Nature Medicine最新文献

{"title":"The arrival of digital twins and in silico trials in drug development.","authors":"Ashley L Eadie,Holly Fernandez Lynch,Naomi Scheinerman,Ravi B Parikh","doi":"10.1038/s41591-026-04344-3","DOIUrl":"https://doi.org/10.1038/s41591-026-04344-3","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"21 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147753307","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":"The TARGET guideline for reporting observational studies of interventions.","authors":"Harrison J Hansford,James H McAuley,Sonja A Swanson,Nazrul Islam,Issa J Dahabreh,Barbra A Dickerman,Matthias Egger,Xabier Garcia-Albeniz,Robert M Golub,Sara Lodi,Margarita Moreno-Betancur,Sallie-Anne Pearson,Sebastian Schneeweiss,Jonathan A C Sterne,Melissa K Sharp,Matthew D Jones,Elizabeth A Stuart,Hopin Lee,Miguel A Hernán,Aidan G Cashin","doi":"10.1038/s41591-026-04358-x","DOIUrl":"https://doi.org/10.1038/s41591-026-04358-x","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"153 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147753309","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":"Ten lessons from a decade of scientific translation at the Crick.","authors":"Stephen Mayhew,Dave Allen,David Roblin","doi":"10.1038/s41591-026-04355-0","DOIUrl":"https://doi.org/10.1038/s41591-026-04355-0","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"26 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147753312","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":"Targeted removal of soluble Fms-like tyrosine kinase 1 in very preterm preeclampsia: a pilot trial","authors":"Ravi Thadhani, Thomas F. Hiemstra, Manu Vatish, Holger Stepan, Ana Sofia Cerdeira, Jeremy Brockelsby, Tim James, Massimiliano Lia, Alissa Cornelis, Elena Krause, Martin R. Spath, Berthold Grüttner, Polina Todorova, Henning Hagmann, Kristen R. Yeung, Bei Xu, Scott Heffernan, Suzanne Pears, Richard Waugh, John Thompson, Jim Iliopoulos, Neroli Sunderland, Murray Killingsworth, Angela Makris, Annemarie Hennessy, Agnes Lo, Adelene Y. Tan, Paul Kussie, Yuchiao Chang, Linda Hanssens, Stefan Miltenyi, Thomas Benzing, S. Ananth Karumanchi","doi":"10.1038/s41591-026-04333-6","DOIUrl":"https://doi.org/10.1038/s41591-026-04333-6","url":null,"abstract":"Soluble Fms-like tyrosine kinase 1 (sFlt-1), a protein secreted by the placenta, plays a central role in the pathogenesis of preeclampsia—a life-threatening pregnancy complication for which no disease-specific treatment currently exists. We developed a strategy to selectively deplete circulating sFlt-1 and then conducted a single-arm, open-label trial to reduce circulating sFlt-1 in women with very preterm preeclampsia. The primary endpoints were safety and tolerability. Extracorporeal apheresis with an adsorber containing high-affinity IgG1 antibodies against sFlt-1 resulted in an approximately 50% reduction of circulating sFlt-1 levels in pregnant baboons. In women with preterm preeclampsia treated with single ascending doses (phase A, n = 7, preapheresis, mean ± s.d., sFlt-1: 15,120 ± 4,484 pg ml−1), maternal and fetal vital signs and umbilical artery pulsatility indices remained stable when comparing measures before, during and after apheresis. In women with very preterm preeclampsia treated with multiple doses (phase B, n = 9, median gestational age 30.3 (interquartile range, 29.3−30.9) weeks, systolic and diastolic blood pressures 146 ± 10 and 92 ± 5 mmHg, respectively, and preapheresis circulating sFlt-1 levels 11,960 ± 3,056 pg ml−1), each apheresis reduced sFlt-1 levels by 16.7 ± 7.6% and mean arterial pressures by 4.1 ± 7.8 mmHg. Reductions in mean arterial pressures after apheresis strongly correlated with reductions in circulating sFlt-1 (R = 0.63, Spearmanʼs correlation). Pregnancy continued from admission for a median of 10 (range, 3−19) days. Compared to antenatal estimated birth weights, neonatal birth weights generally remained stable or increased among those with the longest extensions. Treatment-related adverse events included mild hypocalcemia (n = 3), skin hemorrhage at the puncture site (n = 1) and false labor (n = 1). Selective removal of sFlt-1 by apheresis appeared to be safe and well tolerated in women with very preterm preeclampsia. Controlled trials are needed to confirm the additional safety and efficacy of this approach. ClinicalTrials.gov registration: NCT02923206.