{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T18:43:53Z","timestamp":1775933033814,"version":"3.50.1"},"posted":{"date-parts":[[2025,2,23]]},"group-title":"Cell Biology","reference-count":53,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,2,23]],"date-time":"2025-02-23T00:00:00Z","timestamp":1740268800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,2,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>BACKGROUND AND AIMS<\/jats:title>\n                  <jats:p>\n                    Aberrant cellular glycosylation remains a key event that accompanies and actively sustains gastric neoplastic transformation. Patient-derived organoids (PDOs) have recently emerged as a promising\n                    <jats:italic>ex vivo<\/jats:italic>\n                    model to study human gastric disorders. Since the PDOs glycosylation landscape remains unknown, this study aims to evaluate PDOs as potential\n                    <jats:italic>avatars<\/jats:italic>\n                    of\n                    <jats:italic>in vivo<\/jats:italic>\n                    tissue glycosylation profiles in the gastric context.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>\n                    Fresh gastric mucosa samples derived from non-tumoral obese patients (n=11), adjacent tumor mucosa samples (n=29), and tumor tissue samples derived from gastric cancer (GC) patients (n=30) were used to establish a biobank of gastric PDOs (n=56). The\n                    <jats:italic>N<\/jats:italic>\n                    - and\n                    <jats:italic>O-<\/jats:italic>\n                    glycophenotypes of normal, adjacent, and tumor PDOs and respective\n                    <jats:italic>in vivo<\/jats:italic>\n                    tissues were thoroughly characterized by immunostaining. Additionally, a comparative glycan analysis was performed over time, upon PDO biobanking and xenografting in mice. The binding of two\n                    <jats:italic>Helicobacter pylori<\/jats:italic>\n                    (\n                    <jats:italic>H. pylori<\/jats:italic>\n                    ) isogenic strains with distinct glycan-binding affinities was assessed in parental gastric mucosa tissues and compared with the respective PDOs before and after modulation of their glycan landscape.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>\n                    Our results show that PDOs mimic different phenotypes of the carcinogenic cascade and recapitulate parental gastric tissues\u2019 glycosylation profile. Tumor PDOs recapitulate the inter- and intra-heterogeneity features observed in GC, which is maintained over time, upon biobanking and xenografting. We demonstrated that the expression of type I and type II Lewis antigens is dynamically controlled by PDOs differentiation status, which results in differential binding to\n                    <jats:italic>H. pylori<\/jats:italic>\n                    strains displaying distinct glycan-binding adhesins, mirroring the gastric epithelium tissue interactions.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>\n                    This study established PDOs as invaluable\n                    <jats:italic>ex vivo<\/jats:italic>\n                    tools to study the complex glycan dynamics in both gastric physiological and pathological settings.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.02.21.639100","type":"posted-content","created":{"date-parts":[[2025,2,23]],"date-time":"2025-02-23T19:05:20Z","timestamp":1740337520000},"source":"Crossref","is-referenced-by-count":1,"title":["Patient-derived organoids to study glycosylation dynamics during gastric disease"],"prefix":"10.64898","author":[{"given":"Liliana","family":"Santos-Ferreira","sequence":"first","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"},{"name":"IPATIMUP \u2013 Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal"},{"name":"ICBAS \u2013 Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, Porto, Portugal"}]},{"given":"Henrique O.","family":"Duarte","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"},{"name":"IPATIMUP \u2013 Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal"}]},{"given":"Eva","family":"Moia","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"},{"name":"IPATIMUP \u2013 Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal"}]},{"given":"Ana F.","family":"Costa","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"},{"name":"IPATIMUP \u2013 Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal"},{"name":"ICBAS \u2013 Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, Porto, Portugal"}]},{"given":"\u00c1lvaro M.","family":"Martins","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"},{"name":"IPATIMUP \u2013 Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal"},{"name":"ICBAS \u2013 Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, Porto, Portugal"}]},{"given":"Isabel","family":"Faria-Ramos","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"},{"name":"IPATIMUP \u2013 Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal"}]},{"given":"Rita","family":"Matos","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"},{"name":"IPATIMUP \u2013 Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal"}]},{"given":"Rita","family":"Barros","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"},{"name":"IPATIMUP \u2013 Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal"},{"name":"Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal"},{"name":"Service of Anatomy Pathology of Unidade Local de Sa\u00fade (ULS) de S\u00e3o Jo\u00e3o, Porto, Portugal"}]},{"given":"Marta","family":"Silva","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"}]},{"given":"Sofia","family":"Pedrosa","sequence":"additional","affiliation":[{"name":"Service of Anatomy Pathology of Unidade Local de Sa\u00fade (ULS) de S\u00e3o Jo\u00e3o, Porto, Portugal"}]},{"given":"Diana A.","family":"Batista","sequence":"additional","affiliation":[{"name":"Service of Anatomy Pathology of Unidade Local de Sa\u00fade (ULS) de S\u00e3o Jo\u00e3o, Porto, Portugal"}]},{"given":"Joana","family":"Gomes","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"},{"name":"IPATIMUP \u2013 Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal"}]},{"given":"Thomas","family":"Bor\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Ume\u00e5 University, Ume\u00e5, Sweden"}]},{"given":"Fabiana","family":"Sousa","sequence":"additional","affiliation":[{"name":"Surgery Department of Unidade Local de Sa\u00fade (ULS) de S\u00e3o Jo\u00e3o, Porto, Portugal"},{"name":"Department of Surgery and Physiology Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal"}]},{"given":"Frederica","family":"Casanova-Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Surgery Department of Unidade Local de Sa\u00fade (ULS) de S\u00e3o Jo\u00e3o, Porto, Portugal"},{"name":"Department of Surgery and Physiology Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal"}]},{"given":"Jos\u00e9","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Surgery Department of Unidade Local de Sa\u00fade (ULS) de S\u00e3o Jo\u00e3o, Porto, Portugal"},{"name":"Department of Surgery and Physiology Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal"}]},{"given":"Ana","family":"Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"},{"name":"IPATIMUP \u2013 Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal"},{"name":"ICBAS \u2013 Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, Porto, Portugal"}]},{"given":"Catarina","family":"Gomes","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"},{"name":"IPATIMUP \u2013 Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal"}]},{"given":"Hugo","family":"Santos-Sousa","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"},{"name":"Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal"},{"name":"Surgery Department of Unidade Local de Sa\u00fade (ULS) de S\u00e3o Jo\u00e3o, Porto, Portugal"},{"name":"Obesity Integrated Responsibility Unit (CRI-O), S\u00e3o Jo\u00e3o University Medical Center, Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2493-8282","authenticated-orcid":false,"given":"Sina","family":"Bartfeld","sequence":"additional","affiliation":[{"name":"Si-M\/\u2019Der SimulierteMensh,Technische Universit\u00e4t Berlin and Charit\u00e9-Uniersitatsmedizin Berlin, Berlin, Germany"},{"name":"Institute of Biotechnology, Technische Universit\u00e4t Berlin, Berlin, Germany"}]},{"given":"F\u00e1tima","family":"Carneiro","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"},{"name":"IPATIMUP \u2013 Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal"},{"name":"Department of Pathology, Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal"},{"name":"Department of Pathology of Unidade Local de Sa\u00fade (ULS) de S\u00e3o