{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T16:03:41Z","timestamp":1783613021261,"version":"3.55.0"},"reference-count":35,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T00:00:00Z","timestamp":1662076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondo de Investigaci\u00f3n Sanitaria\u2014Spanish Health Research Fund (FIS)","award":["PI18\/00044"],"award-info":[{"award-number":["PI18\/00044"]}]},{"name":"Fondo de Investigaci\u00f3n Sanitaria\u2014Spanish Health Research Fund (FIS)","award":["PI15\/00028"],"award-info":[{"award-number":["PI15\/00028"]}]},{"name":"Fondo de Investigaci\u00f3n Sanitaria\u2014Spanish Health Research Fund (FIS)","award":["PI18CIII\/00009"],"award-info":[{"award-number":["PI18CIII\/00009"]}]},{"name":"Fondo de Investigaci\u00f3n Sanitaria\u2014Spanish Health Research Fund (FIS)","award":["PI21\/00896"],"award-info":[{"award-number":["PI21\/00896"]}]},{"name":"Fondo de Investigaci\u00f3n Sanitaria\u2014Spanish Health Research Fund (FIS)","award":["FI19\/00067"],"award-info":[{"award-number":["FI19\/00067"]}]},{"name":"Fondo de Investigaci\u00f3n Sanitaria\u2014Spanish Health Research Fund (FIS)","award":["VIII Convocatoria Santander-UAX"],"award-info":[{"award-number":["VIII Convocatoria Santander-UAX"]}]},{"name":"Fondo Europeo de Desarrollo Regional Funds (FEDER)","award":["PI18\/00044"],"award-info":[{"award-number":["PI18\/00044"]}]},{"name":"Fondo Europeo de Desarrollo Regional Funds (FEDER)","award":["PI15\/00028"],"award-info":[{"award-number":["PI15\/00028"]}]},{"name":"Fondo Europeo de Desarrollo Regional Funds (FEDER)","award":["PI18CIII\/00009"],"award-info":[{"award-number":["PI18CIII\/00009"]}]},{"name":"Fondo Europeo de Desarrollo Regional Funds (FEDER)","award":["PI21\/00896"],"award-info":[{"award-number":["PI21\/00896"]}]},{"name":"Fondo Europeo de Desarrollo Regional Funds (FEDER)","award":["FI19\/00067"],"award-info":[{"award-number":["FI19\/00067"]}]},{"name":"Fondo Europeo de Desarrollo Regional Funds (FEDER)","award":["VIII Convocatoria Santander-UAX"],"award-info":[{"award-number":["VIII Convocatoria Santander-UAX"]}]},{"name":"Alfonso X El Sabio University","award":["PI18\/00044"],"award-info":[{"award-number":["PI18\/00044"]}]},{"name":"Alfonso X El Sabio University","award":["PI15\/00028"],"award-info":[{"award-number":["PI15\/00028"]}]},{"name":"Alfonso X El Sabio University","award":["PI18CIII\/00009"],"award-info":[{"award-number":["PI18CIII\/00009"]}]},{"name":"Alfonso X El Sabio University","award":["PI21\/00896"],"award-info":[{"award-number":["PI21\/00896"]}]},{"name":"Alfonso X El Sabio University","award":["FI19\/00067"],"award-info":[{"award-number":["FI19\/00067"]}]},{"name":"Alfonso X El Sabio University","award":["VIII Convocatoria Santander-UAX"],"award-info":[{"award-number":["VIII Convocatoria Santander-UAX"]}]},{"name":"CIBER -Consorcio Centro de Investigaci\u00f3n Biom\u00e9dica en Red- (CIBERES), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovaci\u00f3n","award":["PI18\/00044"],"award-info":[{"award-number":["PI18\/00044"]}]},{"name":"CIBER -Consorcio Centro de Investigaci\u00f3n Biom\u00e9dica en Red- (CIBERES), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovaci\u00f3n","award":["PI15\/00028"],"award-info":[{"award-number":["PI15\/00028"]}]},{"name":"CIBER -Consorcio Centro de Investigaci\u00f3n Biom\u00e9dica en Red- (CIBERES), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovaci\u00f3n","award":["PI18CIII\/00009"],"award-info":[{"award-number":["PI18CIII\/00009"]}]},{"name":"CIBER -Consorcio Centro de Investigaci\u00f3n Biom\u00e9dica en Red- (CIBERES), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovaci\u00f3n","award":["PI21\/00896"],"award-info":[{"award-number":["PI21\/00896"]}]},{"name":"CIBER -Consorcio Centro de Investigaci\u00f3n Biom\u00e9dica en Red- (CIBERES), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovaci\u00f3n","award":["FI19\/00067"],"award-info":[{"award-number":["FI19\/00067"]}]},{"name":"CIBER -Consorcio Centro de Investigaci\u00f3n Biom\u00e9dica en Red- (CIBERES), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovaci\u00f3n","award":["VIII Convocatoria Santander-UAX"],"award-info":[{"award-number":["VIII Convocatoria Santander-UAX"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Respiratory diseases such as bronchiolitis, and those with wheezing episodes, are highly important during infancy due to their potential chronicity. Immune response dysregulation is critical in perpetuating lung damage. Epigenetic modifications including microRNA (miRNA) post-transcriptional regulation are among the factors involved in alleviating inflammation. We evaluated the expression of miR-146a-5p, a