{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T16:04:20Z","timestamp":1762272260347,"version":"build-2065373602"},"reference-count":41,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Computers in Biology and Medicine"],"published-print":{"date-parts":[[2025,11]]},"DOI":"10.1016\/j.compbiomed.2025.111173","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T16:13:20Z","timestamp":1759853600000},"page":"111173","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"PA","title":["A mechanistic modeling framework to interpret ACTH stimulation tests across HPA axis adaptation states and glucocorticoid feedback dynamics"],"prefix":"10.1016","volume":"198","author":[{"given":"Mamta","family":"Yadav","sequence":"first","affiliation":[]},{"given":"Phool","family":"Singh","sequence":"additional","affiliation":[]}],"member":"78","reference":[{"issue":"4","key":"10.1016\/j.compbiomed.2025.111173_b1","doi-asserted-by":"crossref","first-page":"986","DOI":"10.3390\/ijms19040986","article-title":"Role of the hypothalamic\u2013pituitary\u2013adrenal axis in health and disease","volume":"19","author":"DeMorrow","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.compbiomed.2025.111173_b2","doi-asserted-by":"crossref","DOI":"10.3389\/fnbeh.2020.601939","article-title":"The hypothalamic-pituitary-adrenal axis: development, programming actions of hormones, and maternal-fetal interactions","volume":"14","author":"Sheng","year":"2021","journal-title":"Front. Behav. Neurosci."},{"issue":"1","key":"10.1016\/j.compbiomed.2025.111173_b3","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/nyas.12464","article-title":"Circadian endocrine rhythms: the hypothalamic\u2013pituitary\u2013adrenal axis and its actions","volume":"1318","author":"Nicolaides","year":"2014","journal-title":"Ann. New York Acad. Sci."},{"issue":"5","key":"10.1016\/j.compbiomed.2025.111173_b4","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1097\/MED.0b013e32832fa137","article-title":"Stress and obesity: the role of the hypothalamic\u2013pituitary\u2013adrenal axis in metabolic disease","volume":"16","author":"Bose","year":"2009","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"10.1016\/j.compbiomed.2025.111173_b5","article-title":"Fast dynamics in the HPA axis: insight from mathematical and experimental studies","volume":"27","author":"Walker","year":"2022","journal-title":"Curr. Opin. Endocr. Metab. Res."},{"issue":"3","key":"10.1016\/j.compbiomed.2025.111173_b6","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1002\/j.2040-4603.2015.tb00644.x","article-title":"Hypothalamic-pituitary-adrenal axis\u2014feedback control","volume":"5","author":"Keller-Wood","year":"2015","journal-title":"Compr. Physiol."},{"key":"10.1016\/j.compbiomed.2025.111173_b7","doi-asserted-by":"crossref","DOI":"10.1016\/j.pnpbp.2020.109951","article-title":"The HPA axis dysregulation in severe mental illness: Can we shift the blame to gut microbiota?","volume":"102","author":"Misiak","year":"2020","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"10.1016\/j.compbiomed.2025.111173_b8","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3389\/fpsyt.2015.00031","article-title":"Dysregulated hypothalamic\u2013pituitary\u2013adrenal axis function contributes to altered endocrine and neurobehavioral responses to acute stress","volume":"6","author":"Kinlein","year":"2015","journal-title":"Front. Psychiatry"},{"issue":"6","key":"10.1016\/j.compbiomed.2025.111173_b9","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1097\/MEJ.0000000000000693","article-title":"Dysfunction of the hypothalamic-pituitary-adrenal axis in critical illness: a narrative review for emergency physicians","volume":"27","author":"Marino","year":"2020","journal-title":"Eur. J. Emerg. Med."},{"issue":"1","key":"10.1016\/j.compbiomed.2025.111173_b10","article-title":"A review of hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome","volume":"2013","author":"Tomas","year":"2013","journal-title":"Int. Sch. Res. Not."},{"issue":"1","key":"10.1016\/j.compbiomed.2025.111173_b11","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1080\/10253890601130823","article-title":"The hypothalamo\u2013pituitary\u2013adrenal axis in chronic fatigue syndrome and fibromyalgia syndrome","volume":"10","author":"Tanriverdi","year":"2007","journal-title":"Stress"},{"issue":"4","key":"10.1016\/j.compbiomed.2025.111173_b12","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/mp.2016.120","article-title":"HPA axis in major depression: cortisol, clinical symptomatology and genetic variation predict cognition","volume":"22","author":"Keller","year":"2017","journal-title":"Mol. Psychiatry"},{"issue":"8","key":"10.1016\/j.compbiomed.2025.111173_b13","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.cpr.2007.02.005","article-title":"Risk for recurrence in depression","volume":"27","author":"Burcusa","year":"2007","journal-title":"Clin. Psychol. Rev."