{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:16:11Z","timestamp":1790381771554,"version":"4.1.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":631,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["U01CA252965"],"award-info":[{"award-number":["U01CA252965"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD090927"],"award-info":[{"award-number":["R01HD090927"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI144168"],"award-info":[{"award-number":["R01AI144168"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH1910026"],"award-info":[{"award-number":["W81XWH1910026"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R21NS130542"],"award-info":[{"award-number":["R21NS130542"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR002369"],"award-info":[{"award-number":["UL1TR002369"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["U01CA252965"],"award-info":[{"award-number":["U01CA252965"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD090927"],"award-info":[{"award-number":["R01HD090927"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI144168"],"award-info":[{"award-number":["R01AI144168"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH1910026"],"award-info":[{"award-number":["W81XWH1910026"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R21NS130542"],"award-info":[{"award-number":["R21NS130542"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR002369"],"award-info":[{"award-number":["UL1TR002369"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial (NTM) pulmonary disease (PD), which exhibits increasing global incidence. Current microbiologic methods routinely used in clinical practice lack sensitivity and have long latencies, leading to delays in diagnosis and treatment initiation and evaluation. A clustered regularly interspaced short palindromic repeats (CRISPR)\u2013based assay that measures MAC cell-free DNA (cfDNA) concentrations in serum could provide a rapid means to detect MAC infection and monitor response to antimicrobial treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To develop and optimize a CRISPR MAC assay for MAC infection detection and to evaluate its diagnostic and prognostic performance in two MAC disease cohorts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>MAC cfDNA serum concentrations were measured in individuals with diagnoses of MAC disease or who had bronchiectasis or chronic obstructive pulmonary disease diagnoses without histories of NTM PD or NTM-positive sputum cultures. Diagnostic performance was analyzed using pretreatment serum from two cohorts. Serum MAC cfDNA changes during MAC PD treatment were evaluated in a subset of patients with MAC PD who received macrolide-based multidrug regimens.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>The CRISPR MAC assay detected MAC cfDNA in MAC PD with 97.6% (91.6\u201399.7%) sensitivity and 97.6% (91.5\u201399.7%) specificity overall. Serum MAC cfDNA concentrations markedly decreased after MAC-directed treatment initiation in patients with MAC PD who demonstrated MAC culture conversion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study provides preliminary evidence for the utility of a serum-based CRISPR MAC assay to rapidly detect MAC infection and monitor the response to treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202303-0401oc","type":"journal-article","created":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T16:54:55Z","timestamp":1704732895000},"page":"1246-1254","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":18,"title":["Serum Cell-Free DNA-based Detection of\n                    <i>Mycobacterium avium<\/i>\n                    Complex Infection"],"prefix":"10.1093","volume":"209","author":[{"given":"Lin","family":"Li","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences & Sichuan Provincial People\u2019s Hospital, Chengdu, China"},{"name":"Center for Cellular and Molecular Diagnostics, Department of Biochemistry and Molecular Biology, School of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Henkle","sequence":"additional","affiliation":[{"name":"OHSU-PSU School of Public Health and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brady M.","family":"Youngquist","sequence":"additional","affiliation":[{"name":"Center for Cellular and Molecular Diagnostics, Department of Biochemistry and Molecular Biology, School of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seungyeon","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, NIH Clinical Center, NIH, Bethesda, MD; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1896-9736","authenticated-orcid":false,"given":"Kamal","family":"Hamed","sequence":"additional","affiliation":[{"name":"Spero Therapeutics, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Melnick","sequence":"additional","affiliation":[{"name":"Spero Therapeutics, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Lyon","sequence":"additional","affiliation":[{"name":"Center for Cellular and Molecular Diagnostics, Department of Biochemistry and Molecular Biology, School of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences & Sichuan Provincial People\u2019s Hospital, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian M.","family":"Zelazny","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, NIH Clinical Center, NIH, Bethesda, MD; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7255-5409","authenticated-orcid":false,"given":"Tony