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"152 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147751764","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":"The All of Us Research Program’s wearables dataset","authors":"Theresa Patten, Edward A. Preble, Hiral Master, Jennifer Adjemian, Andrea Ramirez, James McClain, Amy Rose Price","doi":"10.1038/s41591-026-04352-3","DOIUrl":"https://doi.org/10.1038/s41591-026-04352-3","url":null,"abstract":"Digital health technologies (DHTs) are revolutionizing medical research, offering unprecedented insights into health monitoring and disease detection through continuous, real-world data collection. Here we characterize the data in one of the largest and most demographically rich DHT datasets as part of the All of Us Research Program. Through a historic device distribution effort, the program reached a broad range of participants nationwide, yielding a DHT dataset with an expanded a large demographic scope. This dataset contains Fitbit data from more than 59,000 participants spanning 14 years with more than 39 million step observations and 31 million sleep observations. Nearly half (46%) of participants with Fitbit data also contributed electronic health records, physical measurements, genomics and survey data. This resource enables researchers to study relationships between digital health metrics and clinical outcomes, advancing DHT methodologies through its large size, broad representation and multi-modal data linkage.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"11360 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147751878","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":"Cross-reactive anti-prophage antibodies and bacterial heteroresistance implicated in phage therapeutic failure.","authors":"F Gordillo Altamirano,D Subedi,M Beiers,M Bucher,S Dahlman,D M Patel,M Parker,D Korneev,M J Robinson,K Pragastis,J Wisniewski,C Rees,H Ramshaw,S F Khan,B J Gardiner,Y Hammerschlag,D Keating,T Kotsimbos,J Hawkey,J J Barr,A Y Peleg","doi":"10.1038/s41591-026-04301-0","DOIUrl":"https://doi.org/10.1038/s41591-026-04301-0","url":null,"abstract":"Phage therapy is an exciting strategy against antimicrobial-resistant bacterial infections, but critical knowledge gaps regarding its clinical application persist. Here we present a case study of a 22-year-old male patient with cystic fibrosis, presenting with a recurrent, invasive and ultimately lethal Bordetella bronchialis infection, who failed compassionate-use phage therapy. Using longitudinal clinical samples, we found that our patient harbored pre-existing antibodies against active prophages induced from the genome of the infecting pathogen. Notably, these antibodies may have contributed to clinical failure by cross-reacting with and effectively neutralizing therapeutic phage. We also uncovered bacterial heteroresistance, characterized by bacterial subpopulations from the initial infection with reduced phage susceptibility, as a possible further contributor to treatment failure. These findings highlight the intricate interplay between host immunology, bacterial genetic diversity and phage biology, bearing broad importance for clinical phage therapy. Future phage therapy patients, especially those with chronic infections, should be screened for antiphage immunity and bacterial heteroresistance before phage treatment.