{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T03:17:05Z","timestamp":1771039025718,"version":"3.50.1"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2017,2,3]],"date-time":"2017-02-03T00:00:00Z","timestamp":1486080000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Res"],"published-print":{"date-parts":[[2017,6]]},"DOI":"10.1038\/pr.2017.25","type":"journal-article","created":{"date-parts":[[2017,2,3]],"date-time":"2017-02-03T17:01:27Z","timestamp":1486141287000},"page":"911-918","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Purification and characterization of microRNAs within middle ear fluid exosomes: implication in otitis media pathophysiology"],"prefix":"10.1038","volume":"81","author":[{"given":"St\u00e9phanie","family":"Val","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marian","family":"Poley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Krueger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo","family":"Nino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristy","family":"Brown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego","family":"Preciado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,2,3]]},"reference":[{"key":"BFpr201725_CR1","unstructured":"Cherry DK, Woodwell DA. National ambulatory medical care survey: 2000 summary. Adv Data. 2002 Jun 5;(328):1\u201332."},{"key":"BFpr201725_CR2","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1177\/0009922810370363","volume":"49","author":"MS Grubb","year":"2010","unstructured":"Grubb MS, Spaugh DC. Treatment failure, recurrence, and antibiotic prescription rates for different acute otitis media treatment methods. Clin Pediatr (Phila) 2010;49:970\u20135.","journal-title":"Clin Pediatr (Phila)"},{"key":"BFpr201725_CR3","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1002\/lary.24190","volume":"124","author":"S Ahmed","year":"2014","unstructured":"Ahmed S, Shapiro NL, Bhattacharyya N. Incremental health care utilization and costs for acute otitis media in children. Laryngoscope 2014;124:301\u20135.","journal-title":"Laryngoscope"},{"key":"BFpr201725_CR4","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1067\/mhn.2001.119326","volume":"125","author":"RM Rosenfeld","year":"2001","unstructured":"Rosenfeld RM, Casselbrant ML, Hannley MT. Implications of the AHRQ evidence report on acute otitis media. Otolaryngol Head Neck Surg 2001;125:440\u20138; discussion 439.","journal-title":"Otolaryngol Head Neck Surg"},{"key":"BFpr201725_CR5","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1177\/000348947108000611","volume":"80","author":"DJ Lim","year":"1971","unstructured":"Lim DJ, Birck H. Ultrastructural pathology of the middle ear mucosa in serous otitis media. Ann Otol Rhinol Laryngol 1971;80:838\u201353.","journal-title":"Ann Otol Rhinol Laryngol"},{"issue":"2 pt. 1","key":"BFpr201725_CR6","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1177\/000348947708600212","volume":"86","author":"M Tos","year":"1977","unstructured":"Tos M, Bak-Pedersen K. Goblet cell population in the pathological middle ear and eustachian tube of children and adults. Ann Otol Rhinol Laryngol 1977;86(2 pt. 1):209\u201318.","journal-title":"Ann Otol Rhinol Laryngol"},{"key":"BFpr201725_CR7","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1177\/00034894051140S106","volume":"194","author":"AF Ryan","year":"2005","unstructured":"Ryan AF, Jung TT, Juhn SK, et al. Recent advances in otitis media. 