Pub Date : 2024-12-11DOI: 10.1038/s41591-024-03359-y
Jinzhuo Wang, Kai Wang, Yunfang Yu, Yuxing Lu, Wenchao Xiao, Zhuo Sun, Fei Liu, Zixing Zou, Yuanxu Gao, Lei Yang, Hong-Yu Zhou, Hanpei Miao, Wenting Zhao, Lisha Huang, Lingchao Zeng, Rui Guo, Ieng Chong, Boyu Deng, Linling Cheng, Xiaoniao Chen, Jing Luo, Meng-Hua Zhu, Daniel Baptista-Hon, Olivia Monteiro, Ming Li, Yu Ke, Jiahui Li, Simiao Zeng, Taihua Guan, Jin Zeng, Kanmin Xue, Eric Oermann, Huiyan Luo, Yun Yin, Kang Zhang, Jia Qu
In many clinical and research settings, the scarcity of high-quality medical imaging datasets has hampered the potential of artificial intelligence (AI) clinical applications. This issue is particularly pronounced in less common conditions, underrepresented populations and emerging imaging modalities, where the availability of diverse and comprehensive datasets is often inadequate. To address this challenge, we introduce a unified medical image–text generative model called MINIM that is capable of synthesizing medical images of various organs across various imaging modalities based on textual instructions. Clinician evaluations and rigorous objective measurements validate the high quality of MINIM’s synthetic images. MINIM exhibits an enhanced generative capability when presented with previously unseen data domains, demonstrating its potential as a generalist medical AI (GMAI). Our findings show that MINIM’s synthetic images effectively augment existing datasets, boosting performance across multiple medical applications such as diagnostics, report generation and self-supervised learning. On average, MINIM enhances performance by 12% for ophthalmic, 15% for chest, 13% for brain and 17% for breast-related tasks. Furthermore, we demonstrate MINIM’s potential clinical utility in the accurate prediction of HER2-positive breast cancer from MRI images. Using a large retrospective simulation analysis, we demonstrate MINIM’s clinical potential by accurately identifying targeted therapy-sensitive EGFR mutations using lung cancer computed tomography images, which could potentially lead to improved 5-year survival rates. Although these results are promising, further validation and refinement in more diverse and prospective settings would greatly enhance the model’s generalizability and robustness.
{"title":"Self-improving generative foundation model for synthetic medical image generation and clinical applications","authors":"Jinzhuo Wang, Kai Wang, Yunfang Yu, Yuxing Lu, Wenchao Xiao, Zhuo Sun, Fei Liu, Zixing Zou, Yuanxu Gao, Lei Yang, Hong-Yu Zhou, Hanpei Miao, Wenting Zhao, Lisha Huang, Lingchao Zeng, Rui Guo, Ieng Chong, Boyu Deng, Linling Cheng, Xiaoniao Chen, Jing Luo, Meng-Hua Zhu, Daniel Baptista-Hon, Olivia Monteiro, Ming Li, Yu Ke, Jiahui Li, Simiao Zeng, Taihua Guan, Jin Zeng, Kanmin Xue, Eric Oermann, Huiyan Luo, Yun Yin, Kang Zhang, Jia Qu","doi":"10.1038/s41591-024-03359-y","DOIUrl":"https://doi.org/10.1038/s41591-024-03359-y","url":null,"abstract":"<p>In many clinical and research settings, the scarcity of high-quality medical imaging datasets has hampered the potential of artificial intelligence (AI) clinical applications. This issue is particularly pronounced in less common conditions, underrepresented populations and emerging imaging modalities, where the availability of diverse and comprehensive datasets is often inadequate. To address this challenge, we introduce a unified medical image–text generative model called MINIM that is capable of synthesizing medical images of various organs across various imaging modalities based on textual instructions. Clinician evaluations and rigorous objective measurements validate the high quality of MINIM’s synthetic images. MINIM exhibits an enhanced generative capability when presented with previously unseen data