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Air-blood interface engineered microfluidic device to mimic shear rate gradient induced human bleeding model 模拟剪切率梯度诱导人体出血模型的气血界面工程微流控装置
Pub Date : 2024-07-31 DOI: arxiv-2407.21356
Shobhit Das, Shilpi Pandey, Oliver Hayden
Microfluidic technology has emerged as a powerful tool for studying complexbiological processes with enhanced precision and control. A microfluidic chipwas designed to emulate human-like microvascular networks with precise controlover channel geometry and flow conditions. By simulating blood flow dynamicsduring bleeding events, we successfully observed the real-time interactions ofplatelets and their aggregation induced by shear rate gradient at the woundsite. Platelet dynamics is primarily influenced by physico-mechanical conditionof blood vessels with pathophysiological condition of blood at close proximityof vascular injury site. This microfluidic platform facilitated theinvestigation of platelet adhesion, activation, and clot formation, providing aunique opportunity to study the spatiotemporal dynamics of platelet aggregationand blood clot. Our findings shed light on the intricate mechanisms underlyingthrombus formation and platelet-mediated aggregation, offering a more accurateand dynamic representation of human haemostasis compared to traditional animalmodels. In the conventional approach, the human bleeding model is tried onmouse due to anatomy and pathological similarities between mouse and humans.This study will simplify and standardize the blood and vasculature conditions.The microfluidic-based replication of the bleeding model holds significantpromise in advancing our understanding of clotting disorders and wound healingprocesses. Furthermore, it paves the way for targeted therapeutic interventionsin managing bleeding disorders and enhancing clinical strategies for promotingefficient wound closure. Ultimately, this study demonstrates the potential ofmicrofluidics to revolutionize haemostasis research and opens up new avenuesfor the development of personalized medicine approaches in the field ofclotting disorders.
微流控技术已成为研究复杂生物学过程的有力工具,其精确性和可控性都得到了提高。我们设计了一种微流控芯片来模拟类似人体的微血管网络,精确控制通道的几何形状和流动条件。通过模拟出血时的血流动态,我们成功地观察到了血小板的实时相互作用以及伤口处剪切率梯度引起的血小板聚集。血小板动力学主要受血管物理机械条件和血管损伤部位附近血液病理生理条件的影响。这种微流控平台有助于研究血小板的粘附、活化和血凝块的形成,为研究血小板聚集和血凝块的时空动态提供了独特的机会。我们的研究结果揭示了血栓形成和血小板介导的聚集的复杂机制,与传统的动物模型相比,更准确、更动态地反映了人体止血过程。在传统方法中,由于小鼠和人类在解剖和病理上的相似性,人类出血模型要在小鼠身上进行试验。这项研究将简化血液和血管条件并使之标准化。此外,它还为有针对性的治疗干预铺平了道路,有助于治疗出血性疾病和加强促进伤口有效闭合的临床策略。最终,这项研究展示了微流体技术彻底改变止血研究的潜力,并为凝血障碍领域个性化医学方法的发展开辟了新途径。
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引用次数: 0
Dimeric Drug Polymeric Micelles with Acid-Active Tumor Targeting and FRET-indicated Drug Release 具有酸活性肿瘤靶向性和 FRET 指示药物释放功能的二聚药物聚合物胶束
Pub Date : 2024-07-30 DOI: arxiv-2407.20538
Xing Guo, Lin Wang, Kayla Duval, Jing Fan, Shaobing Zhou, Zi Chen
Trans-activating transcriptional activator (TAT), a cell-penetrating peptide,has been extensively used for facilitating cellular uptake and nucleartargeting of drug delivery systems. However, the positively charged TAT peptideusually strongly interacts with serum components and undergoes substantialphagocytosis by the reticuloendothelial system, causing a short bloodcirculation in vivo. In this work, an acid-active tumor targeting nanoplatformDA-TAT-PECL was developed to effectively inhibit the nonspecific interactionsof TAT in the bloodstream. 2,3-dimethylmaleic anhydride (DA) was first used toconvert the TAT amines to carboxylic acid, the resulting DA-TAT was furtherconjugated to get DA-TAT-PECL. After self-assembly into polymeric micelles,they were capable of circulating in the physiological condition for a long timeand promoting cell penetration upon accumulation at the tumor site andde-shielding the DA group. Moreover, camptothecin (CPT) was used as theanticancer drug and modified into a dimer (CPT)2-ss-Mal, in which two CPTmolecules were connected by a reduction-labile maleimide thioether bond. TheFRET signal between CPT and maleimide thioether bond was monitored to visualizethe drug release process and effective targeted delivery of antitumor drugs wasdemonstrated. This pH/reduction dual-responsive micelle system provides a newplatform for high fidelity cancer therapy.
