{"title":"Ambient biothermal stress, preconceptional thyrotropin abnormalities, and the risk of preterm birth: a nationwide Chinese cohort study.","authors":"Xinghou He,Mengyao Li,Hongbing Xu,Bin Zhang,Xinyi Lv,Long Wang,Chuanyu Zhao,Xuyang Shan,Yuan He,Yan Fang,Yuanyuan Wang,Huiying Xu,Jihong Xu,Xiaoming Song,Ya Zhang,Hongguang Zhang,Ying Yang,Xu Ma,Wei Huang","doi":"10.1038/s41467-025-64410-1","DOIUrl":"https://doi.org/10.1038/s41467-025-64410-1","url":null,"abstract":"Epidemiologic evidence on thermal stress and preterm birth (PTB) is based on ambient temperature rather than a biothermal metric. Thyrotropin abnormalities have been associated with PTB and may increase thermal vulnerability. However, it remains unknown whether thermal stress and thyrotropin abnormalities synergistically contribute to increased risk of PTB. Here we conducted a nationwide cohort study among 6,218,131 singleton live births in China. Biothermal stress was measured using the Universal Thermal Climate Index. We found that both heat stress and cold stress during each trimester were associated with increased risks of PTB, with hazard ratios ranging from 1.06 (95% confidence interval [CI]: 1.05, 1.07) to 2.33 (95% CI: 2.30, 2.35) and from 1.08 (95% CI: 1.07, 1.09) to 1.68 (95% CI:1.67, 1.70), respectively. Participants with subnormal (<0.37 mIU/L) or supranormal thyrotropin levels (≥4.88 mIU/L) and biothermal stress had higher risks of PTB, compared with those with normal thyrotropin levels and non-thermal stress. Additive interactions were also identified between biothermal stress and thyrotropin abnormalities. We estimated that up to 13.52% of PTB were attributable to biothermal stress and thyrotropin abnormalities. Our study showed a synergistic effect of biothermal stress and preconceptional thyrotropin abnormalities, highlighting the importance of climate adaption measures and thyroid management toward pregnant women under climate change scenario.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"20 1","pages":"9372"},"PeriodicalIF":16.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Engineering unnatural cells with a 21st amino acid as a living epigenetic sensor.","authors":"Yu Hu,Yixian Wang,Linqi Cheng,Chenhang Wang,Yijie Liu,Yufei Wang,Yuda Chen,Shudan Yang,Yiming Guo,Shiyu Jiang,Kaiqiang Yang,Han Xiao","doi":"10.1038/s41467-025-64448-1","DOIUrl":"https://doi.org/10.1038/s41467-025-64448-1","url":null,"abstract":"Living animals rely extensively on post-translational modifications (PTMs) to regulate protein activity, stability, subcellular localization, and protein-protein interactions. These modifications are tightly controlled by the balance of \"writer\" and \"eraser\" enzymes, which add or remove PTMs on proteins. Current strategies to measure writer and eraser activities in living animals largely depend on invasive methods, such as single-cell sequencing, quantitative mass spectrometry, or activity-based probes, which often lack cell or tissue specificity. In this study, we report the development of autonomous cells-both prokaryotic and eukaryotic-with the ability to biosynthesize and genetically encode acetyllysine using the genetic code expansion technology. These engineered living sensors with a site-specific acetyllysine modification can be transplanted into living animals, enabling real-time monitoring of PTM dynamics in living cells and animals. We further demonstrate the utility of these cells in tracking deacetylase activity and assessing the effects of deacetylase inhibitors on PTM dynamics in living animals in real time.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"50 1","pages":"9388"},"PeriodicalIF":16.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pier-Olivier Martel,Rustelle Janse van Vuuren,Julia Degrémont,Sarah Turmel-Couture,Armi M Chaudhari,Eden Dologuele,Lucie Beaulieu,Alexandre Clouet,Patrick Narbonne
