{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T22:10:37Z","timestamp":1793398237645,"version":"4.5.0"},"reference-count":54,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T00:00:00Z","timestamp":1687305600000},"content-version":"unspecified","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005026","name":"Fondation Contre le Cancer","doi-asserted-by":"crossref","award":["2019-094"],"award-info":[{"award-number":["2019-094"]}],"id":[{"id":"10.13039\/501100005026","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","award":["404521405"],"award-info":[{"award-number":["404521405"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"name":"European Union\u2019s Horizon 2020 Research and Innovation Programme - MESI-STRAT","award":["754688"],"award-info":[{"award-number":["754688"]}]},{"DOI":"10.13039\/501100002910","name":"F\u00e9d\u00e9ration Wallonie-Bruxelles","doi-asserted-by":"publisher","award":["ARC 14\/19-058"],"award-info":[{"award-number":["ARC 14\/19-058"]}],"id":[{"id":"10.13039\/501100002910","id-type":"DOI","asserted-by":"publisher"}]},{"name":"BMBF e:Med initiative GlioPATH","award":["01ZX1402"],"award-info":[{"award-number":["01ZX1402"]}]},{"name":"European Research Council","award":["101045257"],"award-info":[{"award-number":["101045257"]}],"id":[{"id":"https:\/\/ror.org\/0472cxd90","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Fonds pour la Recherche Scientifique \u2013 FNRS","award":["22846630"],"award-info":[{"award-number":["22846630"]}]},{"name":"Fonds pour la Recherche Scientifique \u2013 FNRS","award":["EOS O000518F"],"award-info":[{"award-number":["EOS O000518F"]}]},{"name":"Fonds pour la Recherche Scientifique \u2013 FNRS","award":["PDR T.0091.18"],"award-info":[{"award-number":["PDR T.0091.18"]}]},{"name":"Fonds pour la Recherche Scientifique","award":["23638468"],"award-info":[{"award-number":["23638468"]}]},{"name":"Le Fonds de la Recherche Fondamentale Strat\u00e9gique","award":["WELBIO-CR-2019C-05"],"award-info":[{"award-number":["WELBIO-CR-2019C-05"]}]},{"DOI":"10.13039\/501100005026","name":"Stichting Tegen Kanker","doi-asserted-by":"publisher","award":["2018-090"],"award-info":[{"award-number":["2018-090"]}],"id":[{"id":"10.13039\/501100005026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2023,5,12]]},"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan-dioxygenase (TDO) are enzymes catabolizing the essential amino acid tryptophan into kynurenine. Expression of these enzymes is frequently observed in advanced-stage cancers and is associated with poor disease prognosis and immune suppression. Mechanistically, the respective roles of tryptophan shortage and kynurenine production in suppressing immunity remain unclear. Kynurenine was proposed as an endogenous ligand for the aryl hydrocarbon receptor (AHR), which can regulate inflammation and immunity. However, controversy remains regarding the role of AHR in IDO1\/TDO-mediated immune suppression, as well as the involvement of kynurenine. In this study, we aimed to clarify the link between IDO1\/TDO expression, AHR pathway activation and immune suppression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      AHR expression and activation was analyzed by RT-qPCR and western blot analysis in cells engineered to express IDO1\/TDO, or cultured in medium mimicking tryptophan catabolism by IDO1\/TDO. In vitro differentiation of na\u00efve CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells into regulatory T cells (Tregs) was compared in T cells isolated from mice bearing different\n                      <jats:italic>Ahr<\/jats:italic>\n                      alleles or a knockout of\n                      <jats:italic>Ahr<\/jats:italic>\n                      , and cultured in medium with or without tryptophan and kynurenine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We confirmed that IDO1\/TDO expression activated AHR in HEK-293-E cells, as measured by the induction of AHR target genes. Unexpectedly, AHR was also overexpressed on IDO1\/TDO expression. AHR overexpression did not depend on kynurenine but was triggered by tryptophan deprivation. Multiple human tumor cell lines overexpressed\n                      <jats:italic>AHR<\/jats:italic>\n                      on tryptophan deprivation.