{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T06:31:13Z","timestamp":1786343473086,"version":"build-2736575974"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                      serotype 3 (Spn3) is still a major cause of disease despite the implementation of the 13-valent pneumococcal conjugate vaccine. We previously reported on the development of an experimental human colonisation Spn3 model and showed that Spn3 was associated with frequent pharyngeal symptoms. Utilising this model, we compared the microbiological colonisation dynamics of Spn3 in the oropharynx and nasopharynx, along with associated symptoms and polysaccharide antibody responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 96 healthy adults (aged 18\u201350\u202fyears) were nasally inoculated with different dosages and strains of Spn3. Pneumococcal carriage frequency and density post-challenge were determined using culture and multiplex qPCR from nasal wash and saliva samples collected on days 2, 7, and 14 post-challenge. Spn3 density was compared with historical Spn6B data at day 2 post-challenge. IgG antibodies recognising the Spn3 capsular polysaccharide were measured at baseline and day 14 post-challenge in both niches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Spn3 colonisation frequency was found to be similar in the nasopharynx and oropharynx on any day post-challenge, independently of challenge dose or strain tested. In saliva, Spn3 density was greatest at a challenge dose of 80,000 CFU\/naris compared to the lowest or highest exposure doses. Of note, on day 2 post-challenge, Spn3 density was significantly higher than that observed following the Spn6B challenge at the same dose (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.00090). No significant difference in Spn3 density was observed for challenge strain or symptomology on any day post-challenge. Spn3 polysaccharide-specific salivary IgG levels increased from baseline to day 14 in colonised participants (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.0051) with a median IgG fold change of 1.458 [IQR 0.6131\u20134.281], but no increase in IgG levels occurred in uncolonized participants (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.19). Participants colonised with the Spn3 clade I\u03b1 but not clade II had significant increases in polysaccharide-specific IgG from baseline (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.0081).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Given equivalent exposure doses, Spn3 colonised the oropharynx at higher densities than Spn6B. These data could help explain continued Spn3 population transmission despite widespread use of a Spn3-containing pneumococcal conjugate vaccine in the UK paediatric immunization programme. Within Spn3, clade I\u03b1 but not clade II increased mucosal IgG response following colonisation, which could help explain increasing transmission of clade II in the UK and higher transmission of this clade in mouse models.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1830972","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T06:17:59Z","timestamp":1786342679000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Kinetic profile and mucosal capsular polysaccharide IgG responses to serotype 3 pneumococcus in the adult oropharynx following an experimental human challenge"],"prefix":"10.3389","volume":"17","author":[{"given":"Ryan E.","family":"Robinson","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences, Liverpool School of Tropical Medicine","place":["Liverpool, United Kingdom"]},{"name":"Respiratory Research Group, Liverpool University Hospitals Foundation Trust","place":["Liverpool, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tinashe K.","family":"Nyazika","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Liverpool School of Tropical Medicine","place":["Liverpool, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashleigh","family":"Howard","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Liverpool School of Tropical Medicine","place":["Liverpool, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherin","family":"Pojar","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Liverpool School of Tropical Medicine","place":["Liverpool, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Gonzalez-Dias","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Liverpool School of Tropical Medicine","place":["Liverpool, United Kingdom"]},{"name":"Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Mitsi","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Liverpool School of Tropical Medicine","place":["Liverpool, United Kingdom"]},{"name":"Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Court","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Liverpool School of Tropical Medicine","place":["Liverpool, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Hitchins","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Liverpool School of Tropical Medicine","place":["Liverpool, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madlen","family":"Farrar","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Liverpool School of Tropical Medicine","place":["Liverpool, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Liatsikos","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Liverpool School of Tropical Medicine","place":["Liverpool, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Hyder-Wright","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Liverpool School of Tropical Medicine","place":["Liverpool, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Sol\u00f3rzano","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Liverpool School of Tropical Medicine","place":["Liverpool, United Kingdom"]},{"name":"Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta C.","family":"Urban","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Liverpool School of Tropical Medicine","place":["Liverpool, United Kingdom"]},{"name":"Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Burhan","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Liverpool School of Tropical Medicine","place":["Liverpool, United Kingdom"]},{"name":"Respiratory Research Group, Liverpool University Hospitals Foundation Trust","place":["Liverpool, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Begier","sequence":"additional","affiliation":[{"name":"Pfizer Vaccines, Pfizer Inc.","place":["Collegeville, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Theilacker","sequence":"additional","affiliation":[{"name":"Pfizer Vaccines, Pfizer Inc.","place":["Collegeville, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annaliesa S.