Nature Medicine最新文献_第8页

The practical longevity of stockpiled A(H5N1) influenza vaccine 储存的甲型 H5N1 流感疫苗的实际寿命

IF 58.7 1区医学

Nature Medicine Pub Date : 2024-09-26 DOI: 10.1038/s41591-024-03256-4

Richard J. Webby

引用次数: 0

An open-source framework for electronic health record and patient fate exploration 电子健康记录和患者命运探索的开源框架

IF 82.9 1区医学

Nature Medicine Pub Date : 2024-09-25 DOI: 10.1038/s41591-024-03298-8

引用次数: 0

A foundation model for clinician-centered drug repurposing 以临床医生为中心的药物再利用基础模型

IF 82.9 1区医学

Nature Medicine Pub Date : 2024-09-25 DOI: 10.1038/s41591-024-03233-x

Kexin Huang, Payal Chandak, Qianwen Wang, Shreyas Havaldar, Akhil Vaid, Jure Leskovec, Girish N. Nadkarni, Benjamin S. Glicksberg, Nils Gehlenborg, Marinka Zitnik

{"title":"A foundation model for clinician-centered drug repurposing","authors":"Kexin Huang, Payal Chandak, Qianwen Wang, Shreyas Havaldar, Akhil Vaid, Jure Leskovec, Girish N. Nadkarni, Benjamin S. Glicksberg, Nils Gehlenborg, Marinka Zitnik","doi":"10.1038/s41591-024-03233-x","DOIUrl":"https://doi.org/10.1038/s41591-024-03233-x","url":null,"abstract":"Drug repurposing—identifying new therapeutic uses for approved drugs—is often a serendipitous and opportunistic endeavour to expand the use of drugs for new diseases. The clinical utility of drug-repurposing artificial intelligence (AI) models remains limited because these models focus narrowly on diseases for which some drugs already exist. Here we introduce TxGNN, a graph foundation model for zero-shot drug repurposing, identifying therapeutic candidates even for diseases with limited treatment options or no existing drugs. Trained on a medical knowledge graph, TxGNN uses a graph neural network and metric learning module to rank drugs as potential indications and contraindications for 17,080 diseases. When benchmarked against 8 methods, TxGNN improves prediction accuracy for indications by 49.2% and contraindications by 35.1% under stringent zero-shot evaluation. To facilitate model interpretation, TxGNN’s Explainer module offers transparent insights into multi-hop medical knowledge paths that form TxGNN’s predictive rationales. Human evaluation of TxGNN’s Explainer showed that TxGNN’s predictions and explanations perform encouragingly on multiple axes of performance beyond accuracy. Many of TxGNN’s new predictions align well with off-label prescriptions that clinicians previously made in a large healthcare system. TxGNN’s drug-repurposing predictions are accurate, consistent with off-label drug use, and can be investigated by human experts through multi-hop interpretable rationales.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317059","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}

引用次数: 0

Disparities in healthy working life expectancy in different Chinese populations 中国不同人群健康工作预期寿命的差异

IF 82.9 1区医学

Nature Medicine Pub Date : 2024-09-24 DOI: 10.1038/s41591-024-03290-2

引用次数: 0

A toolbox for surfacing health equity harms and biases in large language models 在大型语言模型中揭示健康公平危害和偏差的工具箱

IF 82.9 1区医学

Nature Medicine Pub Date : 2024-09-23 DOI: 10.1038/s41591-024-03258-2

Stephen R. Pfohl, Heather Cole-Lewis, Rory Sayres, Darlene Neal, Mercy Asiedu, Awa Dieng, Nenad Tomasev, Qazi Mamunur Rashid, Shekoofeh Azizi, Negar Rostamzadeh, Liam G. McCoy, Leo Anthony Celi, Yun Liu, Mike Schaekermann, Alanna Walton, Alicia Parrish, Chirag Nagpal, Preeti Singh, Akeiylah Dewitt, Philip Mansfield, Sushant Prakash, Katherine Heller, Alan Karthikesalingam, Christopher Semturs, Joelle Barral, Greg Corrado, Yossi Matias, Jamila Smith-Loud, Ivor Horn, Karan Singhal

