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Relevant temporal bone anatomy for robotic cochlear implantation: An updated terminology combined with anatomical and clinical terms

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Translational Research in Anatomy 2021年 25卷 100138-100138页

作者： Topsakal, Vedat Kachlik, David Bahşi, Ilhan Carlson, Matthew Isaacson, Brandon Broman, Jonas Tubbs, R. Shane Baud, Robert ten Donkelaar, Hans J. Department of Otorhinolaryngology Head and Neck Surgery University Hospital UZ Brussel Brussels Belgium Vrije Univeristeit Brussel Brussels Health Campus Laarbeeklaan 101 Jette 1090 Belgium Department of Anatomy Second Faculty of Medicine Charles University V Ãšvalu 84 Praha 5 15006 Czech Republic Department of Anatomy Gaziantep University Gaziantep 27310 Turkey Department of Otolaryngology Mayo Clinic 200 1st St SW Rochester 55905 MN United States Department of Otolaryngology University of Texas South Western Dallas 75390 TX United States Department of Biomedical and Clinical Sciences University of LinkÃ¶ping LinkÃ¶ping 58183 Sweden Department of Neurosurgery Tulane School of Medicine 1430 Tulane Avenue New Orleans 70112 LA United States Department of Anatomical Sciences S. Georgeâ€™s University Grenada Anatomy Section of Medicine Faculty of Science and Medicine University of Fribourg Fribourg Switzerland SIB Data Mining Swiss Institute for Bioinformatics Geneva Switzerland Department of Neurology And Donders Institute for Brain Cognition and Behavior Radboud University Medical Center P.O. Box 9101 6500 HB Nijmegen Netherlands Donders Institute for Brain Cognition and Behavior Radboud University Medical Center P.O. Box 9101 6500 HB Nijmegen Netherlands

Background: Translational research refers to scientific findings that have been extensively studied in models and find their way to clinical studies. In a certain sense in translational anatomy a similar application of conventional anatomical knowledge finds its way to clinics in the surgical theatre. With the propagation of endoscopic middle ear surgery there has been a renewed interest in many early anatomical terms, even many years after their discovery, which may threaten the correct and classic eponyms. Moreover, the application of robotic ear surgery executing minimal invasive keyhole accesses requires translation of anatomical knowledge to the sub-millimetric level. Purpose: This review reports relevant anatomy of the temporal bone for robotic cochlear implantation reflecting also on recent revisions of terminology. Results: In 2019, the Terminologia Neuroanatomica (TNA 2017) was accepted at the 19th World Congress of the International Federation of Associations of Anatomists (IFAA) in London as its official terminology for the central and peripheral nervous system and the sense organs. This review follows the terminology of in the TNA, but also compares anatomical and clinical terms to bridge the gap between both approaches, and provides brief descriptions and illustrations of relevant structures for robotic cochlear implantation and elaborates on their significance. With the emergence and more widespread use of the endoscopic ear surgery and image guided ear surgery, visualization of certain anatomical structures has improved. Coinciding, there has been a renewed interest in many early anatomical terms, even many years after their discovery, which may threaten the correct and classic eponyms. Conclusions: Consequently, this review also presents an overview of eponyms associated with specific structures over the years. In Supplementary Tables, the changes in terminology are reported. © 2021 The Authors

关键词： Anatomy Robotic cochlear implantation Temporal bone Terminology

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Polygenic enrichment distinguishes disease associations of individual cells in single-cell RNA-seq data

