{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:30:57Z","timestamp":1789543857671,"version":"build-2803163510"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T00:00:00Z","timestamp":1661126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>\n                    Tuberculosis (TB) is a global disease caused by\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (\n                    <jats:italic>Mtb<\/jats:italic>\n                    ) and is manifested as a continuum spectrum of infectious states. Both, the most common and clinically asymptomatic latent tuberculosis infection (LTBI), and the symptomatic disease, active tuberculosis (TB), are at opposite ends of the spectrum. Such binary classification is insufficient to describe the existing clinical heterogeneity, which includes incipient and subclinical TB. The absence of clinically TB-related symptoms and the extremely low bacterial burden are features shared by LTBI, incipient and subclinical TB states. In addition, diagnosis relies on cytokine release after antigenic T cell stimulation, yet several studies have shown that a high proportion of individuals with immunoreactivity never developed disease, suggesting that they were no longer infected. LTBI is estimated to affect to approximately one fourth of the human population and, according to WHO data, reactivation of LTBI is the main responsible of TB cases in developed countries. Assuming the drawbacks associated to the current diagnostic tests at this part of the disease spectrum, properly assessing individuals at real risk of developing TB is a major need. Further, it would help to efficiently design preventive treatment. This quest would be achievable if information about bacterial viability during human silent\n                    <jats:italic>Mtb<\/jats:italic>\n                    infection could be determined. Here, we have evaluated the feasibility of new approaches to detect viable bacilli across the full spectrum of TB disease. We focused on methods that specifically can measure host-independent parameters relying on the viability of\n                    <jats:italic>Mtb<\/jats:italic>\n                    either by its direct or indirect detection.\n                  <\/jats:p>","DOI":"10.3389\/fmed.2022.965359","type":"journal-article","created":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T02:37:36Z","timestamp":1661135856000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Feasibility of novel approaches to detect viable Mycobacterium tuberculosis within the spectrum of the tuberculosis disease"],"prefix":"10.3389","volume":"9","author":[{"given":"Sogol","family":"Alebouyeh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Weinrick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline M.","family":"Achkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J.","family":"Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Prados-Rosales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"S1179","DOI":"10.1093\/infdis\/jir451","article-title":"Incipient and subclinical tuberculosis: defining early disease states in the context of host immune response.","volume":"204","author":"Achkar","year":"2011","journal-title":"J Infect Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e00021","DOI":"10.1128\/CMR.00021-18","article-title":"Incipient and subclinical tuberculosis: a clinical review of early stages and progression of infection.","volume":"31","author":"Drain","year":"2018","journal-title":"Clin Microbiol Rev."},{"key":"B3","doi-asserted-by":"publisher","first-page":"15","DOI":"10.4049\/jimmunol.0903856","article-title":"Understanding latent tuberculosis: a moving target.","volume":"185","author":"Lin","year":"2010","journal-title":"J Immunol."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1172\/JCI136222","article-title":"The knowns and unknowns of latent Mycobacterium tuberculosis infection.","volume":"131","author":"Henry Boom","year":"2021","journal-title":"J Clin Invest."},{"key":"B5","year":"2019","journal-title":"WHO Guidelines TB Prevention &amp; Control 2019 Update."},{"key":"B6","doi-asserted-by":"publisher","first-page":"4525","DOI":"10.1172\/JCI136221","article-title":"The state of latency in microbial pathogenesis.","volume":"130","author":"Pirofski","year":"2020","journal-title":"J Clin Invest."},{"key":"B7","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/nm.3412","article-title":"Sterilization of granulomas is common in active and latent tuberculosis despite within-host variability in bacterial killing.","volume":"20","author":"Lin","year":"2014","journal-title":"Nat Med."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22705-z","article-title":"Genomic analyses of Mycobacterium tuberculosis from human lung resections reveal a high frequency of polyclonal infections.","volume":"12","author":"Moreno-Molina","year":"2021","journal-title":"Nat Commun."},{"key":"B9","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1093\/infdis\/jiy579","article-title":"Anatomic and cellular niches for Mycobacterium Tuberculosis in latent tuberculosis infection.","volume":"219","author":"Mayito","year":"2019","journal-title":"J Infect Dis."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e2771","DOI":"10.1128\/mBio.02771-18","article-title":"Adipose tissue regulates pulmonary pathology during TB infection.","volume":"10","author":"Ayyappan","year":"2019","journal-title":"MBio."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1183\/20734735.0079-2021","article-title":"The definition of tuberculosis infection based on the spectrum of tuberculosis disease.","volume":"17","author":"Migliori","year":"2021","journal-title":"Breathe."