Jo\u00e3o, Porto, Portugal"}]},{"given":"Celso A.","family":"Reis","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"},{"name":"IPATIMUP \u2013 Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal"},{"name":"ICBAS \u2013 Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, Porto, Portugal"},{"name":"Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal"}]},{"given":"Filipe","family":"Pinto","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"},{"name":"IPATIMUP \u2013 Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal"}]}],"member":"54368","reference":[{"key":"2026041110525274000_2025.02.21.639100v1.1","unstructured":"Varki A CR , Esko JD , et al., editors. Essentials of glycobiology: Cold Spring Harbor Laboratory Press, 2022."},{"key":"2026041110525274000_2025.02.21.639100v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3982"},{"key":"2026041110525274000_2025.02.21.639100v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2019.06.006"},{"key":"2026041110525274000_2025.02.21.639100v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-019-0129-4"},{"key":"2026041110525274000_2025.02.21.639100v1.5","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199501000-00005"},{"key":"2026041110525274000_2025.02.21.639100v1.6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra020542"},{"key":"2026041110525274000_2025.02.21.639100v1.7","doi-asserted-by":"publisher","DOI":"10.1586\/epr.10.18"},{"key":"2026041110525274000_2025.02.21.639100v1.8","doi-asserted-by":"publisher","DOI":"10.1126\/science.8018146"},{"key":"2026041110525274000_2025.02.21.639100v1.9","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5349.373"},{"key":"2026041110525274000_2025.02.21.639100v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/srep25575"},{"key":"2026041110525274000_2025.02.21.639100v1.11","doi-asserted-by":"publisher","DOI":"10.1126\/science.1069076"},{"key":"2026041110525274000_2025.02.21.639100v1.12","doi-asserted-by":"publisher","DOI":"10.1172\/JCI34324"},{"key":"2026041110525274000_2025.02.21.639100v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2015.07.001"},{"key":"2026041110525274000_2025.02.21.639100v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2008.5"},{"key":"2026041110525274000_2025.02.21.639100v1.15","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2018.1440171"},{"key":"2026041110525274000_2025.02.21.639100v1.16","first-page":"1003","article-title":"Intestinal metaplasia of human stomach displays distinct patterns of mucin (MUC1, MUC2, MUC5AC, and MUC6) expression","volume":"59","year":"1999","journal-title":"Cancer Res"},{"key":"2026041110525274000_2025.02.21.639100v1.17","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.5A6836.2006"},{"key":"2026041110525274000_2025.02.21.639100v1.18","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwp161"},{"key":"2026041110525274000_2025.02.21.639100v1.19","doi-asserted-by":"publisher","DOI":"10.7150\/thno.33858"},{"key":"2026041110525274000_2025.02.21.639100v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.01.017"},{"key":"2026041110525274000_2025.02.21.639100v1.21","doi-asserted-by":"crossref","unstructured":"Balmana M , Diniz F , Feijao T , et al. Analysis of the Effect of Increased alpha2,3-Sialylation on RTK Activation in MKN45 Gastric Cancer Spheroids Treated with Crizotinib. Int J Mol Sci 2020;21.","DOI":"10.3390\/ijms21030722"},{"key":"2026041110525274000_2025.02.21.639100v1.22","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-021-01801-w"},{"key":"2026041110525274000_2025.02.21.639100v1.23","doi-asserted-by":"publisher","DOI":"10.1007\/s13402-021-00606-z"},{"key":"2026041110525274000_2025.02.21.639100v1.24","doi-asserted-by":"crossref","unstructured":"Pinto F , Santos-Ferreira L , Pinto MT , et al. The Extracellular Small Leucine-Rich Proteoglycan Biglycan Is a Key Player in Gastric Cancer Aggressiveness. Cancers (Basel) 2021;13.","DOI":"10.3390\/cancers13061330"},{"key":"2026041110525274000_2025.02.21.639100v1.25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2214853120"},{"key":"2026041110525274000_2025.02.21.639100v1.26","doi-asserted-by":"publisher","DOI":"10.1007\/s10719-023-10113-y"},{"key":"2026041110525274000_2025.02.21.639100v1.27","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.09.042"},{"key":"2026041110525274000_2025.02.21.639100v1.28","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-020-00662-2"},{"key":"2026041110525274000_2025.02.21.639100v1.29","doi-asserted-by":"crossref","unstructured":"Bartfeld