{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:25:40Z","timestamp":1787790340593,"version":"build-2784847793"},"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T00:00:00Z","timestamp":1698105600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medikine"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Interleukin (IL)-7 is broadly active on T-cell populations, and modified versions have been clinically evaluated for a variety of therapeutic applications, including cancer, lymphopenia, and infectious diseases; and found to be relatively well-tolerated and biologically active. Here we describe novel IL-7R agonists that are unrelated in structure to IL-7, bind to the receptor subunits differently from IL-7, but closely emulate IL-7 biology. The small size, low structural complexity, and the natural amino acid composition of the pharmacologically active peptide MDK1472 allows facile incorporation into protein structures, such as the IgG2-Fc fusion MDK-703. This molecule possesses properties potentially better suited to therapeutic applications than native IL-7 or its derivatives. We compared these compounds with IL-7 for immune cell selectivity, induction of IL-7R signaling, receptor-mediated internalization, proliferation, and generation of immune cell phenotypes in human and non-human primate (NHP) peripheral blood cells\n                    <jats:italic>in vitro<\/jats:italic>\n                    ; and found them to be similar in biological activity to IL-7. In cynomolgus macaques, MDK-703 exhibits a circulating half-life of 46 hr and produces sustained T-cell expansion characteristic of IL-7 treatment. In the huCD34\n                    <jats:sup>+<\/jats:sup>\n                    -engrafted NSG mouse model of the human immune system, MDK-703 induces an immune cell profile very similar to that generated by IL-7-derived compounds; including the pronounced expansion of memory T-cells, particularly the population of stem-like memory T-cells (Tscm) which may be important for anti-tumor activities reported with IL-7 treatment. Clinical administration of IL-7 and modified variants has been reported to induce anti-drug antibodies (ADAs), including IL-7 neutralizing antibodies. The novel peptide agonist reported here scores very low in predicted immunogenicity, and because the peptide lacks sequence similarity with IL-7, the problematic immunogenic neutralization of endogenous cytokine should not occur. The properties we report here implicate MDK-703 as a candidate for clinical evaluation in oncology, anti-viral and other infectious disease, vaccine enhancement, and treatment of lymphopenia.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0286834","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T13:28:39Z","timestamp":1698154119000},"page":"e0286834","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["A mechanistically novel peptide agonist of the IL-7 receptor that addresses limitations of IL-7 cytokine therapy"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1676-5561","authenticated-orcid":true,"given":"William J.","family":"Dower","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angie 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Immunol"},{"issue":"1","key":"pone.0286834.ref003","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4110\/in.2011.11.1.1","article-title":"Seeing is believing: illuminating the source of in vivo interleukin-7.","volume":"11","author":"GY Kim","year":"2011","journal-title":"Immune Netw."},{"issue":"10","key":"pone.0286834.ref004","doi-asserted-by":"crossref","first-page":"2562","DOI":"10.1002\/eji.1830271015","article-title":"Induction of T cell adhesion to extracellular matrix or endothelial cell ligands by soluble or matrix-bound interleukin-7","volume":"27","author":"A Ariel","year":"1997","journal-title":"Eur J Immunol"},{"key":"pone.0286834.ref005","doi-asserted-by":"crossref","first-page":"156049","DOI":"10.1016\/j.cyto.2022.156049","article-title":"IL-7: Comprehensive review","volume":"160","author":"H Winer","year":"2022","journal-title":"Cytokine"},{"issue":"11","key":"pone.0286834.ref006","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1038\/ni1513","article-title":"Fibroblastic reticular cells in lymph nodes regulate the homeostasis of naive T cells","volume":"8","author":"A Link","year":"2007","journal-title":"Nat