\n                      <jats:italic>AHR<\/jats:italic>\n                      overexpression was not dependent on general control non-derepressible 2 (GCN2), and strongly sensitized the AHR pathway. As a result, kynurenine and other tryptophan catabolites, which are weak AHR agonists in normal conditions, strongly induced AHR target genes in tryptophan-depleted conditions. Tryptophan depletion also increased kynurenine uptake by increasing SLC7A5 (LAT1) expression in a GCN2-dependent manner. Tryptophan deprivation potentiated Treg differentiation from na\u00efve CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells isolated from mice bearing an AHR allele of weak affinity similar to the human AHR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Tryptophan deprivation sensitizes the AHR pathway by inducing\n                      <jats:italic>AHR<\/jats:italic>\n                      overexpression and increasing cellular kynurenine uptake. As a result, tryptophan catabolites such as kynurenine more potently activate AHR, and Treg differentiation is promoted. Our results propose a molecular explanation for the combined roles of tryptophan deprivation and kynurenine production in mediating IDO1\/TDO-induced immune suppression.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2023-006728","type":"journal-article","created":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T09:42:18Z","timestamp":1687340538000},"page":"e006728","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":145,"title":["Tryptophan depletion sensitizes the AHR pathway by increasing AHR expression and GCN2\/LAT1-mediated kynurenine uptake, and potentiates induction of regulatory T lymphocytes"],"prefix":"10.1136","volume":"11","author":[{"given":"Marie","family":"Solvay","sequence":"first","affiliation":[{"name":"de Duve Institute, UCLouvain, Brussels, Belgium"},{"name":"Ludwig Institute for Cancer Research, de Duve Institute, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0945-678X","authenticated-orcid":false,"given":"Pauline","family":"Holfelder","sequence":"additional","affiliation":[{"name":"Faculty of Bioscience, Heidelberg University, Heidelberg, Germany"},{"name":"DKTK Division of Metabolic Crosstalk in Cancer, German Cancer Research Center, DKFZ, INF 280, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Klaessens","sequence":"additional","affiliation":[{"name":"de Duve Institute, UCLouvain, Brussels, Belgium"},{"name":"Ludwig Institute for Cancer Research, de Duve Institute, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Pilotte","sequence":"additional","affiliation":[{"name":"de Duve Institute, UCLouvain, Brussels, Belgium"},{"name":"Ludwig Institute for Cancer Research, de Duve Institute, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Stroobant","sequence":"additional","affiliation":[{"name":"de Duve Institute, UCLouvain, Brussels, Belgium"},{"name":"Ludwig Institute for Cancer Research, de Duve Institute, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliette","family":"Lamy","sequence":"additional","affiliation":[{"name":"de Duve Institute, UCLouvain, Brussels, Belgium"},{"name":"Ludwig Institute for Cancer Research, de Duve Institute, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Naulaerts","sequence":"additional","affiliation":[{"name":"de Duve Institute, UCLouvain, Brussels, Belgium"},{"name":"Ludwig Institute for Cancer Research, de Duve Institute, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quentin","family":"Spillier","sequence":"additional","affiliation":[{"name":"Louvain Drug Research Institute, UCLouvain, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8119-1272","authenticated-orcid":false,"given":"Rapha\u00ebl","family":"Fr\u00e9d\u00e9rick","sequence":"additional","affiliation":[{"name":"Louvain Drug Research Institute, UCLouvain, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"De Plaen","sequence":"additional","affiliation":[{"name":"de Duve Institute, UCLouvain, Brussels, Belgium"},{"name":"Ludwig Institute for Cancer Research, de Duve Institute, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6219-1514","authenticated-orcid":false,"given":"Christine","family":"Sers","sequence":"additional","affiliation":[{"name":"Partner Site Berlin, German Cancer Consortium, Heidelberg, Germany"},{"name":"German Cancer Consortium Partner Site Berlin, German Cancer Research Center, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5575-9821","authenticated-orcid":false,"given":"Christiane A","family":"Opitz","sequence":"additional","affiliation":[{"name":"DKTK Division of Metabolic Crosstalk in Cancer, German Cancer Research Center, DKFZ, INF 280, 69120 Heidelberg, Germany"},{"name":"Neurology Clinic and National Center for Tumor Diseases, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4995-3270","authenticated-orcid":false,"given":"Benoit J","family":"Van den Eynde","sequence":"additional","affiliation":[{"name":"de Duve Institute, UCLouvain, Brussels, Belgium"},{"name":"Ludwig Institute for Cancer Research, de Duve Institute, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0993-4849","authenticated-orcid":false,"given":"Jingjing","family":"Zhu","sequence":"additional","affiliation":[{"name":"de Duve Institute, UCLouvain, Brussels, Belgium"},{"name":"Ludwig Institute for Cancer Research, de Duve Institute, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,6,21]]},"reference":[{"key":"2025100305570419000_11.6.e006728.1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2015.00034","article-title":"Tryptophan-degrading enzymes in Tumoral immune resistance","volume":"6","author":"van Baren","year":"2015","journal-title":"Front Immunol"},{"key":"2025100305570419000_11.6.e006728.2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1113873109"},{"key":"2025100305570419000_11.6.e006728.3","doi-asserted-by":"publisher","DOI":"10.1038\/nm934"},{"key":"2025100305570419000_11.6.e006728.4","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1146\/annurev-cancerbio-030419-033635","article-title":"Is there a clinical future for IDO1 inhibitors after the failure of Epacadostat in melanoma?","volume":"4","author":"Van den Eynde","year":"2020","journal-title":"Annu. Rev. Cancer Biol."