{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:17:10Z","timestamp":1787026630804,"version":"build-2736575974"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82274481"],"award-info":[{"award-number":["82274481"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This study aims to develop a predictive model for identifying rheumatoid arthritis (RA) patients at risk of low muscle mass using easily obtainable clinical indicators. The goal is to facilitate targeted screening for individuals at high risk of sarcopenia, optimize diagnostic strategies, reduce the burden of additional testing, and improve the efficiency of early identification and intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study analyzed data from 1,260 RA patients obtained from the National Health and Nutrition Examination Survey (NHANES) database and the Affiliated Hospital of Shandong University of Traditional Chinese Medicine (SHUTCM). Eight machine learning models were developed, including Random Forest, LightGBM, XGBoost, CatBoost, Support Vector Machine (SVM), K-Nearest Neighbors (KNN), Logistic Regression, and a weighted ensemble model. Model performance was evaluated using metrics such as accuracy, area under the receiver operating characteristic curve (AUC), F1 score, Precision, Recall, and Brier score loss. The SHapley Additive exPlanation (SHAP) method was used to rank feature importance and interpret the final model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among all machine learning models, the tree-based weighted ensemble model demonstrated the best performance, achieving an AUC of 0.921, outperforming all individual models. The model exhibited good calibration and higher net clinical benefit in decision curve analysis, especially within the probability threshold range of 0.2 to 0.8, and achieved an AUC of 0.848 on the test set, demonstrating a certain degree of generalizability. SHAP analysis identified BMI, albumin, hemoglobin, age, and creatinine as the most important features for predicting the risk of low muscle mass. SHAP dependency and waterfall plots further showed the model\u2019s decision-making mechanisms. Finally, we developed an online risk prediction calculator based on the FastAPI framework, which automatically generates individualized low muscle mass risk scores based on user input. The tool has been deployed on the Hugging Face platform and is accessible online.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Based on a large, multicenter dataset, we developed and validated an explainable ML model capable of identifying individuals with a high risk of low muscle mass among patients with rheumatoid arthritis. This model may serve as a decision-support tool for clinicians in guiding further screening and diagnosis of sarcopenia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2025.1694320","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T06:36:15Z","timestamp":1763534175000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Development and validation of an interpretable machine learning model for predicting low muscle mass in patients with rheumatoid arthritis: a multicenter study"],"prefix":"10.3389","volume":"12","author":[{"given":"Feiyue","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanhe","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,19]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"S265","DOI":"10.1186\/ar578","article-title":"Epidemiology and genetics of rheumatoid arthritis","volume":"4","author":"Silman","year":"2002","journal-title":"Arthritis Res"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2143","DOI":"10.1093\/rheumatology\/keu224","article-title":"Cardiovascular risk in rheumatoid arthritis: recent advances in the understanding of the pivotal role of inflammation, risk predictors and the impact of treatment","volume":"53","author":"Choy","year":"2014","journal-title":"Rheumatology"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"855141","DOI":"10.3389\/fmed.2022.855141","article-title":"Prevalence of metabolic syndrome in patients with rheumatoid arthritis: an updated systematic review and meta-analysis","volume":"9","author":"Cai","year":"2022","journal-title":"Front Med"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"4924","DOI":"10.1093\/rheumatology\/keac191","article-title":"Elevations in adipocytokines and mortality in rheumatoid arthritis","volume":"61","author":"Baker","year":"2022","journal-title":"Rheumatology"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1097\/RHU.0000000000001980","article-title":"Risk factors and clinical outcomes associated with sarcopenia in rheumatoid arthritis: a systematic review and meta-analysis","volume":"30","author":"Tam","year":"2024","journal-title":"J Clin Rheumatol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"2075","DOI":"10.2147\/IJGM.S349435","article-title":"Sarcopenia may be a risk factor for osteoporosis in Chinese patients with rheumatoid arthritis","volume":"15","author":"Lian","year":"2022","journal-title":"Int J Gen Med"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1007\/s11657-021-01017-1","article-title":"Interactive effect of sarcopenia and falls on vertebral osteoporotic fracture in patients with rheumatoid arthritis","volume":"16","author":"Tong","year":"2021","journal-title":"Arch Osteoporos"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1080\/14397595.2018.1510565","article-title":"Prevalence and factors associated with sarcopenia in patients with rheumatoid arthritis","volume":"29","author":"Torii","year":"2019","journal-title":"Mod Rheumatol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/j.jamda.2011.04.014","article-title":"Sarcopenia with limited mobility: an international consensus","volume":"12","author":"Morley","year":"2011","journal-title":"J Am Med Dir Assoc"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1007\/s40520-023-02438-3","article-title":"Measuring health-related quality of life in sarcopenia: summary