DNA methylation DNMT3A epigenetic regulation growth retardation placental endothelium spatial zonation

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Sex differences in proteomics of cardiovascular disease – Results from the Yale-CMD registry

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IJC Heart and Vasculature 2025年 58卷 101667-101667页

作者： Liu, Yihan Wang, Zuoheng Collins, Sean P. Testani, Jeffery Safdar, Basmah Program in Computational Biology & Biomedical informatics Yale University New Haven CT United States Department of Biostatistics Yale University School of Public Health New Haven CT United States Department of Biomedical Informatics & Data Science Yale University School of Medicine New Haven CT United States Department of Emergency Medicine Vanderbilt University Medical Center Veterans Affairs Tennessee Valley Healthcare System Geriatric Research Education and Clinical Center (GRECC) Nashville TN United States Section of Cardiovascular Medicine Department of Internal Medicine Yale University School of Medicine New Haven CT United States Department of Emergency Medicine Yale University School of Medicine New Haven CT United States

Aims This study assessed sex-specific proteomic profiles by cardiovascular disease (CVD) phenotype (coronary artery disease [CAD] vs coronary microvascular dysfunction [CMD]) and describe their role in sex-specific pathways. Methods: In a secondary biobank analysis of the Yale-CMD registry, adults with ischemic symptoms who underwent cardiac positron emission test/computed tomography were categorized as a) controls (normal coronary flow reserve (CFR) > 2 without perfusion defect or coronary calcification), b) having CMD (CFR < 2 without defect or calcification), or c) having CAD (known CAD or new perfusion defect). Using proximity extension assays (Olink® Explore 3072), we examined 2944 proteins. Differential protein expression was assessed using linear regression models, adjusting for age, race, body mass index, diabetes, dyslipidemia, hypertension, or smoking. Results: Of 190 patients, 91 provided blood samples (mean age, 56 years;66 %, females;48 %, controls;24 %, CAD;27 %, CMD). Among controls, 15 proteins showed sex differences (5 proteins upregulated in females, 10 in males;false discovery rate [FDR < 0.05]). Upregulated in CAD patients were FSHB in females and INSL3 and EDDM3B in males (FDR < 0.05). Among CMD patients, SCGB3A1 and HGFAC were higher in females;INSL3, SPINT3, EDDM3B, and KLK3 were higher in males (FDR < 0.05). Per pathway analysis, females showed upregulation of immune pathways in CAD and lipid and glucose metabolism pathways in CMD. Males showed upregulated endothelial regulation of blood flow in CAD and increased angiogenesis in CMD. Conclusions: Sex differences exist in the proteomic profiles of CAD and CMD patients, highlighting a need for precision medicine. © 2025

关键词： Coronary artery disease Coronary microvascular dysfunction Olink Precision medicine Proteomics Sex differences

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Pairwise Learning for Autism Spectrum Disorder Imbalanced Classification 6

Pairwise Learning for Autism Spectrum Disorder Imbalanced Cl...

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6th IEEE Eurasia Conference on Biomedical Engineering, Healthcare and Sustainability, ECBIOS 2024

作者： Liu, Shu Wu, Qiang Yang, Xin Computational and Data Science PhD Program Middle Tennessee State University MurfreesboroTN United States University of Tennessee Department of Mathematics KnoxvilleTN United States Middle Tennessee State University Department of Computer Science MurfreesboroTN United States

ISBN: (纸本)9798350396133

This paper performs a classification task on data obtained from the Autism Brain Imaging data Exchange (ABIDE) repository. In real-world case analysis, the number of autism spectrum disorder (ASD) patients is much smaller than typically developed people. To address this issue, this paper proposes the utilization of pairwise robust support vector machine (PRSVM) algorithms to classify autism spectrum disorder (ASD) patients. In this project's experiments, the correlation matrix derived from functional magnetic resonance imaging (fMRI) data was employed as a classification feature. A comprehensive evaluation was conducted to compare the classification performance of PRSVM with various machine learning methods. The comparative analysis encompassed various aspects, including different data dimensions, imbalanced ratios, and sample sizes, providing valuable insights into the relative performance of the algorithms under different experimental conditions. The experimental results demonstrate that PRSVM can detect autistic patients more accurately when the data is imbalanced. Moreover, the results indicate that PRSVM outperforms or achieves comparable performance to other conventional classification methods in a variety of situations. Furthermore, our approach can be further improved by augmenting the training set with either exclusively normal person samples or by incorporating patient samples and normal people samples in a proportionate manner. This augmentation strategy holds promising application value, as it contributes to improving the performance and robustness of our method. © 2024 IEEE.

