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Deconstructing the ISTH hemophilia guidelines for the clinician

Journal of thrombosis and haemostasis : JTH 2025年第5期23卷 1483-1495页

作者： Young, Guy Lassila, Riitta Mason, Jane Prasca, Saskia Cancer and Blood Disorders Institute Children's Hospital Los Angeles University of Southern California Keck School of Medicine Los Angeles CA United States HUS Helsinki University Hospital Coagulation Disorders Unit Dept Hematology Comprehensive Cancer Center Helsinki Finland University of Helsinki Research Program Unit in Systems Oncology Helsinki Finland Queensland Haemophilia Centre Cancer Care Services Royal Brisbane and Women's Hospital Brisbane Australia University of Queensland School of Medicine and Department of Haematology and Haemophilia QLD Children's Hospital Brisbane Australia Medicarte IPS National Comprehensive Hemophilia Treatment Center Medellin Colombia

Recently, the International Society on Thrombosis and Haemostasis (ISTH) Hemophilia Guidelines were published in this journal. The authors of these guidelines should be commended for a herculean task that took years to complete, and while this is no doubt a welcome addition to the literature, it does leave many questions for the clinician. This is primarily because 11 of the 13 recommendations are conditional, essentially meaning "that clinicians and patients need to consider individual preferences as well as the specific circumstances in which the decision is being made for implementation of the recommendation." So, in essence, most of the recommendations allow the clinician to decide whether to use them or not. In our view, most clinicians are seeking more concrete recommendations when they search for a guidelines paper. Unfortunately, numerous conditional recommendations have been developed because hemophilia is a rare disease and the ISTH Guidelines rely upon the Grading of Recommendations, Assessment, Development, and Evaluation methodology. We endeavored to "deconstruct" the ISTH recommendations and offer clinicians a more concrete path forward based in part on the guidelines but supplemented with more recent literature and our own extensive experience and perspective managing hemophilia patients of all ages from 4 continents. Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.

关键词： emicizumab guidelines hemophilia therapy

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H&E image analysis pipeline for quantifying morphological features

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Journal of Pathology Informatics 2023年 14卷 100339-100339页

作者： Ariotta, Valeria Lehtonen, Oskari Salloum, Shams Micoli, Giulia Lavikka, Kari Rantanen, Ville Hynninen, Johanna Virtanen, Anni Hautaniemi, Sampsa Research Program in Systems Oncology Research Programs Unit Faculty of Medicine University of Helsinki Helsinki 00014 Finland Department of Obstetrics and Gynaecology University of Turku and Turku University Hospital Turku 200521 Finland Department of Pathology University of Helsinki and HUS Diagnostic Center Helsinki University Hospital Helsinki 00029 Finland

Detecting cell types from histopathological images is essential for various digital pathology applications. However, large number of cells in whole-slide images (WSIs) necessitates automated analysis pipelines for efficient cell type detection. Herein, we present hematoxylin and eosin (H&E) Image Processing pipeline (HEIP) for automatied analysis of scanned H&E-stained slides. HEIP is a flexible and modular open-source software that performs preprocessing, instance segmentation, and nuclei feature extraction. To evaluate the performance of HEIP, we applied it to extract cell types from ovarian high-grade serous carcinoma (HGSC) patient WSIs. HEIP showed high precision in instance segmentation, particularly for neoplastic and epithelial cells. We also show that there is a significant correlation between genomic ploidy values and morphological features, such as major axis of the nucleus. © 2023 The Authors

关键词： Digital pathology Feature extraction Instance segmentation Ovarian high-grade serous carcinoma Ploidy Whole-slide images

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Aberrant glycosylation of α3 integrins as diagnostic markers in epithelial ovarian cancer

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Clinica Chimica Acta 2023年第1期543卷 117323页

