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arXiv 2021年

作者： George, Ashish B. Korolev, Kirill S. Department of Physics Boston University BostonMA02215 United States Biological Design Center Boston University BostonMA02215 United States Carl R. Woese Institute for Genomic Biology Department of Plant Biology University of Illinois at Urbana-Champaign UrbanaIL61801 United States Graduate Program in Bioinformatics Boston University BostonMA02215 United States

Assembling optimal microbial communities is key for various applications in biofuel production, agriculture, and human health. Finding the optimal community is challenging because the number of possible communities grows exponentially with the number of species, and so an exhaustive search cannot be performed even for a dozen species. A heuristic search that improves community function by adding or removing one species at a time is more practical, but it is unknown whether this strategy can discover an optimal or nearly optimal community. Using consumer-resource models with and without cross-feeding, we investigate how the efficacy of search depends on the distribution of resources, niche overlap, cross-feeding, and other aspects of community ecology. We show that search efficacy is determined by the ruggedness of the appropriately-defined ecological landscape. We identify specific ruggedness measures that are both predictive of search performance and robust to noise and low sampling density. The feasibility of our approach is demonstrated using experimental data from a soil microbial community. Overall, our results establish the conditions necessary for the success of the heuristic search and provide concrete design principles for building high-performing microbial consortia. © 2021, CC BY-NC-ND.

关键词： Microorganisms

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METTL4 is an snRNA m6 Am methyltransferase that regulates RNA splicing

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细胞研究（英文版） 2020年第6期30卷 544-547页

作者： Hao Chen Lei Gu Esteban A.Orellana Yuanyuan Wang Jiaojiao Guo Qi Liu Longfei Wang Zhangfei Shen Hao Wu Richard I.Gregory Yi Xing Yang Shi Division of Newborn Medicine and Program in Epigenetics Boston Children's Hospital Harvard Medical School 300 Longwood AvenueBoston MA 02115 USA Stem Cell Program Division of Hematology/Oncology Boston Children's Hospital Department of Biological Chemistry and Molecular Pharmacology Harvard Medical SchoolBoston MA 02115 USA Bioinformatics Interdepartmental Graduate Program University of California Los Angeles Los Angeles CA 90095USA College of Science Northeastern University 360 Huntington Ave. Boston MA 02115 USA Program in Cellular and Molecular Medicine Boston Children's Hospital Boston MA 02115 USA Department of Biological Chemistry and Molecular Pharmacology Harvard Medical School Boston MA 02115 USA Division of Newborn Medicine and Program in Epigenetics Boston Children's Hospital Harvard Medical School 300 Longwood AvenueBoston MA 02115 USA Program in Cellular and Molecular Medicine Boston Children's Hospital Boston MA 02115 USA Department of Biological Chemistry and Molecular Pharmacology Harvard Medical School Boston MA 02115 USA Center for Computational and Genomic Medicine The Children's Hospital of Philadelphia Philadelphia PA 19104 USA Department of Pathology and Laboratory Medicine University of PennsylvaniaPhiladelphia PA 19104 USA

Dear Editor, Protein coding mRNAs and non-coding RNAs are extensively modified by chemical modifications,1 including methylation of the N6 position of adenosine (m6A).2 While mRNA internal m6A methylation is mediated by METTL3 and METTL14, which are members of the MT-A70 family,2 N6-methylation of cap-adjacent N6,2'-O-dimethyladenosine (m6Am) is catalyzed by PCIF1.3-6 Non-coding RNAs are also m6Am methylated internally,7 but the corresponding enzyme remains *** we provide evidence that METTL4 mediates internal m6Am methylation of U2 small nuclear RNA (snRNA).

