Nature Medicine最新文献

{"title":"Inherited mitochondrial genetics as a predictor of immune checkpoint inhibition efficacy in melanoma","authors":"Kelsey R. Monson, Robert Ferguson, Joanna E. Handzlik, Leah Morales, Jiahan Xiong, Vylyny Chat, Sasha Dagayev, Alireza Khodadadi-Jamayran, Danny Simpson, Esther Kazlow, Anabelle Bunis, Chaitra Sreenivasaiah, Milad Ibrahim, Iryna Voloshyna, Wouter Ouwerkerk, Rosalie M. Luiten, Mariaelena Capone, Gabriele Madonna, Yuting Lu, Yongzhao Shao, Anna Pavlick, Michelle Krogsgaard, Janice Mehnert, Hao Tang, Sonia Dolfi, Daniel Tenney, John B. A. G. Haanen, Thomas F. Gajewski, F. Stephen Hodi, Keith T. Flaherty, Kasey Couts, William Robinson, Igor Puzanov, Marc S. Ernstoff, Osama Rahma, Michael Postow, Ryan J. Sullivan, Jason J. Luke, Paolo A. Ascierto, Iman Osman, Tomas Kirchhoff","doi":"10.1038/s41591-025-03699-3","DOIUrl":"https://doi.org/10.1038/s41591-025-03699-3","url":null,"abstract":"<p>Response to immune checkpoint inhibitors (ICIs) in metastatic melanoma (MM) varies among patients, and current baseline biomarkers predicting treatment outcomes are limited. As mitochondrial (MT) metabolism has emerged as an important regulator of host immune function, we explored the association of host MT genetics (MT haplogroups) with ICI efficacy in 1,225 ICI-treated patients with MM from the clinical trial CheckMate-067 and the International Germline Immuno-Oncology Melanoma Consortium. We discovered and validated significant associations of MT haplogroup T (HG-T) with resistance to anti-programmed cell death protein-1-based ICI (both single-agent and combination) and have shown that HG-T is independent from established tumor predictors. We also found that patients belonging to HG-T exhibit a unique nivolumab-resistant baseline peripheral CD8⁺ T cell repertoire compared to other MT haplogroups, providing, to our knowledge, the first link between MT inheritance, host immunity and ICI resistance. The study proposes a host blood-based biomarker with stand-alone clinical value predicting ICI efficacy and points to an ICI-resistance mechanism associated with MT metabolism, with clinical relevance in immuno-oncology.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"31 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144219312","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":"Stem cell therapies advance in Parkinson’s disease and beyond","authors":"","doi":"10.1038/d41591-025-00036-6","DOIUrl":"https://doi.org/10.1038/d41591-025-00036-6","url":null,"abstract":"Landmark trials using stem cells to treat Parkinson’s disease in the USA and Japan mark a turning point for cell therapy in neurodegeneration. Similar approaches to Alzheimer’s disease and amyotrophic lateral sclerosis are also showing early signs of promise.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"1 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211491","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":"Individual variations in glycemic responses to carbohydrates and underlying metabolic physiology","authors":"Yue Wu, Ben Ehlert, Ahmed A. Metwally, Dalia Perelman, Heyjun Park, Andrew Wallace Brooks, Fahim Abbasi, Basil Michael, Alessandra Celli, Caroline Bejikian, Ekrem Ayhan, Yingzhou Lu, Samuel M. Lancaster, Daniel Hornburg, Lucia Ramirez, David Bogumil, Sarah Pollock, Frank Wong, Denver Bradley, Georg Gutjahr, Ekanath Srihari Rangan, Tao Wang, Lettie McGuire, P. Venkat Rangan, Helge Ræder, Zohar Shipony, Doron Lipson, Tracey McLaughlin, Michael P. Snyder","doi":"10.1038/s41591-025-03719-2","DOIUrl":"https://doi.org/10.1038/s41591-025-03719-2","url":null,"abstract":"<p>Elevated postprandial glycemic responses (PPGRs) are associated with type 2 diabetes and cardiovascular disease. PPGRs to the same foods have been shown to vary between individuals, but systematic characterization of the underlying physiologic and molecular basis is lacking. We measured PPGRs using continuous glucose monitoring in 55 well-phenotyped participants challenged with seven different standard carbohydrate meals administered in replicate. We also examined whether preloading a rice meal with fiber, protein or fat (‘mitigators’) altered PPGRs. We performed gold-standard metabolic tests and multi-omics profiling to examine the physiologic and molecular basis for interindividual PPGR differences. Overall, rice was the most glucose-elevating carbohydrate meal, but there was considerable interindividual variability. Individuals with