反式激活转录激活因子(TAT)是一种细胞穿透肽,已被广泛用于促进细胞摄取和核靶向给药系统。然而,带正电荷的 TAT 肽通常会与血清成分产生强烈的相互作用,并被网状内皮系统大量吞噬,导致体内血液循环缩短。本研究开发了一种酸活性肿瘤靶向纳米平台DA-TAT-PECL,以有效抑制TAT在血液中的非特异性相互作用。首先用2,3-二甲基马来酸酐(DA)将TAT胺转化为羧酸,然后进一步共轭得到DA-TAT-PECL。自组装成高分子胶束后,它们能够在生理状态下长期循环,并在肿瘤部位积聚后促进细胞穿透,同时屏蔽DA基团。此外,以喜树碱(CPT)为抗癌药物,将其修饰成二聚体(CPT)2-ss-Mal,其中两个CPT分子通过还原性马来酰亚胺硫醚键连接。通过监测 CPT 与马来酰亚胺硫醚键之间的FRET 信号,可视化药物释放过程,并证明了抗肿瘤药物的有效靶向递送。这种 pH/ 还原双响应胶束系统为高保真癌症治疗提供了一个新平台。
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引用次数: 0
TMA-Grid: An open-source, zero-footprint web application for FAIR Tissue MicroArray De-arraying TMA-Grid:用于 FAIR 组织微阵列去阵列的开源、零足迹网络应用程序
Pub Date : 2024-07-30 DOI: arxiv-2407.21233
Aaron Ge, Monjoy Saha, Maire A. Duggan, Petra Lenz, Mustapha Abubakar, Montserrat García-Closas, Jeya Balasubramanian, Jonas S. Almeida, Praphulla MS Bhawsar
Background: Tissue Microarrays (TMAs) significantly increase analytical efficiency inhistopathology and large-scale epidemiologic studies by allowing multipletissue cores to be scanned on a single slide. The individual cores can bedigitally extracted and then linked to metadata for analysis in a process knownas de-arraying. However, TMAs often contain core misalignments and artifactsdue to assembly errors, which can adversely affect the reliability of theextracted cores during the de-arraying process. Moreover, conventionalapproaches for TMA de-arraying rely on desktop solutions.Therefore, a robustyet flexible de-arraying method is crucial to account for these inaccuraciesand ensure effective downstream analyses. Results: We developed TMA-Grid, an in-browser, zero-footprint, interactive webapplication for TMA de-arraying. This web application integrates aconvolutional neural network for precise tissue segmentation and a gridestimation algorithm to match each identified core to its expected location.The application emphasizes interactivity, allowing users to easily adjustsegmentation and gridding results. Operating entirely in the web-browser,TMA-Grid eliminates the need for downloads or installations and ensures dataprivacy. Adhering to FAIR principles (Findable, Accessible, Interoperable, andReusable), the application and its components are designed for seamlessintegration into TMA research workflows. Conclusions: TMA-Grid provides a robust, user-friendly solution for TMA dearraying on theweb. As an open, freely accessible platform, it lays the foundation forcollaborative analyses of TMAs and similar histopathology imaging data.Availability: Web application: https://episphere.github.io/tma-grid Code:https://github.com/episphere/tma-grid Tutorial: https://youtu.be/miajqyw4BVk
背景:组织芯片(TMA)可以在一张载玻片上扫描多个组织核,从而大大提高了病理学和大规模流行病学研究的分析效率。在去阵列过程中,可以对单个组织核心进行连续提取,然后与元数据链接进行分析。然而,TMA 经常包含由于装配错误造成的核心错位和伪影,这会对去阵列过程中提取核心的可靠性产生不利影响。此外,传统的 TMA 去阵列方法依赖于桌面解决方案。因此,一种稳健而灵活的去阵列方法对于考虑这些误差并确保有效的下游分析至关重要。结果:我们开发了 TMA-Grid,这是一种用于 TMA 去阵列的浏览器内、零足迹、交互式网络应用程序。该网络应用程序集成了一个用于精确组织分割的卷积神经网络和一个网格估算算法,用于将每个已识别的核心与预期位置相匹配。该应用程序强调交互性,允许用户轻松调整分割和网格结果。TMA-Grid 完全在网页浏览器中运行,无需下载或安装,确保了数据的私密性。遵循 FAIR 原则(可查找、可访问、可互操作、可重用),该应用程序及其组件旨在无缝集成到 TMA 研究工作流程中。结论TMA-Grid 为在网络上进行 TMA 采集提供了一个强大、用户友好的解决方案。作为一个开放、可免费访问的平台,它为 TMA 和类似组织病理学成像数据的协作分析奠定了基础:网络应用:https://episphere.github.io/tma-grid 代码:https://github.com/episphere/tma-grid 教程:https://youtu.be/miajqyw4BVk
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引用次数: 0
GP-VLS: A general-purpose vision language model for surgery GP-VLS:用于外科手术的通用视觉语言模型
Pub Date : 2024-07-27 DOI: arxiv-2407.19305
Samuel Schmidgall, Joseph Cho, Cyril Zakka, William Hiesinger