关键词： Epigenetics RNA modification RNA splicing

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A structural haplotype in the 17q21.31 MAPT region is associated with increased risk for chronic traumatic encephalopathy endophenotypes

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Cell Reports Medicine 2025年第5期6卷 102084-102084页

作者： Han, Xudong Zhang, Yichi Petrosky, Jillian N. Bald, Sarah Sherva, Richard M. Labadorf, Adam Cherry, Jonathan D. Chung, Jaeyoon Farrell, Kurt Abdolmohammadi, Bobak Durape, Shruti Martin, Brett M. Palmisano, Joseph N. Farrell, John J. Alvarez, Victor E. Huber, Bertrand R. Dwyer, Brigid Daneshvar, Daniel H. Jun, Gyungah R. Lunetta, Kathryn L. Goldstein, Lee E. Katz, Douglas I. Cantu, Robert C. Shenton, Martha E. Cummings, Jeffrey L. Reiman, Eric M. Stern, Robert A. Alosco, Michael L. Tripodis, Yorghos Farrer, Lindsay A. Stein, Thor D. Crary, John F. McKee, Ann C. Mez, Jesse Bioinformatics Graduate Program Boston University Boston MA United States Section of Biomedical Genetics Department of Medicine Boston University Chobanian & Avedisian School of Medicine Boston MA United States Department of Neurology Boston University Chobanian & Avedisian School of Medicine Boston MA United States Boston University Alzheimer's Disease Research Center Boston University Chobanian & Avedisian School of Medicine Boston MA United States Boston VA Healthcare System Boston MA United States Boston University Chronic Traumatic Encephalopathy Center Boston University Boston MA United States Department of Pathology and Laboratory Medicine Boston University Chobanian & Avedisian School of Medicine Boston MA United States Departments of Pathology Neuroscience and Artificial Intelligence & Human Health Neuropathology Brain Bank & Research CoRE Friedman Brain Institute Ronald M. Loeb Center for Alzheimer's Disease Icahn School of Medicine at Mount Sinai New York NY United States Biostatistics and Epidemiology Data Analytics Center Boston University School of Public Health Boston MA United States Bedford VA Healthcare System Bedford MA United States Braintree Rehabilitation Hospital Braintree MA United States Department of Physical Medicine and Rehabilitation Harvard Medical School Boston MA United States Department of Rehabilitation and Human Performance Brain Injury Research Center Icahn School of Medicine at Mount Sinai New York NY United States Department of Neurology Icahn School of Medicine at Mount Sinai New York NY United States Department of Biostatistics Boston University School of Public Health Boston MA United States Department of Ophthalmology Boston University Chobanian & Avedisian School of Medicine Boston MA United States Departments of Biomedical Electrical & Computer Engineering Boston University College of Engineering Boston MA United States Departments of Radiology and Psychiatry Boston University Chobanian & Avedisia

Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impact (RHI) exposure. Genetic variation in the 17q21.31 region, containing microtubule-associated protein tau (MAPT), has been implicated in tauopathies but has not been investigated in CTE. The region includes a megabase-long inversion (H1/H2) and copy-number variations, including α, β, and γ segments, which can be characterized as nine segregating structural haplotypes. We leveraged array SNP data and a reference panel across the 17q21.31 region to impute structural haplotypes and test their association with CTE endophenotypes in 447 European ancestry brain donors with RHI exposure. The H1β1γ1 haplotype was significantly associated with dementia and semi-quantitative tau burden in multiple cortical and medial temporal regions commonly affected in CTE. H1β1γ1 differential expression analyses in dorsolateral frontal cortex implicated cis-acting genes and inflammatory pathways. Taken together, the H1β1γ1 haplotype may help explain CTE heterogeneity among those with similar RHI exposure. © 2025 The Authors

关键词： 17q21.31 chronic traumatic encephalopathy dementia differential gene expression immune system MAPT repetitive head impacts structural haplotypes tauopathy traumatic brain injury

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Choroid plexus apocrine secretion shapes CSF proteome during mouse brain development

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Nature Neuroscience 2025年 1-14页

作者： Ya’el Courtney Joshua P. Head Neil Dani Frederick B. Shipley Maria K. Lehtinen Olga V. Chechneva Cameron Sadegh Yong Zhang Michael J. Holtzman Towia A. Libermann Department of Pathology Boston Children’s Hospital and Harvard Medical School Boston MA USA Graduate Program in Neuroscience Harvard Medical School Boston MA USA Department of Cell and Developmental Biology Vanderbilt University Nashville TN USA Graduate Program in Biophysics Harvard University Cambridge MA USA Department of Neurosurgery University of California Davis Sacramento CA USA Pulmonary and Critical Care Medicine Department of Medicine Washington University School of Medicine St. Louis MO USA Proteomics Bioinformatics and Systems Biology Center Beth Israel Deaconess Medical Center and Harvard Medical School Boston MA USA

