Microfluidic technology has emerged as a powerful tool for studying complex biological processes with enhanced precision and control. A microfluidic chip was designed to emulate human-like microvascular networks with precise control over channel geometry and flow conditions. By simulating blood flow dynamics during bleeding events, we successfully observed the real-time interactions of platelets and their aggregation induced by shear rate gradient at the wound site. Platelet dynamics is primarily influenced by physico-mechanical condition of blood vessels with pathophysiological condition of blood at close proximity of vascular injury site. This microfluidic platform facilitated the investigation of platelet adhesion, activation, and clot formation, providing a unique opportunity to study the spatiotemporal dynamics of platelet aggregation and blood clot. Our findings shed light on the intricate mechanisms underlying thrombus formation and platelet-mediated aggregation, offering a more accurate and dynamic representation of human haemostasis compared to traditional animal models. In the conventional approach, the human bleeding model is tried on mouse 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 significant promise in advancing our understanding of clotting disorders and wound healing processes. Furthermore, it paves the way for targeted therapeutic interventions in managing bleeding disorders and enhancing clinical strategies for promoting efficient wound closure. Ultimately, this study demonstrates the potential of microfluidics to revolutionize haemostasis research and opens up new avenues for the development of personalized medicine approaches in the field of clotting disorders.
{"title":"Air-blood interface engineered microfluidic device to mimic shear rate gradient induced human bleeding model","authors":"Shobhit Das, Shilpi Pandey, Oliver Hayden","doi":"arxiv-2407.21356","DOIUrl":"https://doi.org/arxiv-2407.21356","url":null,"abstract":"Microfluidic technology has emerged as a powerful tool for studying complex\u0000biological processes with enhanced precision and control. A microfluidic chip\u0000was designed to emulate human-like microvascular networks with precise control\u0000over channel geometry and flow conditions. By simulating blood flow dynamics\u0000during bleeding events, we successfully observed the real-time interactions of\u0000platelets and their aggregation induced by shear rate gradient at the wound\u0000site. Platelet dynamics is primarily influenced by physico-mechanical condition\u0000of blood vessels with pathophysiological condition of blood at close proximity\u0000of vascular injury site. This microfluidic platform facilitated the\u0000investigation of platelet adhesion, activation, and clot formation, providing a\u0000unique opportunity to study the spatiotemporal dynamics of platelet aggregation\u0000and blood clot. Our findings shed light on the intricate mechanisms underlying\u0000thrombus formation and platelet-mediated aggregation, offering a more accurate\u0000and dynamic representation of human haemostasis compared to traditional animal\u0000models. In the conventional approach, the human bleeding model is tried on\u0000mouse due to anatomy and pathological similarities between mouse and humans.\u0000This study will simplify and standardize the blood and vasculature conditions.\u0000The microfluidic-based replication of the bleeding model holds significant\u0000promise in advancing our understanding of clotting disorders and wound healing\u0000processes. Furthermore, it paves the way for targeted therapeutic interventions\u0000in managing bleeding disorders and enhancing clinical strategies for promoting\u0000efficient wound closure. Ultimately, this study demonstrates the potential of\u0000microfluidics to revolutionize haemostasis research and opens up new avenues\u0000for the development of personalized medicine approaches in the field of\u0000clotting disorders.","PeriodicalId":501572,"journal":{"name":"arXiv - QuanBio - Tissues and Organs","volume":"74 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141873269","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}
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 nuclear targeting of drug delivery systems. However, the positively charged TAT peptide usually strongly interacts with serum components and undergoes substantial phagocytosis by the reticuloendothelial system, causing a short blood circulation in vivo. In this work, an acid-active tumor targeting nanoplatform DA-TAT-PECL was developed to effectively inhibit the nonspecific interactions of TAT in the bloodstream. 2,3-dimethylmaleic anhydride (DA) was first used to convert the TAT amines to carboxylic acid, the resulting DA-TAT was further conjugated to get DA-TAT-PECL. After self-assembly into polymeric micelles, they were capable of circulating in the physiological condition for a long time and promoting cell penetration upon accumulation at the tumor site and de-shielding the DA group. Moreover, camptothecin (CPT) was used as the anticancer drug and modified into a dimer (CPT)2-ss-Mal, in which two CPT molecules were connected by a reduction-labile maleimide thioether bond. The FRET signal between CPT and maleimide thioether bond was monitored to visualize the drug release process and effective targeted delivery of antitumor drugs was demonstrated. This pH/reduction dual-responsive micelle system provides a new platform 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。
