Nature Medicine最新文献

{"title":"Uncovering risk factors in the exposome for early-onset colorectal cancer.","authors":"David J Lee, Sylvan Baca, Kimmie Ng","doi":"10.1038/s41591-026-04369-8","DOIUrl":"https://doi.org/10.1038/s41591-026-04369-8","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indoor air purifiers mitigate health impacts of wildfire smoke.","authors":"Karen O'Leary","doi":"10.1038/d41591-026-00024-4","DOIUrl":"https://doi.org/10.1038/d41591-026-00024-4","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Data-driven prioritization of high-risk individuals for weight loss interventions.","authors":"Kamil Demircan, Julia Carrasco-Zanini, Alice Williamson, Carl Beuchel, Linsey Jackson, Werner Römisch-Margl, Aleksander L Hansen, Sarah Finer, David A van Heel, Gabi Kastenmüller, Matthew Coghlan, Ida Moeller, Nicholas J Wareham, Maik Pietzner, Claudia Langenberg","doi":"10.1038/s41591-026-04353-2","DOIUrl":"https://doi.org/10.1038/s41591-026-04353-2","url":null,"abstract":"<p><p>New obesity medications have demonstrated efficacy in trials, but their real-world deployment is partly limited by the absence of approaches that identify individuals for treatment based on risks for obesity-related complications. Here we present a risk prediction model to guide prioritization of high-risk individuals. In a population-based sample of ~200,000 individuals with a body mass index (BMI) exceeding 27 kg m^-², our machine learning framework identified the 20 most informative features, from among thousands tested, that predict future onset of 18 complications of obesity, providing information beyond BMI. An integrated model (OBSCORE) successfully stratified individuals into risk groups based on incidence over 10 years: for example, 5.7%, 1.8%, 0.9%, 0.4% and 0.1% for cardiovascular mortality. We demonstrate generalizability of the model in independent populations of European and non-European ancestry and, in SURMOUNT-1 trial participants, show that weight loss was similar across baseline OBSCORE risk groups and that predicted risks decreased following treatment with tirzepatide. In summary, OBSCORE provides a framework for prioritizing high-risk individuals with overweight or obesity based on their risk of obesity-related complications, complementing BMI-based frameworks.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-dose oral nicotinamide mononucleotide for immune thrombocytopenia: a phase 1/2 trial.","authors":"Huiyuan Li, Yuan Xu, Yunfei Chen, Lulu Ji, Yanmei Xu, Wenting Zheng, Ting Sun, Rongfeng Fu, Xiaolei Pei, Xiaofan Liu, Feng Xue, Wei Liu, Wentian Wang, Ying Chi, Renchi Yang, Jun Wei, Lei Zhang","doi":"10.1038/s41591-026-04366-x","DOIUrl":"https://doi.org/10.1038/s41591-026-04366-x","url":null,"abstract":"<p><p>Autoimmunity remains challenging to treat without broad immunosuppression. We previously showed that anti-CD38 antibody can rapidly elevate platelet counts in refractory immune thrombocytopenia (ITP), but the underlying mechanism was unclear. Here we report that anti-CD38 antibody induces platelet recovery within 3 days, including after retreatment in relapsed cases. Mechanistically, CD38-mediated nicotinamide adenine dinucleotide (NAD⁺) depletion drives M1-like macrophage polarization with increased Fc gamma receptor I (FcγRI) expression, thereby promoting macrophage phagocytosis of opsonized platelets. In mice, CD38 inhibition or nicotinamide mononucleotide (NMN) supplementation restores NAD⁺, reprograms macrophages, downregulates FcγRI and prevents thrombocytopenia. In an ovalbumin immunization model, NMN treatment does not impair antigen-specific antibody production, supporting preservation of humoral responses. Based on these findings, we conducted a single-arm, open-label phase 1/2 trial of low-dose oral NMN (450 mg twice daily for 2 weeks) in adults with steroid-refractory or steroid-dependent ITP. Primary endpoints were safety/tolerability and platelet response (≥50 × 10⁹ per liter within 2 weeks, confirmed by two consecutive measurements one or more days apart, without rescue therapy or dose escalation of thrombopoietin receptor agonists or corticosteroids). Among 25 enrolled patients, no dose-limiting toxicities or treatment-related serious adverse events occurred; NMN was well tolerated, with only mild treatment-related adverse events in 12% and non-severe infections (grade 1) in 8% of patients while immunoglobulin levels remained stable, consistent with preserved humoral immunity. Five patients (20.0%) met the primary platelet-response endpoint. In exploratory analyses, overall, 60% of patients achieved platelet counts more than 1.5× baseline during treatment, and 52% maintained responses through week 8. Together, these data identify the CD38-NAD⁺ axis as an immunometabolic checkpoint in ITP and support further exploration of NMN as a non-antibody-depleting metabolic strategy for antibody-mediated disease. ClinicalTrials.gov identifier: NCT06776510 .