The choroid plexus (ChP) regulates cerebrospinal fluid (CSF) composition, providing essential molecular cues for brain development; yet, embryonic ChP secretory mechanisms remain poorly defined. Here we identify apocrine secretion by embryonic ChP epithelial cells as a key regulator of the CSF proteome and neurodevelopment in male and female mice. We demonstrate that the activation of serotonergic 5-HT2Creceptors (by WAY-161503) triggers sustained Ca2+signaling, driving high-volume apocrine secretion in mouse and human ChP. This secretion alters the CSF proteome, stimulating neural progenitors lining the brain’s ventricles and shifting their developmental trajectory. Inducing ChP secretion in utero in mice disrupts neural progenitor dynamics, cerebral cortical architecture and offspring behavior. Additionally, illness or lysergic acid diethylamide exposure during pregnancy provokes coordinated ChP secretion in the mouse embryo. Our findings reveal a fundamental secretory pathway in the ChP that shapes brain development, highlighting how its disruption can have lasting consequences for brain health.

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Retroactivity Affects the Adaptive Robustness of Transcriptional Regulatory Networks

Retroactivity Affects the Adaptive Robustness of Transcripti...

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American Control Conference

作者： Junmin Wang Calin Belta Bioinformatics Graduate Program Boston University Boston MA 02215 USA Division of Systems Engineering and the Bioinformatics Graduate Program Boston University Boston MA 02215 USA

ISBN: (纸本)9781538679012;9781538679265

Adaptation refers to the system's ability to respond transiently to an input signal and subsequently recover to the initial states. Adaptive robustness, the ability of a network to achieve adaptation, is subject to the loading effects arising from modular interconnections, known as retroactivity. Studying the effects of retroactivity on adaptive robustness facilitates the employment of retroactivity to improve circuit performance in synthetic biology. In this paper, we developed a framework for quantifying adaptive robustness via statistical model checking and used this framework to investigate the effects of retroactivity on adaptive robustness. We found that increasing retroactivity tends to raise adaptive robustness in networks where the output protein does not perform regulatory functions, such as incoherent feedforward loops.

关键词： Self tuning input signal Robustness Circuit optimization Model checking Frameworks synthetic biology Network Gene Regulatory Networks Regulatory

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Prior COVID-19 vaccination and reduced risk of cerebrovascular diseases among COVID-19 survivors

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Journal of Medical Virology 2024年第5期96卷 e29648-e29648页

作者： Chen, Sheng-Yin Hsieh, Tina Yi Jin Hung, Yao-Min Oh, Jae Won Chen, Shen-Kai Wang, Shiow-Ing Chang, Renin Wei, James Cheng-Chung Clinical and Translational Epidemiology Unit Massachusetts General Hospital and Harvard Medical School Boston Morocco Division of Gastroenterology Massachusetts General Hospital and Harvard Medical School Boston Morocco Department of Epidemiology Harvard T. H. Chan School of Public Health Boston Morocco Department of Obstetrics & Gynecology Beth Israel Deaconess Medical Center Boston Morocco Department of Bioinformatics Harvard Medical School Boston Morocco Division of Nephrology Department of Internal Medicine Taipei Veterans General Hospital Taitung Branch Taiwan Master Program in Biomedicine College of Science and Engineering National Taitung University Taitung Taiwan College of Health and Nursing Meiho University Pingtung Taiwan Department of Neurology Brigham and Women's Hospital Boston Morocco Department of Neurology Harvard Medical School Boston MA United States Department of Education Kaohsiung Chang Gung Memorial Hospital Boston MA United States Center for Health Data Science Department of Medical Research Chung Shan Medical University Hospital Taichung Taiwan Institute of Medicine College of Medicine Chung Shan Medical University Taichung Taiwan Department of Nursing Jen-Teh Junior College of Medicine Nursing and Management Miaoli County Taiwan Department of Medical Education and Research Kaohsiung Veterans General Hospital Kaohsiung Taiwan Department of Emergency Medicine Kaohsiung Veterans General Hospital Kaohsiung Taiwan School of Medicine Chung Shan Medical University Taichung Taiwan Department of Recreation and Sports Management Tajen University Pintung Taiwan Department of Allergy Immunology & Rheumatology Chung Shan Medical University Hospital Taichung Taiwan Department of Nursing Chung Shan Medical University Taichung Taiwan Graduate Institute of Integrated Medicine China Medical University Taichung Taiwan Office of Research and Development Asia University Taichung Taiwan

