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TERN-501 monotherapy and combination therapy with TERN-101 in metabolic dysfunction-associated steatohepatitis: the randomized phase 2a DUET trial TERN-501单药治疗和TERN-101联合治疗代谢功能障碍相关脂肪性肝炎：随机2a期DUET试验

IF 82.9 1区医学

Nature Medicine Pub Date : 2025-06-11 DOI: 10.1038/s41591-025-03722-7

Mazen Noureddin, Naim Alkhouri, Eric J. Lawitz, Kris V. Kowdley, Rohit Loomba, Lois Lee, Christopher Jones, Amnon Schlegel, Tonya Marmon, Kacey Anderson, Yizhao Li, Erin Quirk, Stephen A. Harrison

{"title":"TERN-501 monotherapy and combination therapy with TERN-101 in metabolic dysfunction-associated steatohepatitis: the randomized phase 2a DUET trial","authors":"Mazen Noureddin, Naim Alkhouri, Eric J. Lawitz, Kris V. Kowdley, Rohit Loomba, Lois Lee, Christopher Jones, Amnon Schlegel, Tonya Marmon, Kacey Anderson, Yizhao Li, Erin Quirk, Stephen A. Harrison","doi":"10.1038/s41591-025-03722-7","DOIUrl":"https://doi.org/10.1038/s41591-025-03722-7","url":null,"abstract":"Thyroid hormone receptor-β (THRβ) agonism is a validated mechanism for treating metabolic dysfunction-associated steatohepatitis (MASH). DUET was a 12-week, randomized, double-blind, placebo-controlled, multicenter phase 2a study investigating the efficacy, safety and pharmacodynamics and pharmacokinetics of once-daily TERN-501 (THRβ agonist) as monotherapy or combined with TERN-101 (farnesoid X receptor agonist), in patients with presumed MASH. Overall, 162 patients were randomized to: TERN-501 monotherapy (1 mg (n = 23), 3 mg (n = 23) or 6 mg (n = 22)), TERN-101 10-mg monotherapy (n = 24), TERN-501 (3 mg (n = 23) or 6 mg (n = 23)) plus TERN-101 10-mg combination therapy or placebo (n = 24). The primary endpoint was relative change from baseline at week 12 in liver fat content with TERN-501 monotherapy versus placebo, using magnetic resonance imaging proton density fat fraction (MRI-PDFF). Least squares mean (s.e.) changes from baseline at week 12 in MRI-PDFF with TERN-501 were: −15.4% (5.2%) with 1 mg, −27.5% (5.7%) with 3 mg (P = 0.0036) and −44.8% (5.9%) with 6 mg (P < 0.0001), versus −4.0% (5.4%) with placebo. The incidence of adverse events was similar with TERN-501 monotherapy or placebo. In conclusion, TERN-501 treatment resulted in dose-dependent, significant reductions from baseline in MRI-PDFF compared to placebo in patients with MASH. ClinicalTrials.gov registration: NCT05415722.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"17 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260279","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

Author Correction: Intracerebroventricular bivalent CAR T cells targeting EGFR and IL-13Rα2 in recurrent glioblastoma: a phase 1 trial 作者更正：脑室内靶向EGFR和IL-13Rα2的二价CAR - T细胞治疗复发性胶质母细胞瘤：一项1期试验

IF 82.9 1区医学

Nature Medicine Pub Date : 2025-06-11 DOI: 10.1038/s41591-025-03824-2

Stephen J. Bagley, Arati S. Desai, Joseph A. Fraietta, Dana Silverbush, Daniel Chafamo, Nelson F. Freeburg, Gayathri Konanur Gopikrishna, Andrew J. Rech, Ali Nabavizadeh, Linda J. Bagley, Jungmin Park, Danuta Jarocha, Rene Martins, Nicolas Sarmiento, Eileen Maloney, Lester Lledo, Carly Stein, Amy Marshall, Rachel M. Leskowitz, Julie K. Jadlowsky, Shane Mackey, Shannon Christensen, Bike Su Oner, Gabriela Plesa, Andrea Brennan, Vanessa Gonzalez, Fang Chen, David Barrett, Robert Colbourn, MacLean P. Nasrallah, Zissimos Mourelatos, Wei-Ting Hwang, Cecile Alanio, Donald L. Siegel, Carl H. June, Elizabeth O. Hexner, Zev A. Binder, Donald M. O’Rourke