Research Square

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Research Square 2021年

作者： Zhang, Martin Jinye Hou, Kangcheng Pasaniuc, Bogdan Price, Alkes L. Dey, Kushal K. Jagadeesh, Karthik A. Weinand, Kathryn Sakaue, Saori Taychameekiatchai, Aris Rao, Poorvi Pisco, Angela Oliveira Zou, James Wang, Bruce Gandal, Michael Raychaudhuri, Soumya Harvard University United States Osaka University Japan Department of Epidemiology Harvard T.H. Chan School of Public Health BostonMA United States Program in Medical and Population Genetics Broad Institute of MIT and Harvard CambridgeMA United States Bioinformatics Interdepartmental Program University of California Los Angeles Los AngelesCA United States Department of Pathology and Laboratory Medicine David Geffen School of Medicine University of California Los Angeles Los AngelesCA United States Department of Computational Medicine David Geffen School of Medicine University of California Los Angeles Los AngelesCA United States Center for Data Sciences Brigham and Women’s Hospital BostonMA United States Division of Genetics Department of Medicine Brigham and Women’s Hospital Harvard Medical School BostonMA United States Division of Rheumatology Inflammation and Immunity Department of Medicine Brigham and Women’s Hospital Harvard Medical School BostonMA United States Department of Biomedical Informatics Harvard Medical School BostonMA United States Department of Medicine and Liver Center University of California San Francisco San FranciscoCA United States Developmental and Stem Cell Biology Graduate Program University of California San Francisco San FranciscoCA United States Chan Zuckerberg Biohub San FranciscoCA United States Department of Electrical Engineering Stanford University Palo AltoCA United States Department of Biomedical Data Science Stanford University Palo AltoCA United States Department of Psychiatry David Geffen School of Medicine University of California Los Angeles Los AngelesCA United States Department of Human Genetics David Geffen School of Medicine University of California Los Angeles Los AngelesCA United States Program in Neurobehavioral Genetics Semel Institute David Geffen School of Medicine University of California Los Angeles Los AngelesCA United States Versus Arthritis Centre for Genetics and Genomic

Gene expression at the individual cell-level resolution, as quantified by single-cell RNA-sequencing (scRNA-seq), can provide unique insights into the pathology and cellular origin of diseases and complex traits. Here, we introduce single-cell Disease Relevance Score (scDRS), an approach that links scRNA-seq with polygenic risk of disease at individual cell resolution;scDRS identifies individual cells that show excess expression levels for genes in a disease-specific gene set constructed from GWAS data. We determined via simulations that scDRS is well-calibrated and powerful in identifying individual cells associated to disease. We applied scDRS to GWAS data from 74 diseases and complex traits (average N =341K) in conjunction with 16 scRNA-seq data sets spanning 1.3 million cells from 31 tissues and organs. At the cell type level, scDRS broadly recapitulated known links between classical cell types and disease, and also produced novel biologically plausible findings. At the individual cell level, scDRS identified subpopulations of disease-associated cells that are not captured by existing cell type labels, including subpopulations of CD4+ T cells associated with inflammatory bowel disease, partially characterized by their effector-like states;subpopulations of hippocampal CA1 pyramidal neurons associated with schizophrenia, partially characterized by their spatial location at the proximal part of the hippocampal CA1 region;and subpopulations of hepatocytes associated with triglyceride levels, partially characterized by their higher ploidy levels. At the gene level, we determined that genes whose expression across individual cells was correlated with the scDRS score (thus reflecting co-expression with GWAS disease genes) were strongly enriched for gold-standard drug target and Mendelian disease genes. © 2021, CC BY.

关键词： RNA

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Author Correction: Cell segmentation-free inference of cell types from in situ transcriptomics data

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Nature communications 2021年第1期12卷 4103页

作者： Jeongbin Park Wonyl Choi Sebastian Tiesmeyer Brian Long Lars E Borm Emma Garren Thuc Nghi Nguyen Bosiljka Tasic Simone Codeluppi Tobias Graf Matthias Schlesner Oliver Stegle Roland Eils Naveed Ishaque Berlin Institute of Health at Charité-Universitätsmedizin Berlin Digital Health Center Kapelle-Ufer 2 10117 Berlin Germany. Faculty of Biosciences Heidelberg University Heidelberg Germany. Division of Computational Genomics and System Genetics German Cancer Research Center (DKFZ) Heidelberg Germany. Department of Computer Science Boston University Boston MA USA. Allen Institute for Brain Science Seattle WA USA. Division of molecular neurobiology Department of medical biochemistry and biophysics Karolinska Institutet Stockholm Sweden. Bioinformatics and Omics Data Analytics German Cancer Research Center (DKFZ) Heidelberg Germany. Genome Biology Unit European Molecular Biology Laboratory (EMBL) Heidelberg Germany. Berlin Institute of Health at Charité-Universitätsmedizin Berlin Digital Health Center Kapelle-Ufer 2 10117 Berlin Germany. roland.eils@bih-charite.de. Health Data Science Unit Heidelberg University Hospital Heidelberg Germany. roland.eils@bih-charite.de. Berlin Institute of Health at Charité-Universitätsmedizin Berlin Digital Health Center Kapelle-Ufer 2 10117 Berlin Germany. naveed.ishaque@bih-charite.de.