{"title":"Dimeric Drug Polymeric Micelles with Acid-Active Tumor Targeting and FRET-indicated Drug Release","authors":"Xing Guo, Lin Wang, Kayla Duval, Jing Fan, Shaobing Zhou, Zi Chen","doi":"arxiv-2407.20538","DOIUrl":"https://doi.org/arxiv-2407.20538","url":null,"abstract":"Trans-activating transcriptional activator (TAT), a cell-penetrating peptide,\u0000has been extensively used for facilitating cellular uptake and nuclear\u0000targeting of drug delivery systems. However, the positively charged TAT peptide\u0000usually strongly interacts with serum components and undergoes substantial\u0000phagocytosis by the reticuloendothelial system, causing a short blood\u0000circulation in vivo. In this work, an acid-active tumor targeting nanoplatform\u0000DA-TAT-PECL was developed to effectively inhibit the nonspecific interactions\u0000of TAT in the bloodstream. 2,3-dimethylmaleic anhydride (DA) was first used to\u0000convert the TAT amines to carboxylic acid, the resulting DA-TAT was further\u0000conjugated to get DA-TAT-PECL. After self-assembly into polymeric micelles,\u0000they were capable of circulating in the physiological condition for a long time\u0000and promoting cell penetration upon accumulation at the tumor site and\u0000de-shielding the DA group. Moreover, camptothecin (CPT) was used as the\u0000anticancer drug and modified into a dimer (CPT)2-ss-Mal, in which two CPT\u0000molecules were connected by a reduction-labile maleimide thioether bond. The\u0000FRET signal between CPT and maleimide thioether bond was monitored to visualize\u0000the drug release process and effective targeted delivery of antitumor drugs was\u0000demonstrated. This pH/reduction dual-responsive micelle system provides a new\u0000platform for high fidelity cancer therapy.","PeriodicalId":501572,"journal":{"name":"arXiv - QuanBio - Tissues and Organs","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141870224","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}
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 in histopathology and large-scale epidemiologic studies by allowing multiple tissue cores to be scanned on a single slide. The individual cores can be digitally extracted and then linked to metadata for analysis in a process known as de-arraying. However, TMAs often contain core misalignments and artifacts due to assembly errors, which can adversely affect the reliability of the extracted cores during the de-arraying process. Moreover, conventional approaches for TMA de-arraying rely on desktop solutions.Therefore, a robust yet flexible de-arraying method is crucial to account for these inaccuracies and ensure effective downstream analyses. Results: We developed TMA-Grid, an in-browser, zero-footprint, interactive web application for TMA de-arraying. This web application integrates a convolutional neural network for precise tissue segmentation and a grid estimation algorithm to match each identified core to its expected location. The application emphasizes interactivity, allowing users to easily adjust segmentation and gridding results. Operating entirely in the web-browser, TMA-Grid eliminates the need for downloads or installations and ensures data privacy. Adhering to FAIR principles (Findable, Accessible, Interoperable, and Reusable), the application and its components are designed for seamless integration into TMA research workflows. Conclusions: TMA-Grid provides a robust, user-friendly solution for TMA dearraying on the web. As an open, freely accessible platform, it lays the foundation for collaborative 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
{"title":"TMA-Grid: An open-source, zero-footprint web application for FAIR Tissue MicroArray De-arraying","authors":"Aaron Ge, Monjoy Saha, Maire A. Duggan, Petra Lenz, Mustapha Abubakar, Montserrat García-Closas, Jeya Balasubramanian, Jonas S. Almeida, Praphulla MS Bhawsar","doi":"arxiv-2407.21233","DOIUrl":"https://doi.org/arxiv-2407.21233","url":null,"abstract":"Background: Tissue Microarrays (TMAs) significantly increase analytical efficiency in\u0000histopathology and large-scale epidemiologic studies by allowing multiple\u0000tissue cores to be scanned on a single slide. The individual cores can be\u0000digitally extracted and then linked to metadata for analysis in a process known\u0000as de-arraying. However, TMAs often contain core misalignments and artifacts\u0000due to assembly errors, which can adversely affect the reliability of the\u0000extracted cores during the de-arraying process. Moreover, conventional\u0000approaches for TMA de-arraying rely on desktop solutions.Therefore, a robust\u0000yet flexible de-arraying method is crucial to account for these inaccuracies\u0000and ensure effective downstream analyses. Results: We developed TMA-Grid, an in-browser, zero-footprint, interactive web\u0000application for TMA de-arraying. This web application integrates a\u0000convolutional neural network for precise tissue segmentation and a grid\u0000estimation algorithm to match each identified core to its expected location.