domains, demonstrating its potential as a generalist medical AI (GMAI). Our findings show that MINIM’s synthetic images effectively augment existing datasets, boosting performance across multiple medical applications such as diagnostics, report generation and self-supervised learning. On average, MINIM enhances performance by 12% for ophthalmic, 15% for chest, 13% for brain and 17% for breast-related tasks. Furthermore, we demonstrate MINIM’s potential clinical utility in the accurate prediction of HER2-positive breast cancer from MRI images. Using a large retrospective simulation analysis, we demonstrate MINIM’s clinical potential by accurately identifying targeted therapy-sensitive <i>EGFR</i> mutations using lung cancer computed tomography images, which could potentially lead to improved 5-year survival rates. Although these results are promising, further validation and refinement in more diverse and prospective settings would greatly enhance the model’s generalizability and robustness.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"12 1","pages":""},"PeriodicalIF":82.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805113","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 : 2024-12-09DOI: 10.1038/s41591-024-03283-1
Violeta Raverdy, Federica Tavaglione, Estelle Chatelain, Guillaume Lassailly, Antonio De Vincentis, Umberto Vespasiani-Gentilucci, Sami F. Qadri, Robert Caiazzo, Helene Verkindt, Chiara Saponaro, Julie Kerr-Conte, Gregory Baud, Camille Marciniak, Mikael Chetboun, Naima Oukhouya-Daoud, Samuel Blanck, Jimmy Vandel, Lisa Olsson, Rima Chakaroun, Viviane Gnemmi, Emmanuelle Leteurtre, Philippe Lefebvre, Joel T. Haas, Hannele Yki-Järvinen, Sven Francque, Bart Staels, Carel W. Le Roux, Valentina Tremaroli, Philippe Mathurin, Guillemette Marot, Stefano Romeo, François Pattou
Metabolic dysfunction-associated steatotic liver disease (MASLD) exhibits considerable variability in clinical outcomes. Identifying specific phenotypic profiles within MASLD is essential for developing targeted therapeutic strategies. Here we investigated the heterogeneity of MASLD using partitioning around medoids clustering based on six simple clinical variables in a cohort of 1,389 individuals living with obesity. The identified clusters were applied across three independent MASLD cohorts with liver biopsy (totaling 1,099 participants), and in the UK Biobank to assess the incidence of chronic liver disease, cardiovascular disease and type 2 diabetes. Results unveiled two distinct types of MASLD associated with steatohepatitis on histology and liver imaging. The first cluster, liver-specific, was genetically linked and showed rapid progression of chronic liver disease but limited risk of cardiovascular disease. The second cluster, cardiometabolic, was primarily associated with dysglycemia and high levels of triglycerides, leading to a similar incidence of chronic liver disease but a higher risk of cardiovascular disease and type 2 diabetes. Analyses of samples from 831 individuals with available liver transcriptomics and 1,322 with available plasma metabolomics highlighted that these two types of MASLD exhibited distinct liver transcriptomic profiles and plasma metabolomic signatures, respectively. In conclusion, these data provide preliminary evidence of the existence of two distinct types of clinically relevant MASLD with similar liver phenotypes at baseline, but each with specific underlying biological profiles and different clinical trajectories, suggesting the need for tailored therapeutic strategies. Partitioning clustering based on clinical variables applied to multiple patient cohorts identifies two subtypes of metabolic dysfunction-associated steatotic liver disease with different associations to hepatic and cardiovascular outcomes.
