Pub Date : 2024-12-23DOI: 10.1038/s41551-024-01326-z
Jacob T. Robinson, Sumner L. Norman, Matthew R. Angle, Timothy G. Constandinou, Timothy Denison, John P. Donoghue, Ryan M. Field, Andreas Forsland, Sid Kouider, José del R. Millán, Jonathan A. Michaels, Amy L. Orsborn, Chethan Pandarinath, J. Andrew Pruszynski, Christopher J. Rozell, Nishal P. Shah, Maryam M. Shanechi, Mahsa Shoaran, Sameer A. Sheth, Sergey D. Stavisky, Eric Trautmann, Nicolas Vachicouras, Chong Xie
Naming brain–computer interfaces according to their intended application will assist stakeholders in the evaluation of the benefits and risks of neurotechnologies.
根据其预期应用命名脑机接口将有助于利益相关者评估神经技术的收益和风险。
{"title":"An application-based taxonomy for brain–computer interfaces","authors":"Jacob T. Robinson, Sumner L. Norman, Matthew R. Angle, Timothy G. Constandinou, Timothy Denison, John P. Donoghue, Ryan M. Field, Andreas Forsland, Sid Kouider, José del R. Millán, Jonathan A. Michaels, Amy L. Orsborn, Chethan Pandarinath, J. Andrew Pruszynski, Christopher J. Rozell, Nishal P. Shah, Maryam M. Shanechi, Mahsa Shoaran, Sameer A. Sheth, Sergey D. Stavisky, Eric Trautmann, Nicolas Vachicouras, Chong Xie","doi":"10.1038/s41551-024-01326-z","DOIUrl":"https://doi.org/10.1038/s41551-024-01326-z","url":null,"abstract":"Naming brain–computer interfaces according to their intended application will assist stakeholders in the evaluation of the benefits and risks of neurotechnologies.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"125 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874385","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 : 2024-12-23DOI: 10.1038/s41551-024-01311-6
Ahmed A. Metwally, Dalia Perelman, Heyjun Park, Yue Wu, Alokkumar Jha, Seth Sharp, Alessandra Celli, Ekrem Ayhan, Fahim Abbasi, Anna L. Gloyn, Tracey McLaughlin, Michael P. Snyder
The classification of type 2 diabetes and prediabetes does not consider heterogeneity in the pathophysiology of glucose dysregulation. Here we show that prediabetes is characterized by metabolic heterogeneity, and that metabolic subphenotypes can be predicted by the shape of the glucose curve measured via a continuous glucose monitor (CGM) during standardized oral glucose-tolerance tests (OGTTs) performed in at-home settings. Gold-standard metabolic tests in 32 individuals with early glucose dysregulation revealed dominant or co-dominant subphenotypes (muscle or hepatic insulin-resistance phenotypes in 34% of the individuals, and β-cell-dysfunction or impaired-incretin-action phenotypes in 40% of them). Machine-learning models trained with glucose time series from OGTTs from the 32 individuals predicted the subphenotypes with areas under the curve (AUCs) of 95% for muscle insulin resistance, 89% for β-cell deficiency and 88% for impaired incretin action. With CGM-generated glucose curves obtained during at-home OGTTs, the models predicted the muscle-insulin-resistance and β-cell-deficiency subphenotypes of 29 individuals with AUCs of 88% and 84%, respectively. At-home identification of metabolic subphenotypes via a CGM may aid the risk stratification of individuals with early glucose dysregulation.