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Author Correction: Widespread exposure to SARS-CoV-2 in wildlife communities

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Nature communications 2024年第1期15卷 6940页

作者： Amanda R Goldberg Kate E Langwig Katherine L Brown Jeffrey M Marano Pallavi Rai Kelsie M King Amanda K Sharp Alessandro Ceci Christopher D Kailing Macy J Kailing Russell Briggs Matthew G Urbano Clinton Roby Anne M Brown James Weger-Lucarelli Carla V Finkielstein Joseph R Hoyt Department of Biological Sciences Virginia Tech Blacksburg VA USA. Virginia Tech Carilion School of Medicine Virginia Tech Roanoke VA USA. Center for Emerging Zoonotic and Arthropod-borne Pathogens Virginia Tech Blacksburg VA USA. Molecular Diagnostics Laboratory Fralin Biomedical Research Institute Virginia Tech Roanoke VA USA. Department of Biomedical Sciences and Pathobiology Virginia Tech Blacksburg VA USA. Translational Biology Medicine and Health Graduate Program Virginia Tech Roanoke VA USA. Program in Genetics Bioinformatics and Computational Biology Virginia Tech Blacksburg VA USA. Department of Biochemistry Virginia Tech Blacksburg VA USA. Data Services University Libraries Virginia Tech Blacksburg VA USA. Virginia Tech Center for Drug Discovery Virginia Tech Blacksburg VA USA. Academy of Integrated Science Virginia Tech Blacksburg VA USA. Department of Biological Sciences Virginia Tech Blacksburg VA USA. finkielc@vt.edu. Virginia Tech Carilion School of Medicine Virginia Tech Roanoke VA USA. finkielc@vt.edu. Center for Emerging Zoonotic and Arthropod-borne Pathogens Virginia Tech Blacksburg VA USA. finkielc@vt.edu. Molecular Diagnostics Laboratory Fralin Biomedical Research Institute Virginia Tech Roanoke VA USA. finkielc@vt.edu. Virginia Tech Center for Drug Discovery Virginia Tech Blacksburg VA USA. finkielc@vt.edu. Academy of Integrated Science Virginia Tech Blacksburg VA USA. finkielc@vt.edu. Department of Biological Sciences Virginia Tech Blacksburg VA USA. hoytjosephr@***.

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Author Correction: Greengenes2 unifies microbial data in a single reference tree

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Nature biotechnology 2024年第5期42卷 813页