},{"key":"10.1016\/j.compbiomed.2025.111173_b14","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.cpr.2018.07.005","article-title":"Risk factors for relapse and recurrence of depression in adults and how they operate: A four-phase systematic review and meta-synthesis","volume":"64","author":"Buckman","year":"2018","journal-title":"Clin. Psychol. Rev."},{"issue":"3","key":"10.1016\/j.compbiomed.2025.111173_b15","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1037\/0021-843X.108.3.483","article-title":"First onset versus recurrence of depression: differential processes of psychosocial risk","volume":"108","author":"Lewinsohn","year":"1999","journal-title":"J. Abnorm. Psychol."},{"issue":"7","key":"10.1016\/j.compbiomed.2025.111173_b16","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1097\/00152193-200607000-00019","article-title":"ACTH stimulation: Testing the adrenals","volume":"36","author":"Whiteman","year":"2006","journal-title":"Nursing2024"},{"key":"10.1016\/j.compbiomed.2025.111173_b17","article-title":"Predictive value of different thresholds of morning cortisol in diagnosing adrenal insufficiency","volume":"16","author":"Ghasham","year":"2024","journal-title":"Endocr. Metab. Sci."},{"key":"10.1016\/j.compbiomed.2025.111173_b18","series-title":"StatPearls [Internet]","article-title":"Adrenocorticotropic hormone (cosyntropin) stimulation test","author":"Khare","year":"2023"},{"issue":"16","key":"10.1016\/j.compbiomed.2025.111173_b19","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1056\/NEJM199610173351607","article-title":"Adrenal insufficiency","volume":"335","author":"Oelkers","year":"1996","journal-title":"N. Engl. J. Med."},{"issue":"2","key":"10.1016\/j.compbiomed.2025.111173_b20","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1210\/jc.2015-1700","article-title":"ACTH stimulation tests for the diagnosis of adrenal insufficiency: systematic review and meta-analysis","volume":"101","author":"Ospina","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"10","key":"10.1016\/j.compbiomed.2025.111173_b21","doi-asserted-by":"crossref","first-page":"4323","DOI":"10.1210\/jc.2019-00304","article-title":"The low-dose ACTH test: usefulness of combined analysis of serum and salivary maximum cortisol response in pediatrics","volume":"104","author":"Vaiani","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"12","key":"10.1016\/j.compbiomed.2025.111173_b22","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.2522\/ptj.20130597","article-title":"Chronic stress, cortisol dysfunction, and pain: a psychoneuroendocrine rationale for stress management in pain rehabilitation","volume":"94","author":"Hannibal","year":"2014","journal-title":"Phys. Ther."},{"key":"10.1016\/j.compbiomed.2025.111173_b23","series-title":"StatPearls [Internet]","article-title":"Physiology, cortisol","author":"Thau","year":"2023"},{"issue":"4","key":"10.1016\/j.compbiomed.2025.111173_b24","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0895-7177(99)00043-6","article-title":"A dynamical model for the pulsatile secretion of the hypothalamo-pituitary-adrenal axis","volume":"29","author":"Yi-Wei","year":"1999","journal-title":"Math. Comput. Modelling"},{"issue":"2","key":"10.1016\/j.compbiomed.2025.111173_b25","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.mbs.2005.06.006","article-title":"Mathematical modeling of the hypothalamic-pituitary-adrenal system activity","volume":"197","author":"Smiljana Jeli\u0107","year":"2005","journal-title":"Math. Biosci."},{"key":"10.1016\/j.compbiomed.2025.111173_b26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1742-4682-4-8","article-title":"Inclusion of the glucocorticoid receptor in a hypothalamic pituitary adrenal axis model reveals bistability","volume":"4","author":"Gupta","year":"2007","journal-title":"Theor. Biol. Med. Model."},{"issue":"1","key":"10.1016\/j.compbiomed.2025.111173_b27","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1093\/imammb\/dqn003","article-title":"Variability in the secretion of corticotropin-releasing hormone, adrenocorticotropic hormone and cortisol and understandability of the hypothalamic-pituitary-adrenal axis dynamics\u2014a mathematical study based on clinical evidence","volume":"25","author":"Bairagi","year":"2008","journal-title":"Math. Med. Biol.: A J. IMA"},{"issue":"1688","key":"10.1016\/j.compbiomed.2025.111173_b28","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1098\/rspb.2009.2148","article-title":"Origin of ultradian pulsatility in the hypothalamic-pituitary-adrenal axis","volume":"277","author":"Walker","year":"2010","journal-title":"Proc. R. Soc. B: Biol. Sci."