引用次数: 0

T and B cell responses against Epstein–Barr virus in primary sclerosing cholangitis 原发性硬化性胆管炎中T细胞和B细胞对eb病毒的反应

IF 82.9 1区医学

Nature Medicine Pub Date : 2025-06-11 DOI: 10.1038/s41591-025-03692-w

Hesham ElAbd, Mitchell Pesesky, Gabriel Innocenti, Brian K. Chung, Aya K. H. Mahdy, Valeriia Kriukova, Laila Kulsvehagen, Dennis Strobbe, Claudia Stühler, Gabriele Mayr, Damon H. May, Melanie Prinzensteiner, Tim A. Steiert, Florian Tran, Michel V. Hadjihannas, Rainer Günther, Elisa Rosati, Sören Mucha, Wolfgang Lieb, Malte Ziemann, Astrid Dempfle, Felix Braun, Trine Folseraas, Johannes R. Hov, Espen Melum, Petra Bacher, Martina Sterneck, Tobias J. Weismüller, Henrike Lenzen, Bernd Bokemeyer, Bryan Howie, Harlan S. Robins, Christoph Röcken, Stefan Schreiber, Nina Khanna, Anne-Katrin Pröbstel, Christoph Schramm, Thomas Vogl, Tom H. Karlsen, Andre Franke

{"title":"T and B cell responses against Epstein–Barr virus in primary sclerosing cholangitis","authors":"Hesham ElAbd, Mitchell Pesesky, Gabriel Innocenti, Brian K. Chung, Aya K. H. Mahdy, Valeriia Kriukova, Laila Kulsvehagen, Dennis Strobbe, Claudia Stühler, Gabriele Mayr, Damon H. May, Melanie Prinzensteiner, Tim A. Steiert, Florian Tran, Michel V. Hadjihannas, Rainer Günther, Elisa Rosati, Sören Mucha, Wolfgang Lieb, Malte Ziemann, Astrid Dempfle, Felix Braun, Trine Folseraas, Johannes R. Hov, Espen Melum, Petra Bacher, Martina Sterneck, Tobias J. Weismüller, Henrike Lenzen, Bernd Bokemeyer, Bryan Howie, Harlan S. Robins, Christoph Röcken, Stefan Schreiber, Nina Khanna, Anne-Katrin Pröbstel, Christoph Schramm, Thomas Vogl, Tom H. Karlsen, Andre Franke","doi":"10.1038/s41591-025-03692-w","DOIUrl":"https://doi.org/10.1038/s41591-025-03692-w","url":null,"abstract":"Primary sclerosing cholangitis (PSC) is an idiopathic, progressive and incurable liver disease. Here, we aimed for systematic analyses of adaptive immune responses in PSC. By profiling the T cell repertoires of 504 individuals with PSC and 904 healthy controls, we identified 1,008 clonotypes associated with PSC. A substantial fraction of these clonotypes was restricted to known PSC human leukocyte antigen susceptibility alleles and known to target Epstein–Barr virus (EBV) epitopes. We further utilized phage-immunoprecipitation sequencing to determine antibody epitope repertoires of 120 individuals with PSC and 202 healthy controls, which showed a higher burden of anti-EBV responses in PSC than controls. EBV-specific monoclonal antibodies isolated from B cells in PSC livers corroborated convergent B and T cell responses against EBV. By analyzing electronic health records of >116 million people, we identified an association between infectious mononucleosis and PSC (odds ratio, 12; 95% confidence interval, 6.3–22.9), suggesting a link between EBV and PSC.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"28 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260276","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

Global burden of chikungunya virus infections and the potential benefit of vaccination campaigns 基孔肯雅病毒感染的全球负担和疫苗接种运动的潜在益处

IF 82.9 1区医学

Nature Medicine Pub Date : 2025-06-10 DOI: 10.1038/s41591-025-03703-w

Gabriel Ribeiro dos Santos, Fariha Jawed, Christinah Mukandavire, Arminder Deol, Danny Scarponi, Leonard E. G. Mboera, Eric Seruyange, Mathieu J. P. Poirier, Samuel Bosomprah, Augustine O. Udeze, Koussay Dellagi, Nathanael Hozé, Jaffu Chilongola, Gheyath K. Nasrallah, Simon Cauchemez, Henrik Salje