4A. Molecular biology. Ann Otol Rhinol Laryngol Suppl 2005;194:42\u20139.","journal-title":"Ann Otol Rhinol Laryngol Suppl"},{"key":"BFpr201725_CR8","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1001\/archotol.128.5.561","volume":"128","author":"DS Hurst","year":"2002","unstructured":"Hurst DS, Venge P. The impact of atopy on neutrophil activity in middle ear effusion from children and adults with chronic otitis media. Arch Otolaryngol Head Neck Surg 2002;128:561\u20136.","journal-title":"Arch Otolaryngol Head Neck Surg"},{"key":"BFpr201725_CR9","doi-asserted-by":"publisher","first-page":"e0152865","DOI":"10.1371\/journal.pone.0152865","volume":"11","author":"S Val","year":"2016","unstructured":"Val S, Poley M, Brown K, et al. Proteomic characterization of middle ear fluid confirms neutrophil extracellular traps as a predominant innate immune response in chronic otitis media. PLoS One 2016;11:e0152865.","journal-title":"PLoS One"},{"key":"BFpr201725_CR10","first-page":"145","volume":"3","author":"LB King","year":"2013","unstructured":"King LB, Pang B Perez AC, et al. Observation of Viable Nontypeable Haemophilus Influenzae Bacteria within Neutrophil Extracellular Traps in Clinical Samples from Chronic Otitis Media. Otolaryngology 2013;3:145. doi: 10.4172\/2161-119X.1000145.","journal-title":"Otolaryngology"},{"key":"BFpr201725_CR11","doi-asserted-by":"publisher","first-page":"e53837","DOI":"10.1371\/journal.pone.0053837","volume":"8","author":"RB Thornton","year":"2013","unstructured":"Thornton RB, Wiertsema SP, Kirkham LA, et al. Neutrophil extracellular traps and bacterial biofilms in middle ear effusion of children with recurrent acute otitis media\u2013a potential treatment target. PLoS One 2013;8:e53837.","journal-title":"PLoS One"},{"key":"BFpr201725_CR12","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1203\/PDR.0b013e3181eb2ecc","volume":"68","author":"D Preciado","year":"2010","unstructured":"Preciado D, Goyal S, Rahimi M, et al. MUC5B is the predominant mucin glycoprotein in chronic otitis media fluid. Pediatr Res 2010;68:231\u20136.","journal-title":"Pediatr Res"},{"key":"BFpr201725_CR13","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/978-3-319-17888-2_7","volume-title":"Otitis Media State of the Art Concepts and Treatment. Preciado D","author":"S Val","year":"2015","unstructured":"Val S. \u201cBasic Science Concepts in Otitis Media Pathophysiology and Immunity\u201d In: Otitis Media State of the Art Concepts and Treatment. Preciado D, ed. Springer International Publishing: Gewerbestrasse Switzerland. 2015:53\u201379."},{"key":"BFpr201725_CR14","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1177\/000348949610500810","volume":"105","author":"J Sad\u00e9","year":"1996","unstructured":"Sad\u00e9 J, Fuchs C. Secretory otitis media in adults: I. The role of mastoid pneumatizationas a risk factor. Ann Otol Rhinol Laryngol 1996;105:643\u20137.","journal-title":"Ann Otol Rhinol Laryngol"},{"key":"BFpr201725_CR15","doi-asserted-by":"publisher","first-page":"L1157","DOI":"10.1152\/ajplung.2001.280.6.L1157","volume":"280","author":"J Lin","year":"2001","unstructured":"Lin J, Tsuprun V, Kawano H, et al. Characterization of mucins in human middle ear and Eustachian tube. Am J Physiol Lung Cell Mol Physiol 2001;280:L1157\u201367.","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"BFpr201725_CR16","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1007\/s10162-002-3023-9","volume":"4","author":"J Lin","year":"2003","unstructured":"Lin J, Tsuboi Y, Rimell F, et al. Expression of mucins in mucoid otitis media. J Assoc Res Otolaryngol 2003;4:384\u201393.","journal-title":"J Assoc Res Otolaryngol"},{"key":"BFpr201725_CR17","first-page":"98","volume":"1","author":"G Camussi","year":"2011","unstructured":"Camussi G, Deregibus MC, Bruno S, Grange C, Fonsato V, Tetta