作者： Jain, Shruti Parimelazhagan Santhi, Priyadharshini Vinod, Rufus Afrin Ruma, Shamima Huhtinen, Kaisa Pettersson, Kim Sundfeldt, Karin Leivo, Janne Gidwani, Kamlesh Department of Life Technologies and FICAN West Cancer Centre University of Turku Turku 20520 Finland Institute of Biomedicine and FICAN West Cancer Centre University of Turku and Turku University Hospital Turku Finland. Research Program in Systems Oncology Research Programs Unit Faculty of Medicine University of Helsinki Helsinki Finland Department of Obstetrics and Gynecology Institute of Clinical Sciences Sahlgrenska Center for Cancer Research University of Gothenburg Gothenburg Sweden

Background: Glycans are strongly involved in stability and function of integrins (ITG) and tetraspanin protein CD63 and their respective interaction partners as they are dysregulated in the tumorigenic processes. Glycosylation changes is a universal phenomenon of cancer cells. In this study, glycosylation changes in epithelial ovarian cancer (EOC) are explored using tetraspanin and integrin molecules. Methods: ITG and CD63 were immobilized from 10 EOC and 5 benign ovarian cyst fluid on microtiter wells and traced with 3 glycan binding proteins (STn, WGA, UEA) conjugated on europium nanoparticles. Total protein measurements (ITG & CD63 immunoassays) were also performed. The most promising glycovariant candidates identified were then clinically evaluated on the whole cohort of 77 ovarian cyst fluids. Additional testing was performed in ascites fluid samples of liver cirrhosis (n = 2) and EOC (n = 4). Results: Sialylated Tn antibody based glycovariants of ITGα3 (ITGα3^STn) and CD63 (CD63^STn) performed better than corresponding protein epitope-based immunoassays, ITGα3^IA and CD63^IA respectively. Combined ITGα3 based assays (ITGα3^IA + ITGα3^STn) detected 49 out of 55 malignant & borderline cases without detecting any of the 22 benign and healthy cysts. Conclusion: Our findings indicate the potential diagnostic application of ITGα3^STn along with total ITGα3^IA, which could help reduce the unnecessary surgeries. The results encourage studying further the potential use of these novel assays to detect EOC at earlier clinical stages. © 2023 The Author(s)

关键词： CD63 Diagnosis Epithelial ovarian cancer Integrin STn

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Genome-Wide Association Study Reveals Novel Associations of Annexin A13 to Secretory and GAS2L2 with Mucous Otitis Media

Research Square

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research Square 2024年

作者： Bizaki-Vallaskangas, Argyro Rämö, Joel Sliz, Eeva Kivekäs, Ilkka Willberg, Tytti Saarentaus, Elmo Tolppila-Salmi, Sanna Dietz, Aarno Haapaniemi, Teppo Hytönen, Vesa Toivola, Sari Palotie, Aarno Mäkitie, Antti Kettunen, Johannes Department of Otolaryngology Faculty of Medicine and Health Technology Tampere University Tampere Finland Institute for Molecular Medicine Finland The Helsinki Institute of Life Science University of Helsinki Helsinki Finland Biocenter Oulu The Research Unit of Population Health University of Oulu Oulu Finland Department of Otolaryngology Turku University Hospital Turku Finland Department of Otolaryngology University of Eastern Finland Kuopio Finland Fimlab Laboratories Tampere Finland The Stanley Center for Psychiatric Research Program in Medical and Population Genetics The Broad Institute of MIT and Harvard CambridgeMA United States Analytic and Translational Genetics Unit Department of Medicine Department of Neurology Department of Psychiatry Massachusetts General Hospital BostonMA United States Department of Otorhinolaryngology – Head and Neck Surgery Helsinki University Hospital University of Helsinki Helsinki Finland Research Program in Systems Oncology Faculty of Medicine University of Helsinki Helsinki Finland

Purpose: To evaluate the genetics of chronic non-suppurative otitis media (OM). Methods: We performed a genome-wide association study of 429,599 individuals included in the FinnGen study using three different case definitions: any type of chronic non-suppurative OM (7,034 cases), mucous chronic OM (5,953 cases), and secretory chronic OM (1,689 cases). Individuals without otitis media were used as controls (417,745 controls). We used immunohistochemistry of the murine middle ear to evaluate the expression of annexin A13. Results: Four loci were significantly associated (p © 2024, CC BY.