{"title":"Global burden of chikungunya virus infections and the potential benefit of vaccination campaigns","authors":"Gabriel Ribeiro dos Santos, Fariha Jawed, Christinah Mukandavire, Arminder Deol, Danny Scarponi, Leonard E. G. Mboera, Eric Seruyange, Mathieu J. P. Poirier, Samuel Bosomprah, Augustine O. Udeze, Koussay Dellagi, Nathanael Hozé, Jaffu Chilongola, Gheyath K. Nasrallah, Simon Cauchemez, Henrik Salje","doi":"10.1038/s41591-025-03703-w","DOIUrl":"https://doi.org/10.1038/s41591-025-03703-w","url":null,"abstract":"The first vaccine against chikungunya virus (CHIKV) has now been licensed; however, due to a limited knowledge of the underlying global burden, its potential to reduce disease burden remains unknown. We used data from seroprevalence studies, observed cases and mosquito distributions to quantify the underlying CHIKV burden in 180 countries and territories, and we explored the potential impact of vaccination campaigns. We estimate that 104 countries have experienced CHIKV transmission, covering 2.8 billion people, and that, in epidemic settings, the mean duration between outbreaks is 6.2 years, with 8.4% of the susceptible population infected per outbreak. Globally, there are 35 million annual infections, mainly in Southeast Asia, Africa and the Americas. Assuming a vaccine efficacy against disease of 70% and a protection against infection of 40%, vaccinating 50% of individuals over 12 years of age in places and times where the virus circulates would avert 4,436 infections, 0.34 deaths and 17 disability-adjusted life years per 100,000 doses used. These findings highlight the global burden of chikungunya and the potential of CHIKV vaccination campaigns.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"17 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252110","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

Systemic exposures across heavily industrial zones 在重工业区的系统性暴露

IF 82.9 1区医学

Nature Medicine Pub Date : 2025-06-10 DOI: 10.1038/s41591-025-03752-1

Nicolás C. Zanetta-Colombo, Dajie Zhang, Peter B. Marschik

引用次数: 0

Exercise reduces the risk of colon cancer recurrence 运动可以降低结肠癌复发的风险

IF 82.9 1区医学

Nature Medicine Pub Date : 2025-06-09 DOI: 10.1038/d41591-025-00038-4

引用次数: 0

Author Correction: RANO criteria for response assessment of brain metastases based on amino acid PET imaging 作者更正：基于氨基酸PET成像的脑转移反应评估的RANO标准

IF 82.9 1区医学

Nature Medicine Pub Date : 2025-06-09 DOI: 10.1038/s41591-025-03819-z

Nathalie L. Albert, Norbert Galldiks, Benjamin M. Ellingson, Martin J. van den Bent, Susan M. Chang, Francesco Cicone, Eng-Siew Koh, Ian Law, Emilie Le Rhun, Maximilian J. Mair, Jan-Michael Werner, Anna S. Berghoff, Julia Furtner, Giuseppe Minniti, Andrew M. Scott, Susan C. Short, Jana Ivanidze, Derek R. Johnson, Bogdana Suchorska, Nelleke Tolboom, Joerg-Christian Tonn, Antoine Verger, Evanthia Galanis, Priscilla K. Brastianos, Patrick Y. Wen, Michael Weller, Nancy U. Lin, Matthias Preusser

引用次数: 0

Personalized, in vivo gene editing for a newborn 针对新生儿的个性化体内基因编辑

IF 82.9 1区医学

Nature Medicine Pub Date : 2025-06-06 DOI: 10.1038/d41591-025-00037-5

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Climate change as a catalyst for antimicrobial resistance 气候变化是抗菌素耐药性的催化剂

IF 82.9 1区医学

Nature Medicine Pub Date : 2025-06-06 DOI: 10.1038/s41591-025-03705-8

Kevin K. A. Tetteh

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Ovarian aging: a missing diagnosis in reproductive medicine 卵巢老化：生殖医学的一个漏诊

IF 82.9 1区医学