of the SarQoL psychometric properties","volume":"35","author":"Beaudart","year":"2023","journal-title":"Aging Clin Exp Res"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"2793","DOI":"10.1007\/s00198-015-3194-y","article-title":"Comparative performance of current definitions of sarcopenia against the prospective incidence of falls among community-dwelling seniors age 65 and older","volume":"26","author":"Bischoff-Ferrari","year":"2015","journal-title":"Osteoporos Int"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1093\/gerona\/glx245","article-title":"Associations of sarcopenia definitions, and their components, with the incidence of recurrent falling and fractures: the longitudinal aging study Amsterdam","volume":"73","author":"Schaap","year":"2018","journal-title":"J Gerontol A"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1007\/s11547-023-01630-9","article-title":"Quantification of sarcopenia in patients with rheumatoid arthritis by measuring the cross-sectional area of the thigh muscles with magnetic resonance imaging","volume":"128","author":"Salaffi","year":"2023","journal-title":"Radiol Med"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1093\/gerona\/glu010","article-title":"The FNIH sarcopenia project: rationale, study description, conference recommendations, and final estimates","volume":"69","author":"Studenski","year":"2014","journal-title":"J Gerontol A"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1016\/j.jamda.2019.12.012","article-title":"Asian Working Group for Sarcopenia: 2019 consensus update on sarcopenia diagnosis and treatment","volume":"21","author":"Chen","year":"2020","journal-title":"J Am Med Dir Assoc"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1016\/j.eururo.2018.08.038","article-title":"Reporting and interpreting decision curve analysis: a guide for investigators","volume":"74","author":"Van Calster","year":"2018","journal-title":"Eur Urol"},{"key":"ref17","first-page":"4768","article-title":"A unified approach to interpreting model predictions","author":"Lundberg","year":"2017"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/j.reuma.2021.06.005","article-title":"Relationship between polyautoimmunity and sarcopenic obesity in rheumatoid arthritis patients","volume":"18","author":"Mena-V\u00e1zquez","year":"2022","journal-title":"Reumatol Clin"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1186\/ar2658","article-title":"Rheumatoid cachexia: a complication of rheumatoid arthritis moves into the 21st century","volume":"11","author":"Roubenoff","year":"2009","journal-title":"Arthritis Res Ther"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.smim.2016.09.003","article-title":"Nutrients and the microenvironment to feed a T cell army","volume":"28","author":"Johnson","year":"2016","journal-title":"Semin Immunol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1002\/art.40346","article-title":"Weight change during the early rheumatoid arthritis period and risk of subsequent mortality in women with rheumatoid arthritis and matched comparators","volume":"70","author":"Sparks","year":"2018","journal-title":"Arthritis Rheumatol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1711","DOI":"10.1002\/art.39136","article-title":"Weight loss, the obesity paradox, and the risk of death in rheumatoid arthritis","volume":"67","author":"Baker","year":"2015","journal-title":"Arthritis Rheumatol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"3450","DOI":"10.1002\/art.20612","article-title":"Prognostic importance of low body mass index in relation to cardiovascular mortality in rheumatoid arthritis","volume":"50","author":"Kremers","year":"2004","journal-title":"Arthritis Rheum"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1056\/NEJMra1804281","article-title":"Anemia of inflammation","volume":"381","author":"Ganz","year":"2019","journal-title":"N Engl J Med"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1391573","DOI":"10.3389\/fimmu.2024.1391573","article-title":"Association of the systemic immune-inflammation index with anemia: a population-based study","volume":"15","author":"Chen","year":"2024","journal-title":"Front Immunol"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"402s","DOI":"10.3945\/ajcn.116.142323","article-title":"Predictors of anemia in preschool children: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project","volume":"106","author":"Engle-Stone","year":"2017","journal-title":"Am J Clin Nutr"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"939","DOI":"10.2460\/ajvr.1986.47.04.939","article-title":"Bovine longissimus muscle glycogen concentration in response to isometric contraction and exogenous epinephrine","volume":"47","author":"Crouse","year":"1986","journal-title":"Am J Vet Res"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1136\/annrheumdis-2012-202709","article-title":"Anaemia may add information to standardised disease activity assessment to predict radiographic damage in rheumatoid arthritis: a prospective cohort study","volume":"73","author":"M\u00f6ller","year":"2014","journal-title":"Ann Rheum Dis"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e16","DOI":"10.1136\/annrheumdis-2013-203718","article-title":"Anaemia to predict radiographic progression in rheumatoid arthritis","volume":"72","author":"van Steenbergen","year":"2013","journal-title":"Ann Rheum Dis"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.jbspin.2010.05.017","article-title":"Rheumatoid anemia","volume":"78","author":"Masson","year":"2011","journal-title":"Joint Bone Spine"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1056\/NEJMra041809","article-title":"Anemia of chronic disease","volume":"352","author":"Weiss","year":"2005","journal-title":"N Engl J Med"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1530\/EJE-09-0342","article-title":"Activation of the erythropoietin receptor in human skeletal muscle","volume":"161","author":"Rundqvist","year":"2009","journal-title":"Eur J