{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T18:27:45Z","timestamp":1786559265600,"version":"build-2736575974"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173899"],"award-info":[{"award-number":["82173899"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020439","name":"Jiangsu Pharmaceutical Association","doi-asserted-by":"publisher","award":["H202108, A2021024, Q202202, JY202207, Z04JKM2023E040"],"award-info":[{"award-number":["H202108, A2021024, Q202202, JY202207, Z04JKM2023E040"]}],"id":[{"id":"10.13039\/100020439","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hospital Management Innovation Research Project of Jiangsu Provincial Hospital Association","award":["JSYGY-3-2023-264"],"award-info":[{"award-number":["JSYGY-3-2023-264"]}]}],"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>Frailty remains a significant risk factor for adverse health outcomes in hospitalized patients. Few have evaluated frailty risk and its influencing factors in heart failure (HF) patients with acute infections, and previous machine learning models have predominantly overlooked the incorporation of visualization techniques. This study aims to investigate frailty risk factors in this population and develop an interpretable prediction model for frailty.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study enrolled 1498 patients hospitalized for HF with acute infections at Nanjing First Hospital in 2023. Participants were randomly divided into training and testing sets at a 7:3 ratio. Potential predictors were screened through univariate analysis and the least absolute shrinkage and selection operator (LASSO) regression. Eight machine learning algorithms were evaluated to determine the optimal predictive model. Model interpretability was enhanced using the SHapley Additive exPlanations (SHAP) method.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Frailty was prevalent in 80.3% of the cohort. Key predictors included the use of thiazide diuretics, serum albumin, estimated glomerular filtration rate (eGFR), lymphocyte percentage, mean corpuscular hemoglobin concentration (MCHC), capacity for action, age, left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) functional class, history of cerebral infarction, and smoking. Comparative analysis of the eight models revealed that eXtreme Gradient Boosting (XGBoost) achieved superior performance, with the highest area under the receiver operating characteristic curve (AUROC: 0.872) and precision-recall curve (AUPRC: 0.969).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study identified the use of thiazide diuretics as an independent predictor associated with lower frailty probability. We developed an online calculator as a proof-of-concept tool to demonstrate the potential application of the predictive model and facilitate real-time risk estimation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0355848","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T17:33:24Z","timestamp":1786556004000},"page":"e0355848","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Frailty prediction in heart failure patients with acute infections: the potential role of thiazide diuretics?"],"prefix":"10.1371","volume":"21","author":[{"given":"Tinghui","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiling","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9529-7796","authenticated-orcid":true,"given":"Yuying","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"pone.0355848.ref001","doi-asserted-by":"crossref","first-page":"102696","DOI":"10.1016\/j.arr.2025.102696","article-title":"Association of frailty and pre-frailty with all-cause and cardiovascular mortality in diabetes: Three prospective cohorts and a meta-analysis","volume":"106","author":"L Wen","year":"2025","journal-title":"Ageing Res Rev"},{"issue":"1","key":"pone.0355848.ref002","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s40520-025-03067-8","article-title":"Association of dietary intake and whole blood essential trace elements with frailty in older adults: a cross-sectional study","volume":"37","author":"Y Lin","year":"2025","journal-title":"Aging Clin Exp Res"},{"issue":"3","key":"pone.0355848.ref003","doi-asserted-by":"crossref","DOI":"10.1093\/gerona\/56.3.M146","article-title":"Frailty in older adults: evidence for a phenotype","volume":"56","author":"LP Fried","year":"2001","journal-title":"J Gerontol A Biol Sci Med Sci"},{"issue":"4","key":"pone.0355848.ref004","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1002\/ejhf.1768","article-title":"The Heart Failure Association Atlas: rationale, objectives, and methods","volume":"22","author":"PM Seferovi\u0107","year":"2020","journal-title":"Eur J Heart Fail"},{"issue":"1","key":"pone.0355848.ref005","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1186\/s12872-023-03375-9","article-title":"Global, regional, and national burden of heart failure associated with atrial fibrillation","volume":"23","author":"S