{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T05:27:29Z","timestamp":1783402049316,"version":"3.54.6"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"D1","license":[{"start":{"date-parts":[[2021,9,17]],"date-time":"2021-09-17T00:00:00Z","timestamp":1631836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001006","name":"Breast Cancer Research Foundation","doi-asserted-by":"publisher","award":["BCRF-20-100"],"award-info":[{"award-number":["BCRF-20-100"]}],"id":[{"id":"10.13039\/100001006","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA234018"],"award-info":[{"award-number":["R01CA234018"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U24CA224316"],"award-info":[{"award-number":["U24CA224316"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T15LM007092"],"award-info":[{"award-number":["T15LM007092"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100003212","name":"Sara Elizabeth O\u2019Brien Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100003212","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007886","name":"Dana-Farber Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007886","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Syngeneic mouse models are tumors derived from murine cancer cells engrafted on genetically identical mouse strains. They are widely used tools for studying tumor immunity and immunotherapy response in the context of a fully functional murine immune system. Large volumes of syngeneic mouse tumor expression profiles under different immunotherapy treatments have been generated, although a lack of systematic collection and analysis makes data reuse challenging. We present Tumor Immune Syngeneic MOuse (TISMO), a database with an extensive collection of syngeneic mouse model profiles with interactive visualization features. TISMO contains 605 in vitro RNA-seq samples from 49 syngeneic cancer cell lines across 23 cancer types, of which 195 underwent cytokine treatment. TISMO also includes 1518 in vivo RNA-seq samples from 68 syngeneic mouse tumor models across 19 cancer types, of which 832 were from immune checkpoint blockade (ICB) studies. We manually annotated the sample metadata, such as cell line, mouse strain, transplantation site, treatment, and response status, and uniformly processed and quality-controlled the RNA-seq data. Besides data download, TISMO provides interactive web interfaces to investigate whether specific gene expression, pathway enrichment, or immune infiltration level is associated with differential immunotherapy response. TISMO is available at http:\/\/tismo.cistrome.org.<\/jats:p>","DOI":"10.1093\/nar\/gkab804","type":"journal-article","created":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T19:16:31Z","timestamp":1631819791000},"page":"D1391-D1397","source":"Crossref","is-referenced-by-count":124,"title":["TISMO: syngeneic mouse tumor database to model tumor immunity and immunotherapy response"],"prefix":"10.1093","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3905-3244","authenticated-orcid":false,"given":"Zexian","family":"Zeng","sequence":"first","affiliation":[{"name":"Department of Data Science, Dana Farber Cancer Institute, Boston, MA\u00a002215, USA"},{"name":"Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA\u00a002215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl J","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Data Science, Dana Farber Cancer Institute, Boston, MA\u00a002215, USA"},{"name":"Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Data Science, Dana Farber Cancer Institute, Boston, MA\u00a002215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nofal","family":"Ouardaoui","sequence":"additional","affiliation":[{"name":"Department of Data Science, Dana Farber Cancer Institute, Boston, MA\u00a002215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5374-7314","authenticated-orcid":false,"given":"Dian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Data Science, Dana Farber Cancer Institute, Boston, MA\u00a002215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wubing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Data Science, Dana Farber Cancer Institute, Boston, MA\u00a002215, USA"},{"name":"School of Life Science and Technology, Tongji University, Shanghai, 200060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengqing","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA\u00a002215, USA"},{"name":"Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA\u00a002215, USA"},{"name":"Department of Data Science, Dana Farber Cancer Institute, Boston, MA\u00a002215, USA"},{"name":"Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA\u00a002215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Data Science, Dana Farber Cancer Institute, Boston, MA\u00a002215, USA"},{"name":"Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA\u00a002215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Data Science, Dana Farber Cancer Institute, Boston, MA\u00a002215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA\u00a002215, USA"},{"name":"Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA\u00a002215, USA"},{"name":"Department of Data Science, Dana Farber Cancer Institute, Boston, MA\u00a002215, USA"},{"name":"Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA\u00a002215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxin","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA\u00a002215, USA"},{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA\u00a002129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liye","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA\u00a002215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boning","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA\u00a002215, USA"},{"name":"Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA\u00a002215, USA"},{"name":"Department of Data Science, Dana Farber Cancer