Pub Date : 2024-08-12DOI: 10.1038/s41591-024-03186-1
Elisa Gallo, Marcos Quijal-Zamorano, Raúl Fernando Méndez Turrubiates, Cathryn Tonne, Xavier Basagaña, Hicham Achebak, Joan Ballester
The year of 2023 was the warmest on record globally and the second warmest in Europe. Here we applied epidemiological models to temperature and mortality records in 823 contiguous regions from 35 countries to estimate sex- and age-specific heat-related mortality in Europe during 2023 and to quantify the mortality burden avoided by societal adaptation to rising temperatures since the year 2000. We estimated 47,690 (95% confidence interval 28,853 to 66,525) heat-related deaths in 2023, the second highest mortality burden during the study period 2015–2023, only surpassed by 2022. We also estimated that the heat-related mortality burden would have been +80.0% higher in absence of present-century adaptation, especially in the elderly (+100.7% in people aged 80+ years). Our results highlight the importance of historical and ongoing adaptations in saving lives during recent summers and the urgency for more effective strategies to further reduce the mortality burden of forthcoming hotter summers. Analyses of the year 2023, the warmest on record globally, estimated 47,690 heat-related deaths across 35 countries in Europe, which would have been 80% higher in the absence of any societal adaptations.
{"title":"Heat-related mortality in Europe during 2023 and the role of adaptation in protecting health","authors":"Elisa Gallo, Marcos Quijal-Zamorano, Raúl Fernando Méndez Turrubiates, Cathryn Tonne, Xavier Basagaña, Hicham Achebak, Joan Ballester","doi":"10.1038/s41591-024-03186-1","DOIUrl":"10.1038/s41591-024-03186-1","url":null,"abstract":"The year of 2023 was the warmest on record globally and the second warmest in Europe. Here we applied epidemiological models to temperature and mortality records in 823 contiguous regions from 35 countries to estimate sex- and age-specific heat-related mortality in Europe during 2023 and to quantify the mortality burden avoided by societal adaptation to rising temperatures since the year 2000. We estimated 47,690 (95% confidence interval 28,853 to 66,525) heat-related deaths in 2023, the second highest mortality burden during the study period 2015–2023, only surpassed by 2022. We also estimated that the heat-related mortality burden would have been +80.0% higher in absence of present-century adaptation, especially in the elderly (+100.7% in people aged 80+ years). Our results highlight the importance of historical and ongoing adaptations in saving lives during recent summers and the urgency for more effective strategies to further reduce the mortality burden of forthcoming hotter summers. Analyses of the year 2023, the warmest on record globally, estimated 47,690 heat-related deaths across 35 countries in Europe, which would have been 80% higher in the absence of any societal adaptations.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 11","pages":"3101-3105"},"PeriodicalIF":58.7,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918863","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}
Pub Date : 2024-08-09DOI: 10.1038/s41591-024-03166-5
Peter J. Illingworth, Christos Venetis, David K. Gardner, Scott M. Nelson, Jørgen Berntsen, Mark G. Larman, Franca Agresta, Saran Ahitan, Aisling Ahlström, Fleur Cattrall, Simon Cooke, Kristy Demmers, Anette Gabrielsen, Johnny Hindkjær, Rebecca L. Kelley, Charlotte Knight, Lisa Lee, Robert Lahoud, Manveen Mangat, Hannah Park, Anthony Price, Geoffrey Trew, Bettina Troest, Anna Vincent, Susanne Wennerström, Lyndsey Zujovic, Thorir Hardarson
To assess the value of deep learning in selecting the optimal embryo for in vitro fertilization, a multicenter, randomized, double-blind, noninferiority parallel-group trial was conducted across 14 in vitro fertilization clinics in Australia and Europe. Women under 42 years of age with at least two early-stage blastocysts on day 5 were randomized to either the control arm, using standard morphological assessment, or the study arm, employing a deep learning algorithm, intelligent Data Analysis Score (iDAScore), for embryo selection. The primary endpoint was a clinical pregnancy rate with a noninferiority margin of 5%. The trial included 1,066 patients (533 in the iDAScore group and 533 in the morphology group). The iDAScore group exhibited a clinical pregnancy rate of 46.5% (248 of 533 patients), compared to 48.2% (257 of 533 patients) in the morphology arm (risk difference −1.7%; 95% confidence interval −7.7, 4.3; P = 0.62). This study was not able to demonstrate noninferiority of deep learning for clinical pregnancy rate when compared to standard morphology and a predefined prioritization scheme. Australian New Zealand Clinical Trials Registry (ANZCTR) registration: 379161 . A randomized controlled trial evaluating the selection of a single blastocyst for transfer by deep learning did not demonstrate noninferiority in clinical pregnancy rates when compared to trained embryologists using standard morphology criteria.