},{"key":"10.1016\/j.compbiomed.2025.111173_b29","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1007\/s00285-010-0384-2","article-title":"The minimal model of the hypothalamic-pituitary-adrenal axis","volume":"63","author":"Vinther","year":"2011","journal-title":"J. Math. Biol."},{"issue":"2","key":"10.1016\/j.compbiomed.2025.111173_b30","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1002379","article-title":"Modeling cortisol dynamics in the neuro-endocrine axis distinguishes normal, depression, and post-traumatic stress disorder (PTSD) in humans","volume":"8","author":"Sriram","year":"2012","journal-title":"PLoS Comput. Biol."},{"issue":"1","key":"10.1016\/j.compbiomed.2025.111173_b31","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.mbs.2013.08.010","article-title":"Mathematical modeling of the hypothalamic\u2013pituitary\u2013adrenal gland (HPA) axis, including hippocampal mechanisms","volume":"246","author":"Andersen","year":"2013","journal-title":"Math. Biosci."},{"issue":"7","key":"10.1016\/j.compbiomed.2025.111173_b32","doi-asserted-by":"crossref","DOI":"10.15252\/msb.20209510","article-title":"A new model for the HPA axis explains dysregulation of stress hormones on the timescale of weeks","volume":"16","author":"Karin","year":"2020","journal-title":"Mol. Syst. Biol."},{"issue":"5","key":"10.1016\/j.compbiomed.2025.111173_b33","doi-asserted-by":"crossref","first-page":"E965","DOI":"10.1152\/ajpendo.00070.2006","article-title":"Chronic stress induces adrenal hyperplasia and hypertrophy in a subregion-specific manner","volume":"291","author":"Ulrich-Lai","year":"2006","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"issue":"1","key":"10.1016\/j.compbiomed.2025.111173_b34","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1210\/er.2015-1080","article-title":"The functional and clinical significance of the 24-hour rhythm of circulating glucocorticoids","volume":"38","author":"Oster","year":"2017","journal-title":"Endocr. Rev."},{"issue":"4","key":"10.1016\/j.compbiomed.2025.111173_b35","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/0165-1781(87)90094-1","article-title":"The ACTH stimulation test before and after clinical recovery from depression","volume":"20","author":"Amsterdam","year":"1987","journal-title":"Psychiatry Res."},{"key":"10.1016\/j.compbiomed.2025.111173_b36","first-page":"1","article-title":"Glucocorticoid induced adrenal insufficiency is common in steroid treated glomerular diseases-proposed strategy for screening and management","volume":"20","author":"Karangizi","year":"2019","journal-title":"BioMed Central Nephrol."},{"issue":"10","key":"10.1016\/j.compbiomed.2025.111173_b37","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.3390\/ijms18102201","article-title":"Treatment with synthetic glucocorticoids and the hypothalamus-pituitary-adrenal axis","volume":"18","author":"Paragliola","year":"2017","journal-title":"Int. J. Mol. Sci."},{"year":"2015","series-title":"Glucocorticoid therapy and adrenal suppression","author":"Nicolaides","key":"10.1016\/j.compbiomed.2025.111173_b38"},{"key":"10.1016\/j.compbiomed.2025.111173_b39","article-title":"Glucocorticoid induced adrenal insufficiency","volume":"374","author":"Prete","year":"2021","journal-title":"Br. Med. J."},{"issue":"1","key":"10.1016\/j.compbiomed.2025.111173_b40","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1097\/00005792-197601000-00003","article-title":"Glucocorticoid therapy","volume":"55","author":"Axelrod","year":"1976","journal-title":"Medicine"},{"issue":"2","key":"10.1016\/j.compbiomed.2025.111173_b41","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/j.2040-4603.2016.tb00694.x","article-title":"Regulation of the hypothalamic-pituitary-adrenocortical stress response","volume":"6","author":"Herman","year":"2016","journal-title":"Compr. Physiol."}],"container-title":["Computers in Biology and Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0010482525015264?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0010482525015264?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T15:50:03Z","timestamp":1762271403000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0010482525015264"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":41,"alternative-id":["S0010482525015264"],"URL":"https:\/\/doi.org\/10.1016\/j.compbiomed.2025.111173","relation":{},"ISSN":["0010-4825"],"issn-type":[{"type":"print","value":"0010-4825"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A mechanistic modeling framework to interpret ACTH stimulation tests across HPA axis adaptation states and glucocorticoid feedback dynamics","name":"articletitle","label":"Article Title"},{"value":"Computers in Biology and Medicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.compbiomed.2025.111173","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"111173"}}