\u0000The application emphasizes interactivity, allowing users to easily adjust\u0000segmentation and gridding results. Operating entirely in the web-browser,\u0000TMA-Grid eliminates the need for downloads or installations and ensures data\u0000privacy. Adhering to FAIR principles (Findable, Accessible, Interoperable, and\u0000Reusable), the application and its components are designed for seamless\u0000integration into TMA research workflows. Conclusions: TMA-Grid provides a robust, user-friendly solution for TMA dearraying on the\u0000web. As an open, freely accessible platform, it lays the foundation for\u0000collaborative analyses of TMAs and similar histopathology imaging data.\u0000Availability: Web application: https://episphere.github.io/tma-grid Code:\u0000https://github.com/episphere/tma-grid Tutorial: https://youtu.be/miajqyw4BVk","PeriodicalId":501572,"journal":{"name":"arXiv - QuanBio - Tissues and Organs","volume":"213 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141870105","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}
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 on solving task-specific problems, there is a need for general-purpose systems that can understand surgical scenes and interact through natural language. This paper introduces GP-VLS, a general-purpose vision language model for surgery that integrates medical and surgical knowledge with visual scene understanding. For comprehensively evaluating general-purpose surgical models, we propose SurgiQual, which evaluates across medical and surgical knowledge benchmarks as well as surgical vision-language questions. To train GP-VLS, we develop six new datasets spanning medical knowledge, surgical textbooks, and vision-language pairs for tasks like phase recognition and tool identification. We show that GP-VLS significantly outperforms existing open- and closed-source models on surgical vision-language tasks, with 8-21% improvements in accuracy across SurgiQual benchmarks. GP-VLS also demonstrates strong performance on medical and surgical knowledge tests compared to open-source alternatives. Overall, GP-VLS provides an open-source foundation for developing AI assistants to support surgeons across a wide range of tasks and scenarios.
{"title":"GP-VLS: A general-purpose vision language model for surgery","authors":"Samuel Schmidgall, Joseph Cho, Cyril Zakka, William Hiesinger","doi":"arxiv-2407.19305","DOIUrl":"https://doi.org/arxiv-2407.19305","url":null,"abstract":"Surgery requires comprehensive medical knowledge, visual assessment skills,\u0000and procedural expertise. While recent surgical AI models have focused on\u0000solving task-specific problems, there is a need for general-purpose systems\u0000that can understand surgical scenes and interact through natural language. This\u0000paper introduces GP-VLS, a general-purpose vision language model for surgery\u0000that integrates medical and surgical knowledge with visual scene understanding.\u0000For comprehensively evaluating general-purpose surgical models, we propose\u0000SurgiQual, which evaluates across medical and surgical knowledge benchmarks as\u0000well as surgical vision-language questions. To train GP-VLS, we develop six new\u0000datasets spanning medical knowledge, surgical textbooks, and vision-language\u0000pairs for tasks like phase recognition and tool identification. We show that\u0000GP-VLS significantly outperforms existing open- and closed-source models on\u0000surgical vision-language tasks, with 8-21% improvements in accuracy across\u0000SurgiQual benchmarks. GP-VLS also demonstrates strong performance on medical\u0000and surgical knowledge tests compared to open-source alternatives. Overall,\u0000GP-VLS provides an open-source foundation for developing AI assistants to\u0000support surgeons across a wide range of tasks and scenarios.","PeriodicalId":501572,"journal":{"name":"arXiv - QuanBio - Tissues and Organs","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141870226","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}
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 for highly multiplexed imaging of diverse tissues. Based on open science principles, we created the IBEX Knowledge-Base, a resource for reagents, protocols and more, to empower innovation.