{"title":"A toolbox for surfacing health equity harms and biases in large language models","authors":"Stephen R. Pfohl, Heather Cole-Lewis, Rory Sayres, Darlene Neal, Mercy Asiedu, Awa Dieng, Nenad Tomasev, Qazi Mamunur Rashid, Shekoofeh Azizi, Negar Rostamzadeh, Liam G. McCoy, Leo Anthony Celi, Yun Liu, Mike Schaekermann, Alanna Walton, Alicia Parrish, Chirag Nagpal, Preeti Singh, Akeiylah Dewitt, Philip Mansfield, Sushant Prakash, Katherine Heller, Alan Karthikesalingam, Christopher Semturs, Joelle Barral, Greg Corrado, Yossi Matias, Jamila Smith-Loud, Ivor Horn, Karan Singhal","doi":"10.1038/s41591-024-03258-2","DOIUrl":"https://doi.org/10.1038/s41591-024-03258-2","url":null,"abstract":"Large language models (LLMs) hold promise to serve complex health information needs but also have the potential to introduce harm and exacerbate health disparities. Reliably evaluating equity-related model failures is a critical step toward developing systems that promote health equity. We present resources and methodologies for surfacing biases with potential to precipitate equity-related harms in long-form, LLM-generated answers to medical questions and conduct a large-scale empirical case study with the Med-PaLM 2 LLM. Our contributions include a multifactorial framework for human assessment of LLM-generated answers for biases and EquityMedQA, a collection of seven datasets enriched for adversarial queries. Both our human assessment framework and our dataset design process are grounded in an iterative participatory approach and review of Med-PaLM 2 answers. Through our empirical study, we find that our approach surfaces biases that may be missed by narrower evaluation approaches. Our experience underscores the importance of using diverse assessment methodologies and involving raters of varying backgrounds and expertise. While our approach is not sufficient to holistically assess whether the deployment of an artificial intelligence (AI) system promotes equitable health outcomes, we hope that it can be leveraged and built upon toward a shared goal of LLMs that promote accessible and equitable healthcare.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276841","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}

引用次数: 0

Post-hospitalisation COVID-19 cognitive deficits at one year are global and associated with elevated brain injury markers and grey matter volume reduction COVID-19 住院一年后出现的认知障碍是全面性的，与脑损伤标志物升高和灰质体积缩小有关

IF 82.9 1区医学

Nature Medicine Pub Date : 2024-09-23 DOI: 10.1038/s41591-024-03309-8

Greta K. Wood, Brendan F. Sargent, Zain-Ul-Abideen Ahmad, Kukatharmini Tharmaratnam, Cordelia Dunai, Franklyn N. Egbe, Naomi H. Martin, Bethany Facer, Sophie L. Pendered, Henry C. Rogers, Christopher Hübel, Daniel J. van Wamelen, Richard A. I. Bethlehem, Valentina Giunchiglia, Peter J. Hellyer, William Trender, Gursharan Kalsi, Edward Needham, Ava Easton, Thomas A. Jackson, Colm Cunningham, Rachel Upthegrove, Thomas A. Pollak, Matthew Hotopf, Tom Solomon, Sarah L. Pett, Pamela J. Shaw, Nicholas Wood, Neil A. Harrison, Karla L. Miller, Peter Jezzard, Guy Williams, Eugene P. Duff, Steven Williams, Fernando Zelaya, Stephen M. Smith, Simon Keller, Matthew Broome, Nathalie Kingston, Masud Husain, Angela Vincent, John Bradley, Patrick Chinnery, David K. Menon, John P. Aggleton, Timothy R. Nicholson, John-Paul Taylor, Anthony S. David, Alan Carson, Ed Bullmore, Gerome Breen, Adam Hampshire, Benedict D. Michael, Stella-Maria Paddick, E. Charles Leek

{"title":"Post-hospitalisation COVID-19 cognitive deficits at one year are global and associated with elevated brain injury markers and grey matter volume reduction","authors":"Greta K. Wood, Brendan F. Sargent, Zain-Ul-Abideen Ahmad, Kukatharmini Tharmaratnam, Cordelia Dunai, Franklyn N. Egbe, Naomi H. Martin, Bethany Facer, Sophie L. Pendered, Henry C. Rogers, Christopher Hübel, Daniel J. van Wamelen, Richard A. I. Bethlehem, Valentina Giunchiglia, Peter J. Hellyer, William Trender, Gursharan Kalsi, Edward Needham, Ava Easton, Thomas A. Jackson, Colm Cunningham, Rachel Upthegrove, Thomas A. Pollak, Matthew Hotopf, Tom Solomon, Sarah L. Pett, Pamela J. Shaw, Nicholas Wood, Neil A. Harrison, Karla L. Miller, Peter Jezzard, Guy Williams, Eugene P. Duff, Steven Williams, Fernando Zelaya, Stephen M. Smith, Simon Keller, Matthew Broome, Nathalie Kingston, Masud Husain, Angela Vincent, John Bradley, Patrick Chinnery, David K. Menon, John P. Aggleton, Timothy R. Nicholson, John-Paul Taylor, Anthony S. David, Alan Carson, Ed Bullmore, Gerome Breen, Adam Hampshire, Benedict D. Michael, Stella-Maria Paddick, E. Charles Leek","doi":"10.1038/s41591-024-03309-8","DOIUrl":"https://doi.org/10.1038/s41591-024-03309-8","url":null,"abstract":"The spectrum, pathophysiology, and recovery trajectory of persistent post-COVID-19 cognitive deficits are unknown, limiting our ability to develop prevention and treatment strategies. We report the one-year cognitive, serum biomarker, and neuroimaging findings from a prospective, national study of cognition in 351 COVID-19 patients who had required hospitalisation, compared to 2,927 normative matched controls. Cognitive deficits were global and associated with elevated brain injury markers, and reduced anterior cingulate cortex volume one year after COVID-19. The severity of the initial infective insult, post-acute psychiatric symptoms, and a history of encephalopathy were associated with greatest deficits. There was strong concordance between subjective and objective cognitive deficits. Longitudinal follow-up in 106 patients demonstrated a trend toward recovery. Together, these findings support the hypothesis that brain injury in moderate to severe COVID-19 may be immune-mediated, and should guide the development of therapeutic strategies.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276786","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}