关键词： Phospholipids

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The presence of herpesviruses in malignant but not in benign or recurrent pleomorphic adenomas

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Tumor Biology 2021年第1期43卷 249-259页

作者： Jauhiainen, Maria K. Xu, Man Pyoria, Lari Atula, Timo Aro, Katri Markkanen, Anttoni Haglund, Caj Hagstrom, Jaana Makitie, Antti A. Soderlund-Venermo, Maria Sinkkonen, Saku T. Department of Otorhinolaryngology - Head and Neck Surgery Helsinki University Hospital and University of Helsinki Helsinki Finland Department of Virology University of Helsinki Helsinki Finland Research Program in Systems Oncology Faculty of Medicine University of Helsinki Helsinki Finland Department of Pathology Helsinki and Turku University Hospital of Helsinki and Turku Finland Translational Cancer Medicine Research Programs Unit Faculty of Medicine University of Helsinki Helsinki Finland Department of Surgery Helsinki University Hospital and University of Helsinki Helsinki Finland Department of Oral Pathology and Radiology University of Turku Turku Finland

BACKGROUND: The etiology of salivary gland tumors is mainly unknown. The anatomical location of the salivary glands, with the mucosal pathway to the oral cavity and its rich microbiome, raises the question of potential viral background. OBJECTIVE: This study focuses on the potential presence of herpes-, polyoma- and parvoviruses in pleomorphic adenoma (PA), recurrent pleomorphic adenoma (RPA) and carcinoma ex pleomorphic adenoma (CaxPA). METHODS: Thirty different viruses were analyzed by PCR-based assays in 68 formalin-fixed paraffin-embedded salivary gland tumors (25 PA, 31 RPA and 12 CaxPA). RESULTS: Virus DNA was detected altogether in 19/68 (28%) tumor samples. Human herpesviruses 6B and 7 (HHV-6B and HHV-7) and Epstein-Barr virus (EBV) were frequently and almost exclusively found in CaxPA (5/12, 7/12, and 3/12, respectively). Within the 7 CaxPA that were virus-positive, 3 samples contained 3, and 1 sample even 4, different viruses. Infrequent viral positivity was shown for parvovirus B19 and cutavirus, as well as Merkel cell and Malawi polyomaviruses. CONCLUSIONS: Our unexpected finding of herpesvirus DNA almost exclusively in CaxPA tissues deserves further in-depth studies. © 2021-The authors. Published by IOS Press.

关键词： carcinoma ex pleomorphic adenoma herpesvirus Pleomorphic adenoma recurrent pleomorphic adenoma viral etiology

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Corrigendum to "Time to act! - A cross-sectional study on how nutritional risk increases during hospitalization and associates with worse" published in Clinical Nutrition ESPEN 2023 Oct;57:364-374

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Clinical nutrition ESPEN 2023年 58卷 421-423页

