{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T13:44:36Z","timestamp":1768484676180,"version":"3.49.0"},"reference-count":48,"publisher":"American Society of Hematology","issue":"7","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,4,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Anti-CD20 antibodies such as rituximab are broadly used to treat B-cell malignancies. These antibodies can induce various effector functions, including immune cell-mediated antibody-dependent cellular cytotoxicity (ADCC). Neutrophils can induce ADCC toward solid cancer cells by trogoptosis, a cytotoxic mechanism known to be dependent on trogocytosis. However, neutrophils seem to be incapable of killing rituximab-opsonized B-cell lymphoma cells. Nevertheless, neutrophils do trogocytose rituximab-opsonized B-cell lymphoma cells, but this only reduces CD20 surface expression and is thought to render tumor cells therapeutically resistant to further rituximab-dependent destruction. Here, we demonstrate that resistance of B-cell lymphoma cells toward neutrophil killing can be overcome by a combination of CD47-SIRP\u03b1 checkpoint blockade and sodium stibogluconate (SSG), an anti-leishmaniasis drug and documented inhibitor of the tyrosine phosphatase SHP-1. SSG enhanced neutrophil-mediated ADCC of solid tumor cells but enabled trogoptotic killing of B-cell lymphoma cells by turning trogocytosis from a mechanism that contributes to resistance into a cytotoxic anti-cancer mechanism. Tumor cell killing in the presence of SSG required both antibody opsonization of the target cells and disruption of CD47-SIRP\u03b1 interactions. These results provide a more detailed understanding of the role of neutrophil trogocytosis in antibody-mediated destruction of B cells and clues on how to further optimize antibody therapy of B-cell malignancies.<\/jats:p>","DOI":"10.1182\/bloodadvances.2021005367","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T22:01:10Z","timestamp":1640296870000},"page":"2156-2166","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":21,"title":["Sodium stibogluconate and CD47-SIRP\u03b1 blockade overcome resistance of anti-CD20\u2013opsonized B cells to neutrophil killing"],"prefix":"10.1182","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9936-3394","authenticated-orcid":false,"given":"Dieke J.","family":"van Rees","sequence":"first","affiliation":[{"name":"Department of Molecular Hematology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maximilian","family":"Brinkhaus","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bart","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Molecular Hematology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Verkuijlen","sequence":"additional","affiliation":[{"name":"Department of Molecular Hematology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anton T.J.","family":"Tool","sequence":"additional","affiliation":[{"name":"Department of Molecular Hematology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Schornagel","sequence":"additional","affiliation":[{"name":"Department of Molecular Hematology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise W.","family":"Treffers","sequence":"additional","affiliation":[{"name":"Department of Molecular Hematology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9510-6961","authenticated-orcid":false,"given":"Michel","family":"van Houdt","sequence":"additional","affiliation":[{"name":"Department of Molecular Hematology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3190-1891","authenticated-orcid":false,"given":"Arnon P.","family":"Kater","sequence":"additional","affiliation":[{"name":"Department of Hematology, Cancer Center Amsterdam, Lymphoma and Myeloma Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5621-003X","authenticated-orcid":false,"given":"Gestur","family":"Vidarsson","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6218-1324","authenticated-orcid":false,"given":"Andrew R.","family":"Gennery","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7421-3370","authenticated-orcid":false,"given":"Taco W.","family":"Kuijpers","sequence":"additional","affiliation":[{"name":"Department of Molecular Hematology and"},{"name":"Emma