{"title":"Deep learning versus manual morphology-based embryo selection in IVF: a randomized, double-blind noninferiority trial","authors":"Peter J. Illingworth, Christos Venetis, David K. Gardner, Scott M. Nelson, Jørgen Berntsen, Mark G. Larman, Franca Agresta, Saran Ahitan, Aisling Ahlström, Fleur Cattrall, Simon Cooke, Kristy Demmers, Anette Gabrielsen, Johnny Hindkjær, Rebecca L. Kelley, Charlotte Knight, Lisa Lee, Robert Lahoud, Manveen Mangat, Hannah Park, Anthony Price, Geoffrey Trew, Bettina Troest, Anna Vincent, Susanne Wennerström, Lyndsey Zujovic, Thorir Hardarson","doi":"10.1038/s41591-024-03166-5","DOIUrl":"10.1038/s41591-024-03166-5","url":null,"abstract":"To assess the value of deep learning in selecting the optimal embryo for in vitro fertilization, a multicenter, randomized, double-blind, noninferiority parallel-group trial was conducted across 14 in vitro fertilization clinics in Australia and Europe. Women under 42 years of age with at least two early-stage blastocysts on day 5 were randomized to either the control arm, using standard morphological assessment, or the study arm, employing a deep learning algorithm, intelligent Data Analysis Score (iDAScore), for embryo selection. The primary endpoint was a clinical pregnancy rate with a noninferiority margin of 5%. The trial included 1,066 patients (533 in the iDAScore group and 533 in the morphology group). The iDAScore group exhibited a clinical pregnancy rate of 46.5% (248 of 533 patients), compared to 48.2% (257 of 533 patients) in the morphology arm (risk difference −1.7%; 95% confidence interval −7.7, 4.3; P = 0.62). This study was not able to demonstrate noninferiority of deep learning for clinical pregnancy rate when compared to standard morphology and a predefined prioritization scheme. Australian New Zealand Clinical Trials Registry (ANZCTR) registration: 379161 . A randomized controlled trial evaluating the selection of a single blastocyst for transfer by deep learning did not demonstrate noninferiority in clinical pregnancy rates when compared to trained embryologists using standard morphology criteria.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 11","pages":"3114-3120"},"PeriodicalIF":58.7,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41591-024-03166-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141909262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-07DOI: 10.1038/s41591-024-03185-2
Kai Zhang, Rong Zhou, Eashan Adhikarla, Zhiling Yan, Yixin Liu, Jun Yu, Zhengliang Liu, Xun Chen, Brian D. Davison, Hui Ren, Jing Huang, Chen Chen, Yuyin Zhou, Sunyang Fu, Wei Liu, Tianming Liu, Xiang Li, Yong Chen, Lifang He, James Zou, Quanzheng Li, Hongfang Liu, Lichao Sun
Traditional biomedical artificial intelligence (AI) models, designed for specific tasks or modalities, often exhibit limited flexibility in real-world deployment and struggle to utilize holistic information. Generalist AI holds the potential to address these limitations due to its versatility in interpreting different data types and generating tailored outputs for diverse needs. However, existing biomedical generalist AI solutions are typically heavyweight and closed source to researchers, practitioners and patients. Here, we describe BiomedGPT, the first open-source and lightweight vision–language foundation model, designed as a generalist capable of performing various biomedical tasks. BiomedGPT achieved state-of-the-art results in 16 out of 25 experiments while maintaining a computing-friendly model scale. We also conducted human evaluations to assess the capabilities of BiomedGPT in radiology visual question answering, report generation and summarization. BiomedGPT exhibits robust prediction ability with a low error rate of 3.8% in question answering, satisfactory performance with an error rate of 8.3% in writing complex radiology reports, and competitive summarization ability with a nearly equivalent preference score to human experts. Our method demonstrates that effective training with diverse data can lead to more practical biomedical AI for improving diagnosis and workflow efficiency. An open-source and computing-friendly vision–language model achieves state-of-the-art accuracy in 16 out of 25 biomedical tasks, with promising performance in a series of potential clinical applications.
