{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:49:51Z","timestamp":1790034591816,"version":"4.0.1"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research"},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Mycobacterium avium complex (MAC) pulmonary disease presents with heterogeneous clinical phenotypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aimed to elucidate the heterogeneity of MAC pulmonary disease by analyzing gene expression profiles in whole blood cells and identifying factors contributing to its pathogenesis, treatment response, and disease severity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 100 patients with MAC pulmonary disease newly treated with guideline-based therapy (GBT) were analyzed prospectively, and RNA-sequencing was performed on whole blood cells. Unsupervised cluster analysis, differentially \u00adexpressed gene (DEG) analysis, and logistic least absolute shrinkage and selection operator regression were performed to identify key genes of the severe cluster. The expressions of these genes were validated in mice infected with M. avium bacteria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>The cluster analysis identified 3 distinct patient clusters, each with unique clinical characteristic and treatment responses. Notably, Cluster 3 (C3) showed high neutrophil counts, older age, severe disease manifestations, and poor survival, despite sputum culture conversion. DEG analysis identified 6 neutrophil-related genes, FTH1, C19orf59 (MCEMP1), S100A9, SELL, ISG15, and IFITM1, as characteristic of C3. Furthermore, high expression of these genes correlated significantly with poor survival in both the present cohort and a previously reported cohort of pulmonary nontuberculous mycobacterial disease patients. M. avium infection increased S100A9 expression, particularly in old, but not young, mouse lungs, suggesting that increased S100A9 expression is associated with aging and infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Gene expression profiling in MAC pulmonary disease patients identified 3 distinct clusters, with the most severe cluster characterized by neutrophil activation. Six genes were associated with disease severity and prognosis, though their causal roles require further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202503-0665oc","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T20:23:24Z","timestamp":1760473404000},"page":"625-641","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":4,"title":["Transcriptomic profiling in\n                    <i>Mycobacterium avium<\/i>\n                    complex pulmonary disease identifies clusters linked to disease severity and neutrophil activation"],"prefix":"10.1093","volume":"212","author":[{"given":"Chio","family":"Sakai","sequence":"first","affiliation":[{"name":"Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba , Tsukuba, Ibaraki,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizu","family":"Nonaka","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, National Hospital Organization Ibarakihigashi National Hospital , Naka-gun, Ibaraki,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Matsuyama","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba , Tsukuba, Ibaraki,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sosuke","family":"Matsumura","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba , Tsukuba, Ibaraki,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba , Tsukuba, Ibaraki,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kodai","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba , Tsukuba, Ibaraki,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Arai","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, National Hospital Organization Ibarakihigashi National Hospital , Naka-gun, Ibaraki,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Morishima","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba , Tsukuba, Ibaraki,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Muratani","sequence":"additional","affiliation":[{"name":"Department of Genome Biology, Faculty of Medicine, University of Tsukuba , Tsukuba, Ibaraki,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, National Hospital Organization Ibarakihigashi National Hospital , Naka-gun, Ibaraki,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takefumi","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, National Hospital Organization Ibarakihigashi National Hospital , Naka-gun, Ibaraki,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Hizawa","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba , Tsukuba, Ibaraki,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"2026032109355409100_aamaf073-B1","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.resinv.2022.12.002","article-title":"Pathophysiology of pulmonary nontuberculous mycobacterial (NTM) disease","volume":"61","author":"Matsuyama","year":"2023","journal-title":"Respir