{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:48:02Z","timestamp":1791571682337,"version":"4.3.4"},"reference-count":49,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T00:00:00Z","timestamp":1634515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regional Agreement on Medical Training and Clinical Research (ALF)","award":["13733"],"award-info":[{"award-number":["13733"]}]},{"name":"Regional Research and Development funding (FoU)","award":["13793"],"award-info":[{"award-number":["13793"]}]},{"name":"Regional Research and Development funding (FoU)","award":["HALLAND-934928"],"award-info":[{"award-number":["HALLAND-934928"]}]},{"name":"Regional Research and Development funding (FoU)","award":["HALLAND-938256"],"award-info":[{"award-number":["HALLAND-938256"]}]},{"name":"Regional Research and Development funding (FoU)","award":["HALLAND-938539"],"award-info":[{"award-number":["HALLAND-938539"]}]},{"name":"Regional Research and Development funding (FoU)","award":["HALLAND-960551"],"award-info":[{"award-number":["HALLAND-960551"]}]},{"name":"Regional Research and Development funding (FoU)","award":["SK\u00c5NE-2020\/0169"],"award-info":[{"award-number":["SK\u00c5NE-2020\/0169"]}]},{"DOI":"10.13039\/501100002794","name":"Swedish Cancer Society","doi-asserted-by":"publisher","award":["CAN 2017\/997"],"award-info":[{"award-number":["CAN 2017\/997"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>PD-L1 expression assessed by immunohistochemical staining is used for the selection of immunotherapy in non-small cell lung cancer (NSCLC). Appropriate validation of PD-L1 expression in cytology specimens is important as cytology is often the only diagnostic material in NSCLC. In a previous study comprising two different cohorts of paired biopsies and cytological specimens, we found a fairly good cyto-histological correlation of PD-L1 expression in one, whereas only a moderate correlation was found in the other cohort. Therefore, that cohort with additional new cases was now further investigated for the impact of preanalytical factors on PD-L1 concordance in paired biopsies and cytological specimens. A total of 100 formalin-fixed paraffin-embedded cell blocks from 19 pleural effusions (PE), 17 bronchial brushes (BB), and 64 bronchoalveolar lavage (BAL) and concurrent matched biopsies from 80 bronchial biopsies and 20 transthoracic core biopsies from NSCLC patients were stained using the PD-L1 28-8 assay. Using the cutoffs \u22651%, \u22655%, \u226510%, and \u226550% positive tumour cells, the overall agreement between histology and cytology was 77\u201385% (\u03ba 0.51\u20130.70) depending on the applied cutoff value. The concordance was better for BALs (\u03ba 0.53\u20130.81) and BBs (\u03ba 0.55\u20130.85) than for PEs (\u03ba \u22120.16\u20130.48), while no difference was seen for different types of biopsies or histological tumour type. A high number of tumour cells (&gt;500) in biopsies was associated with better concordance at the \u226550% cutoff. In conclusion, the study results suggest that PEs may be less suitable for evaluation of PD-L1 due to limited cyto-histological concordance, while a high amount of tumour cells in biopsies may be favourable when regarding cyto-histological PD-L1 concordance.<\/jats:p>","DOI":"10.3390\/diagnostics11101927","type":"journal-article","created":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T22:52:47Z","timestamp":1634683967000},"page":"1927","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Factors Influencing Concordance of PD-L1 Expression between Biopsies and Cytological Specimens in Non-Small Cell Lung Cancer"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0271-3659","authenticated-orcid":false,"given":"Mohammed S. I.","family":"Mansour","sequence":"first","affiliation":[{"name":"Department of Pathology and Cytology, Halland Hospital Halmstad, SE-301 85 Halmstad, Sweden"},{"name":"Division of Pathology, Department of Clinical Sciences Lund, Lund University, SE-221 00 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Hejny","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cytology, Halland Hospital Halmstad, SE-301 85 Halmstad, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicia","family":"Johansson","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cytology, Halland Hospital Halmstad, SE-301 85 Halmstad, Sweden"},{"name":"Institute of Biomedicine, Sahlgrenska Academy, Gothenburg University, SE-405 30 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joudy","family":"Mufti","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cytology, Halland Hospital Halmstad, SE-301 85 Halmstad, Sweden"},{"name":"Faculty of Natural Science, Kristianstad University, SE-291 88 Kristianstad, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ante","family":"Vidis","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cytology, Halland