{"title":"Data-driven cluster analysis identifies distinct types of metabolic dysfunction-associated steatotic liver disease","authors":"Violeta Raverdy, Federica Tavaglione, Estelle Chatelain, Guillaume Lassailly, Antonio De Vincentis, Umberto Vespasiani-Gentilucci, Sami F. Qadri, Robert Caiazzo, Helene Verkindt, Chiara Saponaro, Julie Kerr-Conte, Gregory Baud, Camille Marciniak, Mikael Chetboun, Naima Oukhouya-Daoud, Samuel Blanck, Jimmy Vandel, Lisa Olsson, Rima Chakaroun, Viviane Gnemmi, Emmanuelle Leteurtre, Philippe Lefebvre, Joel T. Haas, Hannele Yki-Järvinen, Sven Francque, Bart Staels, Carel W. Le Roux, Valentina Tremaroli, Philippe Mathurin, Guillemette Marot, Stefano Romeo, François Pattou","doi":"10.1038/s41591-024-03283-1","DOIUrl":"10.1038/s41591-024-03283-1","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD) exhibits considerable variability in clinical outcomes. Identifying specific phenotypic profiles within MASLD is essential for developing targeted therapeutic strategies. Here we investigated the heterogeneity of MASLD using partitioning around medoids clustering based on six simple clinical variables in a cohort of 1,389 individuals living with obesity. The identified clusters were applied across three independent MASLD cohorts with liver biopsy (totaling 1,099 participants), and in the UK Biobank to assess the incidence of chronic liver disease, cardiovascular disease and type 2 diabetes. Results unveiled two distinct types of MASLD associated with steatohepatitis on histology and liver imaging. The first cluster, liver-specific, was genetically linked and showed rapid progression of chronic liver disease but limited risk of cardiovascular disease. The second cluster, cardiometabolic, was primarily associated with dysglycemia and high levels of triglycerides, leading to a similar incidence of chronic liver disease but a higher risk of cardiovascular disease and type 2 diabetes. Analyses of samples from 831 individuals with available liver transcriptomics and 1,322 with available plasma metabolomics highlighted that these two types of MASLD exhibited distinct liver transcriptomic profiles and plasma metabolomic signatures, respectively. In conclusion, these data provide preliminary evidence of the existence of two distinct types of clinically relevant MASLD with similar liver phenotypes at baseline, but each with specific underlying biological profiles and different clinical trajectories, suggesting the need for tailored therapeutic strategies. Partitioning clustering based on clinical variables applied to multiple patient cohorts identifies two subtypes of metabolic dysfunction-associated steatotic liver disease with different associations to hepatic and cardiovascular outcomes.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 12","pages":"3624-3633"},"PeriodicalIF":58.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41591-024-03283-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793814","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 : 2024-12-09DOI: 10.1038/s41591-024-03366-z
In a cluster analysis study, we identified two types of metabolic dysfunction-associated steatotic liver disease (MASLD) characterized by distinct clinical trajectories. The two types of MASLD show similar liver histology, but one is liver-specific with low cardiovascular risk while the other has high cardiovascular risk and high metabolic risk.
{"title":"Identification of distinct types of steatotic liver disease with specific clinical trajectories","authors":"","doi":"10.1038/s41591-024-03366-z","DOIUrl":"10.1038/s41591-024-03366-z","url":null,"abstract":"In a cluster analysis study, we identified two types of metabolic dysfunction-associated steatotic liver disease (MASLD) characterized by distinct clinical trajectories. The two types of MASLD show similar liver histology, but one is liver-specific with low cardiovascular risk while the other has high cardiovascular risk and high metabolic risk.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 12","pages":"3441-3442"},"PeriodicalIF":58.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793812","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 : 2024-12-09DOI: 10.1038/s41591-024-03349-0
Nadia Harbeck, Eva Ciruelos, Guy Jerusalem, Volkmar Müller, Naoki Niikura, Giuseppe Viale, Rupert Bartsch, Christian Kurzeder, Michaela J. Higgins, Roisin M. Connolly, Sally Baron-Hay, María Gión, Valentina Guarneri, Giampaolo Bianchini, Hans Wildiers, Santiago Escrivá-de-Romaní, Manoj Prahladan, Helen Bridge, Nataliya Kuptsova-Clarkson, Nana Scotto, Sunil Verma, Nancy U. Lin, the DESTINY-Breast12 study group