Immunol"},{"issue":"12","key":"pone.0286834.ref007","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.2174\/138945006779025365","article-title":"The IL-7\/IL-7 receptor axis: understanding its central role in T-cell homeostasis and the challenges facing its utilization as a novel therapy","volume":"7","author":"SC Sasson","year":"2006","journal-title":"Curr Drug Targets"},{"issue":"10","key":"pone.0286834.ref008","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/S1471-4906(01)02028-2","article-title":"Interleukin-7: master regulator of peripheral T-cell homeostasis?","volume":"22","author":"TJ Fry","year":"2001","journal-title":"Trends Immunol"},{"issue":"2","key":"pone.0286834.ref009","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.immuni.2004.07.016","article-title":"Suppression of IL7Ralpha transcription by IL-7 and other prosurvival cytokines: a novel mechanism for maximizing IL-7-dependent T cell survival","volume":"21","author":"JH Park","year":"2004","journal-title":"Immunity"},{"issue":"11","key":"pone.0286834.ref010","doi-asserted-by":"crossref","first-page":"6571","DOI":"10.4049\/jimmunol.174.11.6571","article-title":"The many faces of IL-7: from lymphopoiesis to peripheral T cell maintenance","volume":"174","author":"TJ Fry","year":"2005","journal-title":"J Immunol"},{"issue":"2","key":"pone.0286834.ref011","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/nri2023","article-title":"Interleukin-7 receptor expression: intelligent design","volume":"7","author":"R Mazzucchelli","year":"2007","journal-title":"Nature Rev 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patients with anti-PD-1\/PD-L1 na\u00efve or relapsed\/refractory (R\/R) high-risk skin cancers: The phase 1b report.","volume":"40","author":"B Gastman","year":"2022","journal-title":"J Clin Oncol."},{"issue":"1","key":"pone.0286834.ref015","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/nm.4241","article-title":"T memory stem cells in health and disease","volume":"23","author":"L Gattinoni","year":"2017","journal-title":"Nat Med"},{"issue":"5","key":"pone.0286834.ref016","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/nri2970","article-title":"Harnessing the biology of IL-7 for therapeutic application","volume":"11","author":"CL Mackall","year":"2011","journal-title":"Nat Rev Immunol"},{"issue":"12","key":"pone.0286834.ref017","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1038\/s41590-019-0479-x","article-title":"Flip the coin: IL-7 and IL-7R in health and disease","volume":"20","author":"JT Barata","year":"2019","journal-title":"Nat Immunol"},{"issue":"5","key":"pone.0286834.ref018","doi-asserted-by":"crossref","first-page":"10267","DOI":"10.3390\/ijms160510267","article-title":"Mechanism of action of IL-7 and its potential applications and limitations in cancer immunotherapy","volume":"16","author":"J Gao","year":"2015","journal-title":"Int J Mol Sci"},{"issue":"1","key":"pone.0286834.ref019","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s11523-012-0210-4","article-title":"Interleukin-7 and immune reconstitution in cancer patients: a new paradigm for dramatically increasing overall survival","volume":"7","author":"M Morre","year":"2012","journal-title":"Target Oncol"},{"issue":"8","key":"pone.0286834.ref020","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1182\/blood-2015-05-645077","article-title":"Administration of interleukin-7 increases CD4 T cells in idiopathic CD4 lymphocytopenia","volume":"127","author":"V Sheikh","year":"2016","journal-title":"Blood"},{"issue":"7","key":"pone.0286834.ref021","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1093\/annonc\/mdv173","article-title":"ELYPSE-7: a randomized placebo-controlled phase IIa trial with CYT107 exploring the restoration of CD4+ lymphocyte count in lymphopenic metastatic breast cancer patients","volume":"26","author":"O Tredan","year":"2015","journal-title":"Ann Oncol"},{"issue":"9","key":"pone.0286834.ref022","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1093\/cid\/ciw065","article-title":"Repeated Cycles of Recombinant Human Interleukin 7 in HIV-Infected Patients With Low CD4 T-Cell Reconstitution on Antiretroviral Therapy: Results of 2 Phase II Multicenter Studies","volume":"62","author":"R Thiebaut","year":"2016","journal-title":"Clin Infect Dis"},{"issue":"13","key":"pone.0286834.ref023","doi-asserted-by":"crossref","first-page":"3182","DOI":"10.1158\/1078-0432.CCR-15-2550","article-title":"Adjuvant Immunotherapy to Improve Outcome in High-Risk Pediatric Sarcomas","volume":"22","author":"MS Merchant","year":"2016","journal-title":"Clin Cancer Res"},{"issue":"5","key":"pone.0286834.ref024","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.98960","article-title":"Interleukin-7 restores lymphocytes in septic shock: the IRIS-7 randomized clinical trial.","volume":"3","author":"B Francois","year":"2018","journal-title":"JCI Insight."