{"title":"A generalist vision–language foundation model for diverse biomedical tasks","authors":"Kai Zhang, Rong Zhou, Eashan Adhikarla, Zhiling Yan, Yixin Liu, Jun Yu, Zhengliang Liu, Xun Chen, Brian D. Davison, Hui Ren, Jing Huang, Chen Chen, Yuyin Zhou, Sunyang Fu, Wei Liu, Tianming Liu, Xiang Li, Yong Chen, Lifang He, James Zou, Quanzheng Li, Hongfang Liu, Lichao Sun","doi":"10.1038/s41591-024-03185-2","DOIUrl":"10.1038/s41591-024-03185-2","url":null,"abstract":"Traditional biomedical artificial intelligence (AI) models, designed for specific tasks or modalities, often exhibit limited flexibility in real-world deployment and struggle to utilize holistic information. Generalist AI holds the potential to address these limitations due to its versatility in interpreting different data types and generating tailored outputs for diverse needs. However, existing biomedical generalist AI solutions are typically heavyweight and closed source to researchers, practitioners and patients. Here, we describe BiomedGPT, the first open-source and lightweight vision–language foundation model, designed as a generalist capable of performing various biomedical tasks. BiomedGPT achieved state-of-the-art results in 16 out of 25 experiments while maintaining a computing-friendly model scale. We also conducted human evaluations to assess the capabilities of BiomedGPT in radiology visual question answering, report generation and summarization. BiomedGPT exhibits robust prediction ability with a low error rate of 3.8% in question answering, satisfactory performance with an error rate of 8.3% in writing complex radiology reports, and competitive summarization ability with a nearly equivalent preference score to human experts. Our method demonstrates that effective training with diverse data can lead to more practical biomedical AI for improving diagnosis and workflow efficiency. An open-source and computing-friendly vision–language model achieves state-of-the-art accuracy in 16 out of 25 biomedical tasks, with promising performance in a series of potential clinical applications.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 11","pages":"3129-3141"},"PeriodicalIF":58.7,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899558","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}
Pub Date : 2024-08-02DOI: 10.1038/s41591-024-03146-9
Vivak Parkash, Helen Ashwin, Shoumit Dey, Jovana Sadlova, Barbora Vojtkova, Katrien Van Bocxlaer, Rebecca Wiggins, David Thompson, Nidhi Sharma Dey, Charles L. Jaffe, Eli Schwartz, Petr Volf, Charles J. N. Lacey, Alison M. Layton, Paul M. Kaye
The leishmaniases are globally important parasitic diseases for which no human vaccines are currently available. To facilitate vaccine development, we conducted an open-label observational study to establish a controlled human infection model (CHIM) of sand fly-transmitted cutaneous leishmaniasis (CL) caused by Leishmania major. Between 24 January and 12 August 2022, we exposed 14 participants to L. major-infected Phlebotomus duboscqi. The primary objective was to demonstrate effectiveness of lesion development (take rate) and safety (absence of CL lesion at 12 months). Secondary and exploratory objectives included rate of lesion development, parasite load and analysis of local immune responses by immunohistology and spatial transcriptomics. Lesion development was terminated by therapeutic biopsy (between days 14 and 42 after bite) in ten participants with clinically compatible lesions, one of which was not confirmed by parasite detection. We estimated an overall take rate for CL development of 64% (9/14). Two of ten participants had one and one of ten participants had two lesion recurrences 4–8 months after biopsy that were treated successfully with cryotherapy. No severe or serious adverse events were recorded, but as expected, scarring due to a combination of CL and the biopsy procedure was evident. All participants were lesion free at >12-month follow-up. We provide the first comprehensive map of immune cell distribution and cytokine/chemokine expression in human CL lesions, revealing discrete immune niches. This CHIM offers opportunities for vaccine candidate selection based on human efficacy data and for a greater understanding of immune-mediated pathology. ClinicalTrials.gov identifier: NCT04512742 . The first controlled human infection model of cutaneous leishmaniasis transmitted by sand flies enables assessment of immune responses and parasitism in infected participants that can inform future vaccine and therapeutic development.