C. Exosome\/microvesicle-mediated epigenetic reprogramming of cells. Am J Cancer Res 2011;1:98\u2013110.","journal-title":"Am J Cancer Res"},{"key":"BFpr201725_CR18","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1038\/pr.2014.202","volume":"77","author":"SC Ferrante","year":"2015","unstructured":"Ferrante SC, Nadler EP, Pillai DK, et al. Adipocyte-derived exosomal miRNAs: a novel mechanism for obesity-related disease. Pediatr Res 2015;77:447\u201354.","journal-title":"Pediatr Res"},{"key":"BFpr201725_CR19","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.cell.2009.01.002","volume":"136","author":"DP Bartel","year":"2009","unstructured":"Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell 2009;136:215\u201333.","journal-title":"Cell"},{"key":"BFpr201725_CR20","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1038\/ki.2010.278","volume":"78","author":"G Camussi","year":"2010","unstructured":"Camussi G, Deregibus MC, Bruno S, Cantaluppi V, Biancone L. Exosomes\/microvesicles as a mechanism of cell-to-cell communication. Kidney Int 2010;78:838\u201348.","journal-title":"Kidney Int"},{"key":"BFpr201725_CR21","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1038\/nri2957","volume":"11","author":"LA O\u2019Neill","year":"2011","unstructured":"O\u2019Neill LA, Sheedy FJ, McCoy CE. MicroRNAs: the fine-tuners of Toll-like receptor signalling. Nat Rev Immunol 2011;11:163\u201375.","journal-title":"Nat Rev Immunol"},{"key":"BFpr201725_CR22","first-page":"161","volume":"2","author":"AM Ardekani","year":"2010","unstructured":"Ardekani AM, Naeini MM. The role of microRNAs in human diseases. Avicenna J Med Biotechnol 2010;2:161\u201379.","journal-title":"Avicenna J Med Biotechnol"},{"key":"BFpr201725_CR23","doi-asserted-by":"publisher","first-page":"51","DOI":"10.4068\/cmj.2015.51.2.51","volume":"51","author":"YK Kim","year":"2015","unstructured":"Kim YK. Extracellular microRNAs as biomarkers in human disease. Chonnam Med J 2015;51:51\u20137.","journal-title":"Chonnam Med J"},{"key":"BFpr201725_CR24","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1016\/j.ijporl.2011.02.001","volume":"75","author":"JJ Song","year":"2011","unstructured":"Song JJ, Kwon SK, Cho CG, Park SW, Chae SW. Microarray analysis of microRNA expression in LPS induced inflammation of human middle ear epithelial cells (HMEECs). Int J Pediatr Otorhinolaryngol 2011;75:648\u201351.","journal-title":"Int J Pediatr Otorhinolaryngol"},{"key":"BFpr201725_CR25","doi-asserted-by":"publisher","first-page":"e2016","DOI":"10.1038\/cddis.2015.282","volume":"6","author":"HG Moon","year":"2015","unstructured":"Moon HG, Cao Y, Yang J, Lee JH, Choi HS, Jin Y. Lung epithelial cell-derived extracellular vesicles activate macrophage-mediated inflammatory responses via ROCK1 pathway. Cell Death Dis 2015;6:e2016.","journal-title":"Cell Death Dis"},{"key":"BFpr201725_CR26","doi-asserted-by":"crossref","unstructured":"Lee H, Zhang D, Minhas J, Jin Y. Extracellular Vesicles Facilitate the Intercellular Communications in the Pathogenesis of Lung Injury. Cell Dev Biol. 2016;5:1-7. pii: 175.","DOI":"10.4172\/2168-9296.1000175"},{"key":"BFpr201725_CR27","doi-asserted-by":"publisher","first-page":"e0148612","DOI":"10.1371\/journal.pone.0148612","volume":"11","author":"S Val","year":"2016","unstructured":"Val S, Burgett K, Brown KJ, Preciado D. SuperSILAC quantitative proteome profiling of murine middle ear epithelial cell remodeling with NTHi. PLoS One 2016;11:e0148612.","journal-title":"PLoS One"},{"key":"BFpr201725_CR28","doi-asserted-by":"publisher","first-page":"9484","DOI":"10.18632\/oncotarget.2419","volume":"5","author":"P Leidinger","year":"2014","unstructured":"Leidinger P, Backes C, Dahmke IN, et al. What makes a blood cell based miRNA expression pattern disease specific?