Kularatna","year":"2023","journal-title":"BMC Cardiovasc Disord"},{"key":"pone.0355848.ref006","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.ijcard.2017.11.010","article-title":"The Barthel Index in elderly acute heart failure patients. Frailty matters","volume":"254","author":"A Aimo","year":"2018","journal-title":"Int J Cardiol"},{"issue":"12","key":"pone.0355848.ref007","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1038\/s41440-020-0510-5","article-title":"Frailty and hypertension in older adults: current understanding and future perspectives","volume":"43","author":"P Liu","year":"2020","journal-title":"Hypertens Res"},{"issue":"4","key":"pone.0355848.ref008","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1002\/ejhf.3209","article-title":"Heart failure and respiratory tract infection: cause and consequence of acute decompensation?","volume":"26","author":"B Heidecker","year":"2024","journal-title":"European Journal of Heart Failure"},{"issue":"1","key":"pone.0355848.ref009","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1186\/s12877-021-02299-3","article-title":"Frailty increases the risk for developing urinary tract infection among 79,887 patients with diabetic mellitus and chronic kidney disease","volume":"21","author":"C-T Chao","year":"2021","journal-title":"BMC Geriatr"},{"issue":"11","key":"pone.0355848.ref010","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1001\/jamacardio.2019.3511","article-title":"Association of Frailty With 30-Day Outcomes for Acute Myocardial Infarction, Heart Failure, and Pneumonia Among Elderly Adults","volume":"4","author":"H Kundi","year":"2019","journal-title":"JAMA Cardiol"},{"issue":"1","key":"pone.0355848.ref011","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1186\/s12877-023-03823-3","article-title":"Development and validation of a risk prediction model for frailty in patients with diabetes","volume":"23","author":"F Bu","year":"2023","journal-title":"BMC Geriatr"},{"issue":"1","key":"pone.0355848.ref012","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1186\/s12877-024-05320-7","article-title":"Development and validation of frailty risk prediction model for elderly patients with coronary heart disease","volume":"24","author":"S Liu","year":"2024","journal-title":"BMC Geriatr"},{"issue":"4","key":"pone.0355848.ref013","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.21037\/jtd-24-416","article-title":"Developing and validating machine learning-based prediction models for frailty occurrence in those with chronic obstructive pulmonary disease","volume":"16","author":"Y Chen","year":"2024","journal-title":"J Thorac Dis"},{"issue":"9","key":"pone.0355848.ref014","doi-asserted-by":"crossref","first-page":"455","DOI":"10.3390\/medicina56090455","article-title":"Comparison of Conventional Statistical Methods with Machine Learning in Medicine: Diagnosis, Drug Development, and Treatment","volume":"56","author":"HSR Rajula","year":"2020","journal-title":"Medicina (Kaunas)"},{"issue":"5","key":"pone.0355848.ref015","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1002\/jcsm.13282","article-title":"Explainable machine learning model for predicting skeletal muscle loss during surgery and adjuvant chemotherapy in ovarian cancer","volume":"14","author":"W-H Hsu","year":"2023","journal-title":"J Cachexia Sarcopenia Muscle"},{"issue":"3","key":"pone.0355848.ref016","doi-asserted-by":"crossref","first-page":"277","DOI":"10.26599\/1671-5411.2025.03.002","article-title":"Chinese Guidelines for the Diagnosis and Treatment of Heart Failure 2024","volume":"22","author":"S-Y Zhang","year":"2025","journal-title":"J Geriatr Cardiol"},{"issue":"1","key":"pone.0355848.ref017","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1186\/s12877-020-01801-7","article-title":"A scoping review of the Clinical Frailty Scale","volume":"20","author":"S Church","year":"2020","journal-title":"BMC Geriatr"},{"key":"pone.0355848.ref018","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.gerinurse.2024.08.013","article-title":"Prediction of postoperative mortality in older surgical patients by clinical frailty scale: A systematic review and meta-analysis","volume":"59","author":"H-T Zhang","year":"2024","journal-title":"Geriatr Nurs"},{"issue":"6","key":"pone.0355848.ref019","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1136\/hrt.2005.071233","article-title":"Role of B-type natriuretic peptide (BNP) and NT-proBNP in clinical routine","volume":"92","author":"M Weber","year":"2006","journal-title":"Heart"},{"issue":"12","key":"pone.0355848.ref020","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1016\/S0895-4356(96)00236-3","article-title":"A simulation study of the number of events per variable in logistic regression analysis","volume":"49","author":"P Peduzzi","year":"1996","journal-title":"J Clin Epidemiol"},{"issue":"1","key":"pone.0355848.ref021","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1111\/jocn.17324","article-title":"Status