previously described negative regulator of immunity, in infants with respiratory diseases, in order to study epigenetic regulation of the immune response. Nasopharyngeal aspirate (NPA) was obtained from infants with bronchiolitis (ongoing and post-disease) or with wheezing episodes in addition to healthy controls. Virus presence was determined by nested PCR, while miRNA and gene expression were studied in cells from NPAs using qPCR. Healthy small airway epithelial cells (SAECs) were used as an in vitro model. We observe a reduction in miR-146a-5p expression in infants with either of the two diseases compared to controls, suggesting the potential of this miRNA as a disease biomarker. Post-bronchiolitis, miR-146a-5p expression increases, though without reaching levels of healthy controls. MiR-146a-5p expression correlates inversely with the immune-related gene PTGS2, while its expression correlates directly with TSLP. When heathy donor SAECs are stimulated by poly:IC, we observe an increase in miR-146a-5p, with wounds having a synergistic effect. In conclusion, infants with respiratory diseases present reduced miR-146a-5p expression, possibly affecting immune dysregulation.<\/jats:p>","DOI":"10.3390\/cells11172746","type":"journal-article","created":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T20:48:25Z","timestamp":1662410905000},"page":"2746","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Reduced miR-146a-5p Is a Biomarker of Infant Respiratory Diseases Contributing to Immune Dysregulation in Small Airway Epithelial Cells"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3873-4563","authenticated-orcid":false,"given":"Jos\u00e9 M.","family":"Rodrigo-Mu\u00f1oz","sequence":"first","affiliation":[{"name":"Department of Immunology, Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz (IIS-FJD, UAM), 28040 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) de Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2075-7874","authenticated-orcid":false,"given":"Marta","family":"Gil-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Department of Immunology, Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz (IIS-FJD, UAM), 28040 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) de Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Lorente-Sorolla","sequence":"additional","affiliation":[{"name":"Department of Immunology, Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz (IIS-FJD, UAM), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2394-6849","authenticated-orcid":false,"given":"Beatriz","family":"Sastre","sequence":"additional","affiliation":[{"name":"Department of Immunology, Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz (IIS-FJD, UAM), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4906-4227","authenticated-orcid":false,"given":"Mar\u00eda Luz","family":"Garc\u00eda-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Pediatrics Department, Severo Ochoa Hospital, 28911 Legan\u00e9s, Spain"},{"name":"Translational Research Network in Pediatric Infectious Diseases (RITIP), Madrid, Spain"},{"name":"Department of Pediatrics, Alfonso X El Sabio University, 28691 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) de Enfermedades Infecciosas (CIBERINFEC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6503-3423","authenticated-orcid":false,"given":"Cristina","family":"Calvo","sequence":"additional","affiliation":[{"name":"Translational Research Network in Pediatric Infectious Diseases (RITIP), Madrid, Spain"},{"name":"Department of Pediatrics, Alfonso X El Sabio University, 28691 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) de Enfermedades Infecciosas (CIBERINFEC), 28029 Madrid, Spain"},{"name":"Pediatric Infectious Diseases Department, Hospital Universitario La Paz, 28046 Madrid, Spain"},{"name":"Fundaci\u00f3n Instituto de Investigaci\u00f3n Hospital Universitario La Paz, IdiPaz, 28029 Madrid, Spain"},{"name":"TEDDY Network (European Network of Excellence for Pediatric Clinical Research), 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1840-1198","authenticated-orcid":false,"given":"Inmaculada","family":"Casas","sequence":"additional","affiliation":[{"name":"Translational Research Network in Pediatric Infectious Diseases (RITIP), Madrid, Spain"},{"name":"Respiratory Virus and Influenza Unit, National Microbiology Center (ISCIII), 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6228-1969","authenticated-orcid":false,"given":"Victoria","family":"del Pozo","sequence":"additional","affiliation":[{"name":"Department of Immunology, Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz (IIS-FJD, UAM), 28040 