Y.","family":"Hu","sequence":"additional","affiliation":[{"name":"Center for Cellular and Molecular Diagnostics, Department of Biochemistry and Molecular Biology, School of Medicine, and"},{"name":"Department of Biomedical Engineering, School of Science and Engineering, Tulane University, New Orleans, LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin L.","family":"Winthrop","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Schools of Medicine and Public Health, Oregon Health & Science University, Portland, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Ning","sequence":"additional","affiliation":[{"name":"Center for Cellular and Molecular Diagnostics, Department of Biochemistry and Molecular Biology, School of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"key":"2026012204240820700_bib1","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1513\/AnnalsATS.201412-559OC","article-title":"Population-based incidence of pulmonary nontuberculous mycobacterial disease in Oregon 2007 to 2012","volume":"12","author":"Henkle","year":"2015","journal-title":"Ann Am Thorac Soc"},{"key":"2026012204240820700_bib2","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1164\/rccm.201002-0310OC","article-title":"Nontuberculous mycobacterial lung disease prevalence at four integrated health care delivery systems","volume":"182","author":"Prevots","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012204240820700_bib3","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1164\/rccm.201003-0503OC","article-title":"Pulmonary nontuberculous mycobacterial disease prevalence and clinical features: an emerging public health disease","volume":"182","author":"Winthrop","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012204240820700_bib4","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1164\/rccm.201111-2016OC","article-title":"Prevalence of nontuberculous mycobacterial lung disease in U.S. Medicare beneficiaries","volume":"185","author":"Adjemian","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012204240820700_bib5","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1164\/rccm.201903-0669LE","article-title":"Mycobacterium avium complex diversity within lung disease, as revealed by whole-genome sequencing","volume":"200","author":"Operario","year":"2019","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012204240820700_bib6","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1164\/rccm.200604-571ST","article-title":"An official ATS\/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases","volume":"175","author":"Griffith","year":"2007","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012204240820700_bib7","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/cid\/ciaa241","article-title":"Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS\/ERS\/ESCMID\/IDSA clinical practice guideline","volume":"71","author":"Daley","year":"2020","journal-title":"Clin Infect Dis"},{"key":"2026012204240820700_bib8","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1513\/AnnalsATS.202107-765OC","article-title":"Time to positive culture detection predicts Mycobacterium avium pulmonary disease severity and treatment initiation","volume":"19","author":"Edwards","year":"2022","journal-title":"Ann Am Thorac Soc"},{"key":"2026012204240820700_bib9","doi-asserted-by":"crossref","first-page":"e01234-18","DOI":"10.1128\/JCM.01234-18","article-title":"Toward the development of a circulating free DNA-based in vitro diagnostic test for infectious diseases: a review of evidence for tuberculosis","volume":"57","author":"Fern\u00e1ndez-Carballo","year":"2019","journal-title":"J Clin Microbiol"},{"key":"2026012204240820700_bib10","doi-asserted-by":"crossref","first-page":"5501","DOI":"10.7150\/thno.45554","article-title":"Liquid biopsy for infectious diseases: a focus on microbial cell-free DNA sequencing","volume":"10","author":"Han","year":"2020","journal-title":"Theranostics"},{"key":"2026012204240820700_bib11","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1164\/rccm.201904-0905LE","article-title":"Detection of pneumonia pathogens from plasma cell-free DNA","volume":"201","author":"Langelier","year":"2020","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012204240820700_bib12","doi-asserted-by":"crossref","first-page":"e482","DOI":"10.1016\/S2666-5247(22)00087-8","article-title":"CRISPR detection of circulating cell-free Mycobacterium tuberculosis DNA in adults and children, including children with HIV: a molecular diagnostics study","volume":"3","author":"Huang","year":"2022","journal-title":"Lancet Microbe"},{"key":"2026012204240820700_bib13","doi-asserted-by":"crossref","first-page":"e146031","DOI":"10.1172\/JCI146031","article-title":"Sensitive tracking of circulating viral RNA through all stages of SARS-CoV-2 infection","volume":"131","author":"Huang","year":"2021","journal-title":"J Clin Invest"},{"key":"2026012204240820700_bib14","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.tibtech.2018.12.005","article-title":"CRISPR\/Cas systems towards next-generation biosensing","volume":"37","author":"Li","year":"2019","journal-title":"Trends Biotechnol"},{"key":"2026012204240820700_bib15","doi-asserted-by":"crossref","first-page":"112316","DOI":"10.1016\/j.bios.2020.112316","article-title":"Ultra-sensitive and high-throughput CRISPR-powered COVID-19 diagnosis","volume":"164","author":"Huang","year":"2020","journal-title":"Biosens