{"title":"Safety and reactogenicity of a controlled human infection model of sand fly-transmitted cutaneous leishmaniasis","authors":"Vivak Parkash, Helen Ashwin, Shoumit Dey, Jovana Sadlova, Barbora Vojtkova, Katrien Van Bocxlaer, Rebecca Wiggins, David Thompson, Nidhi Sharma Dey, Charles L. Jaffe, Eli Schwartz, Petr Volf, Charles J. N. Lacey, Alison M. Layton, Paul M. Kaye","doi":"10.1038/s41591-024-03146-9","DOIUrl":"10.1038/s41591-024-03146-9","url":null,"abstract":"The leishmaniases are globally important parasitic diseases for which no human vaccines are currently available. To facilitate vaccine development, we conducted an open-label observational study to establish a controlled human infection model (CHIM) of sand fly-transmitted cutaneous leishmaniasis (CL) caused by Leishmania major. Between 24 January and 12 August 2022, we exposed 14 participants to L. major-infected Phlebotomus duboscqi. The primary objective was to demonstrate effectiveness of lesion development (take rate) and safety (absence of CL lesion at 12 months). Secondary and exploratory objectives included rate of lesion development, parasite load and analysis of local immune responses by immunohistology and spatial transcriptomics. Lesion development was terminated by therapeutic biopsy (between days 14 and 42 after bite) in ten participants with clinically compatible lesions, one of which was not confirmed by parasite detection. We estimated an overall take rate for CL development of 64% (9/14). Two of ten participants had one and one of ten participants had two lesion recurrences 4–8 months after biopsy that were treated successfully with cryotherapy. No severe or serious adverse events were recorded, but as expected, scarring due to a combination of CL and the biopsy procedure was evident. All participants were lesion free at >12-month follow-up. We provide the first comprehensive map of immune cell distribution and cytokine/chemokine expression in human CL lesions, revealing discrete immune niches. This CHIM offers opportunities for vaccine candidate selection based on human efficacy data and for a greater understanding of immune-mediated pathology. ClinicalTrials.gov identifier: NCT04512742 . The first controlled human infection model of cutaneous leishmaniasis transmitted by sand flies enables assessment of immune responses and parasitism in infected participants that can inform future vaccine and therapeutic development.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 11","pages":"3150-3162"},"PeriodicalIF":58.7,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41591-024-03146-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141877687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-02DOI: 10.1038/s41591-024-03183-4
Bing Zhai, Chen Liao, Siddharth Jaggavarapu, Yuanyuan Tang, Thierry Rolling, Yating Ning, Tianshu Sun, Sean A. Bergin, Mergim Gjonbalaj, Edwin Miranda, N. Esther Babady, Oliver Bader, Ying Taur, Geraldine Butler, Li Zhang, Joao B. Xavier, David S. Weiss, Tobias M. Hohl
Breakthrough fungal infections in patients on antimicrobial prophylaxis during allogeneic hematopoietic cell transplantation (allo-HCT) represent a major and often unexplained cause of morbidity and mortality. Candida parapsilosis is a common cause of invasive candidiasis and has been classified as a high-priority fungal pathogen by the World Health Organization. In high-risk allo-HCT recipients on micafungin prophylaxis, we show that heteroresistance (the presence of a phenotypically unstable, low-frequency subpopulation of resistant cells (~1 in 10,000)) underlies breakthrough bloodstream infections by C. parapsilosis. By analyzing 219 clinical isolates from North America, Europe and Asia, we demonstrate widespread micafungin heteroresistance in C. parapsilosis. Standard antimicrobial susceptibility tests, such as broth microdilution or gradient diffusion assays, which guide drug selection for invasive infections, fail to detect micafungin heteroresistance in C. parapsilosis. To facilitate rapid detection of micafungin heteroresistance in C. parapsilosis, we constructed a predictive machine learning framework that classifies isolates as heteroresistant or susceptible using a maximum of ten genomic features. These results connect heteroresistance to unexplained antifungal prophylaxis failure in allo-HCT recipients and demonstrate a proof-of-principle diagnostic approach with the potential to guide clinical decisions and improve patient care. Bloodstream infections with Candida parapsilosis in allogeneic hematopoietic cell transplantation recipients are associated with heteroresistance to the antifungal micafungin, which can be predicted from genomic features using machine learning.