},{"key":"2025100305570419000_11.6.e006728.5","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5380.1191"},{"key":"2025100305570419000_11.6.e006728.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.03.013"},{"key":"2025100305570419000_11.6.e006728.7","doi-asserted-by":"crossref","DOI":"10.1080\/2162402X.2016.1240858","article-title":"The stress kinase Gcn2 does not mediate suppression of antitumor T cell responses by Tryptophan catabolism in experimental Melanomas","volume":"5","author":"Sonner","year":"2016","journal-title":"Oncoimmunology"},{"key":"2025100305570419000_11.6.e006728.8","doi-asserted-by":"publisher","DOI":"10.4161\/onci.21716"},{"key":"2025100305570419000_11.6.e006728.9","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020052"},{"key":"2025100305570419000_11.6.e006728.10","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903670"},{"key":"2025100305570419000_11.6.e006728.11","doi-asserted-by":"publisher","DOI":"10.1038\/nature13323"},{"key":"2025100305570419000_11.6.e006728.12","doi-asserted-by":"publisher","DOI":"10.1038\/nature10491"},{"key":"2025100305570419000_11.6.e006728.13","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.immuni.2017.12.012","article-title":"Regulation of the immune response by the aryl hydrocarbon receptor","volume":"48","author":"Guti\u00e9rrez-V\u00e1zquez","year":"2018","journal-title":"Immunity"},{"key":"2025100305570419000_11.6.e006728.14","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.43.100901.135828"},{"key":"2025100305570419000_11.6.e006728.15","doi-asserted-by":"publisher","DOI":"10.1038\/nature06880"},{"key":"2025100305570419000_11.6.e006728.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2018.02.005"},{"key":"2025100305570419000_11.6.e006728.17","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-019-0370-y"},{"key":"2025100305570419000_11.6.e006728.18","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA117.000631"},{"key":"2025100305570419000_11.6.e006728.19","doi-asserted-by":"crossref","DOI":"10.1177\/1178646920978241","article-title":"Quantification of plasma Kynurenine metabolites following one bout of Sprint interval exercise","volume":"13","author":"Trepci","year":"2020","journal-title":"Int J Tryptophan Res"},{"key":"2025100305570419000_11.6.e006728.20","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-19-0041"},{"key":"2025100305570419000_11.6.e006728.21","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0546-8"},{"key":"2025100305570419000_11.6.e006728.22","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa407"},{"key":"2025100305570419000_11.6.e006728.23","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.112.201111"},{"key":"2025100305570419000_11.6.e006728.24","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1016\/j.cell.2020.07.038","article-title":"Il4I1 is a metabolic immune checkpoint that activates the AhR and promotes tumor progression","volume":"182","author":"Sadik","year":"2020","journal-title":"Cell"},{"key":"2025100305570419000_11.6.e006728.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2006.01.007"},{"key":"2025100305570419000_11.6.e006728.26","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.2000.2037"},{"key":"2025100305570419000_11.6.e006728.27","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfq217"},{"key":"2025100305570419000_11.6.e006728.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.07.156"},{"key":"2025100305570419000_11.6.e006728.29","doi-asserted-by":"publisher","DOI":"10.3945\/an.112.002113"},{"key":"2025100305570419000_11.6.e006728.30","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2010.81"},{"key":"2025100305570419000_11.6.e006728.31","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-3502"},{"key":"2025100305570419000_11.6.e006728.32","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1093\/jn\/nxaa067","article-title":"Atf4 is a fundamental regulator of nutrient sensing and protein turnover","volume":"150","author":"Rasmussen","year":"2020","journal-title":"J Nutr"},{"key":"2025100305570419000_11.6.e006728.33","doi-asserted-by":"crossref","DOI":"10.1080\/2162402X.2018.1486353","article-title":"Upregulation of tryptophanyl-tRNA synthethase adapts human cancer