The effects of COVID-19 vaccination on short-term and long-term cerebrovascular risks among COVID-19 survivors remained unknown. We conducted a national multi-center retrospective cohort study with 151 597 vaccinated and 151 597 unvaccinated COVID-19 patients using the TriNetX database, from January 1, 2020 to December 31, 2023. Patients baseline characteristics were balanced with propensity score matching (PSM). The outcomes were incident cerebrovascular diseases occurred between 1st and 30th days (short-term) after COVID-19 diagnosis. Nine subgroup analyses were conducted to explore potential effect modifications. We performed six sensitivity analyses, including evaluation of outcomes between 1st to 180th days, accounting for competing risk, and incorporating different variant timeline to test the robustness of our results. Kaplan-Meier curves and Log-Rank tests were performed to evaluate survival difference. Cox proportional hazards regressions were adopted to estimate the PSM-adjusted hazard ratios (HR). The overall short-term cerebrovascular risks were lower in the vaccinated group compared to the unvaccinated group (HR: 0.66, 95% CI: 0.56–0.77), specifically cerebral infarction (HR: 0.62, 95% CI: 0.48–0.79), occlusion and stenosis of precerebral arteries (HR: 0.74, 95% CI: 0.53–0.98), other cerebrovascular diseases (HR: 0.57, 95% CI: 0.42–0.77), and sequelae of cerebrovascular disease (HR: 0.39, 95% CI:0.23–0.68). Similarly, the overall cerebrovascular risks were lower in those vaccinated among most subgroups. The long-term outcomes, though slightly attenuated, were consistent (HR: 0.80, 95% CI: 0.73–0.87). Full 2-dose vaccination was associated with a further reduced risk of cerebrovascular diseases (HR: 0.63, 95% CI: 0.50–0.80) compared to unvaccinated patients. Unvaccinated COVID-19 survivors have significantly higher cerebrovascular risks than their vaccinated counterparts. Thus, clinicians are recommended to monitor this population closely for stroke even

关键词： cohort study COVID-19 vaccination strokes

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A systems biology approach uncovers novel disease mechanisms in age-related macular degeneration

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Cell Genomics 2023年第6期3卷 100302-100302页

作者： Orozco, Luz D. Owen, Leah A. Hofmann, Jeffrey Stockwell, Amy D. Tao, Jianhua Haller, Susan Mukundan, Vineeth T. Clarke, Christine Lund, Jessica Sridhar, Akshayalakshmi Mayba, Oleg Barr, Julie L. Zavala, Rylee A. Graves, Elijah C. Zhang, Charles Husami, Nadine Finley, Robert Au, Elizabeth Lillvis, John H. Farkas, Michael H. Shakoor, Akbar Sherva, Richard Kim, Ivana K. Kaminker, Joshua S. Townsend, Michael J. Farrer, Lindsay A. Yaspan, Brian L. Chen, Hsu-Hsin DeAngelis, Margaret M. Department of Bioinformatics and Computational Biology Genentech South San Francisco 94080 CA United States Department of Ophthalmology and Visual Sciences University of Utah School of Medicine The University of Utah Salt Lake City 84132 UT United States Department of Population Health Sciences University of Utah School of Medicine The University of Utah Salt Lake City 84132 UT United States Department of Obstetrics and Gynecology University of Utah School of Medicine The University of Utah Salt Lake City 84132 UT United States Department of Ophthalmology Ross Eye Institute Jacobs School of Medicine and Biomedical Sciences State University of New York University at Buffalo Buffalo 14203 NY United States Department of Pathology Genentech South San Francisco 94080 CA United States Department of Human Genetics Genentech South San Francisco 94080 CA United States Departments of Microchemistry Proteomics and Lipidomics Genentech South San Francisco 94080 CA United States Department of Human Pathobiology & OMNI Reverse Translation Genentech South San Francisco 94080 CA United States Neuroscience Graduate Program Jacobs School of Medicine and Biomedical Sciences State University of New York University at Buffalo Buffalo 14203 NY United States Department of Biochemistry Jacobs School of Medicine and Biomedical Sciences State University of New York University at Buffalo Buffalo 14203 NY United States Veterans Administration Western New York Healthcare System Buffalo 14212 NY United States Department of Medicine Biomedical Genetics Boston University School of Medicine Boston 02118 MA United States Retina Service Massachusetts Eye & Ear Department of Ophthalmology Harvard Medical School Boston 02114 MA United States Genetics Genomics and Bioinformatics Graduate Program Jacobs School of Medicine and Biomedical Sciences State University of New York University at Buffalo Buffalo 14203 NY United States