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Vaccines Research and Development, Pfizer Inc.","place":["Pearl River, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradford D.","family":"Gessner","sequence":"additional","affiliation":[{"name":"Pfizer Vaccines, Pfizer Inc.","place":["Collegeville, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea M.","family":"Collins","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Liverpool School of Tropical Medicine","place":["Liverpool, United Kingdom"]},{"name":"Respiratory Research Group, Liverpool University Hospitals Foundation Trust","place":["Liverpool, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elissavet","family":"Nikolaou","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Liverpool School of Tropical Medicine","place":["Liverpool, United Kingdom"]},{"name":"Infection, Immunity and Global Health, Murdoch Children's Research Institute","place":["Parkville, VIC, Australia"]},{"name":"Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity","place":["Parkville, VIC, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela M.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Liverpool School of Tropical Medicine","place":["Liverpool, United Kingdom"]},{"name":"Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1164\/rccm.202004-1483OC","article-title":"Experimental human pneumococcal colonisation in older adults is feasible and safe, not immunogenic","volume":"203","author":"Adler","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1989","DOI":"10.1093\/infdis\/jiz034","article-title":"Pneumococcal colonization in healthy adult research participants in the conjugate vaccine era, United Kingdom, 2010\u20132017","volume":"219","author":"Adler","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1080\/14760584.2020.1750378","article-title":"Upper respiratory tract colonization with Streptococcus pneumoniae in adults","volume":"19","author":"Arguedas","year":"2020","journal-title":"Expert Rev. Vaccines"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e1007438","DOI":"10.1371\/journal.ppat.1007438","article-title":"Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci","volume":"14","author":"Azarian","year":"2018","journal-title":"PLoS Pathog."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"e9282","DOI":"10.1371\/journal.pone.0009282","article-title":"Realtime PCR is more sensitive than multiplex PCR for diagnosis and serotyping in children with culture negative pneumococcal invasive disease","volume":"5","author":"Azzari","year":"2010","journal-title":"PLoS One"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/S1473-3099(04)00938-7","article-title":"Streptococcus pneumoniae colonisation: the key to pneumococcal disease","volume":"4","author":"Bogaert","year":"2004","journal-title":"Lancet Infect. Dis."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.mib.2017.10.023","article-title":"Bacterial microbiota of the nasal passages across the span of human life","volume":"41","author":"Bomar","year":"2018","journal-title":"Curr. Opin. Microbiol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"2460","DOI":"10.1128\/JCM.02498-06","article-title":"Evaluation and improvement of real-time PCR assays targeting lytA, ply, and psaA genes for detection of pneumococcal DNA","volume":"45","author":"Carvalho","year":"2007","journal-title":"J. Clin. Microbiol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"898","DOI":"10.3389\/fped.2020.587730","article-title":"Carriage dynamics of pneumococcal serotypes in naturally colonized infants in a rural African setting during the first year of life","volume":"8","author":"Chaguza","year":"2021","journal-title":"Front. Pediatr."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1128\/CVI.00591-15","article-title":"Capsular polysaccharide (CPS) release by serotype 3 pneumococcal strains reduces the protective effect of anti-type 3 CPS antibodies","volume":"23","author":"Choi","year":"2016","journal-title":"Clin. Vaccine Immunol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1128\/iai.63.3.757-761.1995","article-title":"Relationship between colonial morphology and adherence of Streptococcus pneumoniae","volume":"63","author":"Cundell","year":"1995","journal-title":"Infect. Immun."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1164\/rccm.201212-2277OC","article-title":"Controlled human infection and rechallenge with Streptococcus pneumoniae reveals the protective efficacy of carriage in healthy adults","volume":"187","author":"Ferreira","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1097\/INF.0000000000004192","article-title":"Serotype 3 antibody response and antibody functionality comapred to serotype 19A following 13-valent pneumococcal conjugate immunization in children","volume":"43","author":"Fuji","year":"2024","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"4147","DOI":"10.1016\/j.vaccine.2019.05.065","article-title":"A post-hoc analysis of serotype-specific vaccine efficacy of 13-valent pneumococcal conjugate vaccine against clinical community acquired pneumonia from a randomized clinical trial in the Netherlands","volume":"37","author":"Gessner","year":"2019","journal-title":"Vaccine"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"6738","DOI":"10.1016\/j.vaccine.2012.08.080","article-title":"Sampling methods for the study of pneumococcal carriage: a systematic review","volume":"30","author":"Gladstone","year":"2012","journal-title":"Vaccine"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1086\/431524","article-title":"Antibody responses to nasopharyngeal carriage of Streptococcus pneumoniae in adults: a longitudinal household study","volume":"192","author":"Goldblatt","year":"2005","journal-title":"J. Infect. Dis."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1728","DOI":"10.1128\/CVI.05252-11","article-title":"Establishment of a new human pneumococcal standard reference serum, 007sp","volume":"18","author":"Goldblatt","year":"2011","journal-title":"Clin. Vaccine Immunol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"845","DOI":"10.3390\/genes10110845","article-title":"Evolution of Streptococcus pneumoniae serotype 3 in England and Wales: a major vaccine evader","volume":"10","author":"Groves","year":"2019","journal-title":"Genes."