作者： Daniel McDonald Yueyu Jiang Metin Balaban Kalen Cantrell Qiyun Zhu Antonio Gonzalez James T Morton Giorgia Nicolaou Donovan H Parks Søren M Karst Mads Albertsen Philip Hugenholtz Todd DeSantis Se Jin Song Andrew Bartko Aki S Havulinna Pekka Jousilahti Susan Cheng Michael Inouye Teemu Niiranen Mohit Jain Veikko Salomaa Leo Lahti Siavash Mirarab Rob Knight Department of Pediatrics University of California San Diego School of Medicine La Jolla CA USA. Department of Electrical and Computer Engineering University of California San Diego La Jolla CA USA. Bioinformatics and Systems Biology Program University of California San Diego La Jolla CA USA. Department of Computer Science and Engineering University of California San Diego La Jolla CA USA. School of Life Sciences Arizona State University Tempe AZ USA. Biodesign Center for Fundamental and Applied Microbiomics Arizona State University Tempe AZ USA. Biostatistics & Bioinformatics Branch Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda MD USA. Halicioglu Data Science Institute University of California San Diego La Jolla CA USA. Australian Centre for Ecogenomics School of Chemistry and Molecular Biosciences The University of Queensland St Lucia Queensland Australia. Department of Obstetrics and Gynecology Columbia University New York NY USA. Department of Chemistry and Bioscience Aalborg University Aalborg Denmark. Department of Informatics Second Genome Brisbane CA USA. Center for Microbiome Innovation Jacobs School of Engineering University of California San Diego La Jolla CA USA. Finnish Institute for Health and Welfare Helsinki Finland. Institute for Molecular Medicine Finland FIMM-HiLIFE Helsinki Finland. Division of Cardiology Brigham and Women's Hospital Boston MA USA. Cedars-Sinai Medical Center Los Angeles CA USA. Cambridge Baker Systems Genomics Initiative Baker Heart and Diabetes Institute Melbourne Victoria Australia. Cambridge Baker Systems Genomics Initiative Department of Public Health and Primary Care University of Cambridge Cambridge UK. Division of Medicine Turku University Hospital and University of Turku Turku Finland. Sapient Bioanalytics LLC San Diego CA USA. Department of Computing University of Turku Turku Finland. Department of Pediatrics Uni

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PO005LBA/#1579 A randomized, phase II/III study of pegylated-liposomal-doxorubicin and atezolizumab (IND #134427) versus pegylated-liposomal-doxorubicin, bevacizumab and atezolizumab versus pegylated-liposomal-doxorubicin and bevacizumab in platinum-resistant ovarian cancer (NRG-GY009)

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International Journal of Gynecological Cancer 2023年 33卷 A4-A4页

作者： Roisin O’Cearbhaill Michael Sill H.o.a. Duong Steven Waggoner Rachel Grisham Floor Backes Robert Mannel Janos Tanyi Matthew Powell Cara Mathews Sharad Ghamande Leah Mcnally Alexander Olawaiye David Bender Linda Duska Heather Lankes Dmitriy Zamarin Russell Schilder Michael Bookman Carol Aghajanian Memorial Sloan Kettering Cancer Center Weill Cornell Medical College Medicine New York USA NRG Oncology Statistics and Data Management Center Biostatistics and Bioinformatics Department Buffalo USA Kaiser-Permanente Sacramento Hematology/oncology Sacramento USA CWRU Case Comprehensive Cancer Center Gynecologic Oncology Cleveland USA Ohio State University Comprehensive Cancer Center Gynecologic Oncology Ohio USA University of Oklahoma Health Sciences Center Obstetrics and Gynecology Oklahoma USA University of Pennsylvania/Abramson Cancer Center Obstetrics and Gynecology Philadelphia USA Washington University Gynecologic Oncology St. Louis USA Women and Infants Hospital Obstetrics and Gynecology Providence USA Georgia Cares Minority Underserved NCORP Gynecologic Oncology Augusta USA Duke Cancer Institute Gynecologic Oncology Durham USA UPMC Hillman Cancer Center Gynecologic Oncology Pittsburgh USA University of Iowa Obstetrics and Gynecology Iowa City USA University of Virginia Cancer Center Gynecologic Oncology Charlottesville USA NRG Oncology Biospecimen Bank-Columbus Translational Science Operations Columbus USA Icahn School of Medicine at Mount Sinai Hematology/oncology New York USA Thomas Jefferson University Gynecologic Medical Oncology Philadelphia USA Kaiser Permanente Northern California Gynecologic Oncology San Francisco USA

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Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

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Nature 2024年第8003期627卷 347-357页

