{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T06:20:21Z","timestamp":1776579621267,"version":"3.51.2"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100002322","name":"CAPES","doi-asserted-by":"crossref","award":["33002010060P2"],"award-info":[{"award-number":["33002010060P2"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mycopathologia"],"published-print":{"date-parts":[[2026,2]]},"DOI":"10.1007\/s11046-025-01030-9","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T14:47:50Z","timestamp":1765550870000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cytometric Analysis of CD3\u2009+\u2009CD4\u2009+\u2009T Populations and Activation and Regulation Status of Na\u00efve and Memory CD4\u2009+\u2009CD45RA T Cells in Immunocompetent Patients with Neurocryptococcosis"],"prefix":"10.1007","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3515-7214","authenticated-orcid":false,"given":"Isabel Feitosa","family":"Maciel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2127-8493","authenticated-orcid":false,"given":"Juliana","family":"Ruiz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3217-5898","authenticated-orcid":false,"given":"Renata Buccheri","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4416-3544","authenticated-orcid":false,"given":"Paula Ordonhez","family":"Rigato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0114-7587","authenticated-orcid":false,"given":"Victor Angelo","family":"Folgosi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5811-5255","authenticated-orcid":false,"given":"Roseli Santos","family":"de Freitas-Xavier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3930-3354","authenticated-orcid":false,"given":"Dewton","family":"de Moraes Vasconcelos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"issue":"1","key":"1030_CR1","doi-asserted-by":"publisher","first-page":"2035","DOI":"10.1038\/s41467-019-10092-5","volume":"10","author":"PM Ashton","year":"2019","unstructured":"Ashton PM, Thanh LT, Trieu PH, Van Anh D, Trinh NM, Beardsley J, et al. Three phylogenetic groups have driven the recent population expansion of Cryptococcus neoformans. Nat Commun. 2019;10(1):2035. https:\/\/doi.org\/10.1038\/s41467-019-10092-5.","journal-title":"Nat Commun"},{"key":"1030_CR2","unstructured":"Pizani AT, Almeida MTG. Criptococose em pacientes HIV positivos: revis\u00e3o sistem\u00e1tica da literatura. Cryptococose in HIV-positive patients: systematic review of literature. Tese de doutorado pela Faculdade de Medicina de S\u00e3o Jos\u00e9 do Rio Preto, FAMERP. 2017; 90\u2013106."},{"issue":"10","key":"1030_CR3","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1111\/myc.12966","volume":"62","author":"X Hou","year":"2019","unstructured":"Hou X, Kou L, Han X, Zhu R, Song L, Liu T. Pulmonary cryptococcosis characteristics in immunocompetent patients-a 20-year clinical retrospective analysis in China. Mycoses. 2019;62(10):937\u201344. https:\/\/doi.org\/10.1111\/myc.12966.","journal-title":"Mycoses"},{"issue":"7","key":"1030_CR4","doi-asserted-by":"publisher","DOI":"10.1590\/0074-02760180060","volume":"113","author":"M Garelnabi","year":"2018","unstructured":"Garelnabi M, May RC. Variability in innate host immune responses to cryptococcosis. Mem Inst Oswaldo Cruz. 2018;113(7):e180060. https:\/\/doi.org\/10.1590\/0074-02760180060.","journal-title":"Mem Inst Oswaldo Cruz"},{"issue":"1","key":"1030_CR5","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-017-2459-9","volume":"17","author":"Q Ruan","year":"2017","unstructured":"Ruan Q, Zhu Y, Chen S, Zhu L, Zhang S, Zhang W. Disseminated cryptococcosis with recurrent multiple abscesses in an immunocompetent patient: a case report and literature review. BMC Infect Dis. 2017;17(1):369. https:\/\/doi.org\/10.1186\/s12879-017-2459-9.","journal-title":"BMC Infect Dis"},{"issue":"4","key":"1030_CR6","doi-asserted-by":"publisher","DOI":"10.3390\/jof3040064","volume":"3","author":"L Mukaremera","year":"2017","unstructured":"Mukaremera L, Nielsen K. Adaptive immunity to Cryptococcus neoformans infections. J Fungi. 