{"title":"Prediction of metabolic subphenotypes of type 2 diabetes via continuous glucose monitoring and machine learning","authors":"Ahmed A. Metwally, Dalia Perelman, Heyjun Park, Yue Wu, Alokkumar Jha, Seth Sharp, Alessandra Celli, Ekrem Ayhan, Fahim Abbasi, Anna L. Gloyn, Tracey McLaughlin, Michael P. Snyder","doi":"10.1038/s41551-024-01311-6","DOIUrl":"https://doi.org/10.1038/s41551-024-01311-6","url":null,"abstract":"<p>The classification of type 2 diabetes and prediabetes does not consider heterogeneity in the pathophysiology of glucose dysregulation. Here we show that prediabetes is characterized by metabolic heterogeneity, and that metabolic subphenotypes can be predicted by the shape of the glucose curve measured via a continuous glucose monitor (CGM) during standardized oral glucose-tolerance tests (OGTTs) performed in at-home settings. Gold-standard metabolic tests in 32 individuals with early glucose dysregulation revealed dominant or co-dominant subphenotypes (muscle or hepatic insulin-resistance phenotypes in 34% of the individuals, and β-cell-dysfunction or impaired-incretin-action phenotypes in 40% of them). Machine-learning models trained with glucose time series from OGTTs from the 32 individuals predicted the subphenotypes with areas under the curve (AUCs) of 95% for muscle insulin resistance, 89% for β-cell deficiency and 88% for impaired incretin action. With CGM-generated glucose curves obtained during at-home OGTTs, the models predicted the muscle-insulin-resistance and β-cell-deficiency subphenotypes of 29 individuals with AUCs of 88% and 84%, respectively. At-home identification of metabolic subphenotypes via a CGM may aid the risk stratification of individuals with early glucose dysregulation.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"39 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874557","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 : 2024-12-23DOI: 10.1038/s41551-024-01287-3
Scott E. James, Sophia Chen, Brandon D. Ng, Jacob S. Fischman, Lorenz Jahn, Alexander P. Boardman, Adhithi Rajagopalan, Harold K. Elias, Alyssa Massa, Dylan Manuele, Katherine B. Nichols, Amina Lazrak, Nicole Lee, Aoife M. Roche, Alexander G. McFarland, Angelina Petrichenko, John K. Everett, Frederic D. Bushman, Teng Fei, Anastasia I. Kousa, Andri L. Lemarquis, Susan DeWolf, Jonathan U. Peled, Santosha A. Vardhana, Christopher A. Klebanoff, Marcel R. M. van den Brink
Resistance to chimaeric antigen receptor (CAR) T cell therapy develops through multiple mechanisms, most notably antigen loss and tumour-induced immune suppression. It has been suggested that T cells expressing multiple CARs may overcome the resistance of tumours and that T cells expressing receptors that switch inhibitory immune-checkpoint signals into costimulatory signals may enhance the activity of the T cells in the tumour microenvironment. However, engineering multiple features into a single T cell product is difficult because of the transgene-packaging constraints of current gene-delivery vectors. Here we describe a cell-sorting method that leverages leucine zippers for the selective single-step immunomagnetic purification of cells co-transduced with two vectors. Such ‘Zip sorting’ facilitated the generation of T cells simultaneously expressing up to four CARs and coexpressing up to three ‘switch’ receptors. In syngeneic mouse models, T cells with multiple CARs and multiple switch receptors eliminated antigenically heterogeneous populations of leukaemia cells coexpressing multiple inhibitory ligands. By combining diverse therapeutic strategies, Zip-sorted multi-CAR multi-switch-receptor T cells can overcome multiple mechanisms of CAR T cell resistance. A cell-sorting method leveraging leucine zippers allows for the generation of T cells displaying multiple chimaeric antigen receptors as well as receptors converting inhibitory signals into stimulatory signals.
{"title":"Leucine zipper-based immunomagnetic purification of CAR T cells displaying multiple receptors","authors":"Scott E. James, Sophia Chen, Brandon D. Ng, Jacob S. Fischman, Lorenz Jahn, Alexander P. Boardman, Adhithi Rajagopalan, Harold K. Elias, Alyssa Massa, Dylan Manuele, Katherine B. Nichols, Amina Lazrak, Nicole Lee, Aoife M. Roche, Alexander G. McFarland, Angelina Petrichenko, John K. Everett, Frederic D. Bushman, Teng Fei, Anastasia I. Kousa, Andri L. Lemarquis, Susan DeWolf, Jonathan U. Peled, Santosha A. Vardhana, Christopher A. Klebanoff, Marcel R. M. van den Brink","doi":"10.1038/s41551-024-01287-3","DOIUrl":"10.1038/s41551-024-01287-3","url":null,"abstract":"Resistance to chimaeric antigen receptor (CAR) T cell therapy develops through multiple mechanisms, most notably antigen loss and tumour-induced immune suppression. It has been suggested that T cells expressing multiple CARs may overcome the resistance of tumours and that T cells expressing receptors that switch inhibitory immune-checkpoint signals into costimulatory signals may enhance the activity of the T cells in the tumour microenvironment. However, engineering multiple features into a single T cell product is difficult because of the transgene-packaging constraints of current gene-delivery vectors. Here we describe a cell-sorting method that leverages leucine zippers for the selective single-step immunomagnetic purification of cells co-transduced with two vectors. Such ‘Zip sorting’ facilitated the generation of T cells simultaneously expressing up to four CARs and coexpressing up to three ‘switch’ receptors. In syngeneic mouse models, T cells with multiple CARs and multiple switch receptors eliminated antigenically heterogeneous populations of leukaemia cells coexpressing multiple inhibitory ligands. By combining diverse therapeutic strategies, Zip-sorted multi-CAR multi-switch-receptor T cells can overcome multiple mechanisms of CAR T cell resistance. A cell-sorting method leveraging leucine zippers allows for the generation of T cells displaying multiple chimaeric antigen receptors as well as receptors converting inhibitory signals into stimulatory signals.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"8 12","pages":"1592-1614"},"PeriodicalIF":26.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874558","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 : 2024-12-23DOI: 10.1038/s41551-024-01335-y
Valeria Caprettini
High-throughput screening led to the identification of artesunate as an antifibrotic agent that targets the glycoprotein myeloid differentiation factor 2 in the infarcted heart.