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) de Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1111\/j.1398-9995.2009.02059.x","article-title":"GA2LEN (Global Allergy and Asthma European Network) addresses the allergy and asthma \u2018epidemic\u2019","volume":"64","author":"Bousquet","year":"2009","journal-title":"Allergy"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13052-017-0348-x","article-title":"Management of acute respiratory diseases in the pediatric population: The role of oral corticosteroids","volume":"43","author":"Cutrera","year":"2017","journal-title":"Ital. J. Pediatr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e1474","DOI":"10.1542\/peds.2014-2742","article-title":"Clinical practice guideline: The diagnosis, management, and prevention of bronchiolitis","volume":"134","author":"Ralston","year":"2014","journal-title":"Pediatrics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1542\/peds.2006-2223","article-title":"Diagnosis and management of bronchiolitis","volume":"118","author":"Lieberthal","year":"2006","journal-title":"Pediatrics"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/S2213-2600(15)00255-6","article-title":"Lower respiratory tract infection caused by respiratory syncytial virus: Current management and new therapeutics","volume":"3","author":"Mazur","year":"2015","journal-title":"Lancet. Respir. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1757-7241-22-23","article-title":"Acute bronchiolitis in infants, a review","volume":"22","author":"Skjerven","year":"2014","journal-title":"Scand. J. Trauma. Resusc. Emerg. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Garcia-Garcia, M.L., Calvo, C., Ruiz, S., Pozo, F., Del Pozo, V., Remedios, L., Exposito, N., Tellez, A., and Casas, I. (2017). Role of viral coinfections in asthma development. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0189083"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1586\/eri.11.92","article-title":"Evidence for a causal relationship between respiratory syncytial virus infection and asthma","volume":"9","author":"Wu","year":"2014","journal-title":"Expert Rev Anti Infect Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"343","DOI":"10.2147\/JAA.S258447","article-title":"Impact of Prematurity and Severe Viral Bronchiolitis on Asthma Development at 6-9 Years","volume":"13","author":"Bracamonte","year":"2020","journal-title":"J. Asthma Allergy"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1136\/thx.2009.115188","article-title":"International prevalence of recurrent wheezing during the first year of life: Variability, treatment patterns and use of health resources","volume":"65","author":"Mallol","year":"2010","journal-title":"Thorax"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1111\/pai.13317","article-title":"Bronchiolitis and recurrent wheezing are distinguished by type 2 innate lymphoid cells and immune response","volume":"32","author":"Sastre","year":"2021","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_12","first-page":"1","article-title":"Risk factors for recurrent wheezing after bronchiolitis in infants: 2-year follow up in China","volume":"21","author":"Chen","year":"2021","journal-title":"BMC Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1111\/pai.12414","article-title":"Risk factors for bronchiolitis, recurrent wheezing, and related hospitalization in preterm infants during the first year of life","volume":"26","author":"Ramilo","year":"2015","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_14","first-page":"srep41653","article-title":"Genome-Wide Association Study of Polymorphisms Predisposing to Bronchiolitis","volume":"7","author":"Pasanen","year":"2017","journal-title":"Sci. Reports"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1007\/s00431-014-2263-0","article-title":"Genetic predisposition of RSV infection-related respiratory morbidity in preterm infants","volume":"173","author":"Drysdale","year":"2014","journal-title":"Eur. J. Pediatr."},{"key":"ref_16","first-page":"1","article-title":"MicroRNAs as Potential Regulators of Immune Response Networks in Asthma and Chronic Obstructive Pulmonary Disease","volume":"11","author":"Sastre","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"578","DOI":"10.3389\/fimmu.2014.00578","article-title":"MicroRNA-146a: A dominant, negative regulator of the innate immune response","volume":"5","author":"Saba","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1001\/archpedi.1983.02140270007003","article-title":"Bronchiolitis: What\u2019s in the Name?","volume":"137","author":"Mcconnochie","year":"1983","journal-title":"Am. J. Dis. Child."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Jia, Y., and Wei, Y. (2020). Modulators of MicroRNA Function in the Immune System. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072357"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1261\/rna.071985.119","article-title":"MiR-146a down-regulates inflammatory response by targeting TLR3 and TRAF6 in Coxsackievirus B infection","volume":"26","author":"Fei","year":"2020","journal-title":"RNA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6387","DOI":"10.1128\/JVI.00619-16","article-title":"Hepatitis C Virus-Induced Upregulation of MicroRNA miR-146a-5p in Hepatocytes Promotes Viral Infection and Deregulates Metabolic Pathways Associated with Liver Disease Pathogenesis","volume":"90","author":"Bandiera","year":"2016","journal-title":"J. Virol."},{"key":"ref_23","first-page":"7321","article-title":"Exosome-delivered microRNAs modulate the inflammatory response to endotoxin","volume":"6","author":"Alexander","year":"2015","journal-title":"Nat. Commun. 2015 61"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Iyer, A., Zurolo, E., Prabowo, A., Fluiter, K., Spliet, W.G.M., van Rijen, P.C., Gorter, J.A., and Aronica, E. (2012). MicroRNA-146a: A Key Regulator of Astrocyte-Mediated Inflammatory Response. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044789"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5102","DOI":"10.4049\/jimmunol.1202397","article-title":"MicroRNA-146a Negatively Regulates the Immunoregulatory Activity of Bone Marrow Stem Cells by Targeting Prostaglandin E2 Synthase-2","volume":"190","author":"Matysiak","year":"2013","journal-title":"J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13601-019-0301-8","article-title":"Reduced expression of miR-146a in human bronchial epithelial cells alters neutrophil migration","volume":"9","author":"Kivihall","year":"2019","journal-title":"Clin. Transl. Allergy"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"L727","DOI":"10.1152\/ajplung.00174.2014","article-title":"MicroRNA-146a and microRNA-146b expression and anti-inflammatory function in human airway smooth muscle","volume":"307","author":"Comer","year":"2014","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1016\/j.jaci.2016.01.029","article-title":"Circulating microRNAs as biomarkers in patients with allergic rhinitis and asthma","volume":"137","author":"Panganiban","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1177\/1753425918763521","article-title":"Plasma microRNA-21, microRNA-146a and IL-13 expression in asthmatic children","volume":"24","author":"Hamed","year":"2018","journal-title":"Innate Immun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12931-020-01351-x","article-title":"Circulating microRNAs correlate to clinical parameters in individuals with allergic and non-allergic asthma","volume":"21","author":"Weidner","year":"2020","journal-title":"Respir. Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Lambert, K.A., Roff, A.N., Panganiban, R.P., Douglas, S., and Ishmael, F.T. (2018). MicroRNA-146a is induced by inflammatory stimuli in airway epithelial cells and augments the anti-inflammatory effects of glucocorticoids. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0205434"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e427","DOI":"10.1002\/ctm2.427","article-title":"Dual role of the miR-146 family in rhinovirus-induced airway inflammation and allergic asthma exacerbation","volume":"11","author":"Laanesoo","year":"2021","journal-title":"Clin. Transl. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.ejphar.2015.04.031","article-title":"Poly(I:C) induced microRNA-146a regulates epithelial barrier and secretion of proinflammatory cytokines in human nasal epithelial cells","volume":"761","author":"Miyata","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_34","first-page":"1","article-title":"Respiratory Syncytial Virus Infection Changes Cargo Composition of Exosome Released from Airway Epithelial Cells","volume":"8","author":"Chahar","year":"2018","journal-title":"Sci. Reports"},{"key":"ref_35","first-page":"1","article-title":"MiR-146a alleviates lung injury caused by RSV infection in young rats by targeting TRAF-6 and regulating JNK\/ERKMAPK signaling pathways","volume":"12","author":"Huang","year":"2022","journal-title":"Sci. Reports"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/17\/2746\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:22:40Z","timestamp":1760142160000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/17\/2746"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,2]]},"references-count":35,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["cells11172746"],"URL":"https:\/\/doi.org\/10.3390\/cells11172746","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,2]]}}}