},{"key":"B12","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1038\/nri.2017.69","article-title":"Heterogeneity in tuberculosis.","volume":"17","author":"Cadena","year":"2017","journal-title":"Nat Rev Immunol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2541","DOI":"10.4049\/jimmunol.1800993","article-title":"The end of the binary era: revisiting the spectrum of tuberculosis.","volume":"201","author":"Lin","year":"2018","journal-title":"J Immunol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"e1125","DOI":"10.1128\/mBio.01125-14","article-title":"Global adaptation to a lipid environment triggers the dormancy- related phenotype of Mycobacterium tuberculosis.","volume":"5","author":"Rodr\u00edguez","year":"2014","journal-title":"MBio."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.1164\/rccm.201607-1431ED","article-title":"New evidence for the complexity of the population structure of Mycobacterium tuberculosis increases the diagnostic and biologic challenges.","volume":"194","author":"Dartois","year":"2016","journal-title":"Am J Respir Crit Care Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1093\/molbev\/msq009","article-title":"A generation time effect on the rate of molecular evolution in invertebrates.","volume":"27","author":"Thomas","year":"2010","journal-title":"Mol Biol Evol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1038\/ng.811","article-title":"Use of whole genome sequencing to estimate the mutation rate of Mycobacterium tuberculosis during latent infection.","volume":"43","author":"Ford","year":"2011","journal-title":"Nat Genet."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0091024","article-title":"Whole genome sequencing of Mycobacterium tuberculosis reveals slow growth and low mutation rates during latent infections in humans.","volume":"9","author":"Colangeli","year":"2014","journal-title":"PLoS One."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18699-9","article-title":"Mycobacterium tuberculosis progresses through two phases of latent infection in humans.","volume":"11","author":"Colangeli","year":"2020","journal-title":"Nat Commun."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k2738","article-title":"Revisiting the timetable of tuberculosis.","volume":"2018","author":"Behr","year":"2018","journal-title":"BMJ."},{"key":"B21","doi-asserted-by":"publisher","first-page":"5571","DOI":"10.1128\/AEM.00744-11","article-title":"Life, death, and in-between: meanings and methods in microbiology.","volume":"77","author":"Davey","year":"2011","journal-title":"Appl Environ Microbiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.chom.2014.11.016","article-title":"Stress and host immunity amplify Mycobacterium tuberculosis phenotypic heterogeneity and induce nongrowing metabolically active forms.","volume":"17","author":"Manina","year":"2015","journal-title":"Cell Host Microbe."},{"key":"B23","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1099\/mic.0.000786","article-title":"Assessment of bacterial viability: a comprehensive review on recent advances and challenges.","volume":"165","author":"Kumar","year":"2019","journal-title":"Microbiology."},{"key":"B24","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1038\/nbt0985-817","article-title":"Viable but non-culturable vibrio cholerae and related pathogens in the environment: implications for release of genetically engineered microorganisms.","volume":"3","author":"Colwell","year":"1985","journal-title":"Bio Technol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"E4832","DOI":"10.1073\/pnas.1705385114","article-title":"Rifamycin action on RNA polymerase in antibiotic-tolerant Mycobacterium tuberculosis results in differentially detectable populations.","volume":"114","author":"Saito","year":"2017","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B26","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1164\/rccm.200905-0661OC","article-title":"Resuscitation-promoting factors reveal an occult population of tubercle bacilli in sputum.","volume":"181","author":"Mukamolova","year":"2010","journal-title":"Am J Respir Crit Care Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.1086\/378563","article-title":"Cell-Wall alterations as an attribute of Mycobacterium tuberculosis in latent infection.","volume":"188","author":"Seiler","year":"2003","journal-title":"J Infect Dis."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.1084\/jem.20151468","article-title":"Transformative tools for tackling tuberculosis.","volume":"212","author":"Gardiner","year":"2015","journal-title":"J Exp Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1827","DOI":"10.1093\/infdis\/jiv312","article-title":"Biomarkers for tuberculosis based on secreted, species-specific, bacterial small molecules.","volume":"212","author":"Pan","year":"2015","journal-title":"J Infect Dis."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD011420.pub2","article-title":"Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in HIV-positive adults.","volume":"2016","author":"Shah","year":"2016","journal-title":"Cochrane Database Syst Rev."},{"key":"B31","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1016\/S1473-3099(19)30307-X","article-title":"Global burden of latent multidrug-resistant tuberculosis: trends and estimates based on mathematical modelling.","volume":"19","author":"Knight","year":"2019","journal-title":"Lancet Infect Dis."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l5770","article-title":"Is Mycobacterium tuberculosis infection life long?","volume":"367","author":"Behr","year":"2019","journal-title":"BMJ."