Surgery requires comprehensive medical knowledge, visual assessment skills,and procedural expertise. While recent surgical AI models have focused onsolving task-specific problems, there is a need for general-purpose systemsthat can understand surgical scenes and interact through natural language. Thispaper introduces GP-VLS, a general-purpose vision language model for surgerythat integrates medical and surgical knowledge with visual scene understanding.For comprehensively evaluating general-purpose surgical models, we proposeSurgiQual, which evaluates across medical and surgical knowledge benchmarks aswell as surgical vision-language questions. To train GP-VLS, we develop six newdatasets spanning medical knowledge, surgical textbooks, and vision-languagepairs for tasks like phase recognition and tool identification. We show thatGP-VLS significantly outperforms existing open- and closed-source models onsurgical vision-language tasks, with 8-21% improvements in accuracy acrossSurgiQual benchmarks. GP-VLS also demonstrates strong performance on medicaland surgical knowledge tests compared to open-source alternatives. Overall,GP-VLS provides an open-source foundation for developing AI assistants tosupport surgeons across a wide range of tasks and scenarios.
外科手术需要全面的医学知识、视觉评估技能和程序专业知识。虽然最近的手术人工智能模型都集中在解决特定任务的问题上,但仍需要能理解手术场景并通过自然语言进行交互的通用系统。本文介绍了 GP-VLS,这是一种用于外科手术的通用视觉语言模型,它将医学和外科知识与视觉场景理解融为一体。为了全面评估通用外科模型,我们提出了 SurgiQual,它可以评估医学和外科知识基准以及外科视觉语言问题。为了训练 GP-VLS,我们开发了六个新的数据集,涵盖医学知识、外科教科书以及相位识别和工具识别等任务的视觉语言对。我们的研究表明,GP-VLS 在外科视觉语言任务上的表现明显优于现有的开源和闭源模型,在 SurgiQual 基准中的准确率提高了 8-21%。与开源替代方案相比,GP-VLS 还在医学和外科知识测试中表现出强劲的性能。总之,GP-VLS 为开发人工智能助手提供了一个开源基础,可以在广泛的任务和场景中为外科医生提供支持。
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引用次数: 0
The IBEX Knowledge-Base: Achieving more together with open science IBEX 知识库:与开放科学携手实现更多目标
Pub Date : 2024-07-26 DOI: arxiv-2407.19059
Andrea J. RadtkeLymphocyte Biology Section and Center for Advanced Tissue Imaging, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Ifeanyichukwu AnidiCritical Care Medicine and Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA, Leanne ArakkalLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Armando Arroyo-MejiasLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Rebecca T. BeuschelLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Katy BornerDepartment of Intelligent Systems Engineering, Indiana University, Bloomington, IN, USA, Colin J. ChuUCL Institute of Ophthalmology and NIHR Moorfields Biomedical Research Centre, London, UK, Beatrice ClarkLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Menna R. ClatworthyCambridge Institute for Therapeutic Immunology and Infectious Diseases, University of Cambridge Department of Medicine, Molecular Immunity Unit, Laboratory of Molecular Biology, Cambridge, UK, Jake ColauttiMcMaster Immunology Research Centre, Schroeder Allergy and Immunology Research Institute, Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada, Joshua CroteauDepartment of Business Development, BioLegend Inc., San Diego, CA, USA, Saven DenhaMcMaster Immunology Research Centre, Schroeder Allergy and Immunology Research Institute, Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada, Rose DeverFunctional Immunogenomics Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA, Walderez O. DutraLaboratory of Cell-Cell Interactions, Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil, Sonja FritzscheMax-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, Spencer FullamDivision of Rheumatology, Rush University Medical Center, Chicago, IL, USA, Michael Y. GernerDepartment of Immunology, University of Washington School of Medicine, Seattle, WA, USA, Anita GolaRobin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY, USA, Kenneth J. GollobCenter for Research in Immuno-oncology, Jonathan M. HernandezSurgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, Jyh Liang HorLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Hiroshi IchiseLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Zhixin JingLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Danny JonigkInstitute of Pathology, Aachen Medical University, RWTH Aachen, Aachen, Germany, Evelyn KandovLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Wolfgang