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"19 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147739194","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":"Targeted therapies plus radiotherapy for diffuse intrinsic pontine glioma: the randomized phase 2 BIOMEDE trial.","authors":"Marie-Anne Debily,Gwenael Le Teuff,Thomas Kergrohen,Pascale Varlet,David Castel,Pierre Leblond,Darren Hargrave,Karsten Nysom,Klas Blomgren,Geoffrey Brian McCowage,Francisco Bautista,Dannis van Vuurden,Chris Jones,Alan Mackay,Elisa Izquierdo,David S Ziegler,Angokai Moussa,Emilie Barret,Stephanie Puget,Kevin Beccaria,Kristian Aquilina,Laurent Riffaud,Stephanie Bolle,Samuel Abbou,Anne-Isabelle Bertozzi,Emilie De Carli,Nathalie Boddaert,Volodia Dangouloff-Ros,Raphael Calmon,Patricia Blanc,Gilles Vassal,Marie-Cécile Le Deley,Jacques Grill","doi":"10.1038/s41591-026-04354-1","DOIUrl":"https://doi.org/10.1038/s41591-026-04354-1","url":null,"abstract":"Diffuse intrinsic pontine glioma (DIPG) is the pediatric tumor with the worst prognosis. BIOMEDE was a randomized phase 2 trial comparing the efficacy in terms of overall survival (OS) (primary endpoint) of epidermal growth factor receptor (EGFR) inhibitor erlotinib, mTOR inhibitor everolimus and multitargeted tyrosine kinase inhibitor dasatinib in combination with radiotherapy in patients with a biopsy-proven DIPG. Tumors were assessed centrally for immunohistochemical biomarkers (EGFR overexpression or PTEN loss) together with whole-exome and RNA sequencing. A cohort of 66 children with the same inclusion criteria and treated previously with temozolomide-based regimen was used to compare outcome. Treatment allocation was performed by randomization in 233 patients, designed so that a drug could not be allocated if the corresponding biomarker was absent: 36 received erlotinib, 102 received dasatinib and 95 received everolimus. The trial was ended for futility of the primary endpoint following the recommendations of the independent data monitoring committee: OS from biopsy was not different from the control cohort (median OS = 10.8 months (95% confidence interval (CI): 9.5-13.0)) in any of the three arms (median OS = 9.7 months (95% CI: 7.8-14.6) for erlotinib; 9.9 months (95% CI: 8.8-11.2) for dasatinib; and 11.9 months (95% CI: 10.7-14.2) for everolimus). Everolimus showed significantly less ocular, renal, skin and gastrointestinal side effects and treatment discontinuation for toxicity (secondary endpoint). TP53 mutations, frequently linked to multiple structural chromosomal aberrations, were the strongest predictor for poor survival in multivariate analysis (hazard ratio = 2.8 (95% CI: 1.9-4.2), P < 0.0001). Both mutations in and activation of the mTOR pathway were associated with a better response to everolimus. Four long-term survivors treated with an mTOR inhibitor were alive free of treatment over 6 years from diagnosis. With comprehensive tumor profiling, BIOMEDE validated prognostic biomarkers as well as informative theranostic biomarkers for future trials. ClinicalTrials.gov: NCT02233049 .","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"23 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147739198","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":"Who owns my health data?","authors":"Paul Webster","doi":"10.1038/s41591-026-04378-7","DOIUrl":"https://doi.org/10.1038/s41591-026-04378-7","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776908","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":"The value of patient-focused drug development.","authors":"Allison Martin,Russ Paulsen","doi":"10.1038/s41591-026-04364-z","DOIUrl":"https://doi.org/10.1038/s41591-026-04364-z","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"13 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147739193","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":"Author Correction: High-dose nusinersen for spinal muscular atrophy: a phase 3 randomized trial.","authors":"Richard S Finkel, Thomas O Crawford, Eugenio Mercuri, Charlotte J Sumner, Maria Del Mar Garcia Romero, John W Day, Jacqueline Montes, Peng Sun, Ben Tichler, Angela D Paradis, Emily Boesch, Jennifer Inra, Ross Littauer, Jihee Sohn, Michael Monine, Giulia Gambino, Richard Foster, Raechel Farewell, Stephanie Fradette","doi":"10.1038/s41591-026-04415-5","DOIUrl":"https://doi.org/10.1038/s41591-026-04415-5","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776869","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}