{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T19:58:22Z","timestamp":1784663902036,"version":"3.55.0"},"reference-count":56,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,10]],"date-time":"2022-12-10T00:00:00Z","timestamp":1670630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Council of Thailand (NRCT)","award":["#PHD59\/0012"],"award-info":[{"award-number":["#PHD59\/0012"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TropicalMed"],"abstract":"<jats:p>The recombinant, modified leucine-rich repeat protein rhKU_Sej_LRR_2271 has been suggested as a candidate for leptospiral vaccine development since it was predicted to be a transmembrane protein containing leucine-rich repeat motifs and immunogenic epitopes. The immunogenic epitopes showed binding affinities with lower IC50 values than peptides of known antigenic proteins, e.g., LipL32. Moreover, this protein was immunoreactive with hyperimmune sera against several serovars. In this study, we aimed to develop a lateral flow strip test using the rhKU_Sej_LRR_2271 protein for the detection of anti-leptospiral IgG in dogs. The lateral flow assay was performed with 184 dog plasma samples and evaluated with a culture method, 16S ribosomal RNA gene (rss) analysis real-time PCR, and LipL32 ELISA. The culture method failed to detect leptospires in the dog blood samples. Six of nine symptomatic dogs gave positive results with the real-time PCR assay. The lateral flow assay and LipL32 ELISA gave positive results with 59 and 50 dogs, respectively. The sensitivity, specificity, and accuracy of the rhKU_Sej_LRR_2271 lateral flow strip test were 70.00, 82.09, and 78.80%, respectively, when compared with LipL32 ELISA. There was a significant association between the LipL32 ELISA and the rhKU_Sej_LRR_2271 lateral flow assay. The rhKU_Sej_LRR_2271 lateral flow strip test has therefore demonstrated a good potential to detect anti-leptospiral IgG in dogs.<\/jats:p>","DOI":"10.3390\/tropicalmed7120427","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T04:05:22Z","timestamp":1670817922000},"page":"427","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Leptospiral Leucine-Rich Repeat Protein-Based Lateral Flow for Assessment of Canine Leptospiral Immunoglobulin G"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0611-540X","authenticated-orcid":false,"given":"Sineenat","family":"Sripattanakul","sequence":"first","affiliation":[{"name":"The Interdisciplinary Graduate Program in Genetic Engineering, The Graduate School, Kasetsart University, Bangkok 10900, Thailand"},{"name":"Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5140-429X","authenticated-orcid":false,"given":"Kanpapat","family":"Boonchuay","sequence":"additional","affiliation":[{"name":"Akkhraratchakumari Veterinary College, Walailak University, Nakhon Si Thammarat 80160, Thailand"},{"name":"One-Health Research Center, Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teerasak","family":"Prapong","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Worawidh","family":"Wajjwalku","sequence":"additional","affiliation":[{"name":"Akkhraratchakumari Veterinary College, Walailak University, Nakhon Si Thammarat 80160, Thailand"},{"name":"One-Health Research Center, Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Katzenmeier","sequence":"additional","affiliation":[{"name":"Akkhraratchakumari Veterinary College, Walailak University, Nakhon Si Thammarat 80160, Thailand"},{"name":"One-Health Research Center, Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8722-8176","authenticated-orcid":false,"given":"Dietmar","family":"Haltrich","sequence":"additional","affiliation":[{"name":"Department of Food Sciences and Technology, University of Natural Resources and Life Sciences, 1180 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratchanee","family":"Hongprayoon","sequence":"additional","affiliation":[{"name":"The Interdisciplinary Graduate Program in Genetic Engineering, The Graduate School, Kasetsart University, Bangkok 10900, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8852-0286","authenticated-orcid":false,"given":"Siriwan","family":"Prapong","sequence":"additional","affiliation":[{"name":"The Interdisciplinary Graduate Program in Genetic Engineering, The Graduate School, Kasetsart University, Bangkok 10900, Thailand"},{"name":"Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,10]]},"reference":[{"key":"ref_1","first-page":"489","article-title":"Leptospira taxonomy: Then and now","volume":"78","author":"Arent","year":"2022","journal-title":"Med. Weter."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1503\/cmaj.071097","article-title":"Leptospirosis in the family dog: A public health perspective","volume":"178","author":"Brown","year":"2008","journal-title":"Can. Med. Assoc. J."},{"key":"ref_3","unstructured":"(2021, August 04). Population of Dog and Cat in 2016. Available online: http:\/\/dcontrol.dld.go.th\/webnew\/index.php\/th\/news-menu\/2018-07-02-08-24-32\/360-dogpop2016."