Bioelectron"},{"key":"2026012204240820700_bib16","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1590\/0074-02760160119","article-title":"Calculation of the ELISA\u2019s cut-off based on the change-point analysis method for detection of Trypanosoma cruzi infection in Bolivian dogs in the absence of controls","volume":"111","author":"Lardeux","year":"2016","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"2026012204240820700_bib17","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1378\/chest.13-1891","article-title":"A preliminary quality of life questionnaire-bronchiectasis: a patient-reported outcome measure for bronchiectasis","volume":"146","author":"Quittner","year":"2014","journal-title":"Chest"},{"key":"2026012204240820700_bib18","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1136\/thoraxjnl-2014-205918","article-title":"Quality of Life Questionnaire\u2013Bronchiectasis: final psychometric analyses and determination of minimal important difference scores","volume":"70","author":"Quittner","year":"2015","journal-title":"Thorax"},{"key":"2026012204240820700_bib19","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.diagmicrobio.2014.01.019","article-title":"Detection of Mycobacterium avium complex DNA directly in clinical respiratory specimens: opportunities for improved turn-around time and cost savings","volume":"79","author":"Tran","year":"2014","journal-title":"Diagn Microbiol Infect Dis"},{"key":"2026012204240820700_bib20","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1164\/rccm.200705-771OC","article-title":"Serodiagnosis of Mycobacterium avium-complex pulmonary disease using an enzyme immunoassay kit","volume":"177","author":"Kitada","year":"2008","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012204240820700_bib21","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1513\/AnnalsATS.201610-801OC","article-title":"Long-term outcomes in a population-based cohort with respiratory nontuberculous mycobacteria isolation","volume":"14","author":"Henkle","year":"2017","journal-title":"Ann Am Thorac Soc"},{"key":"2026012204240820700_bib22","doi-asserted-by":"crossref","first-page":"2813","DOI":"10.3389\/fmicb.2018.02813","article-title":"Assessing response to therapy for nontuberculous mycobacterial lung disease: quo vadis?","volume":"9","author":"Vinnard","year":"2018","journal-title":"Front Microbiol"},{"key":"2026012204240820700_bib23","doi-asserted-by":"crossref","first-page":"S199","DOI":"10.1093\/infdis\/jiaa354","article-title":"Mycobacterium avium complex: addressing gaps in diagnosis and management","volume":"222","author":"Daley","year":"2020","journal-title":"J Infect Dis"},{"key":"2026012204240820700_bib24","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1128\/JCM.02010-16","article-title":"Levels of antibody against glycopeptidolipid core as a marker for monitoring treatment response in Mycobacterium avium complex pulmonary disease: a prospective cohort study","volume":"55","author":"Kitada","year":"2017","journal-title":"J Clin Microbiol"},{"key":"2026012204240820700_bib25","doi-asserted-by":"crossref","first-page":"582","DOI":"10.7883\/yoken.JJID.2016.523","article-title":"Changes in serum IgA antibody levels against the glycopeptidolipid core antigen during antibiotic treatment of Mycobacterium avium complex lung disease","volume":"70","author":"Jhun","year":"2017","journal-title":"Jpn J Infect Dis"},{"key":"2026012204240820700_bib26","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/cei.12253","article-title":"Changes in serum immunomolecules during antibiotic therapy for Mycobacterium avium complex lung disease","volume":"176","author":"Kim","year":"2014","journal-title":"Clin Exp Immunol"},{"key":"2026012204240820700_bib27","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.bjid.2015.09.005","article-title":"Elevated serum CA 19-9 levels in patients with pulmonary nontuberculous mycobacterial disease","volume":"20","author":"Hong","year":"2016","journal-title":"Braz J Infect Dis"},{"key":"2026012204240820700_bib28","doi-asserted-by":"crossref","first-page":"FSO295","DOI":"10.4155\/fsoa-2017-0140","article-title":"Kinetics of circulating cell-free DNA for biomedical applications: critical appraisal of the literature","volume":"4","author":"Khier","year":"2018","journal-title":"Future Sci OA"},{"key":"2026012204240820700_bib29","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/978-1-4939-8973-7_2","article-title":"Cell-Free DNA: an overview of sample types and isolation procedures","volume":"1909","author":"Martignano","year":"2019","journal-title":"Methods Mol Biol"}],"updated-by":[{"DOI":"10.1164\/rccm.v210erratum2","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T00:00:00Z","timestamp":1724976000000}}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/209\/10\/1246\/66426138\/ajrccm_209_10_1246.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/209\/10\/1246\/66426138\/ajrccm_209_10_1246.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T09:24:24Z","timestamp":1769073864000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/209\/10\/1246\/8426943"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5]]},"references-count":29,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,5,15]]},"published-print":{"date-parts":[[2024,5,15]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.202303-0401oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,5]]},"published":{"date-parts":[[2024,5]]},"assertion":[{"value":"2023-03-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}