2017;3(4):64. https:\/\/doi.org\/10.3390\/jof3040064.","journal-title":"J Fungi"},{"key":"1030_CR7","doi-asserted-by":"publisher","first-page":"2389","DOI":"10.3389\/fimmu.2018.02389","volume":"9","author":"CM Shiromizu","year":"2018","unstructured":"Shiromizu CM, Jancic CC. \u03b3\u03b4 T lymphocytes: an effector cell in autoimmunity and infection. Front Immunol. 2018;9:2389. https:\/\/doi.org\/10.3389\/fimmu.2018.02389.","journal-title":"Front Immunol"},{"issue":"1","key":"1030_CR8","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1146\/annurev.immunol.18.1.975","volume":"18","author":"AC Hayday","year":"2000","unstructured":"Hayday AC. \u03b3\u03b4 cells: a right time and a right place for a conserved third way of protection. Annu Rev Immunol. 2000;18(1):975\u20131026. https:\/\/doi.org\/10.1146\/annurev.immunol.18.1.975.","journal-title":"Annu Rev Immunol"},{"issue":"7","key":"1030_CR9","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1038\/nri2781","volume":"10","author":"M Bonneville","year":"2010","unstructured":"Bonneville M, O\u2019Brien RL, Born WK. \u03b3 \u03b4 T cell effector functions: A blend of innate programming and acquired plasticity. Nat Rev Immunol. 2010;10(7):467\u201378. https:\/\/doi.org\/10.1038\/nri2781.","journal-title":"Nat Rev Immunol"},{"issue":"1","key":"1030_CR10","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.coi.2005.11.007","volume":"18","author":"WK Born","year":"2006","unstructured":"Born WK, Reardon CL, O\u2019Brien RL. The function of \u03b3\u03b4 T cells in innate immunity. Curr Opin Immunol. 2006;18(1):31\u20138. https:\/\/doi.org\/10.1016\/j.coi.2005.11.007.","journal-title":"Curr Opin Immunol"},{"issue":"3 Pt 1","key":"1030_CR11","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1006\/clim.2002.5218","volume":"103","author":"J Ismaili","year":"2002","unstructured":"Ismaili J, Olislagers V, Poupot R, Fourni\u00e9 JJ, Goldman M. Human \u03b3\u03b4 T cells induce dendritic cell maturation. Clin Immunol. 2002;103(3 Pt 1):296\u2013302. https:\/\/doi.org\/10.1006\/clim.2002.5218.","journal-title":"Clin Immunol"},{"issue":"10","key":"1030_CR12","doi-asserted-by":"publisher","first-page":"3693","DOI":"10.1182\/blood-2003-04-1016","volume":"102","author":"M Brandes","year":"2003","unstructured":"Brandes M, Willimann K, Lang AB, Nam KH, Jin C, Brenner MB, et al. Flexible migration program regulates \u03b3\u03b4 T-cell involvement in humoral immunity. Blood. 2003;102(10):3693\u2013701. https:\/\/doi.org\/10.1182\/blood-2003-04-1016.","journal-title":"Blood"},{"issue":"5732","key":"1030_CR13","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1126\/science.1110267","volume":"309","author":"M Brandes","year":"2005","unstructured":"Brandes M, Willimann K, Moser B. Professional antigen-presentation function by human \u03b3\u03b4 T cells. Science. 2005;309(5732):264\u20138. https:\/\/doi.org\/10.1126\/science.1110267.","journal-title":"Science"},{"issue":"1","key":"1030_CR14","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/nri3567","volume":"14","author":"DL Farber","year":"2014","unstructured":"Farber DL, Yudanin NA, Restifo NP. Human memory T cells: generation, compartmentalization and homeostasis. Nat Rev Immunol. 