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1017\/S0950268811000884","article-title":"Transmission of Streptococcus pneumoniae in adults may occur through saliva","volume":"140","author":"Levine","year":"2012","journal-title":"Epidemiol. Infect."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1128\/JCM.44.2.525-528.2006","article-title":"Nasopharyngeal versus oropharyngeal sampling for isolation of potential respiratory pathogens in adults","volume":"44","author":"Lieberman","year":"2006","journal-title":"J. Clin. Microbiol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"18977","DOI":"10.1038\/s41598-020-75691-5","article-title":"Divergent serotype replacement trends and increasing diversity in pneumococcal disease in high income settings reduce the benefit of expanding vaccine valency","volume":"10","author":"L\u00f8chen","year":"2020","journal-title":"Sci. Rep."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"613287","DOI":"10.3389\/fcimb.2020.613287","article-title":"Sugar-coated killer: serotype 3 pneumococcal disease","volume":"10","author":"Luck","year":"2020","journal-title":"Front. Cell. Infection Micorbiol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"6310","DOI":"10.1016\/j.vaccine.2019.08.059","article-title":"Pneumococcal conjugate vaccine against serotype 3 pneumococcal pneumonia in adults: a systematic review and pooled analysis","volume":"37","author":"McLaughlin","year":"2019","journal-title":"Vaccine"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.ijid.2019.06.024","article-title":"Pneumococcal carriage, density, and co-colonization dynamics: a longitudinal study in Indonesian infants","volume":"86","author":"Murad","year":"2019","journal-title":"Int. J. Infect. Dis."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"18279","DOI":"10.1038\/s41598-021-97807-1","article-title":"The nose is the best niche for detection of experimental pneumococcal colonisation in adults of all ages, using nasal wash","volume":"11","author":"Nikolaou","year":"2021","journal-title":"Sci. Rep."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"e02020","DOI":"10.1128\/mBio.02020-20","article-title":"Experimental human challenge defines distinct pneumococcal kinetic profiles and mucosal responses between colonized and non-colonized adults","volume":"12","author":"Nikolaou","year":"2021","journal-title":"MBio"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1164\/rccm.201512-2467OC","article-title":"Polysaccharide-specific memory B cells predict protection against experimental human pneumococcal carriage","volume":"194","author":"Pennington","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1136\/thoraxjnl-2019-213725","article-title":"Pneumococcal serotype trends, surveillance and risk factors in UK adult pneumonia, 2013\u201318","volume":"75","author":"Pick","year":"2020","journal-title":"Thorax"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1164\/rccm.202112-2700OC","article-title":"Human infection challenge with serotype 3 pneumococcus","volume":"206","author":"Robinson","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"e0284399","DOI":"10.1371\/journal.pone.0284399","article-title":"Comprehensive review of safety in experimental human pneumococcal challenge","volume":"18","author":"Robinson","year":"2023","journal-title":"PLoS One"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1164\/rccm.201811-2081LE","article-title":"Two randomized trials of the effect of live attenuated influenza vaccine on pneumococcal colonization","volume":"199","author":"Rylance","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"jiae038","DOI":"10.1093\/infdis\/jiae038","article-title":"Evidence of reduced virulence and increased colonization among pneumococcal strains of serotype 3 clade II lineage in mice","author":"Sekulovic","year":"2024","journal-title":"J. Infect. Dis."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"2135","DOI":"10.1093\/cid\/ciy920","article-title":"Effectiveness of 13-valent pneumococcal conjugate vaccine against invasive disease caused by serotype 3 in children: a systematic review and meta-analysis of observational studies","volume":"68","author":"Sings","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"e60520","DOI":"10.1371\/journal.pone.0060520","article-title":"Superiority of trans-oral over trans-nasal sampling in detecting Streptococcus pneumoniae colonization in adults","volume":"8","author":"Trzci\u0144ski","year":"2013","journal-title":"PLoS One"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1097\/EDE.0000000000001135","article-title":"Estimating serotype-specific efficacy of pneumococcal conjugate vaccines using hierarchical models","volume":"31","author":"Warren","year":"2020","journal-title":"Epidemiology"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"4974","DOI":"10.1128\/JCM.42.11.4974-4976.2004","article-title":"Nasopharyngeal versus oropharyngeal sampling for detection of pneumococcal carriage in adults","volume":"42","author":"Watt","year":"2004","journal-title":"J. Clin. Microbiol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"3060","DOI":"10.1038\/s41467-019-11005-2","article-title":"Microinvasion by Streptococcus pneumoniae induces epithelial innate immunity during colonisation at the human mucosal surface","volume":"10","author":"Weight","year":"2019","journal-title":"Nat. Commun."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/s41579-018-0001-8","article-title":"Streptococcus pneumoniae: transmission, colonization and invasion","volume":"16","author":"Weiser","year":"2018","journal-title":"Nat. Rev. Microbiol."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1830972\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T06:18:00Z","timestamp":1786342680000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1830972\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,10]]},"references-count":38,"alternative-id":["10.3389\/fmicb.2026.1830972"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1830972","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,10]]},"article-number":"1830972"}}