Institute, Boston, MA\u00a002215, USA"},{"name":"Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA\u00a002215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Kim","sequence":"additional","affiliation":[{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA\u00a002129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen\u00a0B","family":"Yates","sequence":"additional","affiliation":[{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA\u00a002129, USA"},{"name":"Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA\u00a002114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8213-1658","authenticated-orcid":false,"given":"Myles","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA\u00a002215, USA"},{"name":"Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA\u00a002215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon\u00a0J","family":"Freeman","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA\u00a002215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravindra","family":"Uppaluri","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA\u00a002215, USA"},{"name":"Department of Surgery, Brigham and Women's Hospital, Boston, MA\u00a002215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Manguso","sequence":"additional","affiliation":[{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA\u00a002129, USA"},{"name":"Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA\u00a002114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4736-7339","authenticated-orcid":false,"given":"X\u00a0Shirley","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Data Science, Dana Farber Cancer Institute, Boston, MA\u00a002215, USA"},{"name":"Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA\u00a002215, USA"},{"name":"Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA\u00a002215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,9,17]]},"reference":[{"key":"2022010507314623900_B1","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/s41577-020-0306-5","article-title":"A guide to cancer immunotherapy: from T cell basic science to clinical practice","volume":"20","author":"Waldman","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"2022010507314623900_B2","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.cell.2015.08.068","article-title":"Preclinical mouse cancer models: a maze of opportunities and challenges","volume":"163","author":"Day","year":"2015","journal-title":"Cell"},{"key":"2022010507314623900_B3","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1158\/2159-8290.CD-18-0044","article-title":"Mouse models for cancer immunotherapy research","volume":"8","author":"Olson","year":"2018","journal-title":"Cancer Discov."},{"key":"2022010507314623900_B4","doi-asserted-by":"crossref","first-page":"4118","DOI":"10.3390\/ijms21114118","article-title":"Mouse tumor models for advanced cancer immunotherapy","volume":"21","author":"Chulpanova","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"2022010507314623900_B5","doi-asserted-by":"crossref","first-page":"D825","DOI":"10.1093\/nar\/gkt1159","article-title":"Mouse phenome database","volume":"42","author":"Grubb","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"2022010507314623900_B6","first-page":"D716","article-title":"Mouse Phenome Database: a data repository and analysis suite for curated primary mouse phenotype data","volume":"48","author":"Bogue","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"2022010507314623900_B7","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkl983","article-title":"Mouse Tumor Biology Database (MTB): status update and future directions","volume":"35","author":"Begley","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"2022010507314623900_B8","doi-asserted-by":"crossref","first-page":"D818","DOI":"10.1093\/nar\/gku987","article-title":"Mouse Tumor Biology (MTB): a database of mouse models for human cancer","volume":"43","author":"Bult","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"2022010507314623900_B9","doi-asserted-by":"crossref","first-page":"D586","DOI":"10.1093\/nar\/gkp880","article-title":"The mouse genome database: enhancements and updates","volume":"38","author":"Bult","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"2022010507314623900_B10","doi-asserted-by":"crossref","first-page":"D924","DOI":"10.1093\/nar\/gkaa914","article-title":"The mouse Gene Expression Database (GXD): 2021 update","volume":"49","author":"Baldarelli","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"2022010507314623900_B11","doi-asserted-by":"crossref","first-page":"D1073","DOI":"10.1093\/nar\/gky984","article-title":"PDX finder: a portal for patient-derived tumor xenograft model discovery","volume":"47","author":"Conte","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2022010507314623900_B12","doi-asserted-by":"crossref","first-page":"D991","DOI":"10.1093\/nar\/gks1193","article-title":"NCBI GEO: archive for functional genomics data sets\u2014update","volume":"41","author":"Barrett","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2022010507314623900_B13","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"2022010507314623900_B14","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1093\/bioinformatics\/bts356","article-title":"RSeQC: quality control of RNA-seq experiments","volume":"28","author":"Wang","year":"2012","journal-title":"Bioinformatics"},{"key":"2022010507314623900_B15","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nmeth.4197","article-title":"Salmon provides fast and bias-aware quantification of transcript expression","volume":"14","author":"Patro","year":"2017","journal-title":"Nat. Methods"},{"key":"2022010507314623900_B16","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2022010507314623900_B17","doi-asserted-by":"crossref","first-page":"D325","DOI":"10.1093\/nar\/gkaa1113","article-title":"The Gene Ontology resource: enriching a GOld mine","volume":"49","author":"Gene Ontology Consortium","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"2022010507314623900_B18","doi-asserted-by":"crossref","first-page":"D545","DOI":"10.1093\/nar\/gkaa970","article-title":"KEGG: integrating viruses and cellular