{"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":"77 1","pages":""},"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}
Elena Zappon, Matthias A. F. Gsell, Karli Gillette, Gernot Plank
CDT of human cardiac EP are digital replicas of patient hearts that match like-for-like clinical observations. The ECG, as the most prevalent non-invasive observation of cardiac electrophysiology, is considered an ideal target for CDT calibration. Recent advanced CDT calibration methods have demonstrated their ability to minimize discrepancies between simulated and measured ECG signals, effectively replicating all key morphological features relevant to diagnostics. However, due to the inherent nature of clinical data acquisition and CDT model generation pipelines, discrepancies inevitably arise between the real physical electrophysiology in a patient and the simulated virtual electrophysiology in a CDT. In this study, we aim to qualitatively and quantitatively analyze the impact of these uncertainties on ECG morphology and diagnostic markers. We analyze residual beat-to-beat variability in ECG recordings obtained from healthy subjects and patients. Using a biophysically detailed and anatomically accurate computational model of whole-heart electrophysiology combined with a detailed torso model calibrated to closely replicate measured ECG signals, we vary anatomical factors (heart location, orientation, size), heterogeneity in electrical conductivities in the heart and torso, and electrode placements across ECG leads to assess their qualitative impact on ECG morphology. Our study demonstrates that diagnostically relevant ECG features and overall morphology appear relatively robust against the investigated uncertainties. This resilience is consistent with the narrow distribution of ECG due to residual beat-to-beat variability observed in both healthy subjects and patients.
{"title":"Quantifying variabilities in cardiac digital twin models of the electrocardiogram","authors":"Elena Zappon, Matthias A. F. Gsell, Karli Gillette, Gernot Plank","doi":"arxiv-2407.17146","DOIUrl":"https://doi.org/arxiv-2407.17146","url":null,"abstract":"CDT of human cardiac EP are digital replicas of patient hearts that match\u0000like-for-like clinical observations. The ECG, as the most prevalent non-invasive observation of cardiac\u0000electrophysiology, is considered an ideal target for CDT calibration. Recent\u0000advanced CDT calibration methods have demonstrated their ability to minimize\u0000discrepancies between simulated and measured ECG signals, effectively\u0000replicating all key morphological features relevant to diagnostics. However,\u0000due to the inherent nature of clinical data acquisition and CDT model\u0000generation pipelines, discrepancies inevitably arise between the real physical\u0000electrophysiology in a patient and the simulated virtual electrophysiology in a\u0000CDT. In this study, we aim to qualitatively and quantitatively analyze the impact\u0000of these uncertainties on ECG morphology and diagnostic markers. We analyze\u0000residual beat-to-beat variability in ECG recordings obtained from healthy\u0000subjects and patients. Using a biophysically detailed and anatomically accurate\u0000computational model of whole-heart electrophysiology combined with a detailed\u0000torso model calibrated to closely replicate measured ECG signals, we vary\u0000anatomical factors (heart location, orientation, size), heterogeneity in\u0000electrical conductivities in the heart and torso, and electrode placements\u0000across ECG leads to assess their qualitative impact on ECG morphology. Our study demonstrates that diagnostically relevant ECG features and overall\u0000morphology appear relatively robust against the investigated uncertainties.\u0000This resilience is consistent with the narrow distribution of ECG due to\u0000residual beat-to-beat variability observed in both healthy subjects and\u0000patients.","PeriodicalId":501572,"journal":{"name":"arXiv - QuanBio - Tissues and Organs","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141771812","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}
In the field of deep learning-driven Whole Slide Image (WSI) classification, Multiple Instance Learning (MIL) has gained significant attention due to its ability to be trained using only slide-level diagnostic labels. Previous MIL researches have primarily focused on enhancing feature aggregators for globally analyzing WSIs, but overlook a causal relationship in diagnosis: model's prediction should ideally stem solely from regions of the image that contain diagnostic evidence (such as tumor cells), which usually occupy relatively small areas. To address this limitation and establish the truly causal relationship between model predictions and diagnostic evidence regions, we propose Causal Inference Multiple Instance Learning (CI-MIL). CI-MIL