},{"issue":"6","key":"pone.0286834.ref025","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1111\/cts.12800","article-title":"hIL-7-hyFc, A Long-Acting IL-7, Increased Absolute Lymphocyte Count in Healthy Subjects.","volume":"13","author":"SW Lee","year":"2020","journal-title":"Clin Transl Sci."},{"issue":"2","key":"pone.0286834.ref026","doi-asserted-by":"crossref","first-page":"e213","DOI":"10.1212\/NXI.0000000000000213","article-title":"Interleukin-7 treatment of PML in a patient with idiopathic lymphocytopenia.","volume":"3","author":"DP Miskin","year":"2016","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"issue":"23","key":"pone.0286834.ref027","doi-asserted-by":"crossref","first-page":"6093","DOI":"10.1182\/bloodadvances.2021006591","article-title":"A single administration of hIL-7-hyFc induces long-lasting T-cell expansion with maintained effector functions","volume":"6","author":"S Kim","year":"2022","journal-title":"Blood Adv"},{"issue":"6","key":"pone.0286834.ref028","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1158\/1078-0432.CCR-21-0947","article-title":"Long-Acting Recombinant Human Interleukin-7, NT-I7, Increases Cytotoxic CD8 T Cells and Enhances Survival in Mouse Glioma Models","volume":"28","author":"JL Campian","year":"2022","journal-title":"Clin Cancer Res"},{"issue":"9","key":"pone.0286834.ref029","doi-asserted-by":"crossref","first-page":"e1168","DOI":"10.1002\/cti2.1168","article-title":"Hybrid Fc-fused interleukin-7 induces an inflamed tumor microenvironment and improves the efficacy of cancer immunotherapy","volume":"9","author":"JH Kim","year":"2020","journal-title":"Clin Transl Immunol"},{"issue":"Suppl 2","key":"pone.0286834.ref030","doi-asserted-by":"crossref","first-page":"A439","DOI":"10.1136\/jitc-2021-SITC2021.408","article-title":"408.\u2005Preliminary biomarker and clinical ata of a phase 2a study of NT-I7, a long-acting interleukin-7, plus pembrolizumab: cohort of subjects with checkpoint inhibitor-na\u00efve advanced pancreatic cancer","volume":"9","author":"A Naing","year":"2021","journal-title":"J Immunother Cancer"},{"issue":"15_suppl","key":"pone.0286834.ref031","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1200\/JCO.2021.39.15_suppl.2040","article-title":"A phase I\/II study to evaluate the safety and efficacy of a novel long-acting interleukin-7, NT-I7, for patients with newly diagnosed high-grade gliomas after chemoradiotherapy: The interim result of the phase I data.","volume":"39","author":"JL Campian","year":"2021","journal-title":"J Clin Oncol."},{"key":"pone.0286834.ref032","doi-asserted-by":"crossref","first-page":"S266","DOI":"10.1016\/j.annonc.2022.04.144","article-title":"P-54 Phase 2a study of NT-I7, a long-acting interleukin-7, plus pembrolizumab: Cohort of subjects with checkpoint inhibitor-na\u00efve advanced MSS-colorectal cancer","volume":"33","author":"R Kim","year":"2022","journal-title":"Ann Oncol"},{"key":"pone.0286834.ref033","doi-asserted-by":"crossref","first-page":"S263","DOI":"10.1016\/j.annonc.2022.04.138","article-title":"P-48. Phase 2a study of NT-I7, a long-acting interleukin-7, plus pembrolizumab: Cohort of subjects with checkpoint inhibitor-na\u00efve advanced pancreatic cancer.","volume":"33","author":"A Naing","year":"2022","journal-title":"Ann Oncol."},{"issue":"16_suppl","key":"pone.0286834.ref034","doi-asserted-by":"crossref","first-page":"2514","DOI":"10.1200\/JCO.2022.40.16_suppl.2514","article-title":"Efficacy and safety of NT-I7, long-acting interleukin-7, plus pembrolizumab in patients with advanced solid tumors: Results from the phase 2a study.","volume":"40","author":"A Naing","year":"2022","journal-title":"J Clin Oncol."},{"key":"pone.0286834.ref035","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1200\/JCO.2022.40.16_suppl.1081","article-title":"Phase 1b\/2 study of GX-I7 plus pembrolizumab in patients with refractory or recurrent (R\/R) metastatic triple-negative breast cancer (mTNBC): The KEYNOTE-899 Study.","volume":"40","author":"J Sohn","year":"2022","journal-title":"J Clin Oncol."