\u2013a miRNome analysis of blood cell subsets in lung cancer patients and healthy controls. Oncotarget 2014;5:9484\u201397.","journal-title":"Oncotarget"},{"key":"BFpr201725_CR29","doi-asserted-by":"publisher","first-page":"e0166688","DOI":"10.1371\/journal.pone.0166688","volume":"11","author":"C Tian","year":"2016","unstructured":"Tian C, Li Z, Yang Z, Huang Q, Liu J, Hong B. Plasma microRNA-16 is a biomarker for diagnosis, stratification, and prognosis of hyperacute cerebral infarction. PLoS One 2016;11:e0166688.","journal-title":"PLoS One"},{"key":"BFpr201725_CR30","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.ijporl.2015.11.016","volume":"80","author":"Diego Preciado","year":"2016","unstructured":"Preciado D, Poley M, Tsai S, Tomney A, Brown K, Val S. A proteomic characterization of NTHi lysates. Int J Pediatr Otorhinolaryngol. 2016 Jan;80:8\u201316. doi: 10.1016\/j.ijporl.2015.11.016. PubMed PMID: 26746604; PubMed Central PMCID: PMC4706994.","journal-title":"International Journal of Pediatric Otorhinolaryngology"},{"key":"BFpr201725_CR31","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1038\/pr.2014.187","volume":"77","author":"A Saieg","year":"2015","unstructured":"Saieg A, Brown KJ, Pena MT, Rose MC, Preciado D. Proteomic analysis of pediatric sinonasal secretions shows increased MUC5B mucin in CRS. Pediatr Res 2015;77:356\u201362.","journal-title":"Pediatr Res"},{"key":"BFpr201725_CR32","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/1479-5876-9-9","volume":"9","author":"C L\u00e4sser","year":"2011","unstructured":"L\u00e4sser C, Alikhani VS, Ekstr\u00f6m K, et al. Human saliva, plasma and breast milk exosomes contain RNA: uptake by macrophages. J Transl Med 2011;9:9.","journal-title":"J Transl Med"},{"key":"BFpr201725_CR33","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1186\/1479-5876-9-86","volume":"9","author":"S Keller","year":"2011","unstructured":"Keller S, Ridinger J, Rupp AK, Janssen JW, Altevogt P. Body fluid derived exosomes as a novel template for clinical diagnostics. J Transl Med 2011;9:86.","journal-title":"J Transl Med"},{"key":"BFpr201725_CR34","doi-asserted-by":"publisher","first-page":"6631","DOI":"10.1039\/C5AN00688K","volume":"140","author":"Y Wu","year":"2015","unstructured":"Wu Y, Deng W, Klinke DJ 2nd . Exosomes: improved methods to characterize their morphology, RNA content, and surface protein biomarkers. Analyst 2015;140:6631\u201342.","journal-title":"Analyst"},{"key":"BFpr201725_CR35","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.ymeth.2015.03.013","volume":"87","author":"M Kesimer","year":"2015","unstructured":"Kesimer M, Gupta R. Physical characterization and profiling of airway epithelial derived exosomes using light scattering. Methods 2015;87:59\u201363.","journal-title":"Methods"},{"key":"BFpr201725_CR36","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1189\/jlb.1012539","volume":"94","author":"MP Gantier","year":"2013","unstructured":"Gantier MP. The not-so-neutral role of microRNAs in neutrophil biology. J Leukoc Biol 2013;94:575\u201383.","journal-title":"J Leukoc Biol"},{"key":"BFpr201725_CR37","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/nature07242","volume":"455","author":"D Baek","year":"2008","unstructured":"Baek D, Vill\u00e9n J, Shin C, Camargo FD, Gygi SP, Bartel DP. The impact of microRNAs on protein output. Nature 2008;455:64\u201371.","journal-title":"Nature"},{"key":"BFpr201725_CR38","doi-asserted-by":"publisher","first-page":"1709","DOI":"10.1183\/09031936.00139813","volume":"43","author":"S