作者： Ken Suzuki Konstantinos Hatzikotoulas Lorraine Southam Henry J Taylor Xianyong Yin Kim M Lorenz Ravi Mandla Alicia Huerta-Chagoya Giorgio E M Melloni Stavroula Kanoni Nigel W Rayner Ozvan Bocher Ana Luiza Arruda Kyuto Sonehara Shinichi Namba Simon S K Lee Michael H Preuss Lauren E Petty Philip Schroeder Brett Vanderwerff Mart Kals Fiona Bragg Kuang Lin Xiuqing Guo Weihua Zhang Jie Yao Young Jin Kim Mariaelisa Graff Fumihiko Takeuchi Jana Nano Amel Lamri Masahiro Nakatochi Sanghoon Moon Robert A Scott James P Cook Jung-Jin Lee Ian Pan Daniel Taliun Esteban J Parra Jin-Fang Chai Lawrence F Bielak Yasuharu Tabara Yang Hai Gudmar Thorleifsson Niels Grarup Tamar Sofer Matthias Wuttke Chloé Sarnowski Christian Gieger Darryl Nousome Stella Trompet Soo-Heon Kwak Jirong Long Meng Sun Lin Tong Wei-Min Chen Suraj S Nongmaithem Raymond Noordam Victor J Y Lim Claudia H T Tam Yoonjung Yoonie Joo Chien-Hsiun Chen Laura M Raffield Bram Peter Prins Aude Nicolas Lisa R Yanek Guanjie Chen Jennifer A Brody Edmond Kabagambe Ping An Anny H Xiang Hyeok Sun Choi Brian E Cade Jingyi Tan K Alaine Broadaway Alice Williamson Zoha Kamali Jinrui Cui Manonanthini Thangam Linda S Adair Adebowale Adeyemo Carlos A Aguilar-Salinas Tarunveer S Ahluwalia Sonia S Anand Alain Bertoni Jette Bork-Jensen Ivan Brandslund Thomas A Buchanan Charles F Burant Adam S Butterworth Mickaël Canouil Juliana C N Chan Li-Ching Chang Miao-Li Chee Ji Chen Shyh-Huei Chen Yuan-Tsong Chen Zhengming Chen Lee-Ming Chuang Mary Cushman John Danesh Swapan K Das H Janaka de Silva George Dedoussis Latchezar Dimitrov Ayo P Doumatey Shufa Du Qing Duan Kai-Uwe Eckardt Leslie S Emery Daniel S Evans Michele K Evans Krista Fischer James S Floyd Ian Ford Oscar H Franco Timothy M Frayling Barry I Freedman Pauline Genter Hertzel C Gerstein Vilmantas Giedraitis Clicerio González-Villalpando Maria Elena González-Villalpando Penny Gordon-Larsen Myron Gross Lindsay A Guare Sophie Hackinger Liisa Hakaste Sohee Han Andrew T Hattersley Christian Herder Momoko Horikoshi Annie-Green Howard Willa Centre for Genetics and Genomics Versus Arthritis Centre for Musculoskeletal Research Division of Musculoskeletal and Dermatological Sciences University of Manchester Manchester UK. Department of Diabetes and Metabolic Diseases Graduate School of Medicine University of Tokyo Tokyo Japan. Department of Statistical Genetics Osaka University Graduate School of Medicine Suita Japan. Institute of Translational Genomics Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany. konstantinos.hatzikotoulas@helmholtz-munich.de. Institute of Translational Genomics Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany. Center for Precision Health Research National Human Genome Research Institute National Institutes of Health Bethesda MD USA. British Heart Foundation Cardiovascular Epidemiology Unit Department of Public Health and Primary Care University of Cambridge Cambridge UK. Heart and Lung Research Institute University of Cambridge Cambridge UK. Department of Epidemiology School of Public Health Nanjing Medical University Nanjing China. Department of Biostatistics and Center for Statistical Genetics University of Michigan Ann Arbor MI USA. Corporal Michael J. Crescenz VA Medical Center Philadelphia PA USA. Department of Systems Pharmacology and Translational Therapeutics University of Pennsylvania Perelman School of Medicine Philadelphia PA USA. Department of Genetics University of Pennsylvania Perelman School of Medicine Philadelphia PA USA. Programs in Metabolism and Medical and Population Genetics Broad Institute of Harvard and MIT Cambridge MA USA. Diabetes Unit and Center for Genomic Medicine Massachusetts General Hospital Boston MA USA. TIMI Study Group Division of Cardiovascular Medicine Brigham and Women's Hospital Harvard Medical School Boston MA USA. William Harvey Research Institute Barts and the London School of Medicine and Dentistry Queen Mary University of London L

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes and molecular mechanisms that are often specific to cell type. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.