{"title":"Antifungal heteroresistance causes prophylaxis failure and facilitates breakthrough Candida parapsilosis infections","authors":"Bing Zhai, Chen Liao, Siddharth Jaggavarapu, Yuanyuan Tang, Thierry Rolling, Yating Ning, Tianshu Sun, Sean A. Bergin, Mergim Gjonbalaj, Edwin Miranda, N. Esther Babady, Oliver Bader, Ying Taur, Geraldine Butler, Li Zhang, Joao B. Xavier, David S. Weiss, Tobias M. Hohl","doi":"10.1038/s41591-024-03183-4","DOIUrl":"10.1038/s41591-024-03183-4","url":null,"abstract":"Breakthrough fungal infections in patients on antimicrobial prophylaxis during allogeneic hematopoietic cell transplantation (allo-HCT) represent a major and often unexplained cause of morbidity and mortality. Candida parapsilosis is a common cause of invasive candidiasis and has been classified as a high-priority fungal pathogen by the World Health Organization. In high-risk allo-HCT recipients on micafungin prophylaxis, we show that heteroresistance (the presence of a phenotypically unstable, low-frequency subpopulation of resistant cells (~1 in 10,000)) underlies breakthrough bloodstream infections by C. parapsilosis. By analyzing 219 clinical isolates from North America, Europe and Asia, we demonstrate widespread micafungin heteroresistance in C. parapsilosis. Standard antimicrobial susceptibility tests, such as broth microdilution or gradient diffusion assays, which guide drug selection for invasive infections, fail to detect micafungin heteroresistance in C. parapsilosis. To facilitate rapid detection of micafungin heteroresistance in C. parapsilosis, we constructed a predictive machine learning framework that classifies isolates as heteroresistant or susceptible using a maximum of ten genomic features. These results connect heteroresistance to unexplained antifungal prophylaxis failure in allo-HCT recipients and demonstrate a proof-of-principle diagnostic approach with the potential to guide clinical decisions and improve patient care. Bloodstream infections with Candida parapsilosis in allogeneic hematopoietic cell transplantation recipients are associated with heteroresistance to the antifungal micafungin, which can be predicted from genomic features using machine learning.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 11","pages":"3163-3172"},"PeriodicalIF":58.7,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141877730","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}
Pub Date : 2024-07-30DOI: 10.1038/s41591-024-03153-w
Kai-Feng Pan, Wen-Qing Li, Lian Zhang, Wei-Dong Liu, Jun-Ling Ma, Yang Zhang, Kurt Ulm, Jian-Xi Wang, Lei Zhang, Monther Bajbouj, Lan-Fu Zhang, Ming Li, Michael Vieth, Michael Quante, Le-Hua Wang, Stepan Suchanek, Raquel Mejías-Luque, Heng-Min Xu, Xiao-Han Fan, Xuan Han, Zong-Chao Liu, Tong Zhou, Wei-Xiang Guan, Roland M. Schmid, Markus Gerhard, Meinhard Classen, Wei-Cheng You
Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world’s population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We conducted a community-based, cluster-randomized, controlled, superiority intervention trial in Linqu County, China, with individuals who tested positive for H. pylori using a 13C-urea breath test randomly assigned to receiving either (1) a 10-day, quadruple anti-H. pylori treatment (comprising 20 mg of omeprazole, 750 mg of tetracycline, 400 mg of metronidazole and 300 mg of bismuth citrate) or (2) symptom alleviation treatment with a single daily dosage of omeprazole and bismuth citrate. H. pylori-negative individuals did not receive any treatment. We examined the incidence of gastric cancer as the primary outcome. A total of 180,284 