2014;14(1):24\u201335. https:\/\/doi.org\/10.1038\/nri3567.","journal-title":"Nat Rev Immunol"},{"issue":"1","key":"1030_CR15","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1186\/1471-2334-12-278","volume":"12","author":"KC Rocha","year":"2012","unstructured":"Rocha KC, Pinhal C, Cavalcanti S, Vidal MS, Toscano M, Moraes-Vasconcelos D, et al. Lymphocyte transformation assay for C neoformans antigen is not reliable for detecting cellular impairment in patients with neurocryptococcosis. BMC Infect Dis. 2012;12(1):278. https:\/\/doi.org\/10.1186\/1471-2334-12-278.","journal-title":"BMC Infect Dis"},{"issue":"7","key":"1030_CR16","doi-asserted-by":"publisher","first-page":"2846","DOI":"10.1128\/iai.64.7.2846-2849.1996","volume":"64","author":"A Vecchiarelli","year":"1996","unstructured":"Vecchiarelli A, Retini C, Monari C, Tascini C, Bistoni F, Kozel TR. Purified capsular polysaccharide of Cryptococcus neoformans induces interleukin-10 secretion by human monocytes. Infect Immun. 1996;64(7):2846\u20139. https:\/\/doi.org\/10.1128\/iai.64.7.2846-2849.1996.","journal-title":"Infect Immun"},{"issue":"6754","key":"1030_CR17","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1038\/44385","volume":"401","author":"F Sallusto","year":"1999","unstructured":"Sallusto F, Lenig D, F\u00f6rster R, Lipp M, Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature. 1999;401(6754):708\u201312. https:\/\/doi.org\/10.1038\/44385.","journal-title":"Nature"},{"issue":"12","key":"1030_CR18","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1038\/ni1204-1201","volume":"5","author":"A Lanzavecchia","year":"2004","unstructured":"Lanzavecchia A, Sallusto F. Lead and follow: the dance of the dendritic cell and T cell. Nat Immunol. 2004;5(12):1201\u20132. https:\/\/doi.org\/10.1038\/ni1204-1201.","journal-title":"Nat Immunol"},{"key":"1030_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2012\/652351","volume":"2012","author":"S Suchitha","year":"2012","unstructured":"Suchitha S, Sheeladevi CS, Sunila R, Manjunath GV. Disseminated cryptococcosis in an immunocompetent patient: a case report. Case Rep Pathol. 2012;2012:1\u20133. https:\/\/doi.org\/10.1155\/2012\/652351.","journal-title":"Case Rep Pathol"},{"issue":"12","key":"1030_CR20","doi-asserted-by":"publisher","first-page":"3525","DOI":"10.1002\/eji.200425324","volume":"34","author":"A Harari","year":"2004","unstructured":"Harari A, Vallelian F, Pantaleo G. Phenotypic heterogeneity of antigen-specific CD4 T cells under different conditions of antigen persistence and antigen load. Eur J Immunol. 2004;34(12):3525\u201333. https:\/\/doi.org\/10.1002\/eji.200425324.","journal-title":"Eur J Immunol"},{"issue":"12","key":"1030_CR21","doi-asserted-by":"publisher","first-page":"3525","DOI":"10.1002\/eji.2004253248","volume":"34","author":"S Caserta","year":"2004","unstructured":"Caserta S, Kleczkowska J, Mondino A, Zamoyska R. Phenotypic heterogeneity of antigen-specific CD4 T cells under different conditions of antigen persistence and antigen load. Eur J Immunol. 2004;34(12):3525\u201333. https:\/\/doi.org\/10.1002\/eji.2004253248.","journal-title":"Eur J Immunol"},{"issue":"4","key":"1030_CR22","doi-asserted-by":"publisher","first-page":"570","DOI":"10.3109\/13693780903437876","volume":"48","author":"LP Zhu","year":"2010","unstructured":"Zhu LP, Wu JQ, Xu B, Ou XT, Zhang QQ, Weng XH. Cryptococcal meningitis in non-HIV-infected patients in a Chinese tertiary care hospital, 1997\u20132007. Med Mycol. 