Investig"},{"key":"2026032109355409100_aamaf073-B2","doi-asserted-by":"publisher","first-page":"1600537","DOI":"10.1183\/13993003.00537-2016","article-title":"Natural history of Mycobacterium avium complex lung disease in untreated patients with stable course","volume":"49","author":"Hwang","year":"2017","journal-title":"Eur Respir J"},{"key":"2026032109355409100_aamaf073-B3","doi-asserted-by":"publisher","first-page":"i3","DOI":"10.1093\/jac\/dkx311","article-title":"Meta-analyses and the evidence base for microbial outcomes in the treatment of pulmonary Mycobacterium avium-intracellulare complex disease","volume":"72","author":"Pasipanodya","year":"2017","journal-title":"J Antimicrob Chemother"},{"key":"2026032109355409100_aamaf073-B4","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1016\/j.chest.2018.01.024","article-title":"Microbiologic outcome of interventions against Mycobacterium avium complex pulmonary disease: a systematic review","volume":"153","author":"Diel","year":"2018","journal-title":"Chest"},{"key":"2026032109355409100_aamaf073-B5","doi-asserted-by":"publisher","first-page":"108052","DOI":"10.1016\/j.rmed.2025.108052","article-title":"Relationship between culture conversion and clinical outcomes in nontuberculous mycobacterial pulmonary disease: narrative review","volume":"241","author":"Winthrop","year":"2025","journal-title":"Respir Med"},{"key":"2026032109355409100_aamaf073-B6","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1513\/AnnalsATS.202305-407OC","article-title":"Post-treatment radiographic severity and mortality in Mycobacterium avium complex pulmonary disease","volume":"21","author":"Kim","year":"2024","journal-title":"Ann Am Thorac Soc"},{"key":"2026032109355409100_aamaf073-B7","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1165\/rcmb.2017-0230OC","article-title":"Whole-blood gene expression in pulmonary nontuberculous mycobacterial infection","volume":"58","author":"Cowman","year":"2018","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026032109355409100_aamaf073-B8","doi-asserted-by":"publisher","first-page":"112412","DOI":"10.1016\/j.intimp.2024.112412","article-title":"Single-cell transcriptomics of blood identified IFIT1(+) neutrophil subcluster expansion in NTM-PD patients","volume":"137","author":"Wang","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"2026032109355409100_aamaf073-B9","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s12941-023-00562-6","article-title":"The roles of neutrophils in non-tuberculous mycobacterial pulmonary disease","volume":"22","author":"Alkarni","year":"2023","journal-title":"Ann Clin Microbiol Antimicrob"},{"key":"2026032109355409100_aamaf073-B10","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1038\/s41590-020-0736-z","article-title":"Single-cell transcriptome profiling reveals neutrophil heterogeneity in homeostasis and infection","volume":"21","author":"Xie","year":"2020","journal-title":"Nat Immunol"},{"key":"2026032109355409100_aamaf073-B11","doi-asserted-by":"publisher","first-page":"2406","DOI":"10.3390\/cells10092406","article-title":"Current understanding of the neutrophil transcriptome in health and disease","volume":"10","author":"Garratt","year":"2021","journal-title":"Cells"},{"key":"2026032109355409100_aamaf073-B12","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1007\/s00011-023-01737-9","article-title":"Neutrophil sub-types in maintaining immune homeostasis during steady state, infections and sterile inflammation","volume":"72","author":"Ganesh","year":"2023","journal-title":"Inflamm Res"},{"key":"2026032109355409100_aamaf073-B13","doi-asserted-by":"publisher","first-page":"2000535","DOI":"10.1183\/13993003.00535-2020","article-title":"Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS\/ERS\/ESCMID\/IDSA clinical practice guideline","volume":"56","author":"Daley","year":"2020","journal-title":"Eur Respir J"},{"key":"2026032109355409100_aamaf073-B14","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1164\/rccm.202004-1418OC","article-title":"BACES score for predicting mortality in nontuberculous mycobacterial pulmonary disease","volume":"203","author":"Kim","year":"2021","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032109355409100_aamaf073-B15","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1016\/j.jiac.2023.06.017","article-title":"Prognostic serum biomarkers in non-tuberculous mycobacterial pulmonary disease","volume":"29","author":"Park","year":"2023","journal-title":"J Infect Chemother"},{"key":"2026032109355409100_aamaf073-B16","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"2026032109355409100_aamaf073-B17","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1164\/rccm.201712-2551OC","article-title":"BAL cell gene expression is indicative of outcome and airway basal cell involvement in idiopathic pulmonary