关键词： Diseases

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An Iterative Thresholding Method for the Minimum Compliance Problem

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Communications in computational Physics 2023年第4期33卷 1189-1216页

作者： Luyu Cen Wei Hu Dong Wang Xiaoping Wang Department of Mathematics Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongChina The Program in Applied and Computational Mathematics Princeton UniversityPrincetonNew JerseyUSA School of Science and Engineering The Chinese University of Hong KongShenzhenGuangdong 518172China Shenzhen International Center for Industrial and Applied Mathematics Shenzhen Research Institute of Big DataGuangdong 518172China

In this paper,we propose a simple energy decaying iterative thresholding algorithm to solve the two-phase minimum compliance *** material domain is implicitly represented by its characteristic function,and the problem is formulated into a minimization problem by the principle of minimum complementary *** prove that the energy is decreasing in each *** effective continuation schemes are proposed to avoid trapping into the local *** results on 2D isotropic linear material demonstrate the effectiveness of the proposed methods.

关键词： Minimum compliance convolution thresholding linear elasticity

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Implicit Asymptotic Preserving Method for Linear Transport Equations

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Communications in computational Physics 2017年第6期22卷 157-181页

作者： Qin Li Li Wang Mathematics Department University of Wisconsin-Madison480 Lincoln Dr.MadisonWI 53705USA Departments of Mathematics and Computational Data-Enabled Science and Engineering Program State University of New York at Buffalo244 Mathematics BuildingBuffaloNY 14260USA The Optimization Group TheWisconsin Institute ofDiscoveryMadisonWI 53715USA

The computation of the radiative transfer equation is expensive mainly due to two stiff terms:the transport term and the collision *** stiffness in the former comes from the fact that particles(such as photons)travel at the speed of light,while that in the latter is due to the strong scattering in the optically thick *** study the fully implicit scheme for this equation to account for the *** main challenge in the implicit treatment is the coupling between the spacial and angular coordinates that requires the large size of the to-be-inverted matrix,which is also ill-conditioned and not necessarily *** main idea is to utilize the spectral structure of the ill-conditioned matrix to construct a pre-conditioner,which,along with an exquisite split of the spatial and angular dependence,significantly improve the condition number and allows a matrix-free *** also design a fast solver to compute this pre-conditioner explicitly in *** method is shown to be efficient in both diffusive and free streaming limit,and the computational cost is comparable to the state-of-the-art *** examples including anisotropic scattering and two-dimensional problems are provided to validate the effectiveness of our method.

关键词： Implicitmethod asymptotic preserving pre-conditioner diffusive regime free streaming limit

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Nuclear Neural Networks: Emulating Late Burning Stages in Core Collapse Supernova Progenitors

arXiv

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arXiv 2025年

作者： Grichener, Aldana Renzo, Mathieu Kerzendorf, Wolfgang E. Farmer, Rob de Mink, Selma E. Bellinger, Earl Patrick Chan, Chi-Kwan Chen, Nutan Farag, Ebraheem Justham, Stephen Steward Steward Observatory Department of Astronomy University of Arizona 933 North Cherry Avenue TucsonAZ85721 United States Max Planck Institute for Astrophysics Karl-Schwarzschild-Str. 1 Garching85748 Germany Department of Physics Technion Haifa3200003 Israel Department of Computational Mathematics Science and Engineering Michigan State University East LansingMI48824 United States Department of Physics and Astronomy Michigan State University East LansingMI48824 United States Ludwig-Maximilians-Universitat Munchen Geschwister-Scholl-Platz 1 Munchen80539 Germany Department of Astronomy Yale University New HavenCT06511 United States Steward Observatory Department of Astronomy University of Arizona 933 North Cherry Avenue TucsonAZ85721 United States Data Science Institute University of Arizona 1230 N. Cherry Avenue TucsonAZ85721 United States Program in Applied Mathematics University of Arizona 617 North Santa Rita TucsonAZ85721 United States Machine Learning Research Lab Volkswagen AG Munich38440 Germany

One of the main challenges in modeling massive stars to the onset of core collapse is the computational bottleneck of nucleosynthesis during advanced burning stages. The number of isotopes formed requires solving a large set of fully-coupled stiff ordinary differential equations (ODEs), making the simulations computationally intensive and prone to numerical instability. To overcome this barrier, we design a nuclear neural network (NNN) framework with multiple hidden layers to emulate nucleosynthesis calculations and conduct a proof-of-concept to evaluate its performance. The NNN takes the temperature, density and composition of a burning region as input and predicts the resulting isotopic abundances along with the energy generation and loss rates. We generate training sets for initial conditions corresponding to oxygen core depletion and beyond using large nuclear reaction networks, and compare the predictions of the NNNs to results from a commonly used small net. We find that the NNNs improve the accuracy of the electron fraction by 280 − 660 % and the nuclear energy generation by 250 − 750 %, consistently outperforming the small network across all timesteps. They also achieve significantly better predictions of neutrino losses on relatively short timescales, with improvements ranging from 100 − 106 %. While further work is needed to enhance their accuracy and applicability to different stellar conditions, integrating NNN trained models into stellar evolution codes is promising for facilitating large-scale generation of core-collapse supernova (CCSN) progenitors with higher physical fidelity. © 2025, CC BY.

