Jérémy H. Thalgott, Nicolas Zucker, Thomas Deffieux, Marit S. Koopman, Alexandre Dizeux, Cristina M. Avramut, Roman I. Koning, Hans-Jurgen Mager, Ton J. Rabelink, Mickaël Tanter, Franck Lebrin
{"title":"Publisher Correction: Non-invasive characterization of pericyte dysfunction in mouse brain using functional ultrasound localization microscopy","authors":"Jérémy H. Thalgott, Nicolas Zucker, Thomas Deffieux, Marit S. Koopman, Alexandre Dizeux, Cristina M. Avramut, Roman I. Koning, Hans-Jurgen Mager, Ton J. Rabelink, Mickaël Tanter, Franck Lebrin","doi":"10.1038/s41551-025-01494-6","DOIUrl":"https://doi.org/10.1038/s41551-025-01494-6","url":null,"abstract":"<p>Correction to: <i>Nature Biomedical Engineering</i> https://doi.org/10.1038/s41551-025-01465-x, published online 30 July 2025.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"99 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812844","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}
Salman Ul Hassan Dar, Marvin Seyfarth, Isabelle Ayx, Theano Papavassiliu, Stefan O. Schoenberg, Robert Malte Siepmann, Fabian Christopher Laqua, Jannik Kahmann, Norbert Frey, Bettina Baeßler, Sebastian Foersch, Daniel Truhn, Jakob Nikolas Kather, Sandy Engelhardt
{"title":"Unconditional latent diffusion models memorize patient imaging data","authors":"Salman Ul Hassan Dar, Marvin Seyfarth, Isabelle Ayx, Theano Papavassiliu, Stefan O. Schoenberg, Robert Malte Siepmann, Fabian Christopher Laqua, Jannik Kahmann, Norbert Frey, Bettina Baeßler, Sebastian Foersch, Daniel Truhn, Jakob Nikolas Kather, Sandy Engelhardt","doi":"10.1038/s41551-025-01468-8","DOIUrl":"https://doi.org/10.1038/s41551-025-01468-8","url":null,"abstract":"<p>Generative artificial intelligence models facilitate open-data sharing by proposing synthetic data as surrogates of real patient data. Despite the promise for healthcare, some of these models are susceptible to patient data memorization, where models generate patient data copies instead of novel synthetic samples, resulting in patient re-identification. Here we assess memorization in unconditional latent diffusion models by training them on a variety of datasets for synthetic data generation and detecting memorization with a self-supervised copy detection approach. We show a high degree of patient data memorization across all datasets, with approximately 37.2% of patient data detected as memorized and 68.7% of synthetic samples identified as patient data copies. Latent diffusion models are more susceptible to memorization than autoencoders and generative adversarial networks, and they outperform non-diffusion models in synthesis quality. Augmentation strategies during training, small architecture size and increasing datasets can reduce memorization, while overtraining the models can enhance it. These results emphasize the importance of carefully training generative models on private medical imaging datasets and examining the synthetic data to ensure patient privacy.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"290 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812903","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}
Amin GhavamiNejad, Connor D. Flynn, Armin Geraili, Sako Mirzaie, Fatemeh Esmaeili, Hossein Zargartalebi, Sharif Ahmed, Vuslat B. Juska, Jagotamoy Das, Abdalla Abdrabou, Yi Yun Zhang, Edward H. Sargent, Shana O. Kelley
{"title":"Continuous insulin monitoring using an antibody-protecting zwitterionic microneedle patch","authors":"Amin GhavamiNejad, Connor D. Flynn, Armin Geraili, Sako Mirzaie, Fatemeh Esmaeili, Hossein Zargartalebi, Sharif Ahmed, Vuslat B. Juska, Jagotamoy Das, Abdalla Abdrabou, Yi Yun Zhang, Edward H. Sargent, Shana O. Kelley","doi":"10.1038/s41551-025-01477-7","DOIUrl":"https://doi.org/10.1038/s41551-025-01477-7","url":null,"abstract":"<p>Continuous monitoring of protein and molecular biomarkers is essential for personalized disease tracking, but approaches for in vivo sensing are limited. Monitoring insulin, a peptide hormone, is an unmet need given the importance of this molecule in managing diabetes. Here we report a patch-based system with integrated electrochemical sensors that enables monitoring of insulin levels on an ongoing basis. We report a novel zwitterionic-based hydrogel microneedle patch with integrated molecular pendulum sensors that can measure insulin levels in the interstitial fluid of rats with type 1 diabetes. Our study demonstrates that the zwitterionic poly(carboxybetaine)-based microneedle patch stabilizes the antibody-based recognition elements, allowing them to withstand UV-induced crosslinking during patch fabrication and gamma-irradiation, often required for FDA-standard sterilization. We also investigate the impact of disrupted circadian rhythm on insulin levels, revealing circadian-dependent alterations in insulin absorption efficiency and distribution within the interstitial fluid and plasma. This platform not only enhances our understanding of in vivo insulin behaviour but also holds promise for personalized treatment strategies in diabetes management.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"13 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144792840","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}