作者： Helena Orell Anne Pohju Jetta Tuokkola Kristiina Junttila Anniina Heikkilä Pia Österlund Ursula Schwab Antti Mäkitie Clinical Nutrition Unit Internal Medicine and Rehabilitation University of Helsinki and Helsinki University Hospital Helsinki Finland. Electronic address: helena.orell@hus.fi. Clinical Nutrition Unit Internal Medicine and Rehabilitation University of Helsinki and Helsinki University Hospital Helsinki Finland. Clinical Nutrition Unit Internal Medicine and Rehabilitation University of Helsinki and Helsinki University Hospital Helsinki Finland School for Medicine Institute of Public Health and Clinical Nutrition University of Eastern Finland and Department of Medicine Endocrinology and Clinical Nutrition Kuopio University Hospital Kuopio Finland. Nursing Research Center University of Helsinki and Helsinki University Hospital Helsinki Finland. HUS Nursing Administrative Group University of Helsinki and Helsinki University Hospital Helsinki Finland. Department of Oncology Tampere University Hospital and University of Tampere Tampere Finland Department of Oncology Helsinki University Hospital and University of Helsinki Helsinki Finland Department of Oncology/Pathology Karolinska Institute and Tema Cancer/ GI-cancer Karolinska University Hospital Stockholm Sweden. School for Medicine Institute of Public Health and Clinical Nutrition University of Eastern Finland and Department of Medicine Endocrinology and Clinical Nutrition Kuopio University Hospital Kuopio Finland. Department of Otorhinolaryngology - Head and Neck Surgery Helsinki University Hospital and University of Helsinki Helsinki Finland Research Program in Systems Oncology Faculty of Medicine University of Helsinki Helsinki Finland.

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The proteogenomic subtypes of acute myeloid leukemia

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Cancer Cell 2022年第3期40卷 301-317.e12页

作者： Jayavelu, Ashok Kumar Wolf, Sebastian Buettner, Florian Alexe, Gabriela Häupl, Björn Comoglio, Federico Schneider, Constanze Doebele, Carmen Fuhrmann, Dominik C. Wagner, Sebastian Donato, Elisa Andresen, Carolin Wilke, Anne C. Zindel, Alena Jahn, Dominique Splettstoesser, Bianca Plessmann, Uwe Münch, Silvia Abou-El-Ardat, Khali Makowka, Philipp Acker, Fabian Enssle, Julius C. Cremer, Anjali Schnütgen, Frank Kurrle, Nina Chapuy, Björn Löber, Jens Hartmann, Sylvia Wild, Peter J. Wittig, Ilka Hübschmann, Daniel Kaderali, Lars Cox, Jürgen Brüne, Bernhard Röllig, Christoph Thiede, Christian Steffen, Björn Bornhäuser, Martin Trumpp, Andreas Urlaub, Henning Stegmaier, Kimberly Serve, Hubert Mann, Matthias Oellerich, Thomas Department of Proteomics and Signal Transduction Max Planck Institute of Biochemistry Martinsried Germany Department of Medicine II Hematology/Oncology University Hospital Frankfurt Goethe University Theodor-Stern-Kai 7 Frankfurt Germany German Cancer Consortium (DKTK) Partner Site Frankfurt/Mainz and German Cancer Research Center (DKFZ) Heidelberg Germany Clinical Cooperation Unit Pediatric Leukemia DKFZ and Department of Pediatric Oncology Hematology and Immunology University of Heidelberg Germany Department of Medicine University Hospital Frankfurt Goethe University Frankfurt Germany Division of Hematology/Oncology Department of Pediatric Oncology Dana-Farber Cancer Institute and Boston Children's Hospital Boston MA United States enGene Statistics GmbH Basel Switzerland Department of Biochemistry I Goethe University Frankfurt Germany Division of Stem Cells and Cancer German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance Heidelberg Germany Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH) Heidelberg Germany Bioanalytical Mass Spectrometry Group Max Planck Institute for Biophysical Chemistry Göttingen Germany Department of Medical Hematology and Oncology University Medical Center Göttingen Göttingen Germany Dr. Senckenberg Institute of Pathology University Hospital Frankfurt Frankfurt Germany Functional Proteomics Institute of Cardiovascular Physiology Goethe University Frankfurt Germany Pattern Recognition and Digital Medicine Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) Heidelberg Germany Computational Oncology Molecular Precision Oncology Program National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ) Heidelberg Germany Institute of Bioinformatics University Medicine Greifswald Greifswald Germany Computational Systems Biochemistry Research Group Max Planck Institute of Biochemistry Martinsried Germany Department of Internal Medicine