and influencing factors of frailty in hospitalized patients with chronic heart failure: A cross-sectional study","volume":"34","author":"M Tang","year":"2025","journal-title":"J Clin Nurs"},{"issue":"2","key":"pone.0355848.ref022","first-page":"142","article-title":"Development and validation of dynamic nomogram of frailty risk for older patients hospitalized with heart failure","volume":"10","author":"Q Li","year":"2023","journal-title":"Int J Nurs Sci"},{"issue":"4","key":"pone.0355848.ref023","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1093\/eurjcn\/zvac063","article-title":"Frailty and predictive factors in Chinese hospitalized patients with heart failure: a structural equation model analysis","volume":"22","author":"Y Yang","year":"2023","journal-title":"Eur J Cardiovasc Nurs"},{"issue":"3","key":"pone.0355848.ref024","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1080\/00031305.1992.10475879","article-title":"An Introduction to Kernel and Nearest-Neighbor Nonparametric Regression","volume":"46","author":"NS Altman","year":"1992","journal-title":"The American Statistician"},{"issue":"9","key":"pone.0355848.ref025","doi-asserted-by":"crossref","first-page":"735","DOI":"10.3844\/jcssp.2006.735.739","article-title":"Data Mining: A Preprocessing Engine","volume":"2","author":"LA Shalabi","year":"2006","journal-title":"J of Computer Science"},{"issue":"1","key":"pone.0355848.ref026","doi-asserted-by":"crossref","first-page":"13036","DOI":"10.1038\/s41598-019-49539-6","article-title":"Efficient partition of integer optimization problems with one-hot encoding","volume":"9","author":"S Okada","year":"2019","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0355848.ref027","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s12874-016-0254-8","article-title":"Least absolute shrinkage and selection operator type methods for the identification of serum biomarkers of overweight and obesity: simulation and application","volume":"16","author":"MM Vasquez","year":"2016","journal-title":"BMC Med Res Methodol"},{"key":"pone.0355848.ref028","article-title":"Multiple regression for physiological data analysis: the problem of multicollinearity","volume":"249","author":"BK Slinker","year":"1985","journal-title":"Am J Physiol"},{"key":"pone.0355848.ref029","unstructured":"Lundberg S, Lee SI. A unified approach to interpreting model predictions. In: NIPS, 2017."},{"issue":"7","key":"pone.0355848.ref030","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1002\/ejhf.518","article-title":"Prevalence and prognostic impact of frailty and its components in non-dependent elderly patients with heart failure","volume":"18","author":"MT Vid\u00e1n","year":"2016","journal-title":"Eur J Heart Fail"},{"key":"pone.0355848.ref031","doi-asserted-by":"crossref","first-page":"105810","DOI":"10.1016\/j.archger.2025.105810","article-title":"Interpretable machine learning model for predicting depression in middle-aged and elderly Chinese arthritis patients: A nationwide prospective cohort study","volume":"134","author":"X Xu","year":"2025","journal-title":"Arch Gerontol Geriatr"},{"issue":"6","key":"pone.0355848.ref032","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1111\/ggi.14390","article-title":"Development and validation of a predictive risk model for frailty in elderly patients with multimorbidity","volume":"22","author":"F Huang","year":"2022","journal-title":"Geriatr Gerontol Int"},{"issue":"10","key":"pone.0355848.ref033","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1177\/2047487319827460","article-title":"Multidimensional frailty evaluation in elderly outpatients with chronic heart failure: A prospective study","volume":"26","author":"G Testa","year":"2019","journal-title":"Eur J Prev Cardiol"},{"issue":"6","key":"pone.0355848.ref034","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/s40520-017-0815-7","article-title":"The reverse metabolic syndrome in the elderly: Is it a \u201ccatabolic\u201d syndrome?","volume":"30","author":"F Curcio","year":"2018","journal-title":"Aging Clinical and Experimental Research"},{"issue":"2","key":"pone.0355848.ref035","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/ejhf.1369","article-title":"The use of diuretics in heart failure with congestion - a position statement from the Heart Failure Association of the European Society of Cardiology","volume":"21","author":"W Mullens","year":"2019","journal-title":"Eur J Heart Fail"},{"issue":"5","key":"pone.0355848.ref036","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1093\/eurheartj\/ehac689","article-title":"Combining loop with thiazide diuretics for decompensated heart failure: the CLOROTIC trial","volume":"44","author":"JC Trull\u00e0s","year":"2023","journal-title":"Eur Heart J"},{"key":"pone.0355848.ref037","doi-asserted-by":"crossref","first-page":"177692","DOI":"10.1016\/j.ejphar.2025.177692","article-title":"Efficacy of albumin and loop diuretic Co-administration in reducing