fibrosis","volume":"199","author":"Prasse","year":"2019","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032109355409100_aamaf073-B18","doi-asserted-by":"publisher","first-page":"2401050","DOI":"10.1183\/13993003.01050-2024","article-title":"Targeting neutrophil serine proteases in bronchiectasis","volume":"65","author":"Chalmers","year":"2025","journal-title":"Eur Respir J"},{"key":"2026032109355409100_aamaf073-B19","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1016\/j.jcf.2020.12.015","article-title":"Changes in airway inflammation with pseudomonas eradication in early cystic fibrosis","volume":"20","author":"Garratt","year":"2021","journal-title":"J Cyst Fibros"},{"key":"2026032109355409100_aamaf073-B20","doi-asserted-by":"publisher","first-page":"1851","DOI":"10.1164\/ajrccm.160.6.9902019","article-title":"Markers indicating deterioration of pulmonary Mycobacterium avium-intracellulare infection","volume":"160","author":"Yamazaki","year":"1999","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032109355409100_aamaf073-B21","doi-asserted-by":"publisher","first-page":"5181","DOI":"10.1038\/s41598-022-09017-y","article-title":"Mycobacterium avium-intracellulare complex promote release of pro-inflammatory enzymes matrix metalloproteinases by inducing neutrophil extracellular trap formation","volume":"12","author":"Nakamura","year":"2022","journal-title":"Sci Rep"},{"key":"2026032109355409100_aamaf073-B22","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.ygeno.2005.03.006","article-title":"Identification and expression of a new type II transmembrane protein in human mast cells","volume":"86","author":"Li","year":"2005","journal-title":"Genomics"},{"key":"2026032109355409100_aamaf073-B23","doi-asserted-by":"publisher","first-page":"205ra136","DOI":"10.1126\/scitranslmed.3005964","article-title":"Peripheral blood mononuclear cell gene expression profiles predict poor outcome in idiopathic pulmonary fibrosis","volume":"5","author":"Herazo-Maya","year":"2013","journal-title":"Sci Transl Med"},{"key":"2026032109355409100_aamaf073-B24","doi-asserted-by":"publisher","first-page":"2024","DOI":"10.1111\/all.13439","article-title":"Childhood asthma clusters reveal neutrophil-predominant phenotype with distinct gene expression","volume":"73","author":"Su","year":"2018","journal-title":"Allergy"},{"key":"2026032109355409100_aamaf073-B25","doi-asserted-by":"publisher","first-page":"104472","DOI":"10.1016\/j.ebiom.2023.104472","article-title":"Early peripheral blood MCEMP1 and HLA-DRA expression predicts COVID-19 prognosis","volume":"89","author":"Chan","year":"2023","journal-title":"EBioMedicine"},{"key":"2026032109355409100_aamaf073-B26","doi-asserted-by":"publisher","first-page":"100779","DOI":"10.1016\/j.xcrm.2022.100779","article-title":"Longitudinal characterization of circulating neutrophils uncovers phenotypes associated with severity in hospitalized COVID-19 patients","volume":"3","author":"LaSalle","year":"2022","journal-title":"Cell Rep Med"},{"key":"2026032109355409100_aamaf073-B27","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1016\/0140-6736(90)93237-j","article-title":"Antimicrobial actions of calcium binding leucocyte L1 protein, calprotectin","volume":"336","author":"Steinbakk","year":"1990","journal-title":"Lancet"},{"key":"2026032109355409100_aamaf073-B28","doi-asserted-by":"publisher","first-page":"2893","DOI":"10.3390\/ijms13032893","article-title":"Pro-inflammatory S100A8 and S100A9 proteins: self-assembly into multifunctional native and amyloid complexes","volume":"13","author":"Vogl","year":"2012","journal-title":"Int J Mol Sci"},{"key":"2026032109355409100_aamaf073-B29","doi-asserted-by":"publisher","first-page":"118677","DOI":"10.1016\/j.bbamcr.2020.118677","article-title":"Role of S100 proteins in health and disease","volume":"1867","author":"Gonzalez","year":"2020","journal-title":"Biochim Biophys Acta Mol Cell Res"},{"key":"2026032109355409100_aamaf073-B30","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1111\/imm.13722","article-title":"Roles of S100A8, S100A9 and S100A12 in infection, inflammation and immunity","volume":"171","author":"Xia","year":"2024","journal-title":"Immunology"},{"key":"2026032109355409100_aamaf073-B31","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1007\/s00726-010-0528-0","article-title":"Inflammation-associated S100 proteins: new mechanisms that regulate function","volume":"41","author":"Goyette","year":"2011","journal-title":"Amino Acids"},{"key":"2026032109355409100_aamaf073-B32","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1038\/nm1638","article-title":"Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock","volume":"13","author":"Vogl","year":"2007","journal-title":"Nat Med"},{"key":"2026032109355409100_aamaf073-B33","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/1475-2840-5-6","article-title":"Increased proinflammatory endothelial response to S100A8\/A9 after preactivation through advanced glycation end products","volume":"5","author":"Ehlermann","year":"2006","journal-title":"Cardiovasc