organisms","volume":"49","author":"Kanehisa","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"2022010507314623900_B19","first-page":"D498","article-title":"The reactome pathway knowledgebase","volume":"48","author":"Jassal","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"2022010507314623900_B20","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nature08460","article-title":"Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1","volume":"462","author":"Barbie","year":"2009","journal-title":"Nature"},{"key":"2022010507314623900_B21","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"2022010507314623900_B22","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1093\/biostatistics\/kxj037","article-title":"Adjusting batch effects in microarray expression data using empirical Bayes methods","volume":"8","author":"Johnson","year":"2007","journal-title":"Biostatistics"},{"key":"2022010507314623900_B23","doi-asserted-by":"crossref","first-page":"e0156594","DOI":"10.1371\/journal.pone.0156594","article-title":"Removing batch effects from longitudinal gene expression-quantile normalization plus ComBat as best approach for microarray transcriptome data","volume":"11","author":"M\u00fcller","year":"2016","journal-title":"PLoS One"},{"key":"2022010507314623900_B24","doi-asserted-by":"crossref","first-page":"D947","DOI":"10.1093\/nar\/gkaa609","article-title":"HRT Atlas v1. 0 database: redefining human and mouse housekeeping genes and candidate reference transcripts by mining massive RNA-seq datasets","volume":"49","author":"Hounkpe","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"2022010507314623900_B25","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/978-1-0716-0327-7_16","article-title":"Immunedeconv: an R Package for Unified Access to Computational Methods for Estimating Immune Cell Fractions from Bulk RNA-Sequencing Data","volume":"2120","author":"Sturm","year":"2020","journal-title":"Methods Mol. Biol."},{"key":"2022010507314623900_B26","doi-asserted-by":"crossref","first-page":"W509","DOI":"10.1093\/nar\/gkaa407","article-title":"TIMER2. 0 for analysis of tumor-infiltrating immune cells","volume":"48","author":"Li","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"2022010507314623900_B27","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1186\/s13059-017-1349-1","article-title":"xCell: digitally portraying the tissue cellular heterogeneity landscape","volume":"18","author":"Aran","year":"2017","journal-title":"Genome Biol."},{"key":"2022010507314623900_B28","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nmeth.3337","article-title":"Robust enumeration of cell subsets from tissue expression profiles","volume":"12","author":"Newman","year":"2015","journal-title":"Nat. Methods"},{"key":"2022010507314623900_B29","doi-asserted-by":"crossref","first-page":"e26476","DOI":"10.7554\/eLife.26476","article-title":"Simultaneous enumeration of cancer and immune cell types from bulk tumor gene expression data","volume":"6","author":"Racle","year":"2017","journal-title":"Elife"},{"key":"2022010507314623900_B30","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s13073-019-0638-6","article-title":"Molecular and pharmacological modulators of the tumor immune contexture revealed by deconvolution of RNA-seq data","volume":"11","author":"Finotello","year":"2019","journal-title":"Genome Med"},{"key":"2022010507314623900_B31","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s13073-020-00783-w","article-title":"The murine Microenvironment Cell Population counter method to estimate abundance of tissue-infiltrating immune and stromal cell populations in murine samples using gene expression","volume":"12","author":"Petitprez","year":"2020","journal-title":"Genome medicine"},{"key":"2022010507314623900_B32","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.cell.2019.07.019","article-title":"Opposing functions of interferon coordinate adaptive and innate immune responses to cancer immune checkpoint blockade","volume":"178","author":"Benci","year":"2019","journal-title":"Cell"},{"key":"2022010507314623900_B33","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.cell.2019.06.014","article-title":"Augmenting immunotherapy impact by lowering tumor TNF cytotoxicity threshold","volume":"178","author":"Vredevoogd","year":"2019","journal-title":"Cell"},{"key":"2022010507314623900_B34","doi-asserted-by":"crossref","first-page":"eaar3451","DOI":"10.1126\/sciimmunol.aar3451","article-title":"Tumor immune evasion arises through loss of TNF sensitivity","volume":"3","author":"Kearney","year":"2018","journal-title":"Sci. Immunol."},{"key":"2022010507314623900_B35","doi-asserted-by":"crossref","first-page":"2930","DOI":"10.1172\/JCI91190","article-title":"IFN-\u03b3-related mRNA profile predicts clinical response to PD-1 blockade","volume":"127","author":"Ayers","year":"2017","journal-title":"J. Clin. Invest."},{"key":"2022010507314623900_B36","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/S0952-7915(99)80014-4","article-title":"Antigen presentation by MHC class I and its regulation by interferon \u03b3","volume":"11","author":"Fr\u00fch","year":"1999","journal-title":"Curr. Opin. Immunol."},{"key":"2022010507314623900_B37","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/nature23477","article-title":"Identification of essential genes for cancer immunotherapy","volume":"548","author":"Patel","year":"2017","journal-title":"Nature"}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/50\/D1\/D1391\/42057684\/gkab804.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/50\/D1\/D1391\/42057684\/gkab804.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T07:48:10Z","timestamp":1641368890000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/50\/D1\/D1391\/6371975"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,17]]},"references-count":37,"journal-issue":{"issue":"D1","published-online":{"date-parts":[[2021,9,17]]},"published-print":{"date-parts":[[2022,1,7]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkab804","relation":{},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,1,7]]},"published":{"date-parts":[[2021,9,17]]}}}