2010;48(4):570\u20139. https:\/\/doi.org\/10.3109\/13693780903437876.","journal-title":"Med Mycol"},{"issue":"8","key":"1030_CR23","doi-asserted-by":"publisher","first-page":"5157","DOI":"10.4049\/jimmunol.180.8.5157","volume":"180","author":"L Romani","year":"2008","unstructured":"Romani L, Zelante T, De Luca A, Fallarino F, Puccetti P. IL-17 and therapeutic kynurenines in pathogenic inflammation to fungi. J Immunol. 2008;180(8):5157\u201362. https:\/\/doi.org\/10.4049\/jimmunol.180.8.5157.","journal-title":"J Immunol"},{"issue":"7","key":"1030_CR24","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1084\/jem.20060772","volume":"203","author":"W Liu","year":"2006","unstructured":"Liu W, Putnam AL, Xu-Yu Z, Szot GL, Lee MR, Zhu S, et al. CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med. 2006;203(7):1701\u201311. https:\/\/doi.org\/10.1084\/jem.20060772.","journal-title":"J Exp Med"},{"issue":"1","key":"1030_CR25","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.micinf.2008.10.007","volume":"11","author":"T Zelante","year":"2009","unstructured":"Zelante T, Fallarino F, Bistoni F, Puccetti P, Romani L. Indoleamine 2,3-dioxygenase in infection: the paradox of an evasive strategy that benefits the host. Microbes Infect. 2009;11(1):133\u201341. https:\/\/doi.org\/10.1016\/j.micinf.2008.10.007.","journal-title":"Microbes Infect"},{"issue":"4","key":"1030_CR26","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1007\/s00134-008-1337-8","volume":"35","author":"F Venet","year":"2009","unstructured":"Venet F, Chung CS, Kherouf H, Geeraert A, Malcus C, Poitevin F, et al. Increased circulating regulatory T cells (CD4+CD25 +CD127-) contribute to lymphocyte anergy in septic shock patients. Intensive Care Med. 2009;35(4):678\u201386. https:\/\/doi.org\/10.1007\/s00134-008-1337-8.","journal-title":"Intensive Care Med"},{"issue":"12","key":"1030_CR27","doi-asserted-by":"publisher","first-page":"3596","DOI":"10.1002\/eji.201444963","volume":"44","author":"B Schulze","year":"2014","unstructured":"Schulze B, Piehler D, Eschke M, von Buttlar H, K\u00f6hler G, Sparwasser T, et al. CD4(+) FoxP3(+) regulatory T cells suppress fatal T helper 2 cell immunity during pulmonary fungal infection. Eur J Immunol. 2014;44(12):3596\u2013604. https:\/\/doi.org\/10.1002\/eji.201444963.","journal-title":"Eur J Immunol"},{"issue":"1","key":"1030_CR28","doi-asserted-by":"publisher","first-page":"365","DOI":"10.4049\/jimmunol.1501871","volume":"196","author":"DL Wiesner","year":"2016","unstructured":"Wiesner DL, Smith KD, Kotov DI, Nielsen JN, Bohjanen PR, Nielsen K. Regulatory T Cell induction and retention in the lungs drives suppression of detrimental type 2 Th cells during pulmonary cryptococcal infection. J Immunol. 2016;196(1):365\u201374. https:\/\/doi.org\/10.4049\/jimmunol.1501871.","journal-title":"J Immunol"},{"issue":"1","key":"1030_CR29","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/gene.2013.57","volume":"15","author":"DV Chan","year":"2014","unstructured":"Chan DV, Gibson HM, Aufiero BM, Wilson AJ, Hafner MS, Mi QS, et al. Differential CTLA-4 expression in human CD4+ versus CD8+ T cells is associated with increased NFAT1 and inhibition of CD4+ proliferation. Genes Immun. 2014;15(1):25\u201332. https:\/\/doi.org\/10.1038\/gene.2013.57.","journal-title":"Genes Immun"},{"issue":"3","key":"1030_CR30","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1590\/S0103-507X2012000300014","volume":"24","author":"R Siqueira-Batista","year":"2012","unstructured":"Siqueira-Batista R, Gomes AP, Azevedo SFM, Vitorino RR, de Mendon\u00e7a EG, de Sousa FO, et al. CD4+CD25+ T lymphocytes and regulation of the immune system: perspectives for a pathophysiological understanding of sepsis. Rev Bras Ter Intensiva. 