Diabetol"},{"key":"2026032109355409100_aamaf073-B34","doi-asserted-by":"publisher","first-page":"13382","DOI":"10.3390\/ijms241713382","article-title":"S100A8 and S100A9 in hematologic malignancies: from development to therapy","volume":"24","author":"Razmkhah","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2026032109355409100_aamaf073-B35","doi-asserted-by":"publisher","first-page":"3098","DOI":"10.1172\/JCI130546","article-title":"S100A8\/A9 regulates CD11b expression and neutrophil recruitment during chronic tuberculosis","volume":"130","author":"Scott","year":"2020","journal-title":"J Clin Invest"},{"key":"2026032109355409100_aamaf073-B36","doi-asserted-by":"publisher","first-page":"lnad022","DOI":"10.1093\/lifemedi\/lnad022","article-title":"SenoIndex: S100A8\/S100A9 as a novel aging biomarker","volume":"2","author":"Zhang","year":"2023","journal-title":"Life Med"},{"key":"2026032109355409100_aamaf073-B37","doi-asserted-by":"publisher","first-page":"e75594","DOI":"10.7554\/eLife.75594","article-title":"C\/EBPdelta-induced epigenetic changes control the dynamic gene transcription of S100a8 and S100a9","volume":"11","author":"Jauch-Speer","year":"2022","journal-title":"Elife"},{"key":"2026032109355409100_aamaf073-B38","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.4049\/jimmunol.1302258","article-title":"Role of Th1\/Th17 balance regulated by T-bet in a mouse model of Mycobacterium avium complex disease","volume":"192","author":"Matsuyama","year":"2014","journal-title":"J Immunol"},{"key":"2026032109355409100_aamaf073-B39","doi-asserted-by":"publisher","first-page":"15663","DOI":"10.1038\/s41598-024-66523-x","article-title":"Single-cell transcriptomics by clinical course of Mycobacterium avium complex pulmonary disease","volume":"14","author":"Kim","year":"2024","journal-title":"Sci Rep"},{"key":"2026032109355409100_aamaf073-B40","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1016\/j.chest.2021.10.048","article-title":"Impact of time between diagnosis and treatment for nontuberculous mycobacterial pulmonary disease on culture conversion and all-cause mortality","volume":"161","author":"Im","year":"2022","journal-title":"Chest"},{"key":"2026032109355409100_aamaf073-B41","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1164\/rccm.200208-829OC","article-title":"Sputum sol neutrophil elastase activity in bronchiectasis: differential modulation by syndecan-1","volume":"168","author":"Chan","year":"2003","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032109355409100_aamaf073-B42","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.tube.2008.07.002","article-title":"Impaired antigen-specific CD4(+) T lymphocyte responses in cavitary tuberculosis","volume":"89","author":"Barry","year":"2009","journal-title":"Tuberculosis (Edinb)"},{"key":"2026032109355409100_aamaf073-B43","doi-asserted-by":"publisher","first-page":"1628","DOI":"10.1164\/ajrccm.164.9.2105083","article-title":"Bronchial inflammation and colonization in patients with clinically stable bronchiectasis","volume":"164","author":"Angrill","year":"2001","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032109355409100_aamaf073-B44","doi-asserted-by":"publisher","first-page":"1600903","DOI":"10.1183\/13993003.00903-2016","article-title":"Hypoxia and sterile inflammation in cystic fibrosis airways: mechanisms and potential therapies","volume":"49","author":"Montgomery","year":"2017","journal-title":"Eur Respir J"},{"key":"2026032109355409100_aamaf073-B45","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1164\/rccm.201712-2423OC","article-title":"Blood neutrophils are reprogrammed in bronchiectasis","volume":"198","author":"Bedi","year":"2018","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032109355409100_aamaf073-B46","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1016\/j.diagmicrobio.2016.09.016","article-title":"Clinical characteristics and treatment outcomes of pulmonary disease caused by Mycobacterium chimaera","volume":"86","author":"Moon","year":"2016","journal-title":"Diagn Microbiol Infect Dis"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/advance-article-pdf\/doi\/10.1164\/rccm.202503-0665OC\/66535894\/rccm.202503-0665oc.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/212\/3\/625\/66535894\/rccm.202503-0665oc.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/212\/3\/625\/66535894\/rccm.202503-0665oc.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T13:35:56Z","timestamp":1774100156000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/212\/3\/625\/8437448"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,14]]},"references-count":46,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,10,14]]},"published-print":{"date-parts":[[2026,3,1]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.202503-0665oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,3]]},"published":{"date-parts":[[2025,10,14]]},"assertion":[{"value":"2025-03-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}