KastenmuellerWurzburg Institute of Systems Immunology, Max Planck Research Group at the Julius-Maximilians-Universitat Wurzburg, Wurzburg, Germany, Joshua F. E. KoenigMcMaster Immunology Research Centre, Schroeder Allergy and Immunology Research Institute, Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada, Aanandita KothurkarUCL Institute of Ophthalmology and NIHR Moorfields Biomedical Research Centre, London, UK, Alexandra Y. KreinsInfection Immunity and Inflammation Research and Teaching Department, University College London Great Ormond Street Institute of Child Health, London, UK, Ian LambornLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Yuri LinSurgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, Katia Luciano Pereira MoraisCenter for Research in Immuno-oncology, Aleksandra LunichCritical Care Medicine and Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA, Jean C. S. LuzViral Vector Laboratory, Cancer Institute of Sao Paulo, University of Sao Paulo, SP, Brazil, Ryan B. MacDonaldUCL Institute of Ophthalmology and NIHR Moorfields Biomedical Research Centre, London, UK, Chen MakranzNeuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, Vivien I. MaltezDivision of Allergy, Immunology and Rheumatology, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA, Ryan V. MoriatyDepartment of Cellular and Developmental Biology, Northwestern University, Chicago, IL, USA, Juan M. Ocampo-GodinezLaboratorio de Bioingenieria de Tejidos, Departamento de Estudios de Posgrado e Investigacion, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico, Vitoria M. OlynthoMcMaster Immunology Research Centre, Schroeder Allergy and Immunology Research Institute, Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada, Kartika PadhanLymphocyte Biology Section and Center for Advanced Tissue Imaging, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Kirsten RemmertSurgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, Nathan RichozCambridge Institute for Therapeutic Immunology and Infectious Diseases, University of Cambridge Department of Medicine, Molecular Immunity Unit, Laboratory of Molecular Biology, Cambridge, UK, Edward C. SchromLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Wanjing ShangLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Lihong ShiLaboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Rochelle M. ShihLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Emily SperanzaFlorida Research and Innovation Center, Cleveland Clinic Lerner Research Institute, Port Saint Lucie, FL, USA, Salome StierliInstitute of Anatomy, University of Zurich, Zurich, Switzerland, Sarah A. TeichmannCambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge Biomedical Campus, Cambridge, UK, Tibor Z. VeresLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Megan VierhoutMcMaster Immunology Research Centre, Schroeder Allergy and Immunology Research Institute, Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada, Brianna T. WachterLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Adam K. Wade-VallanceLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Margaret WilliamsCritical Care Medicine and Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA, Nathan ZanggerInstitute of Microbiology, ETH Zurich, Zurich, Switzerland, Ronald N. GermainLymphocyte Biology Section and Center for Advanced Tissue Imaging, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA and Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Ziv YanivBioinformatics and Computational Bioscience Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Iterative Bleaching Extends multipleXity (IBEX) is a versatile method forhighly multiplexed imaging of diverse tissues. Based on open scienceprinciples, we created the IBEX Knowledge-Base, a resource for reagents,protocols and more, to empower innovation.
