{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:54:52Z","timestamp":1788353692472,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Metabolic dysfunction\u2010associated fatty liver disease causes hepatic fat accumulation (steatosis) and fibrosis, which can be measured with ultrasound elastography imaging. The dependencies of elastography\u2010derived hepatic steatosis and fibrosis measures with chronic inflammation, disease states, and physiological determinants of drug dosing (PDODD) were assessed. Liver elastography data for\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20095494 participants (50% female, 12\u201380\u2009years) were obtained from the National Health and Nutrition Examination Survey. Controlled attenuation parameter (CAP) and median liver stiffness (LSM) elastography metrics were used to assess steatosis and fibrosis, and their associations with over 50 key organ systems, disease, and PDODD biomarkers were evaluated with statistical regression, ensemble, and Bayesian learning methods. CAP and LSM increased with age and were greater in males, active liver disease, active hepatitis C, and diabetes or prediabetes. LSM was greater in the presence of congestive heart failure and dialysis. The inflammatory markers C\u2010reactive protein (CRP) and ferritin, body surface area, and hepatic\n                    <jats:italic>R<\/jats:italic>\n                    \u2010value were greater in steatosis and fibrosis. Plasma volume, neutrophil, red blood cell, and platelet counts were greater in steatosis. Drug\u2010induced liver injury index was lower in steatosis and greater in fibrosis. Albumin levels and platelet counts were lower, but the urine albumin\u2010to\u2010creatine ratio was greater in fibrosis. Ensemble learning identified interactions among BMI, age, CRP, ferritin, and liver enzymes contributing to steatosis and fibrosis. Bayesian networks were used to identify directed acyclic graph structures for steatosis and fibrosis. Elastography\u2010derived measures may be useful for individualizing dosing regimens in the presence of metabolic comorbidities presenting dose\u2010selection challenges.\n                  <\/jats:p>","DOI":"10.1111\/cts.70352","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T11:14:47Z","timestamp":1761218087000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Network Modeling of Biomarker Systems in Liver Steatosis and Fibrosis"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5180-7790","authenticated-orcid":false,"given":"Amruta Gajanan","family":"Bhat","sequence":"first","affiliation":[{"name":"Artificial Intelligence and Clinical Pharmacology Laboratory, Department of Pharmaceutical Sciences University at Buffalo, the State University of New York  Buffalo New York USA"},{"name":"Department of Neurology University at Buffalo, the State University of New York  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9943-150X","authenticated-orcid":false,"given":"Murali","family":"Ramanathan","sequence":"additional","affiliation":[{"name":"Artificial Intelligence and Clinical Pharmacology Laboratory, Department of Pharmaceutical Sciences University at Buffalo, the State University of New York  Buffalo New York USA"},{"name":"Department of Neurology University at Buffalo, the State University of New York  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200528060-00005"},{"issue":"2","key":"e_1_2_10_3_1","first-page":"111","article-title":"Generative Models for Age, Race\/Ethnicity, and Disease State Dependence of Physiological Determinants of Drug Dosing","volume":"50","author":"Nair R.","year":"2023","journal-title":"Journal of Pharmacokinetics and Pharmacodynamics"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000670"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2019-318813"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.01.052"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(19)30039-1"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24282"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.04.001"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ultrasmedbio.2003.07.001"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1590\/0100-3984.2019.0028"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.13219"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00261-015-0373-4"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.14218\/JCTH.2021.00311"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.01.043"},{"key":"e_1_2_10_16_1","unstructured":"C. J.Endres nhanesA: NHANES Data Retrieval(2023)."},{"key":"e_1_2_10_17_1","volume-title":"National Center for Health Statistics","author":"National Health and Nutrition Examination Survey","year":"2015"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.12.022"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28394"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.32614\/RJ-2021-041"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1145\/2939672.2939785"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4614-6446-4"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v035.i03"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005973"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-021-09786-5"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231911751"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2037"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-024-03664-8"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2614"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.13275"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0262291"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-59183-4"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes11121509"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920012802138642"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.111.038679"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.23043"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70352","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T05:32:13Z","timestamp":1761370333000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70352"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":35,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1111\/cts.70352"],"URL":"https:\/\/doi.org\/10.1111\/cts.70352","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"2024-12-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70352"}}