{"title":"Niche-associated Type IV collagen promotes GLP-1/Notch receptor activation in the C. elegans germline.","authors":"Pier-Olivier Martel,Rustelle Janse van Vuuren,Julia Degrémont,Sarah Turmel-Couture,Armi M Chaudhari,Eden Dologuele,Lucie Beaulieu,Alexandre Clouet,Patrick Narbonne","doi":"10.1038/s41467-025-64394-y","DOIUrl":"https://doi.org/10.1038/s41467-025-64394-y","url":null,"abstract":"Basement membranes are thin and dense proteinaceous layers that surround tissues to maintain their structure. With age, chronic inflammation typically stiffens this basement membrane through a phenomenon called fibrosis, which is reflected by increasing levels of the basement membrane's main structural component, type IV collagen (COL IV). Tissue fibrosis and elevated Notch signalling are two co-occurring hallmarks of many inflammation-linked diseases, including cancer, but their in vivo relationship has not been clearly defined. Here we show that EMB-9/COL IV accumulation around the C. elegans germline stem cell niche promotes GLP-1/Notch receptor activation in germline stem cells. Moreover, we find that contrasting with previous beliefs, reducing GLP-1/Notch activity in vivo leads to a generalized dramatic increase in EMB-9/COL IV levels, and thereby promotes fibrosis. The generalized fibrosis that comes along with inflammaging may therefore act as a root cause for cancer by promoting Notch signalling, and perhaps other ligand-receptor interactions.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"1 1","pages":"9363"},"PeriodicalIF":16.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"FAP+ fibroblasts orchestrate tumor microenvironment remodeling in renal cell carcinoma with tumor thrombus.","authors":"Jiacheng Ma,Yan Huang,Jie Chen,Yang Li,Rongyan Yao,Xiubin Li,Qiyang Liang,Xinran Chen,Cheng Peng,Kan Liu,Yuanjun Zhai,Xu Zhang,Xin Ma,Xiaowen Wang,Qingbo Huang,Fuchu He","doi":"10.1038/s41467-025-64447-2","DOIUrl":"https://doi.org/10.1038/s41467-025-64447-2","url":null,"abstract":"Tumor thrombus (TT) worsens prognosis and complicates surgery in renal cell carcinoma (RCC), yet its formation mechanisms remain unclear. Here, we perform integrative single-cell and spatial transcriptomic analyses on 71 tissues and 48 sections from RCC patients with or without TT. The cellular and spatial atlas reveals distinct TT-associated tumor microenvironment remodeling characterized by the enrichment of FAP+ fibroblasts. These FAP+ fibroblasts are spatially contiguous to aggressive cancer cells and promote their malignant phenotypes in vitro. Their abundance inversely correlates with functional NK cells, suggesting roles in tumor invasion and immune evasion. Furthermore, single-cell multiomics analysis identifies tumor pericytes as a source of FAP+ fibroblasts and delineates transcription factor dynamics underlying pericyte-fibroblast transition. Finally, high levels of FAP+ fibroblasts are associated with poor prognosis and predict a weaker response to anti-VEGF-based therapy. In conclusion, our study highlights FAP+ fibroblasts as drivers of aggressive RCC with TT, suggesting potential therapeutic targets.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"69 1","pages":"9387"},"PeriodicalIF":16.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fundamental role of spatial positioning of Mycobacterium tuberculosis in mycobacterial survival in macrophages.","authors":"Shivani Sahu,Navin Baid,Deepali Aggarwal,Ankita Sharma,Manisha Gun,Sahanawaz Molla,Anunay Sinha,Ambey Prasad Dwivedi,Amit Tuli,Mahak Sharma,Sanjeev Khosla,Varadharajan Sundaramurthy,Ashwani Kumar","doi":"10.1038/s41467-025-64404-z","DOIUrl":"https://doi.org/10.1038/s41467-025-64404-z","url":null,"abstract":"Mycobacterium tuberculosis is a model intracellular pathogen. The spatial-localization of M. tuberculosis inside macrophages is poorly defined. Here, we determine the spatial-localization of M. tuberculosis inside macrophages with reference to the nucleus. Few M. tuberculosis cells are perinuclear, while most are peripheral. Perinuclear M. tuberculosis are transported to lysosomes, have low