},{"key":"ref_4","first-page":"247","article-title":"Coinfection of Leptospira spp and Toxoplasma gondii among stray dogs in Bangkok, Thailand","volume":"40","author":"Jittapalapong","year":"2009","journal-title":"Southeast Asian J. Trop. Med. Public Health"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Altheimer, K., Jongwattanapisan, P., Luengyosluechakul, S., Pusoonthornthum, R., Prapasarakul, N., Kurilung, A., Broens, E.M., Wagenaar, J.A., Goris, M.G.A., and Ahmed, A.A. (2020). Leptospira infection and shedding in dogs in Thailand. BMC Vet. Res., 16.","DOI":"10.1186\/s12917-020-2230-0"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1089\/vbz.2019.2549","article-title":"Investigation of Leptospira Infection in Stray Animals in Songkhla, Thailand: Leptospirosis Risk Reduction in Human","volume":"20","author":"Ngasaman","year":"2020","journal-title":"Vector Borne Zoonotic Dis."},{"key":"ref_7","first-page":"1","article-title":"Serologic survey of leptospirosis in pigs, dogs, beef cattle, buffaloes and dairy cattle in Chaiyaphum Province","volume":"5","author":"Chotivanich","year":"2000","journal-title":"DLD Tech Paps."},{"key":"ref_8","first-page":"223","article-title":"Seroprevalence of Leptospira Spp. in Cattle and Dogs in Mahasarakham Province, Thailand","volume":"30","author":"Pumipuntu","year":"2016","journal-title":"J. Health Res."},{"key":"ref_9","first-page":"59","article-title":"Preliminary investigation of canine leptospirosis in a rural area of Thailand","volume":"63","author":"Niwetpathomwat","year":"2007","journal-title":"Med. Weter."},{"key":"ref_10","unstructured":"Sakpuaram, T., Wajjwalku, W., Sirinarumithra, T., Kasemsuwan, S., Sithisara, P., and Chanthick, N. (February, January 30). Monitoring of Leptospirosis in healthy vaccinated dogs in Hua-Hin district, Prachuapkhirikhan province between January to December, 2004. Proceedings of the 44th Kasetsart University Annual Conference: Animal, Veterinary Medicine, Bangkok, Thailand."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.14405\/kjvr.2020.60.1.1","article-title":"Genotyping of the causative Leptospira in symptomatic dogs in Thailand","volume":"60","author":"Paungpin","year":"2020","journal-title":"Korean J. Vet. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"178","DOI":"10.4269\/ajtmh.2012.12-0232","article-title":"Cross-sectional study of Leptospira seroprevalence in humans, rats, mice, and dogs in a main tropical sea-port city","volume":"88","author":"Thiry","year":"2013","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/0147-9571(92)90003-A","article-title":"Epidemiology of an outbreak of leptospirosis in man and dog","volume":"15","author":"Venkataraman","year":"1992","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Thaipadungpanit, J., Wuthiekanun, V., Chierakul, W., Smythe, L.D., Petkanchanapong, W., Limpaiboon, R., Apiwatanaporn, A., Slack, A.T., Suputtamongkol, Y., and White, N.J. (2007). A dominant clone of Leptospira interrogans associated with an outbreak of human leptospirosis in Thailand. PLOS Negl. Trop. Dis., 1.","DOI":"10.1371\/journal.pntd.0000056"},{"key":"ref_15","first-page":"281","article-title":"Leptospirosis: An emerging health problem in Thailand","volume":"36","author":"Tangkanakul","year":"2005","journal-title":"Southeast Asian J. Trop. Med. Public Health"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Yatbantoong, N., and Chaiyarat, R. (2019). Factors Associated with Leptospirosis in Domestic Cattle in Salakphra Wildlife Sanctuary, Thailand. Int. J. Environ. Res. Public Health, 16.","DOI":"10.3390\/ijerph16061042"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/0035-9203(66)90300-2","article-title":"Human leptospirosis in Thailand","volume":"60","author":"Sundharagiati","year":"1966","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_18","first-page":"1","article-title":"Prevalence and risk factors associated with serovars of Leptospira in dogs from Culiacan, Sinaloa","volume":"4","author":"Camacho","year":"2017","journal-title":"Vet. Mex. OA"},{"key":"ref_19","first-page":"275","article-title":"Prevalence and Risk Factors Associated with Serovars of Leptospira in Dogs, Related Human Seropositive","volume":"6","year":"2017","journal-title":"J. Dairy Vet. Anim. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.vetpar.2004.11.037","article-title":"Seroepidemiology of leptospirosis, toxoplasmosis, and leishmaniosis among dogs in Ankara, Turkey","volume":"129","author":"Ozdemir","year":"2005","journal-title":"Vet. Parasitol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0378-1135(97)00127-2","article-title":"Seroepidemiology of canine leptospirosis on the island of Barbados","volume":"57","author":"Weekes","year":"1997","journal-title":"Vet. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1678-9199-19-23","article-title":"Toxoplasmosis, leptospirosis and brucellosis in stray dogs housed at the shelter in Umuarama municipality, Paran\u00e1, Brazil","volume":"19","author":"Menegas","year":"2013","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"106438","DOI":"10.1016\/j.mimet.2022.106438","article-title":"Current methods for the diagnosis of leptospirosis: Issues and challenges","volume":"195","author":"Pinto","year":"2022","journal-title":"J. Microbiol. Methods"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1097\/MRM.0000000000000022","article-title":"Leptospiral major outer membrane protein: LipL32","volume":"26","author":"Ghazaei","year":"2015","journal-title":"Rev. Med. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ahmed, A.A., Goris, M.G.A., and Meijer, M.C. (2020). Development of lipL32 real-time PCR combined with an internal and extraction control for pathogenic Leptospira detection. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0241584"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5453","DOI":"10.1007\/s11696-021-01737-1","article-title":"Ultrasensitive nanohybrid electrochemical sensor to detect LipL32 gene of Leptospira interrogans","volume":"75","author":"Nagraik","year":"2021","journal-title":"Chem. Pap."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.jbiosc.2020.06.002","article-title":"Early detection of leptospirosis using Anti-LipL32 carbon nanotube immunofluorescence probe","volume":"130","author":"Sapna","year":"2020","journal-title":"J. Biosci. Bioeng."},{"key":"ref_28","first-page":"191","article-title":"Evaluation of real-time PCR, MAT, and recombinant LipL32-based ELISA for the diagnosis of canine leptospirosis in a disease-endemic South Indian state, Kerala","volume":"42","author":"Joseph","year":"2018","journal-title":"Turkish J. Vet. Anim. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ye, C., Yan, W., Xiang, H., He, H., Yang, M., Ijaz, M., Useh, N., Hsieh, C.-L., McDonough, P.L., and McDonough, S.P. (2014). Recombinant antigens rLipL21, rLoa22, rLipL32 and rLigACon4-8 for serological diagnosis of leptospirosis by enzyme-linked immunosorbent assays in dogs. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0111367"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e12949","DOI":"10.1111\/cmi.12949","article-title":"An extracellular Leptospira interrogans leucine-rich repeat protein binds human E- and VE-cadherins","volume":"21","author":"Eshghi","year":"2019","journal-title":"Cell. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1107\/S139900471500704X","article-title":"Structural characterization of a novel subfamily of leucine-rich repeat proteins from the human pathogen Leptospira interrogans","volume":"71","author":"Miras","year":"2015","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Hsu, S.H., and Yang, C.W. (2022). Insight into the Structure, Functions, and Dynamics of the Leptospira Outer Membrane Proteins with the Pathogenicity. Membranes, 12.","DOI":"10.3390\/membranes12030300"},{"key":"ref_33","first-page":"65","article-title":"Development of leptospira molecular markers by using bioinformation from predicted leucine-rich repeat (LRR) protein genes","volume":"58","author":"Hniman","year":"2007","journal-title":"J. Thail. Vet. Med. Assoc."},{"key":"ref_34","unstructured":"Nitipan, S. (2013). Molecular Cloning and Sequencing Analysis of the Genes Encoding Leucine-Rich Repeat Proteins of Pathogenic Leptospira Borgpetersenii. [Ph.D. Thesis, Kasetsart University]."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.meegid.2012.10.014","article-title":"Identification of epitopes in Leptospira borgpetersenii leucine-rich repeat proteins","volume":"14","author":"Nitipan","year":"2013","journal-title":"Infect. Genet. Evol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.mimet.2017.09.005","article-title":"Leptospira borgpetersenii hybrid leucine-rich repeat protein: Cloning and expression, immunogenic identification and molecular docking evaluation","volume":"142","author":"Sritrakul","year":"2017","journal-title":"J. Microbiol. Methods"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"100649","DOI":"10.1016\/j.imu.2021.100649","article-title":"New potent epitopes from Leptospira borgpetersenii for the stimulation of humoral and cell-mediated immune responses: Experimental and theoretical studies","volume":"25","author":"Tansiri","year":"2021","journal-title":"Inform. Med. Unlocked"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1128\/jcm.30.9.2219-2224.1992","article-title":"Polymerase chain reaction for detection of Leptospira spp. in clinical samples","volume":"30","author":"Amouriaux","year":"1992","journal-title":"J. Clin. Microbiol."},{"key":"ref_39","first-page":"9","article-title":"Rapid diagnosis of leptospirosis by multiplex PCR","volume":"19","author":"Ahmed","year":"2012","journal-title":"Malays. J. Med. Sci."