Iterative Bleaching Extends multipleXity (IBEX) 是一种对不同组织进行高度多重成像的多功能方法。基于开放科学原则,我们创建了 IBEX 知识库,这是一个提供试剂、规程和更多信息的资源库,以增强创新能力。
{"title":"The IBEX Knowledge-Base: Achieving more together with open science","authors":"Andrea J. RadtkeLymphocyte Biology Section and Center for Advanced Tissue Imaging, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Ifeanyichukwu AnidiCritical Care Medicine and Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA, Leanne ArakkalLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Armando Arroyo-MejiasLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Rebecca T. BeuschelLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Katy BornerDepartment of Intelligent Systems Engineering, Indiana University, Bloomington, IN, USA, Colin J. ChuUCL Institute of Ophthalmology and NIHR Moorfields Biomedical Research Centre, London, UK, Beatrice ClarkLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Menna R. ClatworthyCambridge Institute for Therapeutic Immunology and Infectious Diseases, University of Cambridge Department of Medicine, Molecular Immunity Unit, Laboratory of Molecular Biology, Cambridge, UK, Jake ColauttiMcMaster Immunology Research Centre, Schroeder Allergy and Immunology Research Institute, Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada, Joshua CroteauDepartment of Business Development, BioLegend Inc., San Diego, CA, USA, Saven DenhaMcMaster Immunology Research Centre, Schroeder Allergy and Immunology Research Institute, Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada, Rose DeverFunctional Immunogenomics Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA, Walderez O. DutraLaboratory of Cell-Cell Interactions, Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil, Sonja FritzscheMax-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, Spencer FullamDivision of Rheumatology, Rush University Medical Center, Chicago, IL, USA, Michael Y. GernerDepartment of Immunology, University of Washington School of Medicine, Seattle, WA, USA, Anita GolaRobin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY, USA, Kenneth J. GollobCenter for Research in Immuno-oncology, Jonathan M. HernandezSurgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, Jyh Liang HorLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Hiroshi IchiseLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Zhixin JingLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Danny JonigkInstitute of Pathology, Aachen Medical University, RWTH Aachen, Aachen, Germany, Evelyn KandovLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Wolfgang KastenmuellerWurzburg Institute of Systems Immunology, Max Planck Research Group at the Julius-Maximilians-Universitat Wurzburg, Wurzburg, Germany, Joshua F. E. KoenigMcMaster Immunology Research Centre, Schroeder Allergy and Immunology Research Institute, Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada, Aanandita KothurkarUCL Institute of Ophthalmology and NIHR Moorfields Biomedical Research Centre, London, UK, Alexandra Y. KreinsInfection Immunity and Inflammation Research and Teaching Department, University College London Great Ormond Street Institute of Child Health, London, UK, Ian LambornLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Yuri LinSurgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, Katia Luciano Pereira MoraisCenter for Research in Immuno-oncology, Aleksandra LunichCritical Care Medicine and Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA, Jean C. S. LuzViral Vector Laboratory, Cancer Institute of Sao Paulo, University of Sao Paulo, SP, Brazil, Ryan B. MacDonaldUCL Institute of Ophthalmology and NIHR Moorfields Biomedical Research Centre, London, UK, Chen MakranzNeuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, Vivien I. MaltezDivision of Allergy, Immunology and Rheumatology, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA, Ryan V. MoriatyDepartment of Cellular and Developmental Biology, Northwestern University, Chicago, IL, USA, Juan M. Ocampo-GodinezLaboratorio de Bioingenieria de Tejidos, Departamento de Estudios de Posgrado e Investigacion, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico, Vitoria M. OlynthoMcMaster Immunology Research Centre, Schroeder Allergy and Immunology Research Institute, Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada, Kartika PadhanLymphocyte Biology Section and Center for Advanced Tissue Imaging, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Kirsten RemmertSurgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, Nathan RichozCambridge Institute for Therapeutic Immunology and Infectious Diseases, University of Cambridge Department of Medicine, Molecular Immunity Unit, Laboratory of Molecular Biology, Cambridge, UK, Edward C. SchromLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Wanjing ShangLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Lihong ShiLaboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Rochelle M. ShihLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Emily SperanzaFlorida Research and Innovation Center, Cleveland Clinic Lerner Research Institute, Port Saint Lucie, FL, USA, Salome StierliInstitute of Anatomy, University of Zurich, Zurich, Switzerland, Sarah A. TeichmannCambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge Biomedical Campus, Cambridge, UK, Tibor Z. VeresLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Megan VierhoutMcMaster Immunology Research Centre, Schroeder Allergy and Immunology Research Institute, Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada, Brianna T. WachterLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Adam K. Wade-VallanceLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Margaret WilliamsCritical Care Medicine and Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA, Nathan ZanggerInstitute of Microbiology, ETH Zurich, Zurich, Switzerland, Ronald N. GermainLymphocyte Biology Section and Center for Advanced Tissue Imaging, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA and Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, Ziv YanivBioinformatics and Computational Bioscience Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA","doi":"arxiv-2407.19059","DOIUrl":"https://doi.org/arxiv-2407.19059","url":null,"abstract":"Iterative Bleaching Extends multipleXity (IBEX) is a versatile method for\u0000highly multiplexed imaging of diverse tissues. Based on open science\u0000principles, we created the IBEX Knowledge-Base, a resource for reagents,\u0000protocols and more, to empower innovation.","PeriodicalId":501572,"journal":{"name":"arXiv - QuanBio - Tissues and Organs","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141870225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Quantifying variabilities in cardiac digital twin models of the electrocardiogram 量化心电图数字孪生模型的变异性
Pub Date : 2024-07-24 DOI: arxiv-2407.17146
Elena Zappon, Matthias A. F. Gsell, Karli Gillette, Gernot Plank
CDT of human cardiac EP are digital replicas of patient hearts that matchlike-for-like clinical observations. The ECG, as the most prevalent non-invasive observation of cardiacelectrophysiology, is considered an ideal target for CDT calibration. Recentadvanced CDT calibration methods have demonstrated their ability to minimizediscrepancies between simulated and measured ECG signals, effectivelyreplicating all key morphological features relevant to diagnostics. However,due to the inherent nature of clinical data acquisition and CDT modelgeneration pipelines, discrepancies inevitably arise between the real physicalelectrophysiology in a patient and the simulated virtual electrophysiology in aCDT. In this study, we aim to qualitatively and quantitatively analyze the impactof these uncertainties on ECG morphology and diagnostic markers. We analyzeresidual beat-to-beat variability in ECG recordings obtained from healthysubjects and patients. Using a biophysically detailed and anatomically accuratecomputational model of whole-heart electrophysiology combined with a detailedtorso model calibrated to closely replicate measured ECG signals, we varyanatomical factors (heart location, orientation, size), heterogeneity inelectrical conductivities in the heart and torso, and electrode placementsacross ECG leads to assess their qualitative impact on ECG morphology. Our study demonstrates that diagnostically relevant ECG features and overallmorphology appear relatively robust against the investigated uncertainties.This resilience is consistent with the narrow distribution of ECG due toresidual beat-to-beat variability observed in both healthy subjects andpatients.
人体心脏电生理 CDT 是病人心脏的数字复制品,与临床观察结果相似。心电图作为心电生理学最普遍的非侵入性观察指标,被认为是 CDT 校准的理想目标。最新的先进 CDT 校准方法已证明其有能力最大限度地减少模拟和测量心电信号之间的差异,有效地复制与诊断相关的所有关键形态特征。然而,由于临床数据采集和 CDT 模型生成管道的固有性质,患者的真实物理电生理学与 CDT 中模拟的虚拟电生理学之间不可避免地会出现差异。本研究旨在定性和定量分析这些不确定性对心电图形态和诊断指标的影响。我们分析了健康受试者和患者心电图记录中每一拍之间的残余变异性。我们使用生物物理上详细、解剖学上精确的全心电生理学计算模型,并结合详细的躯干模型进行校准,以密切复制测量的心电信号,我们改变了解剖学因素(心脏位置、方向、大小)、心脏和躯干电导率的异质性以及心电图导联的电极位置,以评估它们对心电图形态的定性影响。我们的研究表明,与诊断相关的心电图特征和整体形态在所调查的不确定性面前显得相对稳健。这种稳健性与在健康受试者和患者身上观察到的心电图因残留的节拍间变异性而造成的狭窄分布是一致的。
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引用次数: 0
Establishing Truly Causal Relationship Between Whole Slide Image Predictions and Diagnostic Evidence Subregions in Deep Learning 在深度学习中建立全切片图像预测与诊断证据子区域之间的真正因果关系
Pub Date : 2024-07-24 DOI: arxiv-2407.17157
Tianhang Nan, Yong Ding, Hao Quan, Deliang Li, Mingchen Zou, Xiaoyu Cui
In the field of deep learning-driven Whole Slide Image (WSI) classification,Multiple Instance Learning (MIL) has gained significant attention due to itsability to be trained using only slide-level diagnostic labels. Previous MILresearches have primarily focused on enhancing feature aggregators for globallyanalyzing WSIs, but overlook a causal relationship in diagnosis: model'sprediction should ideally stem solely from regions of the image that containdiagnostic evidence (such as tumor cells), which usually occupy relativelysmall areas. To address this limitation and establish the truly causalrelationship between model predictions and diagnostic evidence regions, wepropose Causal Inference Multiple Instance Learning (CI-MIL). CI-MIL integratesfeature distillation with a novel patch decorrelation mechanism, employing atwo-stage causal inference approach to distill and process patches with highdiagnostic value. Initially, CI-MIL leverages feature distillation to identifypatches likely containing tumor cells and extracts their corresponding featurerepresentations. These features are then mapped to random Fourier featurespace, where a learnable weighting scheme is employed to minimize inter-featurecorrelations, effectively reducing redundancy from homogenous patches andmitigating data bias. These processes strengthen the causal relationshipbetween model predictions and diagnostically relevant regions, making theprediction more direct and reliable. Experimental results demonstrate thatCI-MIL outperforms state-of-the-art methods. Additionally, CI-MIL exhibitssuperior interpretability, as its selected regions demonstrate high consistencywith ground truth annotations, promising more reliable diagnostic assistancefor pathologists.