高通量筛选鉴定出青蒿琥酯是一种抗纤维化药物，可靶向梗死心脏的糖蛋白髓样分化因子2。
{"title":"An antifibrotic therapy for myocardial infarction","authors":"Valeria Caprettini","doi":"10.1038/s41551-024-01335-y","DOIUrl":"10.1038/s41551-024-01335-y","url":null,"abstract":"High-throughput screening led to the identification of artesunate as an antifibrotic agent that targets the glycoprotein myeloid differentiation factor 2 in the infarcted heart.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"8 12","pages":"1509-1509"},"PeriodicalIF":26.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874552","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 : 2024-12-23DOI: 10.1038/s41551-024-01332-1
Filipe V. Almeida
Cas9-based ribonucleoproteins engineered via directed evolution and encapsulated in optimized lipid nanoparticles improve genome-editing efficacies in the livers and lungs of mice.
{"title":"Making CRISPR more deliverable","authors":"Filipe V. Almeida","doi":"10.1038/s41551-024-01332-1","DOIUrl":"10.1038/s41551-024-01332-1","url":null,"abstract":"Cas9-based ribonucleoproteins engineered via directed evolution and encapsulated in optimized lipid nanoparticles improve genome-editing efficacies in the livers and lungs of mice.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"8 12","pages":"1513-1513"},"PeriodicalIF":26.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874556","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 : 2024-12-23DOI: 10.1038/s41551-024-01336-x
Genome editing is powering the generation of increasingly safer and potent multifunctional therapeutic cells.
基因组编辑正在为越来越安全和有效的多功能治疗细胞的产生提供动力。
{"title":"‘CRISPRing’ with therapeutic cells","authors":"","doi":"10.1038/s41551-024-01336-x","DOIUrl":"10.1038/s41551-024-01336-x","url":null,"abstract":"Genome editing is powering the generation of increasingly safer and potent multifunctional therapeutic cells.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"8 12","pages":"1505-1506"},"PeriodicalIF":26.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41551-024-01336-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874386","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 : 2024-12-23DOI: 10.1038/s41551-024-01329-w
Pep Pàmies
Combining neuroimaging with molecular and cellular data reveals how microscale features shape large-scale brain networks.
将神经成像与分子和细胞数据相结合，揭示了微尺度特征如何塑造大规模的大脑网络。
{"title":"Bridging scales in brain connectivity","authors":"Pep Pàmies","doi":"10.1038/s41551-024-01329-w","DOIUrl":"10.1038/s41551-024-01329-w","url":null,"abstract":"Combining neuroimaging with molecular and cellular data reveals how microscale features shape large-scale brain networks.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"8 12","pages":"1515-1515"},"PeriodicalIF":26.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874555","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 : 2024-12-23DOI: 10.1038/s41551-024-01324-1
Francisco Carrillo-Perez, Marija Pizurica, Kathleen Marchal, Olivier Gevaert
Foundation models can be advantageously harnessed to estimate missing data in multimodal biomedical datasets and to generate realistic synthetic samples.