S , Clevers H . Organoids as Model for Infectious Diseases: Culture of Human and Murine Stomach Organoids and Microinjection of Helicobacter Pylori. J Vis Exp 2015.","DOI":"10.3791\/53359"},{"key":"2026041110525274000_2025.02.21.639100v1.30","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-021-00629-4"},{"key":"2026041110525274000_2025.02.21.639100v1.31","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33165-4"},{"key":"2026041110525274000_2025.02.21.639100v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.09.016"},{"key":"2026041110525274000_2025.02.21.639100v1.33","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2017-314549"},{"key":"2026041110525274000_2025.02.21.639100v1.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2024.130566"},{"key":"2026041110525274000_2025.02.21.639100v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80653-6"},{"key":"2026041110525274000_2025.02.21.639100v1.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.05.031"},{"key":"2026041110525274000_2025.02.21.639100v1.37","unstructured":"Ana FC , Emanuel S , Diana C , et al. Monensin as potential drug for treatment of SLeX-positive tumors. medRxiv 2024:2024.03.11.24304048."},{"key":"2026041110525274000_2025.02.21.639100v1.38","first-page":"149","article-title":"Gastric Organoids: An Emerging Model System to Study Helicobacter pylori Pathogenesis","volume":"400","year":"2017","journal-title":"Curr Top Microbiol Immunol"},{"key":"2026041110525274000_2025.02.21.639100v1.39","doi-asserted-by":"publisher","DOI":"10.32074\/1591-951X-166"},{"key":"2026041110525274000_2025.02.21.639100v1.40","first-page":"919","article-title":"Lewis blood group-related antigen expression in normal gastric epithelium, intestinal metaplasia, gastric adenoma, and gastric carcinoma","volume":"88","year":"1993","journal-title":"Am J Gastroenterol"},{"key":"2026041110525274000_2025.02.21.639100v1.41","doi-asserted-by":"publisher","DOI":"10.1007\/s004280100531"},{"key":"2026041110525274000_2025.02.21.639100v1.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2016.01.044"},{"key":"2026041110525274000_2025.02.21.639100v1.43","first-page":"745","article-title":"Expression of Lewisa, Lewisb, Lewisx, Lewisy, siayl-Lewisa, and sialyl-Lewisx blood group antigens in human gastric carcinoma and in normal gastric tissue","volume":"49","year":"1989","journal-title":"Cancer Res"},{"key":"2026041110525274000_2025.02.21.639100v1.44","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-018-6662-8"},{"key":"2026041110525274000_2025.02.21.639100v1.45","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao2774"},{"key":"2026041110525274000_2025.02.21.639100v1.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.027"},{"key":"2026041110525274000_2025.02.21.639100v1.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104314"},{"key":"2026041110525274000_2025.02.21.639100v1.48","doi-asserted-by":"crossref","unstructured":"Yue SSK , Tong Y , Siu HC , et al. Divergent lineage trajectories and genetic landscapes in human gastric intestinal metaplasia organoids associated with early neoplastic progression. Gut 2024:gutjnl-2024-332594.","DOI":"10.1101\/2024.04.03.588024"},{"key":"2026041110525274000_2025.02.21.639100v1.49","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2022.06.021"},{"key":"2026041110525274000_2025.02.21.639100v1.50","doi-asserted-by":"publisher","DOI":"10.1177\/0194599813482879"},{"key":"2026041110525274000_2025.02.21.639100v1.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2015.07.002"},{"key":"2026041110525274000_2025.02.21.639100v1.52","doi-asserted-by":"publisher","DOI":"10.1038\/srep40656"},{"key":"2026041110525274000_2025.02.21.639100v1.53","doi-asserted-by":"crossref","unstructured":"Huang L , Bockorny B , Paul I , et al. PDX-derived organoids model in vivo drug response and secrete biomarkers. JCI Insight 2020;5.","DOI":"10.1172\/jci.insight.135544"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.02.21.639100","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T17:52:57Z","timestamp":1775929977000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.02.21.639100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,23]]},"references-count":53,"URL":"https:\/\/doi.org\/10.1101\/2025.02.21.639100","relation":{},"subject":[],"published":{"date-parts":[[2025,2,23]]},"subtype":"preprint"}}