cells to nutritional stress caused by tryptophan degradation","volume":"7","author":"Adam","year":"2018","journal-title":"Oncoimmunology"},{"key":"2025100305570419000_11.6.e006728.34","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.3168\/jds.2020-18700","article-title":"CRISPR-Cas9-mediated knockout of Gcn2 reveals a critical role in sensing amino acid deprivation in bovine Mammary epithelial cells","volume":"104","author":"Edick","year":"2021","journal-title":"J Dairy Sci"},{"key":"2025100305570419000_11.6.e006728.35","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5232-07.2008"},{"key":"2025100305570419000_11.6.e006728.36","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.00498","article-title":"Pharmacological brake-release of mRNA translation enhances cognitive memory","volume":"2","author":"Sidrauski","year":"2013","journal-title":"Elife"},{"key":"2025100305570419000_11.6.e006728.37","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfi154"},{"key":"2025100305570419000_11.6.e006728.38","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20081438"},{"key":"2025100305570419000_11.6.e006728.39","doi-asserted-by":"crossref","DOI":"10.1186\/s40064-015-0826-9","article-title":"Amino acids inhibit kynurenic acid formation via suppression of kynurenine uptake or kynurenic acid synthesis in rat brain in vitro","volume":"4","author":"Sekine","year":"2015","journal-title":"Springerplus"},{"key":"2025100305570419000_11.6.e006728.40","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-018-04366-7","article-title":"Single cell analysis of Kynurenine and system L amino acid transport in T cells","volume":"9","author":"Sinclair","year":"2018","journal-title":"Nat Commun"},{"key":"2025100305570419000_11.6.e006728.41","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-020-17750-z","article-title":"Blockade of the AHR restricts a Treg-macrophage suppressive axis induced by L-Kynurenine","volume":"11","author":"Campesato","year":"2020","journal-title":"Nat Commun"},{"key":"2025100305570419000_11.6.e006728.42","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/S0026-895X(25)09833-5","article-title":"Analysis of the four alleles of the murine aryl hydrocarbon receptor","volume":"46","author":"Poland","year":"1994","journal-title":"Mol Pharmacol"},{"key":"2025100305570419000_11.6.e006728.43","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(75)90420-8"},{"key":"2025100305570419000_11.6.e006728.44","doi-asserted-by":"crossref","first-page":"27337","DOI":"10.1016\/S0021-9258(18)46990-6","article-title":"Dioxin binding activities of polymorphic forms of mouse and human arylhydrocarbon receptors","volume":"269","author":"Ema","year":"1994","journal-title":"J Biol Chem"},{"key":"2025100305570419000_11.6.e006728.45","doi-asserted-by":"publisher","DOI":"10.1089\/dna.1998.17.811"},{"key":"2025100305570419000_11.6.e006728.46","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.505578"},{"key":"2025100305570419000_11.6.e006728.47","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310190200"},{"key":"2025100305570419000_11.6.e006728.48","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.cotox.2017.02.004","article-title":"The aryl hydrocarbon receptor Repressor - more than a simple feedback inhibitor of Ahr signaling: clues for its role in inflammation and cancer","volume":"2","author":"Vogel","year":"2017","journal-title":"Curr Opin Toxicol"},{"key":"2025100305570419000_11.6.e006728.49","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00915-07"},{"key":"2025100305570419000_11.6.e006728.50","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M412081200"},{"key":"2025100305570419000_11.6.e006728.51","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.molcel.2022.02.007","article-title":"Kynurenine importation by Slc7A11 propagates anti-Ferroptotic signaling","volume":"82","author":"Fiore","year":"2022","journal-title":"Mol Cell"},{"key":"2025100305570419000_11.6.e006728.52","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.11.6752"},{"key":"2025100305570419000_11.6.e006728.53","doi-asserted-by":"publisher","DOI":"10.1124\/mol.53.4.691"},{"key":"2025100305570419000_11.6.e006728.54","doi-asserted-by":"publisher","DOI":"10.1006\/faat.1996.0056"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2023-006728","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T12:57:19Z","timestamp":1759496239000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2023-006728"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6]]},"references-count":54,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6,21]]},"published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1136\/jitc-2023-006728"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2023-006728","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.01.16.524177","asserted-by":"object"}]},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6]]}}}