Age-related macular degeneration (AMD) is a leading cause of blindness, affecting 200 million people worldwide. To identify genes that could be targeted for treatment, we created a molecular atlas at different stages of AMD. Our resource is comprised of RNA sequencing (RNA-seq) and DNA methylation microarrays from bulk macular retinal pigment epithelium (RPE)/choroid of clinically phenotyped normal and AMD donor eyes (n = 85), single-nucleus RNA-seq (164,399 cells), and single-nucleus assay for transposase-accessible chromatin (ATAC)-seq (125,822 cells) from the retina, RPE, and choroid of 6 AMD and 7 control donors. We identified 23 genome-wide significant loci differentially methylated in AMD, over 1,000 differentially expressed genes across different disease stages, and an AMD Müller state distinct from normal or gliosis. Chromatin accessibility peaks in genome-wide association study (GWAS) loci revealed putative causal genes for AMD, including HTRA1 and C6orf223. Our systems biology approach uncovered molecular mechanisms underlying AMD, including regulators of WNT signaling, FRZB and TLE2, as mechanistic players in disease. © 2023 The Authors

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Traveling fronts in self-replicating persistent random walks with multiple internal states

arXiv

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arXiv 2020年

作者： Ishihara, Keisuke George, Ashish B. Cornelius, Ryan Korolev, Kirill S. Max Planck Institute for the Physics of Complex Systems Nöthnitzer Strasse 38 Dresden01187 Germany Max Planck Institute of Molecular Cell Biology and Genetics Pfotenhauer Strasse 108 Dresden01307 Germany Department of Physics Boston University BostonMA02215 United States Graduate Program in Bioinformatics Boston University BostonMA02215 United States

Self-activation coupled to a transport mechanism results in traveling waves that describe polymerization reactions, forest fires, tumor growth, and even the spread of epidemics. Diffusion is a simple and commonly used model of particle transport. Many physical and biological systems are, however, better described by persistent random walks that switch between multiple states of ballistic motion. So far, traveling fronts in persistent random walk models have only been analyzed in special, simplified cases. Here, we formulate the general model of reaction-transport processes in such systems and show how to compute the expansion velocity for arbitrary number of states. For the two-state model, we obtain a closed-form expression for the velocity and report how it is affected by different transport and replication parameters. We also show that nonzero death rates result in a discontinuous transition from quiescence to propagation. We compare our results to a recent observation of a discontinuous onset of propagation in mi-crotubule asters and comment on the universal nature of the underlying mechanism. Copyright © 2020, The Authors. All rights reserved.

关键词： Deforestation

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RETRACTION: AKT3-mediated IWS1 phosphorylation promotes the proliferation of EGFR-mutant lung adenocarcinomas through cell cycle-regulated U2AF2 RNA splicing (Retraction of Vol 12, art no 4624, 2021)

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NATURE COMMUNICATIONS 2022年第1期13卷 1页

作者： Laliotis, Georgios I. Chavdoula, Evangelia Paraskevopoulou, Maria D. Kaba, Abdul La Ferlita, Alessandro Singh, Satishkumar Anastas, Vollter Nair, Keith A., II Orlacchio, Arturo Taraslia, Vasiliki Vlachos, Ioannis Capece, Marina Hatzigeorgiou, Artemis Palmieri, Dario Tsatsanis, Christos Alaimo, Salvatore Sehgal, Lalit Carbone, David P. Coppola, Vincenzo Tsichlis, Philip N. Department of Cancer Biology and Genetics The Ohio State University Columbus OH USA The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute Columbus OH USA School of Medicine University of Crete Heraklion Crete Greece Department of Clinical and Experimental Medicine Bioinformatics Unit University of Catania Catania Italy Tufts Graduate School of Biomedical Sciences Program in Genetics Boston MA USA Department of Medicine Division of Hematology The Ohio State University Columbus OH USA Department of Internal Medicine Division of Medical Oncology The Ohio State University Medical Center Columbus OH USA Institute of Molecular Biology and Biotechnology Foundation for Research and Technology Hellas Heraklion Crete Greece Molecular Oncology Research Institute Tufts Medical Center Boston MA USA DIANA-Lab Hellenic Pasteur Institute Athens Greece