Acute myeloid leukemia (AML) is an aggressive blood cancer with a poor prognosis. We report a comprehensive proteogenomic analysis of bone marrow biopsies from 252 uniformly treated AML patients to elucidate the molecular pathophysiology of AML in order to inform future diagnostic and therapeutic approaches. In addition to in-depth quantitative proteomics, our analysis includes cytogenetic profiling and DNA/RNA sequencing. We identify five proteomic AML subtypes, each reflecting specific biological features spanning genomic boundaries. Two of these proteomic subtypes correlate with patient outcome, but none is exclusively associated with specific genomic aberrations. Remarkably, one subtype (Mito-AML), which is captured only in the proteome, is characterized by high expression of mitochondrial proteins and confers poor outcome, with reduced remission rate and shorter overall survival on treatment with intensive induction chemotherapy. Functional analyses reveal that Mito-AML is metabolically wired toward stronger complex I-dependent respiration and is more responsive to treatment with the BCL2 inhibitor venetoclax. © 2022 Elsevier Inc.

关键词： acute myeloid leukemia BCL-2 inhibitor chemotherapy mitochondrial oxidative phosphorylation multi-omics data integration proteogenomics proteomics venetoclax

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Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021

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The Lancet 2023年第10397期402卷 203-234页

作者： Ong, Kanyin Liane Stafford, Lauryn K. McLaughlin, Susan A. Boyko, Edward J. Vollset, Stein Emil Smith, Amanda E. Dalton, Bronte E. Duprey, Joe Cruz, Jessica A. Hagins, Hailey Lindstedt, Paulina A. Aali, Amirali Abate, Yohannes Habtegiorgis Abate, Melsew Dagne Abbasian, Mohammadreza Abbasi-Kangevari, Zeinab Abbasi-Kangevari, Mohsen ElHafeez, Samar Abd Abd-Rabu, Rami Abdulah, Deldar Morad Abdullah, Abu Yousuf Md Abedi, Vida Abidi, Hassan Aboagye, Richard Gyan Abolhassani, Hassan Abu-Gharbieh, Eman Abu-Zaid, Ahmed Adane, Tigist Demssew Adane, Denberu Eshetie Addo, Isaac Yeboah Adegboye, Oyelola A. Adekanmbi, Victor Adepoju, Abiola Victor Adnani, Qorinah Estiningtyas Sakilah Afolabi, Rotimi Felix Agarwal, Gina Aghdam, Zahra Babaei Agudelo-Botero, Marcela Arriagada, Constanza Elizabeth Aguilera Agyemang-Duah, Williams Ahinkorah, Bright Opoku Ahmad, Danish Ahmad, Rizwan Ahmad, Sajjad Ahmad, Aqeel Ahmadi, Ali Ahmadi, Keivan Ahmed, Ali Ahmed, Luai A. Ahmed, Syed Anees Ajami, Marjan Akinyemi, Rufus Olusola Al Hamad, Hanadi Al Hasan, Syed Mahfuz AL-Ahdal, Tareq Mohammed Ali Alalwan, Tariq A. Al-Aly, Ziyad AlBataineh, Mohammad T. Alcalde-Rabanal, Jacqueline Elizabeth Alemi, Sharifullah Ali, Hassam Alinia, Tahereh Aljunid, Syed Mohamed Almustanyir, Sami Al-Raddadi, Rajaa M. Alvis-Guzman, Nelson Amare, Firehiwot Ameyaw, Edward Kwabena Amiri, Sohrab Amusa, Ganiyu Adeniyi Andrei, Catalina Liliana Anjana, Ranjit Mohan Ansar, Adnan Ansari, Golnoosh Ansari-Moghaddam, Alireza Anyasodor, Anayochukwu Edward Arabloo, Jalal Aravkin, Aleksandr Y. Areda, Demelash Arifin, Hidayat Arkew, Mesay Armocida, Benedetta Arnlov, Johan Artamonov, Anton A. Arulappan, Judie Aruleba, Raphael Taiwo Arumugam, Ashokan Aryan, Zahra Asemu, Mulu Tiruneh Asghari-Jafarabadi, Mohammad Askari, Elaheh Asmelash, Daniel Astell-Burt, Thomas Athar, Mohammad Athari, Seyyed Shamsadin Atout, Maha Moh'd Wahbi Avila-Burgos, Leticia Awaisu, Ahmed Azadnajafabad, Sina Darshan, B.B. Babamohamadi, Hassan Badar, Muhammad Badawi, Alaa Badiye, Ashish D. Baghcheghi, Nayereh Baghe Institute for Health Metrics and Evaluation School of Medicine General Medicine Service Department of Veterans Affairs Seattle WA United States Department of Health Metrics Sciences School of Medicine Faculty of Medicine France Department of Clinical Governance and Quality Improvement Aleta Wondo Hospital Aleta Wondo Ethiopia Department of Nursing Woldia University Woldia Ethiopia Department of Nursing Department of Orthopedic Surgery Orthopaedic Surgery Social Determinants of Health Research Center Non-communicable Diseases Research Center Epidemiology Department Evidence-Based Practice Center Community and Maternity Nursing Unit University of Duhok Duhok Iraq School of Planning Faculty of Environment Department of Public Health Sciences Penn State College of Medicine Pennsylvania State University Hershey PA United States Biocomplexity Institute Virginia Tech Blacksburg VA United States College of Medicine Department of Public Health Laboratory Technology Sciences Department Department of Family and Community Health University of Health and Allied Sciences Ho Ghana Research Center for Immunodeficiencies Department of Biosciences and Nutrition Karolinska University Hospital Huddinge Sweden Clinical Sciences Department Department of Surgery Department of Surgery Department of Obstetrics & Gynecology College of Graduate Health Sciences University of Tennessee Memphis TN United States Department of Obstetrics & Gynecology Department of Clinical and Psychosocial Epidemiology Department of Anesthesia and Critical Care Centre for Social Research in Health Quality and Systems Performance Unit Cancer Institute NSW Sydney NSW Australia Department of Public Health and Tropical Medicine HIV and Infectious Diseases Department Jhpiego Abuja Nigeria Adolescent Research and Care Department Adolescent Friendly Research Initiative and Care Ado Ekiti Nigeria Department of Epidemiology Department of Epidemiology and Medical Statistics Department of Family Medicine McMaster University