integrates feature distillation with a novel patch decorrelation mechanism, employing a two-stage causal inference approach to distill and process patches with high diagnostic value. Initially, CI-MIL leverages feature distillation to identify patches likely containing tumor cells and extracts their corresponding feature representations. These features are then mapped to random Fourier feature space, where a learnable weighting scheme is employed to minimize inter-feature correlations, effectively reducing redundancy from homogenous patches and mitigating data bias. These processes strengthen the causal relationship between model predictions and diagnostically relevant regions, making the prediction more direct and reliable. Experimental results demonstrate that CI-MIL outperforms state-of-the-art methods. Additionally, CI-MIL exhibits superior interpretability, as its selected regions demonstrate high consistency with ground truth annotations, promising more reliable diagnostic assistance for 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。
{"title":"Establishing Truly Causal Relationship Between Whole Slide Image Predictions and Diagnostic Evidence Subregions in Deep Learning","authors":"Tianhang Nan, Yong Ding, Hao Quan, Deliang Li, Mingchen Zou, Xiaoyu Cui","doi":"arxiv-2407.17157","DOIUrl":"https://doi.org/arxiv-2407.17157","url":null,"abstract":"In the field of deep learning-driven Whole Slide Image (WSI) classification,\u0000Multiple Instance Learning (MIL) has gained significant attention due to its\u0000ability to be trained using only slide-level diagnostic labels. Previous MIL\u0000researches have primarily focused on enhancing feature aggregators for globally\u0000analyzing WSIs, but overlook a causal relationship in diagnosis: model's\u0000prediction should ideally stem solely from regions of the image that contain\u0000diagnostic evidence (such as tumor cells), which usually occupy relatively\u0000small areas. To address this limitation and establish the truly causal\u0000relationship between model predictions and diagnostic evidence regions, we\u0000propose Causal Inference Multiple Instance Learning (CI-MIL). CI-MIL integrates\u0000feature distillation with a novel patch decorrelation mechanism, employing a\u0000two-stage causal inference approach to distill and process patches with high\u0000diagnostic value. Initially, CI-MIL leverages feature distillation to identify\u0000patches likely containing tumor cells and extracts their corresponding feature\u0000representations. These features are then mapped to random Fourier feature\u0000space, where a learnable weighting scheme is employed to minimize inter-feature\u0000correlations, effectively reducing redundancy from homogenous patches and\u0000mitigating data bias. These processes strengthen the causal relationship\u0000between model predictions and diagnostically relevant regions, making the\u0000prediction more direct and reliable. Experimental results demonstrate that\u0000CI-MIL outperforms state-of-the-art methods. Additionally, CI-MIL exhibits\u0000superior interpretability, as its selected regions demonstrate high consistency\u0000with ground truth annotations, promising more reliable diagnostic assistance\u0000for pathologists.","PeriodicalId":501572,"journal":{"name":"arXiv - QuanBio - Tissues and Organs","volume":"67 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141771811","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}
Rana Raza Mehdi, Emilio A. Mendiola, Vahid Naeini, Gaurav Choudhary, Reza Avazmohammadi
Accurate assessment of myocardial tissue stiffness is pivotal for the diagnosis 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 myocardial stiffness. The EDPVR can be employed to estimate the intrinsic stiffness of myocardial tissues through image-based in-silico inverse optimization. However, whether $beta$, as an organ-level metric, accurately represents the tissue-level myocardial tissue stiffness in healthy and diseased myocardium remains elusive. We developed a modeling-based approach utilizing a two-parameter material model for the myocardium (denoted by $a_f$ and $b_f$) in image-based in-silico biventricular heart models to generate EDPVRs for different material parameters. Our results indicated a variable relationship between $beta$ and the material parameters depending on the range of the parameters. Interestingly, $beta$ showed a very low sensitivity to $a_f$, once averaged across several LV geometries, and even a negative correlation with $a_f$ for small values of $a_f$. These findings call for a critical assessment of the reliability and confoundedness of EDPVR-derived metrics to represent tissue-level myocardial stiffness. Our results also underscore the necessity to explore image-based in-silico frameworks, promising to provide a high-fidelity and potentially non-invasive assessment of myocardial stiffness.