{"title":"Publisher Correction: Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b/4 trial","authors":"Nadia Harbeck, Eva Ciruelos, Guy Jerusalem, Volkmar Müller, Naoki Niikura, Giuseppe Viale, Rupert Bartsch, Christian Kurzeder, Michaela J. Higgins, Roisin M. Connolly, Sally Baron-Hay, María Gión, Valentina Guarneri, Giampaolo Bianchini, Hans Wildiers, Santiago Escrivá-de-Romaní, Manoj Prahladan, Helen Bridge, Nataliya Kuptsova-Clarkson, Nana Scotto, Sunil Verma, Nancy U. Lin, the DESTINY-Breast12 study group","doi":"10.1038/s41591-024-03349-0","DOIUrl":"10.1038/s41591-024-03349-0","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 12","pages":"3780-3780"},"PeriodicalIF":58.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41591-024-03349-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793813","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 : 2024-12-09DOI: 10.1038/s41591-024-03284-0
Oveis Jamialahmadi, Antonio De Vincentis, Federica Tavaglione, Francesco Malvestiti, Ruifang Li-Gao, Rosellina M. Mancina, Marcus Alvarez, Kyla Gelev, Samantha Maurotti, Umberto Vespasiani-Gentilucci, Frits Richard Rosendaal, Julia Kozlitina, Päivi Pajukanta, François Pattou, Luca Valenti, Stefano Romeo
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by an excess of lipids, mainly triglycerides, in the liver and components of the metabolic syndrome, which can lead to cirrhosis and liver cancer. While there is solid epidemiological evidence that MASLD clusters with cardiometabolic disease, several leading genetic risk factors for MASLD do not increase the risk of cardiovascular disease, suggesting no causal relationship between MASLD and cardiometabolic derangement. In this work, we leveraged measurements of visceral adiposity identifying 27 previously unknown genetic loci associated with MASLD (n = 36,394), six replicated in four independent cohorts (n = 3,903). Next, we generated two partitioned polygenic risk scores based on the presence of lipoprotein retention in the liver. The two polygenic risk scores suggest the presence of at least two distinct types of MASLD, one confined to the liver resulting in a more aggressive liver disease and one that is systemic and results in a higher risk of cardiometabolic disease. These findings shed light on the heterogeneity of MASLD and have the potential to improve the prediction of clinical trajectories and inform precision medicine approaches. The application of partitioned polygenic scores to data from cohorts of patients identifies two distinct subtypes of MASLD with different cardiometabolic risk profiles.
{"title":"Partitioned polygenic risk scores identify distinct types of metabolic dysfunction-associated steatotic liver disease","authors":"Oveis Jamialahmadi, Antonio De Vincentis, Federica Tavaglione, Francesco Malvestiti, Ruifang Li-Gao, Rosellina M. Mancina, Marcus Alvarez, Kyla Gelev, Samantha Maurotti, Umberto Vespasiani-Gentilucci, Frits Richard Rosendaal, Julia Kozlitina, Päivi Pajukanta, François Pattou, Luca Valenti, Stefano Romeo","doi":"10.1038/s41591-024-03284-0","DOIUrl":"10.1038/s41591-024-03284-0","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by an excess of lipids, mainly triglycerides, in the liver and components of the metabolic syndrome, which can lead to cirrhosis and liver cancer. While there is solid epidemiological evidence that MASLD clusters with cardiometabolic disease, several leading genetic risk factors for MASLD do not increase the risk of cardiovascular disease, suggesting no causal relationship between MASLD and cardiometabolic derangement. In this work, we leveraged measurements of visceral adiposity identifying 27 previously unknown genetic loci associated with MASLD (n = 36,394), six replicated in four independent cohorts (n = 3,903). Next, we generated two partitioned polygenic risk scores based on the presence of lipoprotein retention in the liver. The two polygenic risk scores suggest the presence of at least two distinct types of MASLD, one confined to the liver resulting in a more aggressive liver disease and one that is systemic and results in a higher risk of cardiometabolic disease. These findings shed light on the heterogeneity of MASLD and have the potential to improve the prediction of clinical trajectories and inform precision medicine approaches. The application of partitioned polygenic scores to data from cohorts of patients identifies two distinct subtypes of MASLD with different cardiometabolic risk profiles.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 12","pages":"3614-3623"},"PeriodicalIF":58.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41591-024-03284-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793815","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 : 2024-12-06DOI: 10.1038/s41591-024-03410-y
The vascular system has many different functions across the human body beyond its role in oxygen and nutrient transport. We explored vascular cell heterogeneity by integrating single-cell RNA-sequencing data from the Human Cell Atlas and ongoing collaborations across 19 healthy human organs and tissues, and highlight shared and distinct molecular features of vascular beds.
