{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T06:03:17Z","timestamp":1789970597410,"version":"4.0.1"},"reference-count":27,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF22OC0080036"],"award-info":[{"award-number":["NNF22OC0080036"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["isevjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Extracellular Bio"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Metabolic dysfunction\u2010associated steatotic liver disease (MASLD) is highly prevalent in obesity, but scalable tools for biological risk stratification remain limited. In this cross\u2010sectional, single\u2010centre discovery study (MULTISITE), we profiled circulating extracellular vesicle (cEV) surface proteins by EV Array in platelet\u2010poor plasma from individuals with obesity and MASLD (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a036), individuals with obesity without MASLD (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a024), and lean controls (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a027). Liver fat was quantified by magnetic resonance imaging proton density fat fraction (MRI\u2010PDFF). We assessed group differences, associations with continuous PDFF, and exploratory discriminatory performance using single markers, pairwise ratios, and sparse logistic models. We also performed an exploratory PDFF\u2010extremes enrichment analysis within obesity by comparing the top versus bottom 30% of the PDFF distribution (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a018\u00a0vs.\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a018), excluding the middle 40%. Across contrasts, single markers showed modest separation, whereas pairwise ratios provided stronger exploratory signals. In the discovery panel, uncorrected best\u2010ratio AUCs were 0.80\u20130.84 and sparse\u2010model AUCs were 0.79\u20130.84 under internal, non\u2010nested cross\u2010validation across MASLD\u2010focused contrasts. In the focused panel, CD36 and TREM2 were the strongest single\u2010marker signals for MASLD versus lean controls, whereas LRP\u20101\u2010anchored ratios captured obesity\u2010 and liver fat\u2010associated patterns. In the PDFF\u2010extremes analysis, internally cross\u2010validated AUCs reached 0.87\u20130.89 in the discovery panel and 0.86 for LRP\u20101\/FATP5 in the focused panel; these estimates should be interpreted as exploratory, uncorrected discovery\u2010stage observations rather than validated classifier performance. Exploratory benchmarking showed that FLI, but not FIB\u20104, discriminated MASLD\u2010related contrasts strongly, however, these analyses provide contextual benchmarking only and do not establish incremental clinical value of cEV markers beyond routine clinical predictors. These findings nominate biologically coherent cEV surface signatures for future validation in MASLD, anchored by lipid handling\/scavenger pathways and complemented by stress, immune, and coagulation biology.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration<\/jats:bold>\n                    : ClinicalTrials.gov: NCT05699863\n                  <\/jats:p>","DOI":"10.1002\/jex2.70183","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T08:35:14Z","timestamp":1788251714000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extracellular Vesicle Surface Protein Profiling in Metabolic Dysfunction\u2010associated Steatotic Liver Disease in Obesity"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6903-9972","authenticated-orcid":false,"given":"Nahuel Aquiles","family":"Garcia","sequence":"first","affiliation":[{"name":"GECORP  San Miguel del Monte Buenos Aires Argentina"},{"name":"Department of Clinical Biochemistry Aalborg University Hospital  Aalborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirstine","family":"Kl\u00f8ve\u2010Mogensen","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology Aalborg University Hospital  Aalborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3250-8509","authenticated-orcid":false,"given":"Katja Lund","family":"Cliff","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry Aalborg University Hospital  Aalborg Denmark"},{"name":"Department of Clinical Medicine Aalborg University  Aalborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikke","family":"B\u00e6k","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology Aalborg University Hospital  Aalborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malwina","family":"Ulanowska","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry Aalborg University Hospital  Aalborg Denmark"},{"name":"Department of Clinical Medicine Aalborg University  Aalborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2225-3116","authenticated-orcid":false,"given":"Javier Alejandro Donoso","family":"Quezada","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry Aalborg University Hospital  Aalborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malene M\u00f8ller","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology Aalborg University Hospital  Aalborg Denmark"},{"name":"Department of Clinical Medicine Aalborg University  Aalborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aase","family":"Handberg","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry Aalborg University Hospital  Aalborg Denmark"},{"name":"Department of Clinical Medicine Aalborg University  Aalborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5854-1086","authenticated-orcid":false,"given":"Maiken","family":"Mellergaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry Aalborg University Hospital  Aalborg Denmark"},{"name":"Department of Clinical Medicine Aalborg University  Aalborg 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