{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T18:22:49Z","timestamp":1788805369870,"version":"build-2803163510"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Key Laboratory of Respiratory Inflammatory Injury and Precision Diagnosis and Treatment, Chongqing Municipal Health and Health Committee"},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270091"],"award-info":[{"award-number":["82270091"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute Respiratory Distress Syndrome (ARDS) remains a critical condition associated with high mortality rates, prolonged hospitalization, and reduced quality of life despite advances in critical care. The albumin-corrected anion gap (ACAG), an emerging biomarker reflecting acid-base disturbances, has been linked to poor outcomes in various critical illnesses. However, its prognostic value for mortality in ARDS patients remains unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective study analyzed data from ARDS patients admitted to intensive care units (ICUs) in the MIMIC-IV database. Patients were stratified into quartiles (Q1\u2013Q4) based on ACAG levels. The association between ACAG and 28-day all-cause mortality was comprehensively evaluated using restricted cubic splines, Kaplan\u2013Meier survival analysis, and Cox proportional hazards regression. We employed the Boruta algorithm and LASSO (Least Absolute Shrinkage and Selection Operator) regression to identify key predictive factors. Six machine learning algorithms were used to develop predictive models, with performance assessed by the area under the ROC curve (AUC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Higher ACAG levels were significantly associated with increased 28-day mortality risk in ARDS patients (P\u2009&lt;\u20090.001). ACAG remained independently associated with 28-day all-cause mortality after comprehensive adjustment for confounders, with a hazard ratio (HR) of 1.04 (95% CI 1.01\u20131.07, P\u2009=\u20090.003) Subgroup analysis demonstrated that this association persisted across most demographic and clinical subgroups, with significant interactions observed only for myocardial infarction and malignancy (P for interaction\u2009&lt;\u20090.05). Feature selection using Boruta and LASSO analyses consistently identified ACAG as a key predictor. Among the six machine learning models evaluated, the random forest (RF) algorithm demonstrated superior performance with an AUC of 0.73.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Higher ACAG levels are independently associated with increased 28-day all-cause mortality in patients with ARDS. ACAG is a promising predictor of short-term mortality and may guide risk stratification in clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0336662","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T18:25:15Z","timestamp":1763663115000},"page":"e0336662","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Albumin-corrected anion gap as a predictor of 28-day mortality in acute respiratory distress syndrome: A machine learning-based retrospective 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failure: a retrospective study from MIMIC-IV database","volume":"24","author":"N Li","year":"2024","journal-title":"BMC Cardiovasc Disord"},{"issue":"2","key":"pone.0336662.ref020","doi-asserted-by":"crossref","first-page":"2282708","DOI":"10.1080\/0886022X.2023.2282708","article-title":"Association between albumin corrected anion gap and all-cause mortality in critically ill patients with acute kidney injury: a retrospective study based on MIMIC-IV database","volume":"45","author":"P Gao","year":"2023","journal-title":"Ren Fail"},{"issue":"1","key":"pone.0336662.ref021","doi-asserted-by":"crossref","first-page":"16903","DOI":"10.1038\/s41598-023-44182-8","article-title":"The relationship between albumin corrected anion gap levels and mortality in patients with asthma in the ICU","volume":"13","author":"S Wang","year":"2023","journal-title":"Sci 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prevalence studies using Scalex and ScalaR calculators","volume":"22","author":"L Naing","year":"2022","journal-title":"BMC Med Res Methodol"},{"issue":"2","key":"pone.0336662.ref029","first-page":"117","article-title":"Albumin corrected anion gap is an independent risk factor for long-term mortality of patients with sepsis","volume":"29","author":"X He","year":"2017","journal-title":"Zhonghua Wei Zhong Bing Ji Jiu Yi Xue"},{"issue":"1","key":"pone.0336662.ref030","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1053\/j.akdh.2025.01.012","article-title":"Metabolic acidosis","volume":"32","author":"KI Greenberg","year":"2025","journal-title":"Adv Kidney Dis Health"},{"issue":"1","key":"pone.0336662.ref031","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1159\/000502380","article-title":"Progression of Metabolic Acidosis in Chronic Kidney Disease","volume":"6","author":"M Tanemoto","year":"2020","journal-title":"Kidney Dis 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Pratumvinit","year":"2020","journal-title":"Clin Chim Acta"},{"issue":"1","key":"pone.0336662.ref035","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s12882-021-02629-y","article-title":"Albumin levels predict mortality in sepsis patients with acute kidney injury undergoing continuous renal replacement therapy: a secondary analysis based on a retrospective cohort study","volume":"23","author":"S Sheng","year":"2022","journal-title":"BMC Nephrol"},{"issue":"1","key":"pone.0336662.ref036","article-title":"Carbonic anhydrase IX is a critical determinant of pulmonary microvascular endothelial cell pH regulation and angiogenesis during acidosis","volume":"315","author":"JY Lee","year":"2018","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"issue":"1","key":"pone.0336662.ref037","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1097\/00003246-200001000-00021","article-title":"Initial severity of metabolic acidosis predicts the development of acute lung injury in severely traumatized patients","volume":"28","author":"LW Eberhard","year":"2000","journal-title":"Crit Care Med"},{"key":"pone.0336662.ref038","doi-asserted-by":"crossref","first-page":"17534666251315352","DOI":"10.1177\/17534666251315352","article-title":"Association between albumin corrected anion gap and in-hospital mortality in critically ill patients with chronic obstructive pulmonary disease","volume":"19","author":"M Giri","year":"2025","journal-title":"Ther Adv Respir Dis"},{"key":"pone.0336662.ref039","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.gerinurse.2024.10.022","article-title":"Association between albumin corrected anion gap and mortality in septic older adults","volume":"60","author":"Q Zhou","year":"2024","journal-title":"Geriatr Nurs"},{"issue":"7","key":"pone.0336662.ref040","article-title":"Association Between Albumin Corrected Anion Gap and 28-Day All-Cause Mortality in Patients With Acute Respiratory Failure in ICU: A Retrospective Study 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