Background: Diabetes is one of the leading causes of death and disability worldwide, and affects people regardless of country, age group, or sex. Using the most recent evidentiary and analytical framework from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), we produced location-specific, age-specific, and sex-specific estimates of diabetes prevalence and burden from 1990 to 2021, the proportion of type 1 and type 2 diabetes in 2021, the proportion of the type 2 diabetes burden attributable to selected risk factors, and projections of diabetes prevalence through 2050. Methods: Estimates of diabetes prevalence and burden were computed in 204 countries and territories, across 25 age groups, for males and females separately and combined;these estimates comprised lost years of healthy life, measured in disability-adjusted life-years (DALYs;defined as the sum of years of life lost [YLLs] and years lived with disability [YLDs]). We used the Cause of Death Ensemble model (CODEm) approach to estimate deaths due to diabetes, incorporating 25 666 location-years of data from vital registration and verbal autopsy reports in separate total (including both type 1 and type 2 diabetes) and type-specific models. Other forms of diabetes, including gestational and monogenic diabetes, were not explicitly modelled. Total and type 1 diabetes prevalence was estimated by use of a Bayesian meta-regression modelling tool, DisMod-MR 2.1, to analyse 1527 location-years of data from the scientific literature, survey microdata, and insurance claims;type 2 diabetes estimates were computed by subtracting type 1 diabetes from total estimates. Mortality and prevalence estimates, along with standard life expectancy and disability weights, were used to calculate YLLs, YLDs, and DALYs. When appropriate, we extrapolated estimates to a hypothetical population with a standardised age structure to allow comparison in populations with different age structures. We used the comparative r