关键词： Nucleosynthesis

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What affects the performance of POD for the simulation of heat transfer through building component? 8

What affects the performance of POD for the simulation of he...

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8th International Building Physics Conference, IBPC 2021

作者： Hou, Tianfeng Roels, Staf Janssen, Hans KU Leuven Department of Civil Engineering Building Physics Section Leuven3001 Belgium Data Assimilation Research Team RIKEN Center for Computational Science Kobe Japan RIKEN Prediction Science Laboratory Kobe Japan RIKEN Interdisciplinary Theoretical and Mathematical Sciences Program Kobe Japan

The capability of the proper orthogonal decomposition for the simulation of heat transfer in building components is investigated via three applications: linear heat transfer (not coupled to mass transfer), mildly non-linear heat transfer (coupled to air and moisture transfer (hygroscopic)) and highly non-linear heat transfer (coupled to moisture transfer (capillary)). It is shown that increasing non-linearity leads to an increasing number of required construction modes. To further investigate the reason for this degrading performance of POD, the singular values' decay progress from the different training snapshots is addressed in this paper. The results confirm that a fast decay of the singular values implies a high interrelation of the snapshots and a better performance of the POD method. © 2021 Institute of Physics Publishing. All rights reserved.

关键词： Heat transfer

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Representation Learning to Advance Multi-institutional Studies with Electronic Health Record data

arXiv

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arXiv 2025年

作者： Zhou, Doudou Tong, Han Wang, Linshanshan Liu, Suqi Xiong, Xin Gan, Ziming Griffier, Romain Hejblum, Boris Liu, Yun-Chung Hong, Chuan Bonzel, Clara-Lea Cai, Tianrun Pan, Kevin Ho, Yuk-Lam Costa, Lauren Panickan, Vidul A. Gaziano, J. Michael Mandl, Kenneth Jouhet, Vianney Thiebaut, Rodolphe Xia, Zongqi Cho, Kelly Liao, Katherine Cai, Tianxi Department of Statistics and Data Science National University of Singapore Singapore Department of Statistics Columbia University NY United States Harvard T.H. Chan School of Public Health MA United States Harvard Medical School MA United States Department of Statistics University of Chicago ChicagoIL United States Univ. Bordeaux INSERM Bordeaux Population Health Research Center Bordeaux France CHU de Bordeaux Service d’Information Médicale Bordeaux France Inria SISTM Team Talence France Duke University DurhamNC United States VA Boston Healthcare System BostonMA United States Brigham and Women’s Hospital BostonMA United States Brown University ProvidenceRI United States Computational Health Informatics Program Boston Children’s Hospital BostonMA United States Department of Neurology University of Pittsburgh PittsburghPA United States

The adoption of EHRs has expanded opportunities to leverage data-driven algorithms in clinical care and research. A major bottleneck in effectively conducting multi-institutional EHR studies is the data heterogeneity across systems with numerous codes that either do not exist or represent different clinical concepts across institutions. The need for data privacy further limits the feasibility of including multi-institutional patient-level data required to study similarities and differences across patient subgroups. To address these challenges, we developed the GAME algorithm. Tested and validated across 7 institutions and 2 languages, GAME integrates data in several levels: (1) at the institutional level with knowledge graphs to establish relationships between codes and existing knowledge sources, providing the medical context for standard codes and their relationship to each other;(2) between institutions, leveraging language models to determine the relationships between institution-specific codes with established standard codes;and (3) quantifying the strength of the relationships between codes using a graph attention network. Jointly trained embeddings are created using transfer and federated learning to preserve data privacy. In this study, we demonstrate the applicability of GAME in selecting relevant features as inputs for AI-driven algorithms in a range of conditions, e.g., heart failure, rheumatoid arthritis. We then highlight the application of GAME harmonized multi-institutional EHR data in a study of Alzheimer’s disease outcomes and suicide risk among patients with mental health disorders, without sharing patient-level data outside individual institutions. In summary, the GAME algorithm advances the feasibility of multi-institution EHR studies providing a method for code translation and harmonization at the scale with the adaptability needed for high-dimensional data-driven algorithms in clinical research and care. Moreover, we demonstrate that the valuab

关键词： Electronic health record

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Identifying Deprescribing Opportunities With Large Language Models in Older Adults: Retrospective Cohort Study