{"title":"Does EDPVR Represent Myocardial Tissue Stiffness? Toward a Better Definition","authors":"Rana Raza Mehdi, Emilio A. Mendiola, Vahid Naeini, Gaurav Choudhary, Reza Avazmohammadi","doi":"arxiv-2407.15254","DOIUrl":"https://doi.org/arxiv-2407.15254","url":null,"abstract":"Accurate assessment of myocardial tissue stiffness is pivotal for the\u0000diagnosis and prognosis of heart diseases. Left ventricular diastolic stiffness\u0000($beta$) obtained from the end-diastolic pressure-volume relationship (EDPVR)\u0000has conventionally been utilized as a representative metric of myocardial\u0000stiffness. The EDPVR can be employed to estimate the intrinsic stiffness of\u0000myocardial tissues through image-based in-silico inverse optimization. However,\u0000whether $beta$, as an organ-level metric, accurately represents the\u0000tissue-level myocardial tissue stiffness in healthy and diseased myocardium\u0000remains elusive. We developed a modeling-based approach utilizing a\u0000two-parameter material model for the myocardium (denoted by $a_f$ and $b_f$) in\u0000image-based in-silico biventricular heart models to generate EDPVRs for\u0000different material parameters. Our results indicated a variable relationship\u0000between $beta$ and the material parameters depending on the range of the\u0000parameters. Interestingly, $beta$ showed a very low sensitivity to $a_f$, once\u0000averaged across several LV geometries, and even a negative correlation with\u0000$a_f$ for small values of $a_f$. These findings call for a critical assessment\u0000of the reliability and confoundedness of EDPVR-derived metrics to represent\u0000tissue-level myocardial stiffness. Our results also underscore the necessity to\u0000explore image-based in-silico frameworks, promising to provide a high-fidelity\u0000and potentially non-invasive assessment of myocardial stiffness.","PeriodicalId":501572,"journal":{"name":"arXiv - QuanBio - Tissues and Organs","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141771813","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}
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 spatial heterogeneity, which is challenging to recapitulate in traditional cell cultures. This study presents a novel microfluidic device designed to induce zonation in liver cell cultures by establishing an oxygen gradient using standard laboratory gases. The device consists of two layers; a bottom layer containing a gas channel network that delivers high and low oxygenated gases to create three distinct zones within the cell culture chamber in the layer above. Computational simulations and ratiometric oxygen sensing were employed to validate the oxygen gradient, demonstrating that stable oxygen levels were achieved within two hours. Liver zonation was confirmed using immunofluorescence staining, which showed zonated albumin production in HepG2 cells directly correlating with oxygen levels and mimicking in-vivo zonation behavior. This user-friendly device supports studies on liver zonation and related metabolic disease mechanisms in vitro. It can also be utilized for experiments that necessitate precise gas concentration gradients, such as hypoxia-related research areas focused on angiogenesis and cancer development.