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The IL-22-oncostatin M axis promotes intestinal inflammation and tumorigenesis

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Nature immunology 2025年第6期26卷 837-853页

作者： Roodline Cineus Yanjiang Luo Mariia Saliutina Subhakankha Manna Camila A Cancino Luis Velasco Blázquez Lifen Wang Diana Bösel Aya Abdelrahman Joanna E Klementowicz Alexis Scherl Saskia Hainbuch Béatrice Bréart Gino Kwon Agata Konopka Gabriela M Guerra Elena von Coburg Lorenz Gerbeth Juliette Roels Frederik Heinrich Nils Müller Pawel Durek Nikolaus Deigendesch James Ziai Jeffrey Hung Thomas Conrad Anja A Kühl Stefan Wirtz Max Löhning Mary Keir Andreas Diefenbach Mir-Farzin Mashreghi Britta Siegmund Michael Schumann Chiara Romagnani Nathaniel R West Ahmed N Hegazy Department of Gastroenterology Infectious Diseases and Rheumatology Charité-Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin Berlin Germany. German Rheumatology Research Center (DRFZ) Leibniz Institute Berlin Germany. Department of Discovery Oncology Genentech South San Francisco CA USA. Department of Research Pathology Genentech South San Francisco CA USA. Department of Computational Sciences Genentech South San Francisco CA USA. Institute of Medical Immunology Charité-Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin Berlin Germany. Institute of Innate Immunity Department for Systems Immunology and Proteomics Medical Faculty University of Bonn Bonn Germany. Department of Pathology Institute of Medical Genetics and Pathology University Hospital Basel University of Basel Basel Switzerland. Genomics Technology Platform Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) Berlin Germany. Core Unit Genomics Berlin Institute of Health at Charité-Universitätsmedizin Berlin Berlin Germany. iPATH.Berlin Charité-Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin Berlin Germany. Department of Medicine 1 Friedrich-Alexander University Erlangen Germany. Department of Rheumatology and Clinical Immunology Experimental Immunology and Osteoarthritis Research Charité-Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin Berlin Germany. German Rheumatology Research Center (DRFZ) Pitzer Laboratory of Osteoarthritis Research Leibniz Institute Berlin Germany. Department of Immunology Discovery Genentech South San Francisco CA USA. Institute of Microbiology Infectious Diseases and Immunology (I-MIDI) Charité-Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin Berlin Germa

Multicellular cytokine networks drive intestinal inflammation and colitis-associated cancer (CAC). Interleukin-22 (IL-22) exerts both protective and pathogenic effects in the intestine, but the mechanisms that regulate this balance remain unclear. Here, we identify that IL-22 directly induces responsiveness to the IL-6 family cytokine oncostatin M (OSM) in intestinal epithelial cells (IECs) by activating STAT3 and upregulating the OSM receptor. In turn, OSM synergizes with IL-22 to sustain STAT3 activation in IECs and promote proinflammatory epithelial adaptation and immune cell chemotaxis to the inflamed intestine. Conditional deletion of the OSM receptor in IECs protects mice from both colitis and CAC, and pharmacological blockade of OSM attenuates established CAC. Thus, IL-22 and OSM form a pathogenic circuit that drives inflammation and tumorigenesis. Our findings reveal a previously unknown mechanism by which OSM supports intestinal pathology and highlight the IL-22-OSM axis as a promising therapeutic target for inflammatory bowel disease and CAC.