Adenosine Triphosphate/Adenosine Diphosphate, are non-replicating, and tolerate front-line anti-tubercular medicines. M. tuberculosis pathogenicity determines its spatial location. Virulent M. tuberculosis strains are peripheral. However, avirulent M. tuberculosis strains or attenuated deletion mutants are transported to lysosomes in the perinuclear area. Early Secreted Antigenic Target-6 and Culture Filtrate Protein-10 play a critical role in inhibiting mycobacterial transport to the perinuclear space. Induction of centripetal transport of pathogenic M. tuberculosis-laden cargoes to perinuclear region enhances M. tuberculosis's delivery to the lysosomes and reduces mycobacterial growth. Interferon-γ directs M. tuberculosis to lysosomes by modulating their perinuclear localization. Interferon-γ upregulates Transmembrane protein 55B and JNK-interacting protein 4 via transcription factor EB. Increased transmembrane protein 55B and JNK-interacting protein 4 levels tether M. tuberculosis-laden cargoes to the dynein motor, causing their perinuclear delivery to lysosomes. These findings shed light on how mycobacterial metabolism, reproduction, and drug susceptibility are connected to virulence-guided spatial localization.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"50 1","pages":"9368"},"PeriodicalIF":16.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Julia C Rhodes,Rebecca Kahn,Shanna Bolcen,Nong Shang,Yunmi Chung,Monica M Farley,Amber N Britton,Ashley E Moore,Stepy Thomas,Joelle Nadle,Laura B Amsden,Jacek Skarbinski,Kristi R VanWinden,Meghan Barnes,Kerianne Engesser,Patricia Ferrieri,AmberJean P Hansen,Lee H Harrison,Laura Jeffrey,Jessica L Nyholm,Sean T O'Leary,Courtney Olson-Chen,Jemma V Rowlands,Shannon A Seopaul,Ann R Thomas,Htet Htet N Wrigley,Lesley McGee,Sundaram Ajay Vishwanathan,Fahmina Akhter,Bailey Alston,Lily Tao Jia,Yikun Li,Palak Y Patel,Joy Rivers,Jessica E Southwell,Theresa Tran,Panagiotis Maniatis,Stephanie J Schrag
{"title":"A US case-control study to estimate infant group B streptococcal disease serological thresholds of risk-reduction.","authors":"Julia C Rhodes,Rebecca Kahn,Shanna Bolcen,Nong Shang,Yunmi Chung,Monica M Farley,Amber N Britton,Ashley E Moore,Stepy Thomas,Joelle Nadle,Laura B Amsden,Jacek Skarbinski,Kristi R VanWinden,Meghan Barnes,Kerianne Engesser,Patricia Ferrieri,AmberJean P Hansen,Lee H Harrison,Laura Jeffrey,Jessica L Nyholm,Sean T O'Leary,Courtney Olson-Chen,Jemma V Rowlands,Shannon A Seopaul,Ann R Thomas,Htet Htet N Wrigley,Lesley McGee,Sundaram Ajay Vishwanathan,Fahmina Akhter,Bailey Alston,Lily Tao Jia,Yikun Li,Palak Y Patel,Joy Rivers,Jessica E Southwell,Theresa Tran,Panagiotis Maniatis,Stephanie J Schrag","doi":"10.1038/s41467-025-64324-y","DOIUrl":"https://doi.org/10.1038/s41467-025-64324-y","url":null,"abstract":"Maternal vaccines to prevent infant Group B Streptococcus (GBS) disease have progressed through phase II development and may be licensed based on immunologic endpoints, which have yet to be approved by regulatory authorities. Here we present a multistate case control study to characterize the relationship between serotype-specific anti-capsular polysaccharide (CPS) immunoglobulin G concentrations near birth and infant GBS disease risk reduction. Antibody concentration distributions are significantly lower for cases (n = 643) than controls (n = 2801) and serologic thresholds varied by serotype and age at onset, with 80% serotype-specific protective thresholds ranging from 0.52 to 2.49 mcg/mL for early-onset disease (EOD; <7 days old) and 0.02 to 0.14 mcg/mL for late-onset disease (LOD; 7-89 days old). Our study provides the most robust data to date that protection thresholds vary by serotype and are notably lower for LOD than EOD, thereby informing potential serological endpoints for phase III trials evaluating CPS-based maternal GBS vaccine candidates.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"20 1","pages":"9381"},"PeriodicalIF":16.