{"title":"Vascular cells of blood vessels and organs across the human body","authors":"","doi":"10.1038/s41591-024-03410-y","DOIUrl":"10.1038/s41591-024-03410-y","url":null,"abstract":"The vascular system has many different functions across the human body beyond its role in oxygen and nutrient transport. We explored vascular cell heterogeneity by integrating single-cell RNA-sequencing data from the Human Cell Atlas and ongoing collaborations across 19 healthy human organs and tissues, and highlight shared and distinct molecular features of vascular beds.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 12","pages":"3431-3432"},"PeriodicalIF":58.7,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788486","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 : 2024-12-04DOI: 10.1038/s41591-024-03380-1
Mike May
Nature Medicine asks experts to explain the research priorities for the field of GLP-1 receptor agonists such as semaglutide, from sex differences to how they might treat addiction.
{"title":"Seven unanswered questions about blockbuster weight-loss drugs","authors":"Mike May","doi":"10.1038/s41591-024-03380-1","DOIUrl":"10.1038/s41591-024-03380-1","url":null,"abstract":"Nature Medicine asks experts to explain the research priorities for the field of GLP-1 receptor agonists such as semaglutide, from sex differences to how they might treat addiction.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 12","pages":"3389-3391"},"PeriodicalIF":58.7,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41591-024-03380-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763537","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 : 2024-12-03DOI: 10.1038/s41591-024-03378-9
Anita Zaidi
Health data should measure the complexity of women’s lives.
{"title":"How big data can improve women’s health","authors":"Anita Zaidi","doi":"10.1038/s41591-024-03378-9","DOIUrl":"10.1038/s41591-024-03378-9","url":null,"abstract":"Health data should measure the complexity of women’s lives.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 12","pages":"3401-3401"},"PeriodicalIF":58.7,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41591-024-03378-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760808","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 : 2024-12-02DOI: 10.1038/s41591-024-03306-x
Newton Cho, Jordan W. Squair, Viviana Aureli, Nicholas D. James, Léa Bole-Feysot, Inssia Dewany, Nicolas Hankov, Laetitia Baud, Anna Leonhartsberger, Kristina Sveistyte, Michael A. Skinnider, Matthieu Gautier, Achilleas Laskaratos, Katia Galan, Maged Goubran, Jimmy Ravier, Frederic Merlos, Laura Batti, Stéphane Pages, Nadia Berard, Nadine Intering, Camille Varescon, Anne Watrin, Léa Duguet, Stefano Carda, Kay A. Bartholdi, Thomas H. Hutson, Claudia Kathe, Michael Hodara, Mark A. Anderson, Bogdan Draganski, Robin Demesmaeker, Leonie Asboth, Quentin Barraud, Jocelyne Bloch, Grégoire Courtine
A spinal cord injury (SCI) disrupts the neuronal projections from the brain to the region of the spinal cord that produces walking, leading to various degrees of paralysis. Here, we aimed to identify brain regions that steer the recovery of walking after incomplete SCI and that could be targeted to augment this recovery. To uncover these regions, we constructed a space–time brain-wide atlas of transcriptionally active and spinal cord-projecting neurons underlying the recovery of walking after incomplete SCI. Unexpectedly, interrogation of this atlas nominated the lateral hypothalamus (LH). We demonstrate that glutamatergic neurons located in the LH (LHVglut2) contribute to the recovery of walking after incomplete SCI and that augmenting their activity improves walking. We translated this discovery into a deep brain stimulation therapy of the LH (DBSLH) that immediately augmented walking in mice and rats with SCI and durably increased recovery through the reorganization of residual lumbar-terminating projections from brainstem neurons. A pilot clinical study showed that DBSLH immediately improved walking in two participants with incomplete SCI and, in conjunction with rehabilitation, mediated functional recovery that persisted when DBSLH was turned off. There were no serious adverse events related to DBSLH. These results highlight the potential of targeting specific brain regions to maximize the engagement of spinal cord-projecting neurons in the recovery of neurological functions after SCI. Further trials must establish the safety and efficacy profile of DBSLH, including potential changes in body weight, psychological status, hormonal profiles and autonomic functions. Whole-brain anatomical and activity surveys identify the lateral hypothalamus as a key driver of recovery from spinal cord injury, leading to a deep brain stimulation therapy that augments the recovery of walking in humans.