},{"issue":"5274","key":"pone.0286834.ref036","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1126\/science.273.5274.458","article-title":"Small peptides as potent mimetics of the protein hormone erythropoietin","volume":"273","author":"NC Wrighton","year":"1996","journal-title":"Science"},{"issue":"5319","key":"pone.0286834.ref037","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1126\/science.276.5319.1696","article-title":"Peptide agonist of the thrombopoietin receptor as potent as the natural cytokine","volume":"276","author":"SE Cwirla","year":"1997","journal-title":"Science"},{"issue":"7","key":"pone.0286834.ref038","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.4161\/hv.24615","article-title":"The two-faced T cell epitope: examining the host-microbe interface with JanusMatrix","volume":"9","author":"L Moise","year":"2013","journal-title":"Hum Vaccin Immunother"},{"issue":"9","key":"pone.0286834.ref039","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1080\/21645515.2015.1061159","article-title":"iVAX: An integrated toolkit for the selection and optimization of antigens and the design of epitope-driven vaccines.","volume":"11","author":"L Moise","year":"2015","journal-title":"Hum Vaccin Immunother"},{"issue":"4","key":"pone.0286834.ref040","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/j.immuni.2019.03.028","article-title":"The gamma(c) Family of Cytokines: Basic Biology to Therapeutic Ramifications.","volume":"50","author":"WJ Leonard","year":"2019","journal-title":"Immunity"},{"issue":"9","key":"pone.0286834.ref041","article-title":"The common cytokine receptor gamma chain family of cytokines","volume":"10","author":"JX Lin","year":"2018","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"1","key":"pone.0286834.ref042","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41577-022-00735-y","article-title":"Role of thymic stromal lymphopoietin in allergy and beyond","volume":"23","author":"R Ebina-Shibuya","year":"2023","journal-title":"Nature Rev Immunol"},{"issue":"3","key":"pone.0286834.ref043","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1097\/01.cji.0000210386.55951.c2","article-title":"IL-7 administration to humans leads to expansion of CD8+ and CD4+ cells but a relative decrease of CD4+ T-regulatory cells","volume":"29","author":"SA Rosenberg","year":"2006","journal-title":"J Immunother"},{"issue":"7","key":"pone.0286834.ref044","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1084\/jem.20060772","article-title":"CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells","volume":"203","author":"W Liu","year":"2006","journal-title":"J Exp Med"},{"issue":"3","key":"pone.0286834.ref045","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.it.2005.01.004","article-title":"IL-7: maintaining T-cell memory and achieving homeostasis","volume":"26","author":"LM Bradley","year":"2005","journal-title":"Trends Immunol"},{"issue":"12","key":"pone.0286834.ref046","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1084\/jem.20020066","article-title":"Interleukin (IL)-15 and IL-7 jointly regulate homeostatic proliferation of memory phenotype CD8+ cells but are not required for memory phenotype CD4+ cells.","volume":"195","author":"JT Tan","year":"2002","journal-title":"J Exp Med"},{"issue":"6","key":"pone.0286834.ref047","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/ni.2018","article-title":"Normal T cell homeostasis: the conversion of naive cells into memory-phenotype cells","volume":"12","author":"J Sprent","year":"2011","journal-title":"Nat Immunol"},{"issue":"3","key":"pone.0286834.ref048","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.4049\/jimmunol.181.3.1806","article-title":"CTLA4 expression is an indicator and regulator of steady-state CD4+ FoxP3+ T cell homeostasis","volume":"181","author":"AL Tang","year":"2008","journal-title":"J Immunol"},{"issue":"2","key":"pone.0286834.ref049","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/icb.2015.80","article-title":"IL-7 induces clathrin-mediated endocytosis of CD127 and subsequent degradation by the proteasome in primary human CD8 T cells","volume":"94","author":"EM Faller","year":"2016","journal-title":"Immunol Cell Biol"},{"issue":"16","key":"pone.0286834.ref050","doi-asserted-by":"crossref","first-page":"3269","DOI":"10.1182\/blood-2009-10-246876","article-title":"IL-7 induces rapid