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Photocatalytic non-oxidative dehydrogenation of ethane to ethene with near unit selectivity.","authors":"Xiaoyu Sui,Jiwu Zhao,Pu Zhang,Ying Wang,Hangbin Zheng,Haihua Zeng,Pengzhao Wang,Yanyan Jia,Na Wen,Zhengxin Ding,Zizhong Zhang,Sheng Dai,Chao Xu,Rusheng Yuan,Wenxin Dai,Xianzhi Fu,Jinlin Long","doi":"10.1038/s41467-025-64389-9","DOIUrl":"https://doi.org/10.1038/s41467-025-64389-9","url":null,"abstract":"The non-oxidative dehydrogenation of light alkanes to alkenes is thermodynamically limited by the trade-off between the cleavage of C-H and C-C bonds. Unlocking the thermodynamic bottleneck with photocatalysis is prone to eliminate undesirable side reactions such as deep dehydrogenation, cracking, isomerization, and polymerization. Herein, we show the photocatalytic non-oxidative dehydrogenation of ethane to ethene and hydrogen at ambient conditions, which is enabled by grafting of Ni single atoms to modulate the surface electronic structure of Pd nanoparticles photo-deposited on the surface of anatase TiO2 nanoparticles, modifying the ethane dehydrogenation pathway. A high rate of 8.2 ± 0.2 mmol·g-1·h-1 for the stoichiometric conversion of ethane to ethene and hydrogen is achieved with a 100% ethene selectivity in a flow reactor under solar light irradiation. The apparent quantum efficiency reaches ~22.3% at 350 nm by using the optimal T-Ni0.6Pd0.24 photocatalyst. Solar-driven non-oxidative alkane dehydrogenation offers a route to light alkenes with high performance, and selectivity.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"105 1","pages":"9386"},"PeriodicalIF":16.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haidong Zhao,Jesse B Tack,Gerard J Kluitenberg,M B Kirkham,Gretchen F Sassenrath,Lina Zhang,Nenghan Wan,Zhijuan Liu,Jin Zhao,Amanda Ashworth,Prasanna H Gowda,Xiaomao Lin
{"title":"Concurrent improvements in maize yield and drought resistance through breeding advances in the U.S.Corn Belt.","authors":"Haidong Zhao,Jesse B Tack,Gerard J Kluitenberg,M B Kirkham,Gretchen F Sassenrath,Lina Zhang,Nenghan Wan,Zhijuan Liu,Jin Zhao,Amanda Ashworth,Prasanna H Gowda,Xiaomao Lin","doi":"10.1038/s41467-025-64454-3","DOIUrl":"https://doi.org/10.1038/s41467-025-64454-3","url":null,"abstract":"Drought increasingly challenges rainfed maize (Zea mays L.) production worldwide, with pressures expected to intensify under future climate scenarios. Recent studies have examined the genetic and physiological bases of yield and drought tolerance improvements in maize; however, comprehensive, field-based quantification of synchronous improvements of yield and drought resistance across diverse environmental conditions remain limited. By compiling a dataset of 92,096 hybrid-trial observations across the U.S. Corn Belt (2000-2020), our environmental index approach provides evidence of consistent yield increases across diverse environmental conditions. Using linear mixed-effects modeling, we reveal these gains are accompanied by enhanced drought resistance during the grain filling period. Projections suggest that by 2100, new hybrids could transform drought resistance, reducing yield losses by 17.8% compared to old hybrids, suggesting the potential of breeding innovations to buffer maize against drought stress. This study highlights recent breeding efforts, reinforcing adaptative capacity of maize and providing a promising pathway to sustain food security in a warming climate.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"109 1","pages":"9389"},"PeriodicalIF":16.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francesco Piccialli,Sara Amitrano,Donato Cerciello,Anna Borrelli,Edoardo Prezioso,Marzia Canzaniello