Qian Li, Zakiullah Ali, Christian Zakian, Massimiliano di Pietro, Judith Honing, Maria O’Donovan, Krzysztof Flisikowski, Vassilis Sarantos, Guillaume Pierre, Jerome Gloriod, Wolfgang Drexler, Vasilis Ntziachristos
{"title":"Tethered optoacoustic and optical coherence tomography capsule endoscopy for label-free assessment of Barrett’s oesophageal neoplasia","authors":"Qian Li, Zakiullah Ali, Christian Zakian, Massimiliano di Pietro, Judith Honing, Maria O’Donovan, Krzysztof Flisikowski, Vassilis Sarantos, Guillaume Pierre, Jerome Gloriod, Wolfgang Drexler, Vasilis Ntziachristos","doi":"10.1038/s41551-025-01462-0","DOIUrl":"https://doi.org/10.1038/s41551-025-01462-0","url":null,"abstract":"<p>Endoscopic detection of oesophageal cancer (EC) often occurs late in disease development, leading to high mortality rates. Improved technologies are urgently needed for earlier EC detection. Here we research an endoscopic ultra-broadband acoustic detection scheme and introduce a 360-degree hybrid optoacoustic and optical coherence endoscopy to enable interrogation of surface and subsurface precancerous and cancerous features at a three-dimensional micrometre scale. In the following pilot tissue investigation, the dual-modal imaging features are assessed for classifying different mucosal types in Barrett’s oesophagus (BE)—a precursor of EC. We find that human lesions of different grades, such as metaplastic, dysplastic and cancerous mucosa, exhibit distinctly different imaging features that are unique to the hybrid modality. Based on these features, a classification system is developed and evaluated for identifying BE neoplasia. The results show accurate BE neoplasia detection due to the complementarity of the two imaging modalities. Therefore, this study highlights the ability of the new dual-modality feature set to improve the detection performance of any of the two modalities operating in stand-alone mode and enhance diagnostic accuracy.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"31 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786736","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}
Kshitiz Parihar, Di-Ao Liu, Ghmkin Hassan, David A. Issadore, Paul A. Janmey, Valerie M. Weaver, Wei Guo, Ravi Radhakrishnan
{"title":"Mechanical regulation of extracellular vesicle activity during tumour progression","authors":"Kshitiz Parihar, Di-Ao Liu, Ghmkin Hassan, David A. Issadore, Paul A. Janmey, Valerie M. Weaver, Wei Guo, Ravi Radhakrishnan","doi":"10.1038/s41551-025-01446-0","DOIUrl":"10.1038/s41551-025-01446-0","url":null,"abstract":"Extracellular vesicles (EVs) are naturally occurring membrane-bound vesicles secreted by cells. Functionalized with surface-targeting molecules and carrying signalling proteins and nucleic acids as cargo, EVs can rewire pathways and alter biological processes in recipient cells. Tumour-derived EVs have key roles in cancer progression, particularly in metastasis, by promoting tumour cell invasion and the establishment of pre-metastatic niches. An evolving understanding of EVs in cancer highlights a complex intercellular communication network within and beyond the tumour microenvironment that involves cancer cells and non-cancerous cell types, such as fibroblasts and endothelial cells. More recently, EVs have also been recognized for their role in modulating interactions between host and immune cells and in reprogramming the tumour immune microenvironment. In this Review, we discuss EV biogenesis and function in diverse mechanobiological and mechanoimmunological contexts, highlighting how mechanical cues influence EV targeting and activity. The intricate interplay between mechanical forces and EV dynamics contributes to tumour progression and links EVs to key disease hallmarks. This Review discusses how mechanical cues can influence extracellular vesicle targeting and activity.","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"9 8","pages":"1202-1221"},"PeriodicalIF":26.8,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786737","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}
Samir Hossainy, Seounghun Kang, J. Emiliano Gómez Medellín, Aaron T. Alpar, Kirsten C. Refvik, Yvonne Yoyo Ma, Ivan Vuong, Kevin Chang, Thomas Wang, Ani Solanki, Stuart J. Rowan, Jeffrey A. Hubbell