},{"key":"B33","doi-asserted-by":"publisher","first-page":"532","DOI":"10.5588\/ijtld.12.0737","article-title":"Screening for pulmonary tuberculosis in HIV-infected individuals: AIDS clinical trials group protocol A5253.","volume":"17","author":"Swindells","year":"2013","journal-title":"Int J Tuberc Lung Dis."},{"key":"B34","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1586\/eri.10.9","article-title":"Diagnosis of pulmonary tuberculosis in children: new advances.","volume":"8","author":"Zar","year":"2010","journal-title":"Expert Rev Anti Infect Ther."},{"key":"B35","doi-asserted-by":"publisher","first-page":"4161","DOI":"10.1128\/JCM.01743-13","article-title":"Exploring alternative biomaterials for diagnosis of pulmonary tuberculosis in HIV-negative patients by use of the geneXpert MTB\/RIF assay.","volume":"51","author":"Shenai","year":"2013","journal-title":"J Clin Microbiol."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.103007","article-title":"A novel, rapid (within hours) culture-free diagnostic method for detecting live Mycobacterium tuberculosis with high sensitivity.","volume":"60","author":"Wang","year":"2020","journal-title":"EBioMedicine."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-015-2197-6","article-title":"Dormant non-culturable Mycobacterium tuberculosis retains stable low-abundant mRNA.","volume":"16","author":"Ignatov","year":"2015","journal-title":"BMC Genomics."},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001502","article-title":"The enduring hypoxic response of Mycobacterium tuberculosis.","volume":"3","author":"Rustad","year":"2008","journal-title":"PLoS One."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1838","DOI":"10.1128\/JCM.02476-10","article-title":"Evaluation of fluoromycobacteriophages for detecting drug resistance in Mycobacterium tuberculosis.","volume":"49","author":"Rond\u00f3n","year":"2011","journal-title":"J Clin Microbiol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1126\/science.8484123","article-title":"Rapid assessment of drug susceptibilities of Mycobacterium tuberculosis by means of luciferase reporter phages.","volume":"260","author":"Jacobs","year":"1993","journal-title":"Science."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1128\/JCM.06192-11","article-title":"\u03c6 2GFP10, a high-intensity fluorophage, enables detection and rapid drug susceptibility testing of Mycobacterium tuberculosis directly from sputum samples.","volume":"50","author":"Jain","year":"2012","journal-title":"J Clin Microbiol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"2188","DOI":"10.1128\/JCM.03530-14","article-title":"A novel reporter phage to detect tuberculosis and rifampin resistance in a high-HIV-burden population.","volume":"53","author":"O\u2019Donnell","year":"2015","journal-title":"J Clin Microbiol."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.01471","article-title":"Fluoromycobacteriophages can detect viable Mycobacterium tuberculosis and determine phenotypic rifampicin resistance in 3-5 days from sputum collection.","volume":"9","author":"Rond\u00f3n","year":"2018","journal-title":"Front Microbiol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1093\/femsre\/fuz006","article-title":"Mycobacterium tuberculosis infection of host cells in space and time.","volume":"43","author":"Bussi","year":"2019","journal-title":"FEMS Microbiol Rev."},{"key":"B45","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.virol.2012.09.026","article-title":"On the nature of mycobacteriophage diversity and host preference.","volume":"434","author":"Jacobs-Sera","year":"2012","journal-title":"Virology."},{"key":"B46","doi-asserted-by":"publisher","first-page":"3220","DOI":"10.1128\/JB.00592-16","article-title":"Fluorescent reporter DS6A mycobacteriophages reveal unique variations in infectibility and phage production in mycobacteria.","volume":"198","author":"Mayer","year":"2016","journal-title":"J Bacteriol."},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22020735","article-title":"Mycobacteriophages as potential therapeutic agents against drug-resistant tuberculosis.","volume":"22","author":"Allu\u00e9-Guardia","year":"2021","journal-title":"Int J Mol Sci."},{"key":"B48","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1007\/s12275-019-8629-2","article-title":"Ribosome dependence of persister cell formation and resuscitation.","volume":"57","author":"Wood","year":"2019","journal-title":"J Microbiol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1128\/jcm.37.2.290-295.1999","article-title":"Quantitative analysis of mRNA as a marker for viability of Mycobacterium tuberculosis.","volume":"37","author":"Hellyer","year":"1999","journal-title":"J Clin Microbiol."},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054886","article-title":"Molecular viability testing of bacterial pathogens from a complex human sample matrix.","volume":"8","author":"Weigel","year":"2013","journal-title":"PLoS One."},{"key":"B51","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1111\/j.1469-0691.2012.03779.x","article-title":"Evaluation of the detection of Mycobacterium tuberculosis with metabolic activity in culture-negative human clinical samples.","volume":"19","author":"Cubero","year":"2013","journal-title":"Clin Microbiol Infect."},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22833-6","article-title":"Mycobacterium tuberculosis precursor rRNA as a measure of treatment-shortening activity of drugs and regimens.","volume":"12","author":"Walter","year":"2021","journal-title":"Nat Commun."