the highest PPGR to potatoes (potato-spikers) were more insulin resistant and had lower beta cell function, whereas grape-spikers were more insulin sensitive. Rice-spikers were more likely to be Asian individuals, and bread-spikers had higher blood pressure. Mitigators were less effective in reducing PPGRs in insulin-resistant as compared to insulin-sensitive participants. Multi-omics signatures of PPGR and metabolic phenotypes were discovered, including insulin-resistance-associated triglycerides, hypertension-associated metabolites and PPGR-associated microbiome pathways. These results demonstrate interindividual variability in PPGRs to carbohydrate meals and mitigators and their association with metabolic and molecular profiles.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"260 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211492","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":"Atezolizumab plus paclitaxel and bevacizumab as first-line treatment of advanced triple-negative breast cancer: the ATRACTIB phase 2 trial","authors":"María Gion, Isabel Blancas, Patricia Cortez-Castedo, Alfonso Cortés-Salgado, Frederik Marmé, Salvador Blanch, Serafín Morales, Nieves Díaz, Isabel Calvo-Plaza, Sabela Recalde, Alejandro Martínez-Bueno, Manuel Ruiz-Borrego, Elisenda Llabrés, María Teresa Taberner, Michelino de Laurentiis, Silvia García-Vicente, José Antonio Guerrero, Olga Boix, Jose Rodríguez-Morató, Miguel Sampayo-Cordero, Gabriele Antonarelli, José Manuel Pérez-García, Javier Cortés, Antonio Llombart-Cussac","doi":"10.1038/s41591-025-03734-3","DOIUrl":"https://doi.org/10.1038/s41591-025-03734-3","url":null,"abstract":"<p>Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with poor prognosis. The current first-line treatment for advanced TNBC (aTNBC) is determined by the expression of programmed cell death-ligand 1 (PD-L1). In the ATRACTIB trial—a multicenter, single-arm, phase 2 study—we evaluated the combination of atezolizumab, paclitaxel and bevacizumab as first-line treatment for patients with aTNBC, independently of PD-L1 status. The primary endpoint was investigator-assessed progression-free survival. One hundred female patients were enrolled, with most evaluable tumors being PD-L1-negative (97.6%). The primary endpoint was met, with a median progression-free survival of 11.0 months (95% confidence interval (CI): 9.0–13.4; <i>P</i> &lt; 0.001). The objective response rate was 63.0% (95% CI: 52.8–72.4) and median overall survival was 27.4 months (95% CI: 23.4–37.4). No treatment-related deaths or new safety signals were observed. This combination demonstrated significant antitumor activity as first-line therapy for aTNBC patients and merits further investigation. ClinicalTrials.gov Identifier: NCT04408118.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"8 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211488","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":"Peri-operative atezolizumab in early-stage triple-negative breast cancer: final results and ctDNA analyses from the randomized phase 3 IMpassion031 trial","authors":"Elizabeth A. Mittendorf, Zoe June Assaf, Nadia Harbeck, Hong Zhang, Shigehira Saji, Kyung Hae Jung, Roberto Hegg, Andreas Koehler, Joohyuk Sohn, Hiroji Iwata, Melinda L. Telli, Cristiano Ferrario, Kevin Punie, Aditi Qamra, Max Dieterich, Yun Xu, Mario Liste-Hermoso, Esther Shearer-Kang, Luciana Molinero, Stephen Y. Chui, Carlos H. Barrios","doi":"10.1038/s41591-025-03725-4","DOIUrl":"https://doi.org/10.1038/s41591-025-03725-4","url":null,"abstract":"<p>Previously published results demonstrated that the randomized phase 3 IMpassion031 trial met its primary objective: adding atezolizumab to neoadjuvant chemotherapy significantly improved pathologic complete response (pCR) rate in patients with stage II/III triple-negative breast cancer (TNBC). Here we report the prespecified final analysis of the secondary endpoints with 3 years’ follow-up, together with exploratory analyses of circulating tumor (ct)DNA. Patients with previously untreated stage II/III TNBC enrolled in 75 academic and community sites in 13 countries were randomized 1:1 to receive neoadjuvant chemotherapy with either peri-operative atezolizumab (<i>n</i> = 165) or preoperative placebo (<i>n</i> = 168). Descriptive secondary endpoints included event-free, disease-free and overall survival. Long-term outcomes favored the atezolizumab group (event-free survival hazard ratio (HR), 0.76; 95% confidence