Children\u2019s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin","family":"van Bruggen","sequence":"additional","affiliation":[{"name":"Department of Molecular Hematology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanke L.","family":"Matlung","sequence":"additional","affiliation":[{"name":"Department of Molecular Hematology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timo K.","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Department of Molecular Hematology and"},{"name":"Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","published-online":{"date-parts":[[2022,3,31]]},"reference":[{"issue":"18","key":"2022033115292008700_B1","doi-asserted-by":"crossref","first-page":"3160","DOI":"10.1182\/blood-2013-04-497446","article-title":"Neutrophils mediate antibody-induced antitumor effects in mice","volume":"122","author":"Albanesi","year":"2013","journal-title":"Blood."},{"issue":"16, pt 1","key":"2022033115292008700_B2","first-page":"5866","article-title":"Neutrophils contribute to the biological antitumor activity of rituximab in a non-Hodgkin\u2019s lymphoma severe combined immunodeficiency mouse model","volume":"9","author":"Hernandez-Ilizaliturri","year":"2003","journal-title":"Clin Cancer Res."},{"issue":"4","key":"2022033115292008700_B3","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.ccell.2015.03.004","article-title":"Synergistic innate and adaptive immune response to combination immunotherapy with anti-tumor antigen antibodies and extended serum half-life IL-2","volume":"27","author":"Zhu","year":"2015","journal-title":"Cancer Cell."},{"issue":"3","key":"2022033115292008700_B4","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.4049\/jimmunol.171.3.1581","article-title":"Complement activation determines the therapeutic activity of rituximab in\u00a0vivo","volume":"171","author":"Di Gaetano","year":"2003","journal-title":"J Immunol."},{"issue":"2","key":"2022033115292008700_B5","first-page":"176","article-title":"The role of complement in the therapeutic activity of rituximab in a murine B lymphoma model homing in lymph nodes","volume":"91","author":"Golay","year":"2006","journal-title":"Haematologica."},{"issue":"9","key":"2022033115292008700_B6","first-page":"1002","article-title":"Rituximab-mediated antibody-dependent cellular cytotoxicity against neoplastic B cells is stimulated strongly by interleukin-2","volume":"88","author":"Golay","year":"2003","journal-title":"Haematologica."},{"issue":"5","key":"2022033115292008700_B7","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.leukres.2009.10.029","article-title":"Nonfucosylated anti-CD20 antibody potentially induces apoptosis in lymphoma cells through enhanced interaction with FcgammaRIIIb on neutrophils","volume":"34","author":"Nakagawa","year":"2010","journal-title":"Leuk Res."},{"issue":"19","key":"2022033115292008700_B8","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1182\/blood-2016-08-735605","article-title":"Human neutrophils mediate trogocytosis rather than phagocytosis of CLL B cells opsonized with anti-CD20 antibodies","volume":"129","author":"Valgardsdottir","year":"2017","journal-title":"Blood."},{"issue":"5","key":"2022033115292008700_B9","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1182\/blood-2014-10-569244","article-title":"Fc\u03b3-receptor-mediated trogocytosis impacts mAb-based therapies: historical precedence and recent developments","volume":"125","author":"Taylor","year":"2015","journal-title":"Blood."},{"issue":"10","key":"2022033115292008700_B10","doi-asserted-by":"crossref","first-page":"3111","DOI":"10.1002\/art.34560","article-title":"Rituximab mediates loss of CD19 on B cells in the absence of cell death","volume":"64","author":"Jones","year":"2012","journal-title":"Arthritis Rheum."},{"issue":"6","key":"2022033115292008700_B11","doi-asserted-by":"crossref","first-page":"3438","DOI":"10.4049\/jimmunol.1101189","article-title":"Loss of CD20 and bound CD20 antibody from opsonized B cells occurs more rapidly because of trogocytosis mediated by Fc receptor-expressing effector cells than direct internalization by the B cells","volume":"187","author":"Beum","year":"2011","journal-title":"J Immunol."