Hamaguchi","year":"2014","unstructured":"Hamaguchi S, Hirose T, Matsumoto N, et al. Neutrophil extracellular traps in bronchial aspirates: a quantitative analysis. Eur Respir J 2014;43:1709\u201318.","journal-title":"Eur Respir J"},{"key":"BFpr201725_CR39","doi-asserted-by":"publisher","first-page":"7855","DOI":"10.1007\/s00216-014-8040-0","volume":"406","author":"KE Petersen","year":"2014","unstructured":"Petersen KE, Manangon E, Hood JL, et al. A review of exosome separation techniques and characterization of B16-F10 mouse melanoma exosomes with AF4-UV-MALS-DLS-TEM. Anal Bioanal Chem 2014;406:7855\u201366.","journal-title":"Anal Bioanal Chem"},{"key":"BFpr201725_CR40","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1128\/IAI.01128-15","volume":"84","author":"T Hirano","year":"2015","unstructured":"Hirano T, Kodama S, Kawano T, Suzuki M. Accumulation of regulatory T cells and chronic inflammation in the middle ear in a mouse model of chronic otitis media with effusion induced by combined eustachian tube blockage and nontypeable haemophilus influenzae infection. Infect Immun 2015;84:356\u201364.","journal-title":"Infect Immun"},{"key":"BFpr201725_CR41","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1159\/000341163","volume":"17","author":"Q Huang","year":"2012","unstructured":"Huang Q, Zhang Z, Zheng Y, et al. Hypoxia-inducible factor and vascular endothelial growth factor pathway for the study of hypoxia in a new model of otitis media with effusion. Audiol Neurootol 2012;17:349\u201356.","journal-title":"Audiol Neurootol"},{"key":"BFpr201725_CR42","doi-asserted-by":"publisher","first-page":"E377","DOI":"10.1002\/lary.24698","volume":"124","author":"MF Bhutta","year":"2014","unstructured":"Bhutta MF, Cheeseman MT, Brown SD. Myringotomy in the Junbo mouse model of chronic otitis media alleviates inflammation and cellular hypoxia. Laryngoscope 2014;124:E377\u201383.","journal-title":"Laryngoscope"},{"issue":"1","key":"BFpr201725_CR43","doi-asserted-by":"publisher","first-page":"20920","DOI":"10.3402\/jev.v2i0.20920","volume":"2","author":"Malene J\u00f8rgensen","year":"2013","unstructured":"J\u00f8rgensen M, B\u00e6k R, Pedersen S, S\u00f8ndergaard EK, Kristensen SR, Varming K. Extracellular Vesicle (EV) Array: microarray capturing of exosomes and other extracellular vesicles for multiplexed phenotyping. J Extracell Vesicles. 2013;2. doi: 10.3402\/jev.v2i0.20920. PubMed PMID: 24009888; PubMed Central PMCID: PMC3760630.","journal-title":"Journal of Extracellular Vesicles"}],"container-title":["Pediatric Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/pr201725.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/pr201725","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/pr.2017.25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"http:\/\/www.nature.com\/articles\/pr201725.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T21:03:37Z","timestamp":1684616617000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/pr201725"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,3]]},"references-count":43,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2017,6]]}},"alternative-id":["BFpr201725"],"URL":"https:\/\/doi.org\/10.1038\/pr.2017.25","relation":{},"ISSN":["0031-3998","1530-0447"],"issn-type":[{"value":"0031-3998","type":"print"},{"value":"1530-0447","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,3]]},"assertion":[{"value":"3 October 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 December 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 February 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}