引用次数: 0

Molecular profiling of BRAF-V600E-mutant metastatic colorectal cancer in the phase 3 BEACON CRC trial BEACON CRC 三期试验中 BRAF-V600E 突变转移性结直肠癌的分子图谱分析

IF 82.9 1区医学

Nature Medicine Pub Date : 2024-09-23 DOI: 10.1038/s41591-024-03235-9

Scott Kopetz, Danielle A. Murphy, Jie Pu, Fortunato Ciardiello, Jayesh Desai, Eric Van Cutsem, Harpreet Singh Wasan, Takayuki Yoshino, Hedieh Saffari, Xiaosong Zhang, Phineas Hamilton, Tao Xie, Rona Yaeger, Josep Tabernero

{"title":"Molecular profiling of BRAF-V600E-mutant metastatic colorectal cancer in the phase 3 BEACON CRC trial","authors":"Scott Kopetz, Danielle A. Murphy, Jie Pu, Fortunato Ciardiello, Jayesh Desai, Eric Van Cutsem, Harpreet Singh Wasan, Takayuki Yoshino, Hedieh Saffari, Xiaosong Zhang, Phineas Hamilton, Tao Xie, Rona Yaeger, Josep Tabernero","doi":"10.1038/s41591-024-03235-9","DOIUrl":"https://doi.org/10.1038/s41591-024-03235-9","url":null,"abstract":"The BEACON CRC study demonstrated that encorafenib (Enco)+cetuximab (Cetux)±binimetinib (Bini) significantly improved overall survival (OS) versus Cetux + chemotherapy in previously treated patients with BRAF-V600E-mutant mCRC, providing the basis for the approval of the Enco+Cetux regimen in the United States and the European Union. A greater understanding of biomarkers predictive of response to Enco+Cetux±Bini treatment is of clinical relevance. In this prespecified, exploratory biomarker analysis of the BEACON CRC study, we characterize genomic and transcriptomic correlates of clinical outcomes and acquired resistance mechanisms through integrated clinical and molecular analysis, including whole-exome and -transcriptome tissue sequencing and circulating tumor DNA genomic profiling. Tumors with higher immune signatures showed a trend towards increased OS benefit with Enco+Bini+Cetux. RAS, MAP2K1 and MET alterations were most commonly acquired with Enco+Cetux±Bini, and more frequent in patients with a high baseline cell-cycle gene signature; baseline TP53 mutation was associated with acquired MET amplification. Acquired mutations were subclonal and polyclonal, with evidence of increased tumor mutation rate with Enco+Cetux±Bini and mutational signatures (SBS17a/b). These findings support treatment with Enco+Cetux±Bini for patients with BRAF-V600E-mutant mCRC and provide insights into the biology of response and resistance to MAPK-pathway-targeted therapy. ClinicalTrials.gov registration: NCT02928224","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276789","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}

引用次数: 0

Patient attitudes toward the AI doctor 患者对人工智能医生的态度

IF 82.9 1区医学

Nature Medicine Pub Date : 2024-09-23 DOI: 10.1038/s41591-024-03272-4

Aaron Fanous, Kirsten Steffner, Roxana Daneshjou

引用次数: 0

Lipid profiling identifies modifiable signatures of cardiometabolic risk in children and adolescents with obesity 脂质分析确定肥胖儿童和青少年心脏代谢风险的可调节特征

IF 82.9 1区医学

Nature Medicine Pub Date : 2024-09-20 DOI: 10.1038/s41591-024-03279-x

Yun Huang, Karolina Sulek, Sara E. Stinson, Louise Aas Holm, Min Kim, Kajetan Trost, Kourosh Hooshmand, Morten Asp Vonsild Lund, Cilius E. Fonvig, Helene Bæk Juel, Trine Nielsen, Lars Ängquist, Peter Rossing, Maja Thiele, Aleksander Krag, Jens-Christian Holm, Cristina Legido-Quigley, Torben Hansen