},{"issue":"13","key":"2022033115292008700_B12","doi-asserted-by":"crossref","first-page":"3946","DOI":"10.1016\/j.celrep.2018.05.082","article-title":"Neutrophils kill antibody-opsonized cancer cells by trogoptosis","volume":"23","author":"Matlung","year":"2018","journal-title":"Cell Rep."},{"issue":"45","key":"2022033115292008700_B13","doi-asserted-by":"crossref","first-page":"18342","DOI":"10.1073\/pnas.1106550108","article-title":"CD47-signal regulatory protein-\u03b1 (SIRP\u03b1) interactions form a barrier for antibody-mediated tumor cell destruction","volume":"108","author":"Zhao","year":"2011","journal-title":"Proc Natl Acad Sci USA."},{"issue":"2","key":"2022033115292008700_B14","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.smim.2016.02.004","article-title":"Immunoreceptors on neutrophils","volume":"28","author":"van Rees","year":"2016","journal-title":"Semin Immunol."},{"issue":"6","key":"2022033115292008700_B15","doi-asserted-by":"crossref","first-page":"3391","DOI":"10.4049\/jimmunol.167.6.3391","article-title":"Sodium stibogluconate is a potent inhibitor of protein tyrosine phosphatases and augments cytokine responses in hemopoietic cell lines","volume":"167","author":"Pathak","year":"2001","journal-title":"J Immunol."},{"issue":"10","key":"2022033115292008700_B16","doi-asserted-by":"crossref","first-page":"5978","DOI":"10.4049\/jimmunol.169.10.5978","article-title":"Anticancer activity of sodium stibogluconate in synergy with IFNs","volume":"169","author":"Yi","year":"2002","journal-title":"J Immunol."},{"key":"2022033115292008700_B17","doi-asserted-by":"crossref","first-page":"935","DOI":"10.3389\/fonc.2020.00935","article-title":"Shp1 in solid cancers and their therapy","volume":"10","author":"Varone","year":"2020","journal-title":"Front Oncol."},{"issue":"5","key":"2022033115292008700_B18","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1159\/000490106","article-title":"Targeting SHP-1, 2 and SHIP pathways: A novel strategy for cancer treatment?","volume":"95","author":"Dempke","year":"2018","journal-title":"Oncology."},{"issue":"2","key":"2022033115292008700_B19","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1042\/BST20150251","article-title":"SHP-1: the next checkpoint target for cancer immunotherapy?","volume":"44","author":"Watson","year":"2016","journal-title":"Biochem Soc Trans."},{"issue":"4","key":"2022033115292008700_B20","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1182\/blood.V78.4.1105.1105","article-title":"Membrane surface antigen expression on neutrophils: a reappraisal of the use of surface markers for neutrophil activation","volume":"78","author":"Kuijpers","year":"1991","journal-title":"Blood."},{"issue":"12","key":"2022033115292008700_B21","doi-asserted-by":"crossref","first-page":"3456","DOI":"10.4049\/jimmunol.2000961","article-title":"Glycine 236 in the lower hinge region of human IgG1 differentiates Fc\u03b3R from complement effector function","volume":"205","author":"Brinkhaus","year":"2020","journal-title":"J Immunol."},{"issue":"1","key":"2022033115292008700_B22","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1158\/1535-7163.MCT-18-0341","article-title":"Immune effector functions of human IgG2 antibodies against EGFR","volume":"18","author":"R\u00f6sner","year":"2019","journal-title":"Mol Cancer Ther."},{"issue":"7","key":"2022033115292008700_B23","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1182\/blood-2007-01-070656","article-title":"Increased natural killer cell expression of CD16, augmented binding and ADCC activity to rituximab among individuals expressing the FcgammaRIIIa-158 V\/V and V\/F polymorphism","volume":"110","author":"Hatjiharissi","year":"2007","journal-title":"Blood."},{"issue":"5","key":"2022033115292008700_B24","doi-asserted-by":"crossref","first-page":"105","DOI":"10.21037\/atm.2019.01.42","article-title":"NK-mediated antibody-dependent cell-mediated cytotoxicity in solid tumors: biological evidence and clinical perspectives","volume":"7","author":"Lo Nigro","year":"2019","journal-title":"Ann Transl Med."},{"issue":"1","key":"2022033115292008700_B25","doi-asserted-by":"crossref","first-page":"34382","DOI":"10.1038\/srep34382","article-title":"Intravital imaging reveals improved Kupffer cell-mediated phagocytosis as a mode of action of glycoengineered anti-CD20 antibodies","volume":"6","author":"Grandjean","year":"2016","journal-title":"Sci Rep."