eligible participants from 980 villages were enrolled over 11.8 years of follow-up, and a total of 1,035 cases of incident gastric cancer were documented. Individuals receiving anti-H. pylori therapy showed a modest reduction in gastric cancer incidence in intention-to-treat analyses (hazard ratio 0.86, 95% confidence interval 0.74–0.99), with a stronger effect observed for those having successful H. pylori eradication (hazard ratio 0.81, 95% confidence interval 0.69–0.96) than for those who failed treatment. Moderate adverse effects were reported in 1,345 participants during the 10-day treatment. We observed no severe intolerable adverse events during either treatment or follow-up. The findings suggest the potential for H. pylori mass screening and eradication as a public health policy for gastric cancer prevention. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000979 . A cluster-randomized trial carried out across 980 villages in a high-risk region in China found that systematic treatment of antibiotics, omeprazole and bismuth modestly reduced gastric cancer incidence in Helicobacter pylori-positive populations.
{"title":"Gastric cancer prevention by community eradication of Helicobacter pylori: a cluster-randomized controlled trial","authors":"Kai-Feng Pan, Wen-Qing Li, Lian Zhang, Wei-Dong Liu, Jun-Ling Ma, Yang Zhang, Kurt Ulm, Jian-Xi Wang, Lei Zhang, Monther Bajbouj, Lan-Fu Zhang, Ming Li, Michael Vieth, Michael Quante, Le-Hua Wang, Stepan Suchanek, Raquel Mejías-Luque, Heng-Min Xu, Xiao-Han Fan, Xuan Han, Zong-Chao Liu, Tong Zhou, Wei-Xiang Guan, Roland M. Schmid, Markus Gerhard, Meinhard Classen, Wei-Cheng You","doi":"10.1038/s41591-024-03153-w","DOIUrl":"10.1038/s41591-024-03153-w","url":null,"abstract":"Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world’s population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We conducted a community-based, cluster-randomized, controlled, superiority intervention trial in Linqu County, China, with individuals who tested positive for H. pylori using a 13C-urea breath test randomly assigned to receiving either (1) a 10-day, quadruple anti-H. pylori treatment (comprising 20 mg of omeprazole, 750 mg of tetracycline, 400 mg of metronidazole and 300 mg of bismuth citrate) or (2) symptom alleviation treatment with a single daily dosage of omeprazole and bismuth citrate. H. pylori-negative individuals did not receive any treatment. We examined the incidence of gastric cancer as the primary outcome. A total of 180,284 eligible participants from 980 villages were enrolled over 11.8 years of follow-up, and a total of 1,035 cases of incident gastric cancer were documented. Individuals receiving anti-H. pylori therapy showed a modest reduction in gastric cancer incidence in intention-to-treat analyses (hazard ratio 0.86, 95% confidence interval 0.74–0.99), with a stronger effect observed for those having successful H. pylori eradication (hazard ratio 0.81, 95% confidence interval 0.69–0.96) than for those who failed treatment. Moderate adverse effects were reported in 1,345 participants during the 10-day treatment. We observed no severe intolerable adverse events during either treatment or follow-up. The findings suggest the potential for H. pylori mass screening and eradication as a public health policy for gastric cancer prevention. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000979 . A cluster-randomized trial carried out across 980 villages in a high-risk region in China found that systematic treatment of antibiotics, omeprazole and bismuth modestly reduced gastric cancer incidence in Helicobacter pylori-positive populations.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 11","pages":"3250-3260"},"PeriodicalIF":58.7,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794827","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}