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Chemical-Induced Disease Detection Using Invariance-based Pattern Learning Model 1

Chemical-Induced Disease Detection Using Invariance-based Pa...

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1st International Workshop on Digital Disease Detection using Social Media, DDDSM 2017, co-located with the 8th International Joint Conference on Natural Language Processing, IJCNLP 2017

作者： Warikoo, Neha Chang, Yung-Chun Hsu, Wen-Lian Institute of Biomedical Informatics National Yang-Ming University Taipei112 Taiwan Bioinformatics Program Taiwan International Graduate Program Institute of Information Science Academia Sinica Taipei115 Taiwan Institute of Information Science Academia Sinica Taipei115 Taiwan Graduate Institute of Data Science Taipei Medical University Taipei106 Taiwan

ISBN: (纸本)9781948087070

In this work, we introduce a novel feature engineering approach named "algebraic invariance" to identify discriminative patterns for learning relation pair features for the chemical-disease relation (CDR) task of BioCreative V. Our method exploits the existing structural similarity of the key concepts of relation descriptions from the CDR corpus to generate robust linguistic patterns for SVM tree kernel-based learning. Preprocessing of the training data classifies the entity pairs as either related or unrelated to build instance types for both inter-sentential and intra-sentential scenarios. An invariant function is proposed to process and optimally cluster similar patterns for both positive and negative instances. The learning model for CDR pairs is based on the SVM tree kernel approach, which generates feature trees and vectors and is modeled on suitable invariance based patterns, bringing brevity, precision and context to the identifier features. Results demonstrate that our method outperformed compared approaches, achieved a high recall rate of 85.08%, and averaged an F1-score of 54.34% without the use of any additional knowledge bases. © 2017 AFNLP

关键词： Forestry

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Comparative analyses for plant virus-based cancer immunotherapy drug development

Cell Biomaterials

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Cell Biomaterials 2025年

作者： Anthony O. Omole Hannah S. Newton Edward Cedrone Kimia Nematpour Shaojun Xie Yongmei Zhao Bao Tran Marina A. Dobrovolskaia Nicole F. Steinmetz Aiiso Yufeng Li Family Department of Chemical and Nano Engineering University of California San Diego La Jolla San Diego CA 92093 USA Shu and K.C. Chien and Peter Farrell Collaboratory University of California San Diego La Jolla San Diego CA 92093 USA Center for Nano-ImmunoEngineering University of California San Diego La Jolla San Diego CA 92093 USA Moores Cancer Center University of California San Diego La Jolla San Diego CA 92093 USA Nanotechnology Characterization Lab Cancer Research Technology Program Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute Frederick MD 21702 USA Sequencing Facility Bioinformatics Group Biomedical Informatics and Data Science Directorate Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute Frederick MD 21702 USA CCR Sequencing Facility Cancer Research Technology Program Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute Frederick MD 21702 USA Department of Bioengineering University of California San Diego La Jolla San Diego CA 92093 USA Department of Radiology University of California San Diego La Jolla San Diego CA USA Institute for Materials Discovery and Design University of California San Diego La Jolla San Diego CA 92093 USA Center for Engineering in Cancer Institute of Engineering Medicine University of California San Diego La Jolla San Diego CA 92093 USA

Cowpea mosaic virus (CPMV) is a plant virus with potent anti-tumor efficacy. Intratumoral CPMV, but not cowpea chlorotic mottle virus (CCMV), reprograms the tumor microenvironment priming durable, systemic anti-tumor immunity. Here, we performed a side-by-side mechanism of action comparison between CPMV and CCMV. Through immune-multiplexing and trafficking studies we observed that CPMV and CCMV are taken up by innate immune cells at similar rates but are processed differently. While CCMV induces proinflammatory interleukins 22, 23, and 27, CPMV is a strong inducer of type I, II, and III interferons, which contribute to the activation and enhancement of immune cell function. We observed that CPMV RNAs activate Toll-like receptor (TLR) 7 upon delivery—and not CCMV RNAs; CPMV RNAs persist longer within cells compared with CCMV. Taken together, this work identifies determinants for CPMV’s unique mechanism for intratumoral immunotherapy. It also broadens our understanding of the utility of plant viruses for biomedical applications.