Endocrinol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"590","DOI":"10.7705\/biomedica.5765","article-title":"Sarcopenia and blood albumin: a systematic review with meta-analysis","volume":"41","author":"Silva-Fhon","year":"2021","journal-title":"Biomedica"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"e59321","DOI":"10.1371\/journal.pone.0059321","article-title":"C-reactive protein\/albumin ratio predicts 90-day mortality of septic patients","volume":"8","author":"Ranzani","year":"2013","journal-title":"PLoS One"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1128\/MCB.21.2.414-424.2001","article-title":"Interleukin-6-induced STAT3 and AP-1 amplify hepatocyte nuclear factor 1-mediated transactivation of hepatic genes, an adaptive response to liver injury","volume":"21","author":"Leu","year":"2001","journal-title":"Mol Cell Biol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1172\/JCI23640","article-title":"The IL-6-gp130-STAT3 pathway in hepatocytes triggers liver protection in T cell-mediated liver injury","volume":"115","author":"Klein","year":"2005","journal-title":"J Clin Invest"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.ejcb.2011.09.008","article-title":"Hepatic acute phase proteins\u2014regulation by IL-6- and IL-1-type cytokines involving STAT3 and its crosstalk with NF-\u03baB-dependent signaling","volume":"91","author":"Bode","year":"2012","journal-title":"Eur J Cell Biol"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"e39776","DOI":"10.1097\/MD.0000000000039776","article-title":"Relationship between albumin and rheumatoid arthritis: evidence from NHANES and Mendelian randomization","volume":"103","author":"Liu","year":"2024","journal-title":"Medicine"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"770674","DOI":"10.3389\/fnut.2022.770674","article-title":"Prognostic value of serum albumin level in critically ill patients: observational data from large intensive care unit databases","volume":"9","author":"Jin","year":"2022","journal-title":"Front Nutr"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/s41413-025-00438-9","article-title":"Pathophysiology of myopenia in rheumatoid arthritis","volume":"13","author":"Jin","year":"2025","journal-title":"Bone Res"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s12929-021-00714-w","article-title":"Rheumatoid cachexia: the underappreciated role of myoblast, macrophage and fibroblast interplay in the skeletal muscle niche","volume":"28","author":"Ollewagen","year":"2021","journal-title":"J Biomed Sci"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.3390\/biom13071075","article-title":"Should cystatin C eGFR become routine clinical practice?","volume":"13","author":"Spencer","year":"2023","journal-title":"Biomolecules"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"1122922","DOI":"10.3389\/fpubh.2023.1122922","article-title":"Sarcopenia index based on serum creatinine and cystatin C is associated with mortality in middle-aged and older adults in Chinese: a retrospective cohort study from the China health and retirement longitudinal study","volume":"11","author":"Wu","year":"2023","journal-title":"Front Public Health"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"11534","DOI":"10.1038\/s41598-018-29808-6","article-title":"A sarcopenia index based on serum creatinine and cystatin C cannot accurately detect either low muscle mass or sarcopenia in urban community-dwelling older people","volume":"8","author":"He","year":"2018","journal-title":"Sci Rep"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.clnesp.2023.06.002","article-title":"Serum creatinine-to-cystatin C ratio as an indicator of sarcopenia in hemodialysis patients","volume":"56","author":"Yajima","year":"2023","journal-title":"Clin Nutr ESPEN"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/s13539-012-0079-1","article-title":"Serum creatinine as a marker of muscle mass in chronic kidney disease: results of a cross-sectional study and review of literature","volume":"4","author":"Patel","year":"2013","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"e23569","DOI":"10.1002\/jcla.23569","article-title":"The value of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as complementary diagnostic tools in the diagnosis of rheumatoid arthritis: a multicenter retrospective study","volume":"35","author":"Jin","year":"2021","journal-title":"J Clin Lab Anal"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"117","DOI":"10.3390\/medicina59010117","article-title":"Association between novel hematological indices and measures of disease activity in patients with rheumatoid arthritis","volume":"59","author":"Choe","year":"2023","journal-title":"Medicina"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"183","DOI":"10.4274\/MMJ.galenos.2024.60533","article-title":"Systemic immune-inflammation index in evaluation of inflammation in rheumatoid arthritis patients","volume":"39","author":"Dervisevic","year":"2024","journal-title":"Medeni Med J"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"2689","DOI":"10.1007\/s10067-017-3815-2","article-title":"The association between the lymphocyte-monocyte ratio and disease activity in rheumatoid arthritis","volume":"36","author":"Du","year":"2017","journal-title":"Clin Rheumatol"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1136\/ard-2022-223356","article-title":"EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update","volume":"82","author":"Smolen","year":"2023","journal-title":"Ann Rheum Dis"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1694320\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T06:36:20Z","timestamp":1763534180000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1694320\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,19]]},"references-count":51,"alternative-id":["10.3389\/fmed.2025.1694320"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1694320","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,19]]},"article-number":"1694320"}}