},{"key":"ref_40","first-page":"311","article-title":"Leptospira borgpetersenii Leucine-Rich Repeat Proteins and Derived Peptides in an Indirect ELISA Development for theDiagnosis of Canine Leptospiral Infections","volume":"7","author":"Sripattanakul","year":"2022","journal-title":"Trop. Med. Int. Health"},{"key":"ref_41","unstructured":"Stangroom, J. (2022, October 20). Easy Fisher Exact Test Calculator. Available online: https:\/\/www.socscistatistics.com\/tests\/fisher\/default2.aspx."},{"key":"ref_42","unstructured":"Stangroom, J. (2022, October 20). Chi Square Calculator for 2 \u00d7 2. Available online: https:\/\/www.socscistatistics.com\/tests\/chisquare\/default.aspx."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"932137","DOI":"10.3389\/fcimb.2022.932137","article-title":"Host and Species-Specificities of Pattern Recognition Receptors Upon Infection with Leptospira interrogans","volume":"12","author":"Bonhomme","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"453","DOI":"10.4161\/viru.25180","article-title":"Prediction of molecular mimicry candidates in human pathogenic bacteria","volume":"4","author":"Doxey","year":"2013","journal-title":"Virulence"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1111\/jvim.14865","article-title":"Evaluation of 3 Serological Tests for Early Detection of Leptospira-specific Antibodies in Experimentally Infected Dogs","volume":"32","author":"Lizer","year":"2018","journal-title":"J. Vet. Intern. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.vetmic.2004.07.018","article-title":"Recombinant LipL32 antigen-based single serum dilution ELISA for detection of canine leptospirosis","volume":"103","author":"Dey","year":"2004","journal-title":"Vet. Microbiol."},{"key":"ref_47","first-page":"1089","article-title":"Comparative studies on seroepidemiology of canine leptospirosis by micro agglutination test (MAT) and recombinant Lip L32 ELISA","volume":"79","author":"Gupta","year":"2009","journal-title":"Indian J. Anim. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.rvsc.2017.03.017","article-title":"Molecular detection and isolation of pathogenic Leptospira from asymptomatic humans, domestic animals and water sources in Nan province, a rural area of Thailand","volume":"115","author":"Kurilung","year":"2017","journal-title":"Res. Vet. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"343","DOI":"10.7883\/yoken.JJID.2019.061","article-title":"A Novel Genotype of Leptospira interrogans Recovered from Leptospirosis Outbreak Samples from Southern Thailand","volume":"72","author":"Thongdee","year":"2019","journal-title":"Jpn. J. Infect. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1099\/00222615-43-2-110","article-title":"Evaluation of the polymerase chain reaction for early diagnosis of leptospirosis","volume":"43","author":"Brown","year":"1995","journal-title":"J. Med. Microbiol."},{"key":"ref_51","first-page":"148","article-title":"Seroprevalence and risk factors associated with leptospirosis in dogs","volume":"37","author":"Meeyam","year":"2006","journal-title":"Southeast Asian J. Trop. Med. Public Health"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/j.cvsm.2010.07.008","article-title":"Canine leptospirosis","volume":"40","author":"Goldstein","year":"2010","journal-title":"Vet. Clin. North Am. Small Anim. Pract."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.cvsm.2019.02.008","article-title":"Diagnosis of Canine Leptospirosis","volume":"49","author":"Reagan","year":"2019","journal-title":"Vet. Clin. Small Anim. Pract."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.vetmic.2008.12.021","article-title":"Onset and duration of protective immunity against clinical disease and renal carriage in dogs provided by a bi-valent inactivated leptospirosis vaccine","volume":"137","author":"Minke","year":"2009","journal-title":"Vet. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Riediger, I.N., Stoddard, R.A., Ribeiro, G.S., Nakatani, S.M., Moreira, S.D.R., Skraba, I., Biondo, A.W., Reis, M.G., Hoffmaster, A.R., and Vinetz, J.M. (2017). Rapid, actionable diagnosis of urban epidemic leptospirosis using a pathogenic Leptospira lipL32-based real-time PCR assay. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005940"},{"key":"ref_56","unstructured":"IDEXX Laboratories (2022, April 14). Diagnosing and Managing Canine Leptospirosis. Available online: https:\/\/www.idexx.com\/files\/canine-leptospirosis-test-dx-update.pdf."}],"container-title":["Tropical Medicine and Infectious Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2414-6366\/7\/12\/427\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:37:56Z","timestamp":1760146676000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2414-6366\/7\/12\/427"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,10]]},"references-count":56,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["tropicalmed7120427"],"URL":"https:\/\/doi.org\/10.3390\/tropicalmed7120427","relation":{},"ISSN":["2414-6366"],"issn-type":[{"value":"2414-6366","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,10]]}}}