{"title":"Lipid profiling identifies modifiable signatures of cardiometabolic risk in children and adolescents with obesity","authors":"Yun Huang, Karolina Sulek, Sara E. Stinson, Louise Aas Holm, Min Kim, Kajetan Trost, Kourosh Hooshmand, Morten Asp Vonsild Lund, Cilius E. Fonvig, Helene Bæk Juel, Trine Nielsen, Lars Ängquist, Peter Rossing, Maja Thiele, Aleksander Krag, Jens-Christian Holm, Cristina Legido-Quigley, Torben Hansen","doi":"10.1038/s41591-024-03279-x","DOIUrl":"https://doi.org/10.1038/s41591-024-03279-x","url":null,"abstract":"Pediatric obesity is a progressive, chronic disease that can lead to serious cardiometabolic complications. Here we investigated the peripheral lipidome in 958 children and adolescents with overweight or obesity and 373 with normal weight, in a cross-sectional study. We also implemented a family-based, personalized program to assess the effects of obesity management on 186 children and adolescents in a clinical setting. Using mass spectrometry-based lipidomics, we report an increase in ceramides, alongside a decrease in lysophospholipids and omega-3 fatty acids with obesity metabolism. Ceramides, phosphatidylethanolamines and phosphatidylinositols were associated with insulin resistance and cardiometabolic risk, whereas sphingomyelins showed inverse associations. Additionally, a panel of three lipids predicted hepatic steatosis as effectively as liver enzymes. Lipids partially mediated the association between obesity and cardiometabolic traits. The nonpharmacological management reduced levels of ceramides, phospholipids and triglycerides, indicating that lowering the degree of obesity could partially restore a healthy lipid profile in children and adolescents.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275957","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}

引用次数: 0

High-throughput identification of repurposable neuroactive drugs with potent anti-glioblastoma activity 高通量鉴定具有强效抗胶质母细胞瘤活性的可再利用神经活性药物

IF 82.9 1区医学

Nature Medicine Pub Date : 2024-09-20 DOI: 10.1038/s41591-024-03224-y

Sohyon Lee, Tobias Weiss, Marcel Bühler, Julien Mena, Zuzanna Lottenbach, Rebekka Wegmann, Miaomiao Sun, Michel Bihl, Bartłomiej Augustynek, Sven P. Baumann, Sandra Goetze, Audrey van Drogen, Patrick G. A. Pedrioli, David Penton, Yasmin Festl, Alicia Buck, Daniel Kirschenbaum, Anna M. Zeitlberger, Marian C. Neidert, Flavio Vasella, Elisabeth J. Rushing, Bernd Wollscheid, Matthias A. Hediger, Michael Weller, Berend Snijder

{"title":"High-throughput identification of repurposable neuroactive drugs with potent anti-glioblastoma activity","authors":"Sohyon Lee, Tobias Weiss, Marcel Bühler, Julien Mena, Zuzanna Lottenbach, Rebekka Wegmann, Miaomiao Sun, Michel Bihl, Bartłomiej Augustynek, Sven P. Baumann, Sandra Goetze, Audrey van Drogen, Patrick G. A. Pedrioli, David Penton, Yasmin Festl, Alicia Buck, Daniel Kirschenbaum, Anna M. Zeitlberger, Marian C. Neidert, Flavio Vasella, Elisabeth J. Rushing, Bernd Wollscheid, Matthias A. Hediger, Michael Weller, Berend Snijder","doi":"10.1038/s41591-024-03224-y","DOIUrl":"https://doi.org/10.1038/s41591-024-03224-y","url":null,"abstract":"Glioblastoma, the most aggressive primary brain cancer, has a dismal prognosis, yet systemic treatment is limited to DNA-alkylating chemotherapies. New therapeutic strategies may emerge from exploring neurodevelopmental and neurophysiological vulnerabilities of glioblastoma. To this end, we systematically screened repurposable neuroactive drugs in glioblastoma patient surgery material using a clinically concordant and single-cell resolved platform. Profiling more than 2,500 ex vivo drug responses across 27 patients and 132 drugs identified class-diverse neuroactive drugs with potent anti-glioblastoma efficacy that were validated across model systems. Interpretable molecular machine learning of drug–target networks revealed neuroactive convergence on AP-1/BTG-driven glioblastoma suppression, enabling expanded in silico screening of more than 1 million compounds with high patient validation accuracy. Deep multimodal profiling confirmed Ca2+-driven AP-1/BTG-pathway induction as a neuro-oncological glioblastoma vulnerability, epitomized by the anti-depressant vortioxetine synergizing with current standard-of-care chemotherapies in vivo. These findings establish an actionable framework for glioblastoma treatment rooted in its neural etiology.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275956","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}

引用次数: 0