},{"issue":"2","key":"2022033115292008700_B26","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1172\/JCI66776","article-title":"Macrophages eliminate circulating tumor cells after monoclonal antibody therapy","volume":"124","author":"G\u00fcl","year":"2014","journal-title":"J Clin Invest."},{"issue":"12","key":"2022033115292008700_B27","doi-asserted-by":"crossref","first-page":"5098","DOI":"10.1172\/JCI70972","article-title":"The mechanism of anti-CD20-mediated B cell depletion revealed by intravital imaging","volume":"123","author":"Montalvao","year":"2013","journal-title":"J Clin Invest."},{"issue":"10","key":"2022033115292008700_B28","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1158\/2326-6066.CIR-18-0319","article-title":"Cellular cytotoxicity of next-generation CD20 monoclonal antibodies","volume":"6","author":"VanDerMeid","year":"2018","journal-title":"Cancer Immunol Res."},{"issue":"18","key":"2022033115292008700_B29","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1182\/blood.2020005571","article-title":"Macrophage hypophagia as a mechanism of innate immune exhaustion in mAb-induced cell clearance","volume":"136","author":"Pinney","year":"2020","journal-title":"Blood."},{"issue":"1","key":"2022033115292008700_B30","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1746-1596-6-33","article-title":"The predictive significance of CD20 expression in B-cell lymphomas","volume":"6","author":"Prevodnik","year":"2011","journal-title":"Diagn Pathol."},{"issue":"4","key":"2022033115292008700_B31","first-page":"1101","article-title":"Predictive significance of the cut-off value of CD20 expression in patients with B-cell lymphoma","volume":"24","author":"Horvat","year":"2010","journal-title":"Oncol Rep."},{"issue":"2","key":"2022033115292008700_B32","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1158\/2326-6066.CIR-20-0491","article-title":"Kindlin3-dependent CD11b\/CD18-integrin activation is required for potentiation of neutrophil cytotoxicity by CD47-SIRP\u03b1 checkpoint disruption","volume":"9","author":"Bouti","year":"2021","journal-title":"Cancer Immunol Res."},{"issue":"2","key":"2022033115292008700_B33","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1002\/eji.201747215","article-title":"Genetic variation of human neutrophil Fc\u03b3 receptors and SIRP\u03b1 in antibody-dependent cellular cytotoxicity towards cancer cells","volume":"48","author":"Treffers","year":"2018","journal-title":"Eur J Immunol."},{"issue":"1","key":"2022033115292008700_B34","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1172\/JCI110980","article-title":"Recombinant immune interferon increases immunoglobulin G Fc receptors on cultured human mononuclear phagocytes","volume":"72","author":"Guyre","year":"1983","journal-title":"J Clin Invest."},{"issue":"6","key":"2022033115292008700_B35","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.1172\/JCI114921","article-title":"Monocytes and polymorphonuclear neutrophils of patients with streptococcal pharyngitis express increased numbers of type I IgG Fc receptors","volume":"86","author":"Guyre","year":"1990","journal-title":"J Clin Invest."},{"issue":"7","key":"2022033115292008700_B36","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1021\/acsmedchemlett.5b00118","article-title":"Exploring the existing drug space for novel pTyr mimetic and SHP2 inhibitors","volume":"6","author":"He","year":"2015","journal-title":"ACS Med Chem Lett."},{"issue":"10","key":"2022033115292008700_B37","doi-asserted-by":"crossref","first-page":"7435","DOI":"10.4049\/jimmunol.177.10.7435","article-title":"Thrice-weekly low-dose rituximab decreases CD20 loss via shaving and promotes enhanced targeting in chronic lymphocytic leukemia","volume":"177","author":"Williams","year":"2006","journal-title":"J Immunol."},{"issue":"4","key":"2022033115292008700_B38","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/sj.leu.2402424","article-title":"Analysis of CD20-dependent cellular cytotoxicity by G-CSF-stimulated neutrophils","volume":"16","author":"van der Kolk","year":"2002","journal-title":"Leukemia."