JMIR Aging

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JMIR Aging 2025年 8卷 e69504页

作者： Socrates, Vimig Wright, Donald S. Huang, Thomas Fereydooni, Soraya Dien, Christine Chi, Ling Albano, Jesse Patterson, Brian Kanaparthy, Naga Sasidhar Wright, Catherine X. Loza, Andrew Chartash, David Iscoe, Mark Taylor, Richard Andrew Department of Biomedical Informatics and Data Science School of Medicine Yale University New Haven CT United States Program of Computational Biology and Bioinformatics Yale University New Haven CT United States Department of Emergency Medicine School of Medicine Yale University New Haven CT United States VA Connecticut Healthcare System US Department of Veterans Affairs West Haven CT United States Department of Pharmacy Yale New Haven Hospital New Haven CT United States BerbeeWalsh Department of Emergency Medicine University of Wisconsin–Madison Madison WI United States Section of Cardiovascular Medicine Department of Internal Medicine Yale School of Medicine New Haven CT United States School of Medicine University College Dublin Dublin Ireland Department of Biostatistics School of Public Health Yale University New Haven CT United States

Background: Polypharmacy, the concurrent use of multiple medications, is prevalent among older adults and associated with increased risks for adverse drug events including falls. Deprescribing, the systematic process of discontinuing potentially inappropriate medications, aims to mitigate these risks. However, the practical application of deprescribing criteria in emergency settings remains limited due to time constraints and criteria complexity. Objective: This study aims to evaluate the performance of a large language model (LLM)–based pipeline in identifying deprescribing opportunities for older emergency department (ED) patients with polypharmacy, using 3 different sets of criteria: Beers, Screening Tool of Older People’s Prescriptions, and Geriatric Emergency Medication Safety Recommendations. The study further evaluates LLM confidence calibration and its ability to improve recommendation performance. Methods: We conducted a retrospective cohort study of older adults presenting to an ED in a large academic medical center in the Northeast United States from January 2022 to March 2022. A random sample of 100 patients (712 total oral medications) was selected for detailed analysis. The LLM pipeline consisted of two steps: (1) filtering high-yield deprescribing criteria based on patients’ medication lists, and (2) applying these criteria using both structured and unstructured patient data to recommend deprescribing. Model performance was assessed by comparing model recommendations to those of trained medical students, with discrepancies adjudicated by board-certified ED physicians. Selective prediction, a method that allows a model to abstain from low-confidence predictions to improve overall reliability, was applied to assess the model’s confidence and decision-making thresholds. Results: The LLM was significantly more effective in identifying deprescribing criteria (positive predictive value: 0.83;negative predictive value: 0.93;McNemar test for paired proportion

关键词： calibration deprescribing emergency medicine geriatrics large language models natural language processing potentially inappropriate medication list

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Transforming agriculture with Machine Learning, Deep Learning, and IoT: perspectives from Ethiopia—challenges and opportunities

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Discover Agriculture 2024年第1期2卷 1-34页

作者： Benti, Natei Ermias Chaka, Mesfin Diro Semie, Addisu Gezahegn Warkineh, Bikila Soromessa, Teshome Computational Data Science Program College of Natural and Computational Sciences Addis Ababa University Addis Ababa Ethiopia Department of Plant Biology and Biodiversity Management College of Natural and Computational Sciences Addis Ababa University Addis Ababa Ethiopia Center for Environmental Science College of Natural and Computational Sciences Addis Ababa University Addis Ababa Ethiopia

Agriculture holds a crucial position in maintaining livelihoods and securing food sources, particularly in nations such as Ethiopia, where a substantial portion of the population depends on agricultural pursuits. However, meeting the growing demand for food production amidst population growth presents considerable challenges. Recent advancements in technology, particularly in the areas of Machine Learning (ML), Deep Learning (DL), and the Internet of Things (IoT) offer promising solutions to address these challenges. This paper explores the potential of integrating ML, DL, and IoT technologies in agriculture to revolutionize the sector. By harnessing data-driven insights, farmers can make informed decisions regarding crop management, soil health, and weather patterns, leading to optimized resource allocation and increased productivity. Moreover, IoT devices enable the real-time monitoring and control of agricultural operations, enhancing sustainability and productivity. Despite the opportunities presented by these technologies, there are also challenges to overcome, such as data quality, connectivity issues, and the need for farmer education. However, with concerted efforts and investment, Ethiopia and other agricultural regions can unlock the full potential of ML, DL, and IoT technologies to ensure food security, alleviate poverty, and drive economic development. This review paper offers perspectives on the present status, challenges, and future possibilities regarding the integration of ML, DL, and IoT in agriculture. It underscores the transformative potential of these technologies within the sector.

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