Pub Date : 2024-07-18DOI: 10.1038/s41591-024-03159-4
Juan Fortea, Lídia Vaqué-Alcázar, Jordi Pegueroles, Daniel Alcolea, Olivia Belbin, Oriol Dols-Icardo, Laura Videla, Juan Domingo Gispert, Marc Suárez-Calvet, Sterling C. Johnson, Reisa Sperling, Alexandre Bejanin, Alberto Lleó, Víctor Montal
{"title":"Reply to: Challenges to identifying risk versus protective factors in Alzheimer’s disease","authors":"Juan Fortea, Lídia Vaqué-Alcázar, Jordi Pegueroles, Daniel Alcolea, Olivia Belbin, Oriol Dols-Icardo, Laura Videla, Juan Domingo Gispert, Marc Suárez-Calvet, Sterling C. Johnson, Reisa Sperling, Alexandre Bejanin, Alberto Lleó, Víctor Montal","doi":"10.1038/s41591-024-03159-4","DOIUrl":"10.1038/s41591-024-03159-4","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 11","pages":"3096-3097"},"PeriodicalIF":58.7,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723969","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}
Pub Date : 2023-11-13DOI: 10.1038/s41591-023-02582-3
Philipp Schommers, Dae Sung Kim, Maike Schlotz, Christoph Kreer, Ralf Eggeling, Anna Hake, Melanie Stecher, Juyeon Park, Caelan E. Radford, Adam S. Dingens, Meryem S. Ercanoglu, Henning Gruell, Stanley Odidika, Marten Dahlhaus, Lutz Gieselmann, Elvin Ahmadov, Rene Y. Lawong, Eva Heger, Elena Knops, Christoph Wyen, Tim Kümmerle, Katja Römer, Stefan Scholten, Timo Wolf, Christoph Stephan, Isabelle Suárez, Nagarajan Raju, Anurag Adhikari, Stefan Esser, Hendrik Streeck, Ralf Duerr, Aubin J. Nanfack, Susan Zolla-Pazner, Christof Geldmacher, Otto Geisenberger, Arne Kroidl, Wiston William, Lucas Maganga, Nyanda Elias Ntinginya, Ivelin S. Georgiev, Jörg J. Vehreschild, Michael Hoelscher, Gerd Fätkenheuer, Jason J. Lavinder, Jesse D. Bloom, Michael S. Seaman, Clara Lehmann, Nico Pfeifer, George Georgiou, Florian Klein
Human immunodeficiency virus type 1 (HIV-1)-neutralizing antibodies (nAbs) that prevent infection are the main goal of HIV vaccine discovery. But as no nAb-eliciting vaccines are yet available, only data from HIV-1 neutralizers—persons with HIV-1 who naturally develop broad and potent nAbs—can inform about the dynamics and durability of nAb responses in humans, knowledge which is crucial for the design of future HIV-1 vaccine regimens. To address this, we assessed HIV-1-neutralizing immunoglobulin G (IgG) from 2,354 persons with HIV-1 on or off antiretroviral therapy (ART). Infection with non-clade B viruses, CD4+ T cell counts <200 µl−1, being off ART and a longer time off ART were independent predictors of a more potent and broad neutralization. In longitudinal analyses, we found nAb half-lives of 9.3 and 16.9 years in individuals with no- or low-level viremia, respectively, and 4.0 years in persons who newly initiated ART. Finally, in a potent HIV-1 neutralizer, we identified lower fractions of serum nAbs and of nAb-encoding memory B cells after ART initiation, suggesting that a decreasing neutralizing serum activity after antigen withdrawal is due to lower levels of nAbs. These results collectively show that HIV-1-neutralizing responses can persist for several years, even at low antigen levels, suggesting that an HIV-1 vaccine may elicit a durable nAb response. Human immunodeficiency virus type 1 (HIV-1)-neutralizing responses can persist for several years, even at low antigen levels, suggesting that an HIV-1 vaccine may be able to elicit a durable antibody response.