interval (CI), 0.47–1.21; disease-free survival HR, 0.76; 95% CI, 0.44–1.30; overall survival HR, 0.56; 95% CI, 0.30–1.04). Among patients without pCR, 14 of 70 (20%) atezolizumab-treated and 33 of 99 (33%) placebo-treated patients received additional adjuvant therapy, frequently capecitabine. In exploratory biomarker analyses, patients with baseline ctDNA-negative status (6%) had excellent long-term outcomes. Most patients (87%) had cleared ctDNA at surgery. ctDNA-positive status at surgery identified a subset of non-pCR patients with poorest prognosis. Long-term safety was consistent with primary results. These data show that adding atezolizumab to chemotherapy for stage II/III TNBC is associated with favorable long-term outcomes, and ctDNA dynamics provide prognostic value beyond pCR. ClinicalTrials.gov identifier: NCT03197935.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"313 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211490","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":"Anti-sporozoite monoclonal antibody for malaria prevention: secondary efficacy outcome of a phase 2 randomized trial","authors":"Jeff Skinner, Kassoum Kayentao, Aissata Ongoiba, Sara A. Healy, Zonghui Hu, Anne C. Preston, Amadou Niangaly, Philipp Schwabl, Hamidou Cisse, Safiatou Doumbo, Didier Doumtabe, Abdrahamane Traore, Shanping Li, Mary E. Peterson, Annette M. Seilie, Chris Chavtur, Weston Staubus, Ming Chang, Katrina Kelley, Hamadi Traore, Adama Djiguiba, Mamadou Keita, Adama Ouattara, M’Bouye Doucoure, Mohamed Keita, Djelika Diarra, Mamadou Sylla, Dramane Diakite, Mamadou Konate, Siriman Traore, Amatigué Zéguimé, Amagana Dolo, Daniel E. Neafsey, Sean C. Murphy, Boubacar Traore, Robert A. Seder, Peter D. Crompton","doi":"10.1038/s41591-025-03739-y","DOIUrl":"https://doi.org/10.1038/s41591-025-03739-y","url":null,"abstract":"<p>CIS43LS is a long-acting monoclonal antibody specific for the <i>Plasmodium falciparum</i> circumsporozoite protein expressed on sporozoites. We previously reported that CIS43LS is protective against <i>P.</i> <i>falciparum</i> infection as detected by thick blood smear (TBS; primary endpoint) in a phase 2 double-blind randomized trial involving 330 healthy Malian adults receiving placebo or a single intravenous infusion of 10 mg kg⁻¹ or 40 mg kg⁻¹ of CIS43LS (1:1:1). At enrollment, all participants received artemether–lumefantrine to clear possible <i>P.</i> <i>falciparum</i> infection. Although TBS examination is the standard assay to assess efficacy in malaria vaccines trials in endemic areas, it has poor analytical sensitivity; therefore, it remained unknown whether CIS43LS had achieved sterile protection against infection. Here we report the prespecified secondary efficacy endpoint that used a <i>Plasmodium</i> 18S rRNA quantitative reverse transcription–PCR (qRT–PCR) assay that is ~2,000-fold more sensitive than TBS. We analyzed 5,015 dried blood spots collected before CIS43LS or placebo administration and biweekly thereafter over a 6-month malaria season. At 6 months, efficacy of CIS43LS against qRT–PCR-detected infection assessed in a time-to-event analysis was 87.4% for 40 mg kg⁻¹ (adjusted 95% confidence interval (CI), 79.5–92.3; <i>P</i> &lt; 0.001) and 77.0% for 10 mg kg⁻¹ (adjusted 95% CI, 65.0–84.0; <i>P</i> &lt; 0.001) versus placebo. A post hoc analysis with a gametocyte mRNA-specific qRT–PCR assay showed 6-month efficacy against gametocytemia of 87.7% for 40 mg kg⁻¹ (adjusted 95% CI, 75.6–93.8; <i>P</i> &lt; 0.001) and 73.0% for 10 mg kg⁻¹ (adjusted 95% CI, 54.0–84.0; <i>P</i> &lt; 0.001), versus placebo. These data indicate that a single dose of anti-sporozoite monoclonal antibodies can achieve durable, sterile protection against <i>P.</i> <i>falciparum</i> infection, underscoring their potential to reduce malaria disease burden and transmission. ClinicalTrials.gov identifier: NCT04329104.