</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An agentic framework for autonomous scientific discovery in cancer pathology.","authors":"Florian Trost, Bide Zhang, Ines Aring, Marcus Bauer, Lennert Glamann, Michael Wessolly, Kyra Johnson, Heike Göbel, Tristan Lerbs, Taban Sangenne, Peter Herrmann, Fabian Mairinger, Christopher Kopp, Sebastian Michels, Anna Rasokat, Matthias Heldwein, Steffen Wagner, Birgid Schömig-Markiefka, Jürgen Wolf, Sylvia Hartmann, Claudia Wickenhauser, Andrey Bychkov, Jens Peter Klussmann, Alexander Quaas, Reinhard Buettner, Yuri Tolkach","doi":"10.1038/s41591-026-04357-y","DOIUrl":"10.1038/s41591-026-04357-y","url":null,"abstract":"<p><p>Artificial intelligence has advanced cancer pathology, but many systems still depend on hand-crafted features, are hard to explain and rely on fragmented workflows. We introduce SPARK (System of Pathology Agents for Research and Knowledge), a foundational agentic artificial intelligence approach that uses language as a universal interface to autonomously generate biologically driven concepts for tumor analysis. SPARK turns biological ideas into analytical tools and works directly with complex pathology data without extra model training. We evaluated SPARK across 18 patient cohorts spanning five cancer types (lung adenocarcinoma, lung squamous cell carcinoma, colorectal cancer, breast cancer and oropharyngeal squamous cell carcinoma) and more than 5,400 patients with available histopathology images and clinical/follow-up information, in both prognostic and predictive settings and on a well characterized spatial biology breast cancer dataset (patient n = 625). We found that SPARK produced clinically and biologically relevant concepts correlated with prognosis, known pathological variables and predictive biomarkers, including patterns of tumor progression and temporal change inferred from static images. A dedicated module allows for human interaction with SPARK. Further prospective validation is needed to evaluate the clinical utility of the tools created by SPARK. All code, parameters and results are openly released to help researchers and clinicians improve diagnostic precision and deepen tumor biology insights.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting referral need for febrile children in low-resource community settings in South and Southeast Asia.","authors":"Arjun Chandna, Constantinos Koshiaris, Raman Mahajan, Riris Adono Ahmad, Dinh Thi Van Anh, Khalid Shams Choudhury, Suy Keang, Nguyen The Nguyen Phung, Sayaphet Rattanavong, Souphaphone Vannachone, Chris Painter, Mikhael Yosia, Naomi Waithira, Mohammad Yazid Abdad, Janjira Thaipadungpanit, Paul Turner, Phan Huu Phuc, Dinesh Mondal, Mayfong Mayxay, Bui Thanh Liem, Elizabeth A Ashley, Eggi Arguni, Rafael Perera-Salazar, Melissa Richard-Greenblatt, Yoel Lubell, Sakib Burza","doi":"10.1038/s41591-026-04338-1","DOIUrl":"https://doi.org/10.1038/s41591-026-04338-1","url":null,"abstract":"<p><p>In resource-constrained community settings, identifying which febrile children require referral remains a major unmet need. Current World Health Organization (WHO) danger signs have limited accuracy, resulting in missed severe illness and unnecessary referrals. Here we developed and validated clinical prediction models to support referral decisions using data from 3,405 children aged 1-59 months presenting with community-acquired acute febrile illnesses to seven hospitals across Bangladesh, Cambodia, Indonesia, Laos and Vietnam. Cambodian data were held out for external validation. The model using simple clinical parameters (sensitivity 74.7% (95% confidence interval (CI): 59.4-88.1); specificity 99.1% (95% CI: 97.7-99.7)) outperformed WHO criteria (sensitivity 55.5% (95% CI: 39.4-72.7); specificity 82.6% (95% CI: 77.1-87.6)) for identification