{"title":"Thermoreversibly assembled polymersomes for highly efficient loading, processing and delivery of protein and siRNA biologics","authors":"Samir Hossainy, Seounghun Kang, J. Emiliano Gómez Medellín, Aaron T. Alpar, Kirsten C. Refvik, Yvonne Yoyo Ma, Ivan Vuong, Kevin Chang, Thomas Wang, Ani Solanki, Stuart J. Rowan, Jeffrey A. Hubbell","doi":"10.1038/s41551-025-01469-7","DOIUrl":"https://doi.org/10.1038/s41551-025-01469-7","url":null,"abstract":"<p>Versatile technologies that can deliver both RNA and protein payloads could streamline development, simplify manufacturing and expand the capabilities of combination therapies. Here we demonstrate an efficient approach to forming ca. 100 nm polymer vesicles (polymersomes) capable of rapid self-assembly without organic solvents, avoiding the need for post-encapsulation purification. Block copolymers are designed with a lower critical solution temperature that renders them soluble in aqueous medium under standard refrigeration, but they spontaneously assemble at room temperature into large batches of nanoparticles with predictable size and morphology. The nanomaterials are designed with charged and biofunctional moieties to drive payload affinity and in vivo targeting, while both siRNA and proteins can be encapsulated during warming at >75% loading efficiencies. Formulations can be stored in a dry state for greater hydrolytic stability under standard refrigeration and can be diluted directly from the vial, bypassing the need for purification required for high scalability. We use our system for in vivo delivery in protein subunit vaccination, immune tolerance induction and siRNA interference therapy in cancer.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"144 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786735","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}
Héctor Estrada, Thomas Deffieux, Justine Robin, Mickaël Tanter, Daniel Razansky
{"title":"Imaging the brain by traversing the skull with light and sound","authors":"Héctor Estrada, Thomas Deffieux, Justine Robin, Mickaël Tanter, Daniel Razansky","doi":"10.1038/s41551-025-01433-5","DOIUrl":"https://doi.org/10.1038/s41551-025-01433-5","url":null,"abstract":"<p>Optical and ultrasonic techniques for imaging the living brain have traditionally been limited to low-resolution interrogations or highly invasive craniotomy procedures. Localization-based techniques for super-resolution ultrasound and optical imaging, as well as hybrid optoacoustic techniques, are now enabling multiscale interrogations of the brain to exploit anatomical, functional and molecular contrasts non-invasively or minimally invasively. However, the skull bone remains a substantial obstacle to the transcranial application of light- and sound-based imaging techniques. Our knowledge of the skull’s acoustic properties inherited from transcranial ultrasound has been primarily limited to a narrowband and normal-incidence-angle detection regimen, which is inapplicable to more advanced ultrasound and optoacoustic brain imaging technology. In this Perspective, we examine the transcranial wave-propagation problem, as well as recent efforts to characterize and model skull-induced distortions and develop compensatory strategies. We then summarize recent preclinical and human applications of brain imaging and delve into the most pressing challenges facing this dynamic field at the crossroads of physics, engineering and medicine.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"26 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144778611","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":"Tumour-resident oncolytic bacteria trigger potent anticancer effects through selective intratumoural thrombosis and necrosis","authors":"Seigo Iwata, Taisei Nishiyama, Matomo Sakari, Yuki Doi, Naoki Takaya, Yusuke Ogitani, Hiroshi Nagano, Keisuke Fukuchi, Eijiro Miyako","doi":"10.1038/s41551-025-01459-9","DOIUrl":"https://doi.org/10.1038/s41551-025-01459-9","url":null,"abstract":"<p>Intratumoural bacteria represent a promising drug-free strategy in cancer therapy. Here we demonstrate that a tumour-resident bacterial consortium—<i>Proteus mirabilis</i> (A-gyo) and <i>Rhodopseudomonas palustris</i> (UN-gyo)—in a precise 3:97 ratio (A-gyo:UN-gyo), exhibits potent antitumour efficacy independent of immune cell infiltration. In both immunocompetent and immunocompromised mouse models, including human tumour xenografts, intravenous administration of the bacterial consortium led to complete tumour remission, prolonged survival, and no observable systemic toxicity or cytokine release syndrome. Genomic and phenotypic analyses revealed A-gyo’s unique non-pathogenic profile and impaired motility, while UN-gyo modulated A-gyo’s biogenic activity, enhanced safety and promoted cancer-specific transformation. Mechanistically, the bacterial consortium triggered selective intratumoural thrombosis and vascular collapse—supported by cytokine induction, fibrin deposition and platelet aggregation—culminating in widespread tumour necrosis. The consortium also proliferated within tumours, formed biofilms and exerted direct oncolytic effects. This natural bacterial synergy—achieved without genetic engineering—offers a self-regulating and controllable strategy for safe, tumour-targeted therapy.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"69 1","pages":""},"PeriodicalIF":28.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144778613","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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