},{"issue":"19","key":"2022033115292008700_B39","doi-asserted-by":"crossref","first-page":"4097","DOI":"10.1158\/0008-5472.CAN-15-0781","article-title":"Anti-CD20 therapy acts via Fc\u03b3RIIIA to diminish responsiveness of human natural killer cells","volume":"75","author":"Capuano","year":"2015","journal-title":"Cancer Res."},{"issue":"17","key":"2022033115292008700_B40","doi-asserted-by":"crossref","first-page":"6291","DOI":"10.1128\/MCB.23.17.6291-6299.2003","article-title":"Vav1 dephosphorylation by the tyrosine phosphatase SHP-1 as a mechanism for inhibition of cellular cytotoxicity","volume":"23","author":"Stebbins","year":"2003","journal-title":"Mol Cell Biol."},{"key":"2022033115292008700_B41","doi-asserted-by":"crossref","first-page":"619925","DOI":"10.3389\/fimmu.2020.619925","article-title":"\u03b22 integrin signaling cascade in neutrophils: More than a single function","volume":"11","author":"Bouti","year":"2021","journal-title":"Front Immunol."},{"issue":"9","key":"2022033115292008700_B42","doi-asserted-by":"crossref","first-page":"6388","DOI":"10.4049\/jimmunol.177.9.6388","article-title":"Vav proteins in neutrophils are required for FcgammaR-mediated signaling to Rac GTPases and nicotinamide adenine dinucleotide phosphate oxidase component p40(phox)","volume":"177","author":"Utomo","year":"2006","journal-title":"J Immunol."},{"issue":"5","key":"2022033115292008700_B43","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/S1074-7613(03)00305-4","article-title":"SLP-76 regulates Fcgamma receptor and integrin signaling in neutrophils","volume":"19","author":"Newbrough","year":"2003","journal-title":"Immunity."},{"issue":"5","key":"2022033115292008700_B44","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1093\/infdis\/157.5.973","article-title":"Immunochemotherapy for intracellular Leishmania donovani infection: gamma interferon plus pentavalent antimony","volume":"157","author":"Murray","year":"1988","journal-title":"J Infect Dis."},{"issue":"6","key":"2022033115292008700_B45","doi-asserted-by":"crossref","DOI":"10.1111\/pim.12431","article-title":"Expression profiling of Sudanese visceral leishmaniasis patients pre- and post-treatment with sodium stibogluconate","volume":"39","author":"Salih","year":"2017","journal-title":"Parasite Immunol."},{"issue":"12","key":"2022033115292008700_B46","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.18632\/oncotarget.563","article-title":"Phosphatase inhibitor, sodium stibogluconate, in combination with interferon (IFN) alpha 2b: phase I trials to identify pharmacodynamic and clinical effects","volume":"2","author":"Yi","year":"2011","journal-title":"Oncotarget."},{"key":"2022033115292008700_B47","doi-asserted-by":"crossref","first-page":"81","DOI":"10.7150\/jca.2.81","article-title":"Phase I dose escalation study of sodium stibogluconate (SSG), a protein tyrosine phosphatase inhibitor, combined with interferon alpha for patients with solid tumors","volume":"2","author":"Naing","year":"2011","journal-title":"J Cancer."},{"issue":"18","key":"2022033115292008700_B48","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1056\/NEJMoa1807315","article-title":"CD47 blockade by Hu5F9-G4 and rituximab in non-Hodgkin\u2019s lymphoma","volume":"379","author":"Advani","year":"2018","journal-title":"N Engl J Med."}],"container-title":["Blood Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/bloodadvances\/article-pdf\/6\/7\/2156\/1884765\/advancesadv2021005367.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/bloodadvances\/article-pdf\/6\/7\/2156\/1884765\/advancesadv2021005367.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T08:36:15Z","timestamp":1674203775000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/bloodadvances\/article\/6\/7\/2156\/483242\/Sodium-stibogluconate-and-CD47-SIRP-blockade"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,31]]},"references-count":48,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,4,12]]}},"URL":"https:\/\/doi.org\/10.1182\/bloodadvances.2021005367","relation":{},"ISSN":["2473-9529","2473-9537"],"issn-type":[{"value":"2473-9529","type":"print"},{"value":"2473-9537","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,31]]}}}