{"title":"Hypothalamic deep brain stimulation augments walking after spinal cord injury","authors":"Newton Cho, Jordan W. Squair, Viviana Aureli, Nicholas D. James, Léa Bole-Feysot, Inssia Dewany, Nicolas Hankov, Laetitia Baud, Anna Leonhartsberger, Kristina Sveistyte, Michael A. Skinnider, Matthieu Gautier, Achilleas Laskaratos, Katia Galan, Maged Goubran, Jimmy Ravier, Frederic Merlos, Laura Batti, Stéphane Pages, Nadia Berard, Nadine Intering, Camille Varescon, Anne Watrin, Léa Duguet, Stefano Carda, Kay A. Bartholdi, Thomas H. Hutson, Claudia Kathe, Michael Hodara, Mark A. Anderson, Bogdan Draganski, Robin Demesmaeker, Leonie Asboth, Quentin Barraud, Jocelyne Bloch, Grégoire Courtine","doi":"10.1038/s41591-024-03306-x","DOIUrl":"10.1038/s41591-024-03306-x","url":null,"abstract":"A spinal cord injury (SCI) disrupts the neuronal projections from the brain to the region of the spinal cord that produces walking, leading to various degrees of paralysis. Here, we aimed to identify brain regions that steer the recovery of walking after incomplete SCI and that could be targeted to augment this recovery. To uncover these regions, we constructed a space–time brain-wide atlas of transcriptionally active and spinal cord-projecting neurons underlying the recovery of walking after incomplete SCI. Unexpectedly, interrogation of this atlas nominated the lateral hypothalamus (LH). We demonstrate that glutamatergic neurons located in the LH (LHVglut2) contribute to the recovery of walking after incomplete SCI and that augmenting their activity improves walking. We translated this discovery into a deep brain stimulation therapy of the LH (DBSLH) that immediately augmented walking in mice and rats with SCI and durably increased recovery through the reorganization of residual lumbar-terminating projections from brainstem neurons. A pilot clinical study showed that DBSLH immediately improved walking in two participants with incomplete SCI and, in conjunction with rehabilitation, mediated functional recovery that persisted when DBSLH was turned off. There were no serious adverse events related to DBSLH. These results highlight the potential of targeting specific brain regions to maximize the engagement of spinal cord-projecting neurons in the recovery of neurological functions after SCI. Further trials must establish the safety and efficacy profile of DBSLH, including potential changes in body weight, psychological status, hormonal profiles and autonomic functions. Whole-brain anatomical and activity surveys identify the lateral hypothalamus as a key driver of recovery from spinal cord injury, leading to a deep brain stimulation therapy that augments the recovery of walking in humans.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 12","pages":"3676-3686"},"PeriodicalIF":58.7,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760024","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 : 2024-12-02DOI: 10.1038/s41591-024-03433-5
The updated Declaration of Helsinki empowers ethics committees to require community engagement and equitable partnerships
{"title":"Declaration of Helsinki embraces health equity","authors":"","doi":"10.1038/s41591-024-03433-5","DOIUrl":"10.1038/s41591-024-03433-5","url":null,"abstract":"The updated Declaration of Helsinki empowers ethics committees to require community engagement and equitable partnerships","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"30 12","pages":"3383-3383"},"PeriodicalIF":58.7,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41591-024-03433-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758174","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号