{"title":"Design, Fabrication, and Characterization of a User-Friendly Microfluidic Device for Studying Liver Zonation-on-Chip (ZoC)","authors":"Reza Mahdavi, Sameereh Hashemi Najafabadi, Mohammad Adel Ghiass, Silmu Valaskivi, Hannu Välimäki, Joose Kreutzer, Charlotte Hamngren Blomqvist, Stefano Romeo, Pasi Kallio, Caroline Beck Adiels","doi":"arxiv-2407.12976","DOIUrl":"https://doi.org/arxiv-2407.12976","url":null,"abstract":"Liver zonation is a fundamental characteristic of hepatocyte spatial\u0000heterogeneity, which is challenging to recapitulate in traditional cell\u0000cultures. This study presents a novel microfluidic device designed to induce\u0000zonation in liver cell cultures by establishing an oxygen gradient using\u0000standard laboratory gases. The device consists of two layers; a bottom layer\u0000containing a gas channel network that delivers high and low oxygenated gases to\u0000create three distinct zones within the cell culture chamber in the layer above.\u0000Computational simulations and ratiometric oxygen sensing were employed to\u0000validate the oxygen gradient, demonstrating that stable oxygen levels were\u0000achieved within two hours. Liver zonation was confirmed using\u0000immunofluorescence staining, which showed zonated albumin production in HepG2\u0000cells directly correlating with oxygen levels and mimicking in-vivo zonation\u0000behavior. This user-friendly device supports studies on liver zonation and\u0000related metabolic disease mechanisms in vitro. It can also be utilized for\u0000experiments that necessitate precise gas concentration gradients, such as\u0000hypoxia-related research areas focused on angiogenesis and cancer development.","PeriodicalId":501572,"journal":{"name":"arXiv - QuanBio - Tissues and Organs","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141742639","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}
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 how these changes affect the formation of ordered tissues remains elusive. Here we find that the emergence of a nematic liquid crystal phase occurs in cells during gastrulation in the development of embryos of fish, frogs, and fruit flies. Moreover, the spatial correlations in all three organisms are long-ranged and follow a similar power-law decay (y~$x^{-alpha}$ ) with $alpha$ less than unity for the nematic order parameter, suggesting a common underlying physical mechanism unifies events in these distantly related species. All three species exhibit similar propagation of the nematic phase, reminiscent of nucleation and growth phenomena. Finally, we use a theoretical model along with disruptions of cell adhesion and cell specification to characterize the minimal features required for formation of the nematic phase. Our results provide a framework for understanding a potentially universal features of metazoan embryogenesis and shed light on the advent of ordered structures during animal development.
{"title":"Emergence of cellular nematic order is a conserved feature of gastrulation in animal embryos","authors":"Xin Li, Robert J. Huebner, Margot L. K. Williams, Jessica Sawyer, Mark Peifer, John B. Wallingford, D. Thirumalai","doi":"arxiv-2407.12124","DOIUrl":"https://doi.org/arxiv-2407.12124","url":null,"abstract":"Cells undergo dramatic changes in morphology during embryogenesis, yet how\u0000these changes affect the formation of ordered tissues remains elusive. Here we\u0000find that the emergence of a nematic liquid crystal phase occurs in cells\u0000during gastrulation in the development of embryos of fish, frogs, and fruit\u0000flies. Moreover, the spatial correlations in all three organisms are\u0000long-ranged and follow a similar power-law decay (y~$x^{-alpha}$ ) with\u0000$alpha$ less than unity for the nematic order parameter, suggesting a common\u0000underlying physical mechanism unifies events in these distantly related\u0000species. All three species exhibit similar propagation of the nematic phase,\u0000reminiscent of nucleation and growth phenomena. Finally, we use a theoretical\u0000model along with disruptions of cell adhesion and cell specification to\u0000characterize the minimal features required for formation of the nematic phase.\u0000Our results provide a framework for understanding a potentially universal\u0000features of metazoan embryogenesis and shed light on the advent of ordered\u0000structures during animal development.","PeriodicalId":501572,"journal":{"name":"arXiv - QuanBio - Tissues and Organs","volume":"50 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141742640","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}