mortality among septic patients with hypoalbuminemia","volume":"999","author":"B Wang","year":"2025","journal-title":"Eur J Pharmacol"},{"issue":"3","key":"pone.0355848.ref038","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1093\/cid\/ciz879","article-title":"Challenges and progress toward determining pneumonia etiology","volume":"71","author":"PM Meyer Sauteur","year":"2020","journal-title":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America"},{"issue":"31","key":"pone.0355848.ref039","doi-asserted-by":"crossref","first-page":"2978","DOI":"10.1093\/eurheartj\/ehad463","article-title":"Prevention and treatment of diuretic resistance in acute heart failure: when to use which combination of diuretics?","volume":"44","author":"P Martens","year":"2023","journal-title":"Eur Heart J"},{"issue":"6","key":"pone.0355848.ref040","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1253\/circj.CJ-16-0216","article-title":"Prognostic Impact of Loop Diuretics in Patients With Chronic Heart Failure\u3000- Effects of Addition of Renin-Angiotensin-Aldosterone System Inhibitors and \u03b2-Blockers","volume":"80","author":"M Miura","year":"2016","journal-title":"Circ J"},{"issue":"1","key":"pone.0355848.ref041","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1186\/s12877-024-05275-9","article-title":"Association between frailty and hypoproteinaemia in older patients: meta-analysis and systematic review","volume":"24","author":"L Zhang","year":"2024","journal-title":"BMC Geriatr"},{"issue":"1","key":"pone.0355848.ref042","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s12199-021-00946-0","article-title":"Lower albumin levels are associated with frailty measures, trace elements, and an inflammation marker in a cross-sectional study in Tanushimaru","volume":"26","author":"M Yamamoto","year":"2021","journal-title":"Environmental Health and Preventive Medicine"},{"issue":"11","key":"pone.0355848.ref043","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/j.cardfail.2021.04.016","article-title":"Estimated Glomerular Filtration Rate Variability in Patients With Heart Failure and Chronic Kidney Disease","volume":"27","author":"AM Hein","year":"2021","journal-title":"J Card Fail"},{"issue":"1","key":"pone.0355848.ref044","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s12872-025-04567-1","article-title":"Interacting and joint effects of frailty and inflammation on cardiovascular disease risk and the mediating role of inflammation in middle-aged and elderly populations","volume":"25","author":"Z Xu","year":"2025","journal-title":"BMC Cardiovasc Disord"},{"issue":"3","key":"pone.0355848.ref045","doi-asserted-by":"crossref","first-page":"53","DOI":"10.3390\/diseases9030053","article-title":"Lymphocytes as a Biomarker of Frailty Syndrome: A Scoping Review","volume":"9","author":"R Navarro-Mart\u00ednez","year":"2021","journal-title":"Diseases"},{"issue":"1","key":"pone.0355848.ref046","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s12603-020-1455-8","article-title":"Clinical Frailty Scale and Biomarkers for Assessing Frailty in Elder Inpatients in China","volume":"25","author":"L Xu","year":"2021","journal-title":"J Nutr Health Aging"},{"issue":"2","key":"pone.0355848.ref047","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1002\/ehf2.14225","article-title":"Mean corpuscular haemoglobin concentration and outcomes in heart failure with preserved ejection fraction","volume":"10","author":"M Choy","year":"2023","journal-title":"ESC Heart Fail"},{"issue":"3","key":"pone.0355848.ref048","doi-asserted-by":"crossref","DOI":"10.1002\/ctm2.372","article-title":"Glycine and N-acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Results of a pilot clinical trial","volume":"11","author":"P Kumar","year":"2021","journal-title":"Clin Transl Med"},{"key":"pone.0355848.ref049","doi-asserted-by":"crossref","first-page":"101513","DOI":"10.1016\/j.redox.2020.101513","article-title":"Physical activity and exercise: Strategies to manage frailty","volume":"35","author":"J Angulo","year":"2020","journal-title":"Redox Biol"},{"key":"pone.0355848.ref050","doi-asserted-by":"crossref","first-page":"1588288","DOI":"10.3389\/fcvm.2025.1588288","article-title":"Prevalence and determinants of multidimensional frailty in hospitalized older adults with coronary heart disease: a LASSO regression analysis","volume":"12","author":"P Zhu","year":"2025","journal-title":"Front Cardiovasc Med"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0355848","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T17:33:34Z","timestamp":1786556014000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0355848"}},"subtitle":[],"editor":[{"given":"Francesco","family":"Curcio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,8,12]]},"references-count":50,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8,12]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0355848","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,12]]}}}