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Maternal human papillomavirus infection and the risk of congenital malformations: A nationwide population-based cohort study

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Journal of Medical Virology 2024年第4期96卷 e29549-e29549页

作者： Hsieh, Tina Yi Jin Chen, Thomas Yen Ting Liao, Pei-Lun Huang, Jing-Yang Ma, Kevin Sheng-Kai Hung, Yao-Min Chang, Renin Wei, James Cheng-Chung Department of Obstetrics and Gynecology Beth Israel Deaconess Medical Center Boston MA United States Department of Bioinformatics Harvard Medical School Boston MA United States Department of Otolaryngology-Head and Neck Surgery Kaohsiung Medical University Hospital Kaohsiung Taiwan Institute of Medicine Chung Shan Medical University Taichung Taiwan Center for Health Data Science Department of Medical Research Chung Shan Medical University Hospital Taichung Taiwan Department of Epidemiology Harvard T.H. Chan School of Public Health Boston MA United States Department of Dermatology Massachusetts General Hospital Boston MA United States Division of Pharmacoepidemiology and Pharmacoeconomics Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston MA United States Center for Global Health Perelman School of Medicine University of Pennsylvania Philadelphia PA United States Division of Nephrology Department of Internal Medicine Taipei Veterans General Hospital Taitung Branch Taipei Taiwan Master Program in Biomedicine College of Science and Engineering National Taitung University Taitung Taiwan College of Health and Nursing Meiho University Pingtung Taiwan Department of Medical Education and Research Kaohsiung Veterans General Hospital Kaohsiung Taiwan Department of Emergency Medicine Kaohsiung Veterans General Hospital Kaohsiung Taiwan Department of Recreation and Sports Management Tajen University Pingtung Taiwan Department of Allergy Immunology & Rheumatology Chung Shan Medical University Hospital Taichung Taiwan Department of Nursing Chung Shan Medical University Taichung Taiwan Graduate Institute of Integrated Medicine China Medical University Taichung Taiwan Department of Medical Research Taichung Veterans General Hospital Taichung Taiwan

Previous research has explored theories regarding the vertical transmission of human papillomavirus (HPV) infection and its association with adverse pregnancy and perinatal outcomes. However, the impact of maternal HPV infection on congenital anomalies (CAs) in offspring remains relatively understudied. We conducted a population-based cohort study linking the Taiwan Birth Registry, Taiwan Death Registry, and National Health Insurance Research Database, in which newborns born in Taiwan between 2009 and 2015 were included. We established a maternal HPV infection cohort comprising 37 807 newborns and matched them with a comparison group of 151 228 newborns at a 1:4 ratio based on index year, age, and sex. The study examined a composite outcome and subgroups of different types of congenital malformations. Differences in cumulative incidence of CAs were assessed using Kaplan–Meier curves and log-rank tests. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazard regressions. No significant association was found between HPV infection and the broad spectrum of CAs (aHR: 1.04, 95% confidence interval [CI]: 0.98–1.10;log-rank test p = 0.14). However, we observed a 19% increased risk of musculoskeletal CAs in the maternal HPV infection group (aHR: 1.19;95% CI: 1.05–1.34) compared to those without maternal HPV exposure. Other factors, including the type of HPV (aHR: 0.65;95% CI: 0.16–2.63), the timing of exposure (during or before pregnancy), and maternal age (aHR for <30 years: 1.02, 95% CI: 0.94–1.1;aHR for 30–39 years: 1.05, 95% CI: 0.99–1.11;aHR for ≥40 years: 0.88, 95% CI: 0.67–1.17), did not significantly affect the risk for any CA. In conclusion, gestation detection of HPV infection was associated with musculoskeletal CAs but not other major CAs. Prospective studies are warranted to elucidate the necessity of prenatal screening in populations at risk. © 2024 Wiley Periodicals LLC.

关键词： adverse pregnancy congenital malformations human papillomavirus infection outcomes

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