2012;24(3):294\u2013301.","journal-title":"Rev Bras Ter Intensiva"},{"issue":"12","key":"1030_CR31","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1038\/ni1003","volume":"4","author":"F Fallarino","year":"2003","unstructured":"Fallarino F, Grohmann U, Hwang KW, Orabona C, Vacca C, Bianchi R, et al. Modulation of tryptophan catabolism by regulatory T cells. Nat Immunol. 2003;4(12):1206\u201312. https:\/\/doi.org\/10.1038\/ni1003.","journal-title":"Nat Immunol"},{"issue":"2","key":"1030_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.mycmed.2021.101230","volume":"32","author":"IF Maciel","year":"2022","unstructured":"Maciel IF, de Freitas-Xavier RS, Vicentini AP, Apoliano CF, Ruiz Fernandes J, Dias AdosS, et al. Evaluation of IFN-\u03b3 secretion after stimulation with C. neoformans and C. gattii antigens in individuals with frequent exposure to the fungus. J Mycol Med. 2022;32(2):101230. https:\/\/doi.org\/10.1016\/j.mycmed.2021.101230.","journal-title":"J Mycol Med"},{"key":"1030_CR33","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/S0065-2164(08)01005-8","volume":"67","author":"H Ma","year":"2009","unstructured":"Ma H, May RC. Virulence in Cryptococcus species. Adv Appl Microbiol. 2009;67:131\u201390. https:\/\/doi.org\/10.1016\/S0065-2164(08)01005-8.","journal-title":"Adv Appl Microbiol"},{"issue":"5","key":"1030_CR34","doi-asserted-by":"publisher","first-page":"2093","DOI":"10.4049\/jimmunol.1100978","volume":"187","author":"D Di Mitri","year":"2011","unstructured":"Di Mitri D, Azevedo RI, Henson SM, Libri V, Riddell NE, Macaulay R, et al. Reversible senescence in human CD4+CD45RA+CD27\u2212 memory T cells. J Immunol. 2011;187(5):2093\u2013100. https:\/\/doi.org\/10.4049\/jimmunol.1100978.","journal-title":"J Immunol"}],"container-title":["Mycopathologia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11046-025-01030-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11046-025-01030-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11046-025-01030-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T20:02:55Z","timestamp":1771099375000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11046-025-01030-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,12]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["1030"],"URL":"https:\/\/doi.org\/10.1007\/s11046-025-01030-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-6844830\/v1","asserted-by":"object"}]},"ISSN":["0301-486X","1573-0832"],"issn-type":[{"value":"0301-486X","type":"print"},{"value":"1573-0832","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,12]]},"assertion":[{"value":"20 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All the authors declare no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"The protocol was evaluated and approved by the Ethics Committee for the Evaluation of Research Projects [CAPPesq] of the the Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo. [n\n                      o\n                      . 1.483.420\/2016] and the Institute of Infectious Diseases of the Em\u00edlio Ribas Hospital [n\n                      o\n                      .1.569.194]","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"All the patients or their legal guardians signed an informed consent form.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}}],"article-number":"3"}}