基础模型可以被有利地利用来估计多模态生物医学数据集中的缺失数据并生成真实的合成样本。
{"title":"Synthetic multimodal data modelling for data imputation","authors":"Francisco Carrillo-Perez, Marija Pizurica, Kathleen Marchal, Olivier Gevaert","doi":"10.1038/s41551-024-01324-1","DOIUrl":"https://doi.org/10.1038/s41551-024-01324-1","url":null,"abstract":"Foundation models can be advantageously harnessed to estimate missing data in multimodal biomedical datasets and to generate realistic synthetic samples.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"281 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874387","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 : 2024-12-23DOI: 10.1038/s41551-024-01334-z
Jennifer Haskell
An agonist of the neurokinin 2 receptor induced weight loss and increased energy expenditure in obese mice and monkeys with diabetes.
一种神经激肽2受体激动剂在肥胖的糖尿病小鼠和猴子中引起体重减轻和能量消耗增加。
{"title":"Targeting NK2R reverses cardiometabolic dysfunction","authors":"Jennifer Haskell","doi":"10.1038/s41551-024-01334-z","DOIUrl":"10.1038/s41551-024-01334-z","url":null,"abstract":"An agonist of the neurokinin 2 receptor induced weight loss and increased energy expenditure in obese mice and monkeys with diabetes.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"8 12","pages":"1510-1510"},"PeriodicalIF":26.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874554","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}
The engraftment of haematopoietic stem and progenitor cells (HSPCs), particularly in cord-blood transplants, remains challenging. Here we report the role of the corticotropin-releasing hormone (CRH) in enhancing the homing and engraftment of human-cord-blood HSPCs in bone marrow through mechanical remodelling. By using microfluidics, intravital two-photon imaging and long-term-engraftment assays, we show that treatment with CRH substantially enhances HSPC adhesion, motility and mechanical remodelling, ultimately leading to improved bone-marrow homing and engraftment in immunodeficient mice. CRH induces Ras homologue gene family member A (RhoA)-dependent nuclear translocation of the yes-associated protein (YAP), which upregulates the expression of genes encoding extracellular-matrix proteins (notably, thrombospondin-2 (THBS2)). This process guides the mechanical remodelling of HSPCs via modulation of the actin cytoskeleton and the extracellular matrix, with THBS2 interacting with the integrin αvβ3 and coordinating the nuclear translocation of YAP upon CRH/CRH-receptor-1 (CRH/CRHR1) signalling. Overall, the CRH/CRHR1/RhoA/YAP/THBS2/αvβ3 axis has a central role in modulating HSPC behaviour via a mechanical feedback loop involving THBS2, αvβ3, the actin cytoskeleton and YAP signalling. Our findings may suggest avenues for optimizing the transplantation of HSPCs.
{"title":"Enhanced engraftment of human haematopoietic stem cells via mechanical remodelling mediated by the corticotropin-releasing hormone","authors":"Mingming Wu, Haoxiang Yang, Senquan Liu, Lai Jiang, Tingting Liang, Yan Wang, Mingming Zhu, Xian Song, Hao Liu, Jinghao Shen, Shuangzi Wang, Xiaoyu Zhu, Cheng-Kui Qu, Linzhao Cheng, Hongyuan Jiang, Fang Ni","doi":"10.1038/s41551-024-01316-1","DOIUrl":"https://doi.org/10.1038/s41551-024-01316-1","url":null,"abstract":"<p>The engraftment of haematopoietic stem and progenitor cells (HSPCs), particularly in cord-blood transplants, remains challenging. Here we report the role of the corticotropin-releasing hormone (CRH) in enhancing the homing and engraftment of human-cord-blood HSPCs in bone marrow through mechanical remodelling. By using microfluidics, intravital two-photon imaging and long-term-engraftment assays, we show that treatment with CRH substantially enhances HSPC adhesion, motility and mechanical remodelling, ultimately leading to improved bone-marrow homing and engraftment in immunodeficient mice. CRH induces Ras homologue gene family member A (RhoA)-dependent nuclear translocation of the yes-associated protein (YAP), which upregulates the expression of genes encoding extracellular-matrix proteins (notably, thrombospondin-2 (THBS2)). This process guides the mechanical remodelling of HSPCs via modulation of the actin cytoskeleton and the extracellular matrix, with THBS2 interacting with the integrin αvβ3 and coordinating the nuclear translocation of YAP upon CRH/CRH-receptor-1 (CRH/CRHR1) signalling. Overall, the CRH/CRHR1/RhoA/YAP/THBS2/αvβ3 axis has a central role in modulating HSPC behaviour via a mechanical feedback loop involving THBS2, αvβ3, the actin cytoskeleton and YAP signalling. Our findings may suggest avenues for optimizing the transplantation of HSPCs.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"92 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874559","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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