clathrin-mediated internalization and JAK3-dependent degradation of IL-7Ralpha in T cells","volume":"115","author":"CM Henriques","year":"2010","journal-title":"Blood"},{"issue":"4","key":"pone.0286834.ref051","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1182\/blood-2008-11-191288","article-title":"Injection of glycosylated recombinant simian IL-7 provokes rapid and massive T-cell homing in rhesus macaques","volume":"114","author":"S Beq","year":"2009","journal-title":"Blood"},{"key":"pone.0286834.ref052","doi-asserted-by":"crossref","first-page":"747324","DOI":"10.3389\/fimmu.2021.747324","article-title":"Interleukin-7 biology and its effects on immune cells: mediator of generation, differentiation, survival, and homeostasis.","volume":"12","author":"D Chen","year":"2021","journal-title":"Front Immunol."},{"issue":"1","key":"pone.0286834.ref053","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s13613-023-01109-w","article-title":"Intravenously administered interleukin-7 to reverse lymphopenia in patients with septic shock: a double-blind, randomized, placebo-controlled trial.","volume":"13","author":"T Daix","year":"2023","journal-title":"Ann Intensive Care."},{"key":"pone.0286834.ref054","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.ijbiomac.2016.02.006","article-title":"Eun C-y, Choi D, Jeong SH. Biophysical stability of hyFc fusion protein with regards to buffers and various excipients","volume":"86","author":"JY Lim","year":"2016","journal-title":"Int J Biol Macromol"},{"issue":"Suppl 2","key":"pone.0286834.ref055","first-page":"A657","article-title":"625.\u2005A phase 1 single ascending dose study evaluating the safety, tolerability, and pharmacodynamic effects of MDK-703, an IL-7 mimetic with extended half-life","volume":"10","author":"R Friend","year":"2022","journal-title":"J Immunother Cancer"},{"issue":"12","key":"pone.0286834.ref056","doi-asserted-by":"crossref","first-page":"5649","DOI":"10.4049\/jimmunol.1201286","article-title":"IL-7 abrogates suppressive activity of human CD4+CD25+FOXP3+ regulatory T cells and allows expansion of alloreactive and autoreactive T cells","volume":"189","author":"AK Heninger","year":"2012","journal-title":"J Immunol"},{"issue":"13_Supplement","key":"pone.0286834.ref057","doi-asserted-by":"crossref","first-page":"5565","DOI":"10.1158\/1538-7445.AM2018-5565","article-title":"Abstract 5565: Potency-reduced IL15\/IL15R\u03b1 heterodimeric Fc-fusions display enhanced in vivo activity through increased exposure","volume":"78","author":"MJ Bernett","year":"2018","journal-title":"Cancer Res"},{"issue":"1","key":"pone.0286834.ref058","doi-asserted-by":"crossref","first-page":"12506","DOI":"10.1038\/s41598-022-16616-2","article-title":"Transgenic expression of IL-7 regulates CAR-T cell metabolism and enhances in vivo persistence against tumor cells","volume":"12","author":"L Li","year":"2022","journal-title":"Sci Rep"},{"key":"pone.0286834.ref059","doi-asserted-by":"crossref","first-page":"723888","DOI":"10.3389\/fonc.2021.723888","article-title":"Immunotherapeutic Potential of T Memory Stem Cells.","volume":"11","author":"Y Li","year":"2021","journal-title":"Front Oncol"},{"issue":"19","key":"pone.0286834.ref060","doi-asserted-by":"crossref","first-page":"4898","DOI":"10.1182\/bloodadvances.2020002394","article-title":"Tumor burden, inflammation, and product attributes determine outcomes of axicabtagene ciloleucel in large B-cell lymphoma.","volume":"4","author":"FL Locke","year":"2020","journal-title":"Blood Adv."},{"key":"pone.0286834.ref061","first-page":"DC2021","article-title":"Peptidyl IL-2\/15R\u03b2\u03b3c-restricted agonists, highly-attenuated and linked to anti-PD-1 antibodies to achieve selectivity and amplified potency in stimulating PD-1high lymphocytes","author":"WJ Dower","year":"2021","journal-title":"Society for Immunotherapy of Cancer (SITC)"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0286834","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T13:29:12Z","timestamp":1698154152000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0286834"}},"subtitle":[],"editor":[{"given":"Suresh","family":"Pallikkuth","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,10,24]]},"references-count":61,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0286834","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.05.24.542196","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,24]]}}}