of children at risk of severe disease (death or organ support within 2 days). Including either pulse oximetry or the host biomarker soluble TREM1 (sTREM1) increased sensitivity to 88.9% (95% CI: 76.7-97.8; pulse oximetry) and 89.2% (95% CI: 76.9-97.5; sTREM1), respectively. The pulse oximetry-based model achieved these gains with a threefold reduction in referral rates. These approaches appear cost-effective (pulse oximetry incremental cost effectiveness ratio (ICER) = $26.28; sTREM1 ICER = $196.46) and could improve triage for febrile illness in low-resource settings by enabling more accurate referral decisions. They warrant evaluation in community-based trials.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical trials for continuously monitored and updated AI systems.","authors":"Wouter A C van Amsterdam,Michael Oberst,Jean Feng,Jenna Wiens,Shengpu Tang,Shalmali Joshi,Rajesh Ranganath,Mark Sendak,Uri Shalit,Julia E Vogt,Brett Beaulieu-Jones,Muhammad Mamdani,David Kent,Patrick J Heagerty,Thomas R Fleming,Anna Goldenberg","doi":"10.1038/s41591-026-04368-9","DOIUrl":"https://doi.org/10.1038/s41591-026-04368-9","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"6 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147754517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Australia legislates against genetic discrimination in life insurance.","authors":"Jane Tiller","doi":"10.1038/s41591-026-04372-z","DOIUrl":"https://doi.org/10.1038/s41591-026-04372-z","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"1 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147754799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A reasonably likely surrogate endpoint for metabolic dysfunction-associated steatohepatitis.","authors":"Arun J Sanyal,Michelle T Long,Nancy Obuchowski,Roberto A Calle,Raj Vuppalanchi,Brent Neuschwander-Tetri,Rohit Loomba,Katherine Yates,Patricia Grebenstein,Melissa A Jones,Tania N Kamphaus, ","doi":"10.1038/s41591-026-04267-z","DOIUrl":"https://doi.org/10.1038/s41591-026-04267-z","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"72 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147754797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AI framework for multidisease detection via retinal imaging.","authors":"Xiayin Zhang,Qinyi Li,Yinhao Liang,Chunran Lai,Jiahui Cao,Yangqin Feng,Wenyi Hu,Hongyang Jiang,Chunxin Liu,Feng Zhang,Shan Wang,Ying Fang,Cuomu Duojie,Lumei Hu,Fan Xu,Kaiyi Chi,Miao Lin,Li Li,Yih Chung Tham,Yukun Zhou,Carol Y Cheung,Xiaohong Yang,Bin Sheng,Zhuoting Zhu,Ching-Yu Cheng,Wing W Y Ng,Honghua Yu","doi":"10.1038/s41591-026-04359-w","DOIUrl":"https://doi.org/10.1038/s41591-026-04359-w","url":null,"abstract":"The rising burden of endocrine and metabolic diseases demands scalable and accessible screening tools. Here we developed Reti-Pioneer, a multitask retinal imaging framework that integrates quality-aware modules with pre-trained foundation models for efficient, multidisease detection. In general, the framework was developed using 107,730 color fundus photographs from both community-based and hospital-based cohorts and achieved area under the receiver operating characteristic curve values on internal test data of 0.833 (95% confidence interval 0.810-0.856) for type 2 diabetes mellitus, 0.832 (0.799-0.866) for gout, 0.787 (0.742-0.833) for osteoporosis, 0.740 (0.726-0.755) for hypertension, 0.736 (0.721-0.751) for hyperlipidemia and 0.699 (0.667-0.730) for thyroid disease. The framework generalized well to six external cohorts from both resource-limited and high-resource settings, and showed biological interpretability via plasma proteomic correlations. In a primary care silent trial, it completed screening in 30.6 ± 6.0 s per case, notably faster than standard laboratory workflows. A subsequent clinical pilot for type 2 diabetes mellitus yielded an area under the receiver operating characteristic curve of 0.776 (0.710-0.842) and negative predictive value of 0.966 (0.946-0.983), surpassing the Finnish Diabetes Risk Score, with high acceptance from clinicians and patients. Overall, Reti-Pioneer could provide a translatable, low-cost pathway from oculomics to actionable clinical screening.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"2 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147754803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}