{"title":"Dynamics and durability of HIV-1 neutralization are determined by viral replication","authors":"Philipp Schommers, Dae Sung Kim, Maike Schlotz, Christoph Kreer, Ralf Eggeling, Anna Hake, Melanie Stecher, Juyeon Park, Caelan E. Radford, Adam S. Dingens, Meryem S. Ercanoglu, Henning Gruell, Stanley Odidika, Marten Dahlhaus, Lutz Gieselmann, Elvin Ahmadov, Rene Y. Lawong, Eva Heger, Elena Knops, Christoph Wyen, Tim Kümmerle, Katja Römer, Stefan Scholten, Timo Wolf, Christoph Stephan, Isabelle Suárez, Nagarajan Raju, Anurag Adhikari, Stefan Esser, Hendrik Streeck, Ralf Duerr, Aubin J. Nanfack, Susan Zolla-Pazner, Christof Geldmacher, Otto Geisenberger, Arne Kroidl, Wiston William, Lucas Maganga, Nyanda Elias Ntinginya, Ivelin S. Georgiev, Jörg J. Vehreschild, Michael Hoelscher, Gerd Fätkenheuer, Jason J. Lavinder, Jesse D. Bloom, Michael S. Seaman, Clara Lehmann, Nico Pfeifer, George Georgiou, Florian Klein","doi":"10.1038/s41591-023-02582-3","DOIUrl":"10.1038/s41591-023-02582-3","url":null,"abstract":"Human immunodeficiency virus type 1 (HIV-1)-neutralizing antibodies (nAbs) that prevent infection are the main goal of HIV vaccine discovery. But as no nAb-eliciting vaccines are yet available, only data from HIV-1 neutralizers—persons with HIV-1 who naturally develop broad and potent nAbs—can inform about the dynamics and durability of nAb responses in humans, knowledge which is crucial for the design of future HIV-1 vaccine regimens. To address this, we assessed HIV-1-neutralizing immunoglobulin G (IgG) from 2,354 persons with HIV-1 on or off antiretroviral therapy (ART). Infection with non-clade B viruses, CD4+ T cell counts <200 µl−1, being off ART and a longer time off ART were independent predictors of a more potent and broad neutralization. In longitudinal analyses, we found nAb half-lives of 9.3 and 16.9 years in individuals with no- or low-level viremia, respectively, and 4.0 years in persons who newly initiated ART. Finally, in a potent HIV-1 neutralizer, we identified lower fractions of serum nAbs and of nAb-encoding memory B cells after ART initiation, suggesting that a decreasing neutralizing serum activity after antigen withdrawal is due to lower levels of nAbs. These results collectively show that HIV-1-neutralizing responses can persist for several years, even at low antigen levels, suggesting that an HIV-1 vaccine may elicit a durable nAb response. Human immunodeficiency virus type 1 (HIV-1)-neutralizing responses can persist for several years, even at low antigen levels, suggesting that an HIV-1 vaccine may be able to elicit a durable antibody response.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"29 11","pages":"2763-2774"},"PeriodicalIF":82.9,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10667105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92155386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-13DOI: 10.1038/s41591-023-02618-8
Maryam Shahmanesh, Natsayi Chimbindi, Frances M. Cowan
Two modelling studies offer compelling evidence that less-than-perfect adherence to HIV pre-exposure prophylaxis can still provide reasonable protection for cisgender women — providing optimism for a more person-centered approach and lower discontinuation rates.
{"title":"Person-centered HIV PrEP for cisgender women","authors":"Maryam Shahmanesh, Natsayi Chimbindi, Frances M. Cowan","doi":"10.1038/s41591-023-02618-8","DOIUrl":"10.1038/s41591-023-02618-8","url":null,"abstract":"Two modelling studies offer compelling evidence that less-than-perfect adherence to HIV pre-exposure prophylaxis can still provide reasonable protection for cisgender women — providing optimism for a more person-centered approach and lower discontinuation rates.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"29 11","pages":"2707-2708"},"PeriodicalIF":82.9,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92155389","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}
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