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The IBEX Imaging Knowledge-Base: A Community Resource Enabling Adoption and Development of Immunofluoresence Imaging Methods

arXiv

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arXiv 2024年

作者： Yaniv, Ziv Anidi, Ifeanyichukwu U. Arakkal, Leanne Arroyo-Mejías, Armando J. Beuschel, Rebecca T. Börner, Katy Chu, Colin J. Clark, Beatrice Clatworthy, Menna R. Colautti, Jake Coscia, Fabian Croteau, Joshua Denha, Saven Dever, Rose Dutra, Walderez O. Fritzsche, Sonja Fullam, Spencer Gerner, Michael Y. Gola, Anita Gollob, Kenneth J. Hernandez, Jonathan M. Hor, Jyh Liang Ichise, Hiroshi Jing, Zhixin Jonigk, Danny Kandov, Evelyn Kastenmüller, Wolfgang Koenig, Joshua F.E. Kothurkar, Aanandita Kortekaas, Rosa K. Kreins, Alexandra Y. Lamborn, Ian T. Lin, Yuri Morais, Katia Luciano Pereira Lunich, Aleksandra Luz, Jean C.S. MacDonald, Ryan B. Makranz, Chen Maltez, Vivien I. McDonough, John E. Moriarty, Ryan V. Ocampo-Godinez, Juan M. Olyntho, Vitoria M. Oxenius, Annette Padhan, Kartika Remmert, Kirsten Richoz, Nathan Schrom, Edward C. Shang, Wanjing Shi, Lihong Shih, Rochelle M. Speranza, Emily Stierli, Salome Teichmann, Sarah A. Veres, Tibor Z. Vierhout, Megan Wachter, Brianna T. Williams, Margaret Zangger, Nathan Germain, Ronald N. Radtke, Andrea J. Bioinformatics and Computational Bioscience Branch National Institute of Allergy and Infectious Diseases National Institutes of Health BethesdaMD United States Critical Care Medicine and Pulmonary Branch National Heart Lung and Blood Institute National Institutes of Health BethesdaMD United States Lymphocyte Biology Section Laboratory of Immune System Biology NIAID NIH BethesdaMD United States Department of Intelligent Systems Engineering Indiana University BloomingtonIN United States UCL Institute of Ophthalmology NIHR Moorfields Biomedical Research Centre London United Kingdom Cambridge Institute for Therapeutic Immunology and Infectious Diseases University of Cambridge Department of Medicine Molecular Immunity Unit Laboratory of Molecular Biology Cambridge United Kingdom McMaster Immunology Research Centre Schroeder Allergy and Immunology Research Institute Department of Medicine Faculty of Health Sciences McMaster University HamiltonON Canada Spatial Proteomics Group Berlin Germany Department of Business Development BioLegend Inc. San DiegoCA United States Functional Immunogenomics Unit National Institute of Arthritis and Musculoskeletal and Skin Diseases National Institutes of Health BethesdaMD United States Laboratory of Cell-Cell Interactions Department of Morphology Institute of Biological Sciences Universidade Federal de Minas Gerais MG Belo Horizonte Brazil Division of Rheumatology Rush University Medical Center ChicagoIL United States Department of Immunology University of Washington School of Medicine SeattleWA United States Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development The Rockefeller University New YorkNY United States Hospital Israelita Albert Einstein SP Sao Paulo Brazil Surgical Oncology Program National Cancer Institute National Institutes of Health BethesdaMD United States Institute of Pathology Aachen Medical University RWTH Aachen Aachen Germany Hannover Germany Würzburg Institute

The iterative bleaching extends multiplexity (IBEX) Knowledge-Base is a central portal for researchers adopting IBEX and related 2D and 3D immunofluorescence imaging methods. The design of the Knowledge-Base is modeled after efforts in the open-source software community and includes three facets: a development platform (GitHub), static website, and service for data archiving. The Knowledge-Base facilitates the practice of open science throughout the research life cycle by providing validation data for recommended and non-recommended reagents, e.g., primary and secondary antibodies. In addition to reporting negative data, the Knowledge-Base empowers method adoption and evolution by providing a venue for sharing protocols, videos, datasets, software, and publications. A dedicated discussion forum fosters a sense of community among researchers while addressing questions not covered in published manuscripts. Together, scientists from around the world are advancing scientific discovery at a faster pace, reducing wasted time and effort, and instilling greater confidence in the resulting data. © 2024, CC BY.

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