{"title":"A digital twin framework for urban parking management and mobility forecasting.","authors":"Francesco Piccialli,Sara Amitrano,Donato Cerciello,Anna Borrelli,Edoardo Prezioso,Marzia Canzaniello","doi":"10.1038/s41467-025-65306-w","DOIUrl":"https://doi.org/10.1038/s41467-025-65306-w","url":null,"abstract":"Rapid urbanization and population growth have created significant challenges in urban mobility management, such as traffic congestion, inefficient public transportation, and environmental pollution. Here we present the development and implementation of a digital framework for urban parking management and mobility forecasting. The framework integrates a wide range of historical and real-time data, including parking meter transactions, revenue records, street occupancy rates, parking violations, and sensor-based parking slot utilization. Additionally, the data encompass weather conditions, temporal patterns (such as weekdays and peak hours), and agent shift schedules. Descriptive statistics are used to identify key patterns, while the Spatial-Temporal Identity model is used for the predictive phase, and the Conditional Variational Generative Adversarial Network is used for the generative phase of the digital twin. The algorithm allows forecasting parking demand and mapping data for spatial planning and resource allocation. Moreover, the integration of the Generative Artificial Intelligence model generates realistic what-if scenarios for virtual testing of mobility strategies before real-world implementation. The results highlight the framework's potential to enhance urban mobility management, especially by improving parking meter placement and reducing inefficiencies and improving accessibility. Validation on real-world data from the city of Caserta, confirms the robustness and adaptivity of the proposed framework, although expanding the dataset and refining specific components are necessary for fully realizing its potential and ensuring sustainable urban planning.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"45 1","pages":"9400"},"PeriodicalIF":16.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Constantinos Koshiaris,Ariel Wang,Lucinda Archer,Richard D Riley,Kym Ie Snell,Richard J Stevens,Amitava Banerjee,Subhashisa Swain,Andrew Clegg,Christopher E Clark,Rupert A Payne,F D Richard Hobbs,Margaret Ogden,Richard J McManus,James P Sheppard,
{"title":"Predicting hypotension, syncope, and fracture risk in patients indicated for antihypertensive treatment: the STRATIFY models.","authors":"Constantinos Koshiaris,Ariel Wang,Lucinda Archer,Richard D Riley,Kym Ie Snell,Richard J Stevens,Amitava Banerjee,Subhashisa Swain,Andrew Clegg,Christopher E Clark,Rupert A Payne,F D Richard Hobbs,Margaret Ogden,Richard J McManus,James P Sheppard, ","doi":"10.1038/s41467-025-64408-9","DOIUrl":"https://doi.org/10.1038/s41467-025-64408-9","url":null,"abstract":"Antihypertensives are associated with increased risk of syncope, hypotension, and fractures, but the highest-risk individuals are unclear. This study aimed to develop and validate three models to predict these outcomes in patients with an indication for antihypertensive treatment. A cohort study was conducted using data from Clinical Practice Research Datalink (CPRD). Patients aged 40+ with systolic blood pressure 130-179 mmHg were included. Outcomes were first hypotension, syncope, or fracture leading to hospitalization or death within 10 years. Models were derived from CPRD GOLD data (n = 1,773,224) and validated with CPRD Aurum data (n = 3,805,366). Each model had 31-37 predictors. Validation demonstrated strong discriminative ability (10-year C-statistic: hypotension 0.824; syncope 0.819; fracture 0.790), with close agreement between predicted and observed risks for the hypotension and syncope models. Some underprediction was observed for the fracture model. These models could be used to help reassure patients about the relatively low risk of harm from antihypertensive treatment, or identify the small number of individuals with a higher risk where additional monitoring may be indicated.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"109 1","pages":"9371"},"PeriodicalIF":16.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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