在深度学习驱动的全切片图像(WSI)分类领域,多实例学习(MIL)因其仅使用切片级诊断标签就能进行训练而备受关注。以往的 MIL 研究主要集中在增强全局分析 WSI 的特征聚合器,但忽略了诊断中的因果关系:模型的预测最好只来自图像中包含诊断证据(如肿瘤细胞)的区域,而这些区域通常占据的面积相对较小。为了解决这一局限性,并在模型预测和诊断证据区域之间建立真正的因果关系,我们提出了因果推理多实例学习(CI-MIL)。CI-MIL 将特征提炼与新颖的斑块去相关性机制相结合,采用两阶段因果推理方法来提炼和处理具有高诊断价值的斑块。首先,CI-MIL 利用特征蒸馏来识别可能含有肿瘤细胞的斑块,并提取其相应的特征表示。然后将这些特征映射到随机傅立叶特征空间,在此采用可学习的加权方案来最小化特征间的相关性,从而有效减少同质斑块的冗余并减轻数据偏差。这些过程加强了模型预测与诊断相关区域之间的因果关系,使预测更加直接可靠。实验结果表明,CI-MIL 优于最先进的方法。此外,CI-MIL 还表现出更高的可解释性,因为其所选区域与地面实况注释高度一致,有望为病理学家提供更可靠的诊断帮助。
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引用次数: 0
Does EDPVR Represent Myocardial Tissue Stiffness? Toward a Better Definition EDPVR 是否代表心肌组织僵硬度?努力获得更好的定义
Pub Date : 2024-07-21 DOI: arxiv-2407.15254
Rana Raza Mehdi, Emilio A. Mendiola, Vahid Naeini, Gaurav Choudhary, Reza Avazmohammadi
Accurate assessment of myocardial tissue stiffness is pivotal for thediagnosis and prognosis of heart diseases. Left ventricular diastolic stiffness($beta$) obtained from the end-diastolic pressure-volume relationship (EDPVR)has conventionally been utilized as a representative metric of myocardialstiffness. The EDPVR can be employed to estimate the intrinsic stiffness ofmyocardial tissues through image-based in-silico inverse optimization. However,whether $beta$, as an organ-level metric, accurately represents thetissue-level myocardial tissue stiffness in healthy and diseased myocardiumremains elusive. We developed a modeling-based approach utilizing atwo-parameter material model for the myocardium (denoted by $a_f$ and $b_f$) inimage-based in-silico biventricular heart models to generate EDPVRs fordifferent material parameters. Our results indicated a variable relationshipbetween $beta$ and the material parameters depending on the range of theparameters. Interestingly, $beta$ showed a very low sensitivity to $a_f$, onceaveraged across several LV geometries, and even a negative correlation with$a_f$ for small values of $a_f$. These findings call for a critical assessmentof the reliability and confoundedness of EDPVR-derived metrics to representtissue-level myocardial stiffness. Our results also underscore the necessity toexplore image-based in-silico frameworks, promising to provide a high-fidelityand potentially non-invasive assessment of myocardial stiffness.
准确评估心肌组织僵硬度对心脏病的诊断和预后至关重要。从舒张末期压力-容积关系(EDPVR)中获得的左心室舒张僵硬度($beta$)一直被用作心肌僵硬度的代表性指标。EDPVR 可通过基于图像的室内反优化来估计心肌组织的内在刚度。然而,作为器官水平的指标,$beta$是否能准确代表健康和患病心肌的组织水平心肌组织僵硬度仍是一个未知数。我们开发了一种基于建模的方法,利用心肌的双参数材料模型(用 $a_f$ 和 $b_f$ 表示),在基于模拟的双心室心脏模型中生成不同材料参数的 EDPVR。我们的结果表明,$beta$与材料参数之间的关系因参数范围而异。有趣的是,$beta$对$a_f$的敏感性很低,一旦在几种LV几何形状中平均化,甚至在$a_f$值很小的情况下与$a_f$呈负相关。这些发现要求对 EDPVR 衍生的指标代表组织水平心肌僵硬度的可靠性和混杂性进行严格评估。我们的研究结果还强调了探索基于图像的硅内框架的必要性,该框架有望提供高保真和潜在的无创心肌僵硬度评估。
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引用次数: 0
Design, Fabrication, and Characterization of a User-Friendly Microfluidic Device for Studying Liver Zonation-on-Chip (ZoC) 设计、制造和表征用于研究肝脏片上分区(ZoC)的用户友好型微流控装置
Pub Date : 2024-07-17 DOI: arxiv-2407.12976
Reza Mahdavi, Sameereh Hashemi Najafabadi, Mohammad Adel Ghiass, Silmu Valaskivi, Hannu Välimäki, Joose Kreutzer, Charlotte Hamngren Blomqvist, Stefano Romeo, Pasi Kallio, Caroline Beck Adiels