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"112 2 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201543","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 international Delphi consensus for reporting of setting in psychedelic clinical trials","authors":"Chloé Pronovost-Morgan, Kyle T. Greenway, Leor Roseman","doi":"10.1038/s41591-025-03685-9","DOIUrl":"https://doi.org/10.1038/s41591-025-03685-9","url":null,"abstract":"<p>Psychedelic substances exhibit complex interactions with the ‘set and setting’ of use, that is, the mental state of the user and the environment in which a psychedelic experience takes place. Despite these contextual variables’ known importance, psychedelic research has lacked methodological rigor in reporting extra-pharmacological factors. This study aimed to generate consensus-based guidelines for reporting settings in psychedelic clinical research, according to an international group of psychedelic researchers, clinicians and past trial participants. We conducted a Delphi consensus study composed of four iterative rounds of quasi-anonymous online surveys. A total of 89 experts from 17 countries independently listed potentially important psychedelic setting variables. There were 770 responses, synthesized into 49 distinct items that were subsequently rated, debated and refined. The process yielded 30 extra-pharmacological variables reaching predefined consensus ratings:i.e., ‘important’ or ‘very important’ for ≥70% of experts. These items compose the Reporting of Setting in Psychedelic Clinical Trials (ReSPCT) guidelines, categorized into physical environment, dosing session procedure, therapeutic framework and protocol, and subjective experiences. Emergent findings reveal significant ambiguities in current conceptualizations of set and setting. The ReSPCT guidelines and accompanying explanatory document provide a new standard for the design and documentation of extra-pharmacological variables in psychedelic clinical research.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"35 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201546","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 generative AI-discovered TNIK inhibitor for idiopathic pulmonary fibrosis: a randomized phase 2a trial","authors":"Zuojun Xu, Feng Ren, Ping Wang, Jie Cao, Chunting Tan, Dedong Ma, Li Zhao, Jinghong Dai, Yipeng Ding, Haohui Fang, Huiping Li, Hong Liu, Fengming Luo, Ying Meng, Pinhua Pan, Pingchao Xiang, Zuke Xiao, Sujata Rao, Carol Satler, Sang Liu, Yuan Lv, Heng Zhao, Shan Chen, Hui Cui, Mikhail Korzinkin, David Gennert, Alex Zhavoronkov","doi":"10.1038/s41591-025-03743-2","DOIUrl":"https://doi.org/10.1038/s41591-025-03743-2","url":null,"abstract":"<p>Despite substantial progress in artificial intelligence (AI) for generative chemistry, few novel AI-discovered or AI-designed drugs have reached human clinical trials. Here we present the results of the first phase 2a multicenter, double-blind, randomized, placebo-controlled trial testing the safety and efficacy of rentosertib (formerly ISM001-055), a first-in-class AI-generated small-molecule inhibitor of TNIK, a first-in-class target in idiopathic pulmonary fibrosis (IPF) discovered using generative AI. IPF is an age-related progressive lung condition with no current therapies available that reverse the degenerative course of disease. Patients were randomized to 12 weeks of treatment with 30 mg rentosertib once daily (QD, <i>n</i> = 18), 30 mg rentosertib twice daily (BID, <i>n</i> = 18), 60 mg rentosertib QD (<i>n</i> = 18) or placebo (<i>n</i> = 17). The primary endpoint was the percentage of patients who have at least one treatment-emergent adverse event, which was similar across all treatment arms (72.2% in patients receiving 30 mg rentosertib QD (<i>n</i> = 13/18), 83.3% for 30 mg rentosertib BID (<i>n</i> = 15/18), 83.3% for 60 mg rentosertib QD (<i>n</i> = 15/18) and 70.6% for placebo (<i>n</i> = 12/17)). Treatment-related serious adverse event rates were low and comparable across treatment groups, with the most common events leading to treatment discontinuation related to liver toxicity or diarrhea. Secondary endpoints included pharmacokinetic dynamics (<i>C</i>_max, <i>C</i>_trough, <i>t</i>_max, AUC_{0–<i>t</i>/<i>τ</i>/∞} and <i>t</i>_1/2), changes in lung function as measured by forced vital capacity, diffusion capacity of the lung for carbon monoxide, forced expiry in 1 s and change in the Leicester Cough Questionnaire score, change in 6-min walk distance and the number and hospitalization duration of acute exacerbations of IPF. We observed increased forced vital capacity at the highest dosage with a mean change of +98.4 ml (95% confidence interval 10.9 to 185.9) for patients in the 60 mg rentosertib QD group, compared with −20.3 ml (95% confidence interval −116.1 to 75.6) for the placebo group. These results suggest that targeting TNIK with rentosertib is safe and well tolerated and warrants further investigation in larger-scale clinical trials of longer duration. ClinicalTrials.gov registration number: NCT05938920.