关键词： plant viruses intratumoral immunotherapy cowpea mosaic virus cowpea chlorotic mottle virus cancer nanotechnology

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OTHR-04. DEVELOPMENT OF A FUNCTIONAL PLATFORM FOR REAL-TIME PERSONALIZED DRUG SENSITIVITY PROFILING OF PATIENT-DERIVED 3D FRESH TUMOR TISSUE CULTURES IN THE PEDIATRIC PRECISION ONCOLOGY PROGRAM INFORM

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Neuro-Oncology 2023年第SUPPLEMENT_1期25卷 i74–i75页

作者： Heike Peterziel Nora Jamaladdin Dina ElHarouni Xenia F Gerloff Sonja Herter Petra Fiesel Yannick Berker Mirjam Blattner-Johnson Kathrin Schramm Barbara C Jones David Reuss Laura Turunen Aileen Friedenauer Tim Holland-Letz Martin Sill Lena Weiser Christopher Previti Gnanaprakash Balasubramanian Nicolas U Gerber Johannes Gojo Caroline Hutter Ingrid Øra Olli Lohi Antonis Kattamis Bram de Wilde Frank Westermann Stephan Tippelt Norbert Graf Michaela Nathrath Monika Sparber-Sauer Astrid Sehested Christof M Kramm Uta Dirksen Olli Kallioniemi Stefan M Pfister Cornelis M van Tilburg David T W Jones Jani Saarela Vilja Pietiäinen Natalie Jäger Matthias Schlesner Annette Kopp-Schneider Sina Oppermann Till Milde Olaf Witt Ina Oehme Hopp Children’s Cancer Center Heidelberg (KiTZ) Heidelberg Germany Clinical Cooperation Unit Pediatric Oncology German Cancer Research Center (DKFZ) National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Consortium (DKTK) Heidelberg Germany Bioinformatics and Omics Data Analytics German Cancer Research Center (DKFZ) Division of Pediatric Neurooncology German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK) Heidelberg Germany Clinical Cooperation Unit Neuropathology German Cancer Research Center (DKFZ) Heidelberg Germany Division of Pediatric Glioma Research German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK) Heidelberg Germany Division of Pediatric Glioma Research German Cancer Research Center (DKFZ) Department of Pediatric Oncology Hematology Immunology and Pulmonology Heidelberg University Hospital and German Cancer Consortium (DKTK) Heidelberg Germany Department Neuropathology at Institute of Pathology Heidelberg University Hospital Heidelberg Germany Institute for Molecular Medicine Finland (FIMM) Helsinki Institute of Life Science (HiLIFE) University of Helsinki Helsinki Finland Division of Biostatistics German Cancer Research Center (DKFZ) Heidelberg Heidelberg Germany Division of Pediatric Neurooncology German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK) Heidelberg Germany Core Facility Omics IT and Data Management (ODCF) German Cancer Research Center (DKFZ) Heidelberg Germany Department of Oncology University Children’s Hospital Zürich Zürich Switzerland Department of Pediatrics and Adolescent Medicine Comprehensive Cancer Center and Comprehensive Center for Pediatrics Medical University of Vienna Vienna Austria St. Anna Children’s Hospital Department of Pediatrics and Adolescent Medicine Medical University of Vienna and St. Anna Children’s Cancer Research Institute (CCRI) Vienna Austria Children’s Hospital Pediatric Oncology Skåne University Hospital Lund &amp Karolinska Univ

The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75-78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs.

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