},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1126\/science.93.2408.190","article-title":"The staining of acid-fast tubercle bacteria.","volume":"93","author":"Richards","year":"1941","journal-title":"Science."},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.02021","article-title":"A fluorescent probe for detecting Mycobacterium Tuberculosis and identifying genes critical for cell entry.","volume":"7","author":"Yang","year":"2016","journal-title":"Front Microbiol."},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aam6310","article-title":"Rapid detection of Mycobacterium tuberculosis in sputum with a solvatochromic trehalose probe.","volume":"10","author":"Kamariza","year":"2018","journal-title":"Sci Transl Med."},{"key":"B56","doi-asserted-by":"publisher","first-page":"12911","DOI":"10.1073\/pnas.1222041110","article-title":"Sulfatase-activated fluorophores for rapid discrimination of mycobacterial species and strains.","volume":"110","author":"Beatty","year":"2013","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B57","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1099\/mic.0.27629-0","article-title":"Genetic analysis of the \u03b2-lactamases of Mycobacterium tuberculosis and Mycobacterium smegmatis and susceptibility to \u03b2-lactam antibiotics.","author":"Flores","year":"2005","journal-title":"Microbiology."},{"key":"B58","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1038\/nchem.1435","article-title":"Rapid point-of-care detection of the tuberculosis pathogen using a BlaC-specific fluorogenic probe.","volume":"4","author":"Xie","year":"2012","journal-title":"Nat Chem."},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aar4470","article-title":"Rapid and specific labeling of single live Mycobacterium tuberculosis with a dual-targeting fluorogenic probe.","volume":"10","author":"Cheng","year":"2018","journal-title":"Sci Transl Med."},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-98176-5","article-title":"Flow cytometry method for absolute counting and single-cell phenotyping of mycobacteria.","volume":"11","author":"Barr","year":"2021","journal-title":"Sci Rep."},{"key":"B61","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1021\/acscentsci.0c01345","article-title":"Chemiluminescent protease probe for rapid. sensitive, and inexpensive detection of live Mycobacterium tuberculosis.","volume":"7","author":"Babin","year":"2021","journal-title":"ACS Cent Sci."},{"key":"B62","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.chembiol.2016.01.003","article-title":"Systematic survey of serine hydrolase activity in mycobacterium tuberculosis defines changes associated with persistence.","volume":"23","author":"Ortega","year":"2016","journal-title":"Cell Chem Biol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1172\/JCI44261","article-title":"Mycobacteria release active membrane vesicles that modulate immune responses in a TLR2-dependent manner in mice.","volume":"121","author":"Prados-Rosales","year":"2011","journal-title":"J Clin Invest."},{"key":"B64","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.4049\/jimmunol.1402894","article-title":"Bacterial membrane vesicles mediate the release of mycobacterium tuberculosis lipoglycans and lipoproteins from infected macrophages.","volume":"195","author":"Athman","year":"2015","journal-title":"J Immunol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"e1921","DOI":"10.1128\/mBio.01921-14","article-title":"Mycobacterial membrane vesicles administered systemically in mice induce a protective immune response to surface compartments of Mycobacterium tuberculosis.","volume":"5","author":"Prados-Rosales","year":"2014","journal-title":"MBio."},{"key":"B66","doi-asserted-by":"publisher","first-page":"E4790","DOI":"10.1073\/pnas.1320118110","article-title":". Genetic regulation of vesiculogenesis and immunomodulation in Mycobacterium tuberculosis.","volume":"110","author":"Rath","year":"2013","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2013.00004","article-title":"Latent tuberculosis: models, computational efforts and the pathogen\u2019s regulatory mechanisms during dormancy.","volume":"1","author":"Magombedze","year":"2013","journal-title":"Front Bioeng Biotechnol."},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-99754-3","article-title":"Risk assessment of latent tuberculosis infection through a multiplexed cytokine biosensor assay and machine learning feature selection.","volume":"11","author":"Robison","year":"2021","journal-title":"Sci Rep."},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.745592","article-title":"Differential diagnosis of latent tuberculosis infection and active tuberculosis: a key to a successful tuberculosis control strategy.","volume":"12","author":"Gong","year":"2021","journal-title":"Front Microbiol."},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2016.08.001","article-title":"Point-of-care detection of extracellular vesicles: sensitivity optimization and multiple-target detection.","volume":"87","author":"Oliveira-Rodr\u00edguez","year":"2017","journal-title":"Biosens Bioelectron."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.965359\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T02:37:39Z","timestamp":1661135859000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.965359\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,22]]},"references-count":70,"alternative-id":["10.3389\/fmed.2022.965359"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2022.965359","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,22]]},"article-number":"965359"}}