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"135 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201542","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":"Pooled analysis of 3,741 stool metagenomes from 18 cohorts for cross-stage and strain-level reproducible microbial biomarkers of colorectal cancer","authors":"Gianmarco Piccinno, Kelsey N. Thompson, Paolo Manghi, Andrew R. Ghazi, Andrew Maltez Thomas, Aitor Blanco-Míguez, Francesco Asnicar, Katarina Mladenovic, Federica Pinto, Federica Armanini, Michal Punčochář, Elisa Piperni, Vitor Heidrich, Gloria Fackelmann, Giulio Ferrero, Sonia Tarallo, Long H. Nguyen, Yan Yan, Nazim A. Keles, Bilge G. Tuna, Veronika Vymetalkova, Mario Trompetto, Vaclav Liska, Tomas Hucl, Pavel Vodicka, Beatrix Bencsiková, Martina Čarnogurská, Vlad Popovici, Federica Marmorino, Chiara Cremolini, Barbara Pardini, Francesca Cordero, Mingyang Song, Andrew T. Chan, Lisa Derosa, Laurence Zitvogel, Curtis Huttenhower, Alessio Naccarati, Eva Budinska, Nicola Segata","doi":"10.1038/s41591-025-03693-9","DOIUrl":"https://doi.org/10.1038/s41591-025-03693-9","url":null,"abstract":"<p>Associations between the gut microbiome and colorectal cancer (CRC) have been uncovered, but larger and more diverse studies are needed to assess their potential clinical use. We expanded upon 12 metagenomic datasets of patients with CRC (<i>n</i>‚Äâ=‚Äâ930), adenomas (<i>n</i>‚Äâ=‚Äâ210) and healthy control individuals (<i>n</i>‚Äâ=‚Äâ976; total <i>n</i>‚Äâ=‚Äâ2,116) with 6 new cohorts (<i>n</i>‚Äâ=‚Äâ1,625) providing granular information on cancer stage and the anatomic location of tumors. We improved CRC prediction accuracy based solely on gut metagenomics (average area under the curve‚Äâ=‚Äâ0.85) and highlighted the contribution of 19 newly profiled species and distinct <i>Fusobacterium nucleatum</i> clades. Specific gut species distinguish left-sided versus right-sided CRC (area under the curve‚Äâ=‚Äâ0.66) with an enrichment of oral-typical microbes. We identified strain-specific CRC signatures with the commensal <i>Ruminococcus bicirculans</i> and <i>Faecalibacterium prausnitzii</i> showing subclades associated with late-stage CRC. Our analysis confirms that the microbiome can be a clinical target for CRC screening and characterizes it as a biomarker for CRC progression.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201541","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":"Bridging the vaccine divide","authors":"Nicaise Ndembi, Leon Mutesa, Claude Mambo Muvunyi, Jerome H. Kim","doi":"10.1038/s41591-025-03728-1","DOIUrl":"https://doi.org/10.1038/s41591-025-03728-1","url":null,"abstract":"<p>The African Union (AU) has prioritized local production of health countermeasures since its inception, with heightened focus following the COVID-19 pandemic and challenges such as cholera, Ebola, malaria, mpox, Marburg and other emerging diseases. One of its efforts was the development of the Pharmaceutical Manufacturing Plan for Africa in 2007¹. The plan aims to strengthen the continental capacity to produce affordable, high-quality essential medicines, improving health outcomes while fostering economic benefits. The AU’s Agenda 2063 further reinforces the development of resilient health systems and local pharmaceutical manufacturing to achieve health sovereignty².</p><p>These goals confront a stark reality in Africa. In 2024 alone, the continent had to deal with over 160 disease outbreaks³. Yet as many as 70–90% of drugs consumed in sub-Saharan Africa are imported, and &lt;1% of global vaccine production occurs on the continent⁴. This limited manufacturing capacity exacerbates delays in accessing life-saving vaccines during public health crises, as exemplified during the COVID-19 pandemic⁵ and the current mpox outbreak⁶. Moreover, over-reliance on imports — often coupled with inadequate cold-chain infrastructure — hinders the timely distribution of vaccines⁷. Diseases such as cholera and typhoid further emphasize the necessity of regional solutions and end-to-end vaccine production systems. The oral cholera vaccine (OCV) technology transfer from the International Vaccine Institute to the Biovac Institute in South Africa exemplifies how strengthening manufacturing capacity can address vaccine shortages amid recurring outbreaks.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"36 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144193126","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}