Liver zonation is a fundamental characteristic of hepatocyte spatialheterogeneity, which is challenging to recapitulate in traditional cellcultures. This study presents a novel microfluidic device designed to inducezonation in liver cell cultures by establishing an oxygen gradient usingstandard laboratory gases. The device consists of two layers; a bottom layercontaining a gas channel network that delivers high and low oxygenated gases tocreate three distinct zones within the cell culture chamber in the layer above.Computational simulations and ratiometric oxygen sensing were employed tovalidate the oxygen gradient, demonstrating that stable oxygen levels wereachieved within two hours. Liver zonation was confirmed usingimmunofluorescence staining, which showed zonated albumin production in HepG2cells directly correlating with oxygen levels and mimicking in-vivo zonationbehavior. This user-friendly device supports studies on liver zonation andrelated metabolic disease mechanisms in vitro. It can also be utilized forexperiments that necessitate precise gas concentration gradients, such ashypoxia-related research areas focused on angiogenesis and cancer development.
肝分区是肝细胞空间异质性的一个基本特征,在传统细胞培养物中重现这一特征具有挑战性。本研究提出了一种新型微流控装置,旨在利用标准实验室气体建立氧梯度,从而诱导肝细胞培养物中的分带。该装置由两层组成;底层包含一个气体通道网络,可输送高氧和低氧气体,在上层的细胞培养箱中形成三个不同的区域。采用计算模拟和比率氧传感技术来确定氧梯度,结果表明在两小时内就能达到稳定的氧水平。使用免疫荧光染色法确认了肝脏分区,结果显示 HepG2 细胞中分区白蛋白的产生与氧水平直接相关,并模拟了体内分区行为。这种用户友好型设备支持体外肝脏分带和相关代谢疾病机制的研究。它还可用于需要精确气体浓度梯度的实验,例如与缺氧有关的、侧重于血管生成和癌症发展的研究领域。
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引用次数: 0
Emergence of cellular nematic order is a conserved feature of gastrulation in animal embryos 细胞线序的出现是动物胚胎胃形成的一个保守特征
Pub Date : 2024-07-16 DOI: arxiv-2407.12124
Xin Li, Robert J. Huebner, Margot L. K. Williams, Jessica Sawyer, Mark Peifer, John B. Wallingford, D. Thirumalai
Cells undergo dramatic changes in morphology during embryogenesis, yet howthese changes affect the formation of ordered tissues remains elusive. Here wefind that the emergence of a nematic liquid crystal phase occurs in cellsduring gastrulation in the development of embryos of fish, frogs, and fruitflies. Moreover, the spatial correlations in all three organisms arelong-ranged and follow a similar power-law decay (y~$x^{-alpha}$ ) with$alpha$ less than unity for the nematic order parameter, suggesting a commonunderlying physical mechanism unifies events in these distantly relatedspecies. All three species exhibit similar propagation of the nematic phase,reminiscent of nucleation and growth phenomena. Finally, we use a theoreticalmodel along with disruptions of cell adhesion and cell specification tocharacterize the minimal features required for formation of the nematic phase.Our results provide a framework for understanding a potentially universalfeatures of metazoan embryogenesis and shed light on the advent of orderedstructures during animal development.
细胞在胚胎发育过程中形态发生了巨大变化,但这些变化如何影响有序组织的形成仍是个谜。在这里,我们发现在鱼类、青蛙和果蝇的胚胎发育过程中,细胞中出现了向列液晶相。此外,所有这三种生物的空间相关性都是长范围的,并且遵循相似的幂律衰减(y~$x^{-alpha}$),向列阶次参数的$alpha$小于一,这表明在这些亲缘关系较远的物种中,有一种共同的基本物理机制将事件统一起来。所有三个物种都表现出类似的向列相传播,让人联想到成核和生长现象。最后,我们利用一个理论模型以及细胞粘附和细胞规格的破坏来描述形成向列相所需的最小特征。我们的结果为理解元古宙胚胎发生的潜在普遍特征提供了一个框架,并揭示了动物发育过程中有序结构的出现。
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引用次数: 0
期刊
arXiv - QuanBio - Tissues and Organs
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