Hospital Halmstad, SE-301 85 Halmstad, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Mager","sequence":"additional","affiliation":[{"name":"Division of Respiratory and Internal Medicine, Department of Clinical Medicine, Halland Hospital Halmstad, SE-301 85 Halmstad, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Dejmek","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine in Malm\u00f6, Lund University, SE-205 02 Malm\u00f6, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Seidal","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cytology, Halland Hospital Halmstad, SE-301 85 Halmstad, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7402-138X","authenticated-orcid":false,"given":"Hans","family":"Brunnstr\u00f6m","sequence":"additional","affiliation":[{"name":"Division of Pathology, Department of Clinical Sciences Lund, Lund University, SE-221 00 Lund, Sweden"},{"name":"Department of Genetics and Pathology, Laboratory Medicine Region Sk\u00e5ne, SE-221 85 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1056\/NEJMoa1504627","article-title":"Nivolumab versus Docetaxel in Advanced Squamous-Cell Non\u2013Small-Cell Lung Cancer","volume":"373","author":"Brahmer","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1056\/NEJMoa1507643","article-title":"Nivolumab versus Docetaxel in Advanced Nonsquamous Non\u2013Small-Cell Lung Cancer","volume":"373","author":"Borghaei","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1016\/S0140-6736(15)01281-7","article-title":"Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): A randomised controlled trial","volume":"387","author":"Herbst","year":"2016","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0140-6736(16)32517-X","article-title":"Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): A phase 3, open-label, multicentre randomised controlled trial","volume":"389","author":"Rittmeyer","year":"2017","journal-title":"Lancet"},{"key":"ref_5","unstructured":"(2021, July 05). US Food and Drug Administration: KEYTRUDA (Pembrolizumab), Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/125514Orig1s054lbl.pdf."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/j.jtho.2016.04.014","article-title":"PD-L1 Expression in Lung Cancer","volume":"11","author":"Yu","year":"2016","journal-title":"J. Thorac. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1056\/NEJMoa1709937","article-title":"Durvalumab after Chemoradiotherapy in Stage III Non\u2013Small-Cell Lung Cancer","volume":"377","author":"Antonia","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/s00262-017-1954-6","article-title":"PD-1 and PD-L1 antibodies in cancer: Current status and future directions","volume":"66","author":"Balar","year":"2017","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"504","DOI":"10.6004\/jnccn.2017.0050","article-title":"Non\u2013Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology","volume":"15","author":"Ettinger","year":"2017","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1056\/NEJMoa1809697","article-title":"Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC","volume":"379","author":"Antonia","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1016\/S0140-6736(18)32409-7","article-title":"Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): A randomised, open-label, controlled, phase 3 trial","volume":"393","author":"Mok","year":"2019","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1038\/s41598-020-58674-4","article-title":"Clinical efficacy and safety of anti-PD-1\/PD-L1 inhibitors for the treatment of advanced or metastatic cancer: A systematic review and meta-analysis","volume":"10","author":"Sun","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"897292","DOI":"10.4061\/2011\/897292","article-title":"Advances in Fine Needle Aspiration Cytology for the Diagnosis of Pulmonary Carcinoma","volume":"2011","author":"Hasanovic","year":"2011","journal-title":"Pathol. Res. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1097\/JTO.0b013e318206a221","article-title":"International Association for the Study of Lung Cancer\/American Thoracic Society\/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma","volume":"6","author":"Travis","year":"2011","journal-title":"J. Thorac. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1111\/apm.12328","article-title":"The prevalence of EGFR mutations in non-small cell lung cancer in an unselected Caucasian population","volume":"123","author":"Skov","year":"2015","journal-title":"APMIS Acta Pathol. Microbiol. Immunol. Scand."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.jtho.2019.12.107","article-title":"PD-L1 Testing for Lung Cancer in 2019: Perspective From the IASLC Pathology Committee","volume":"15","author":"Lantuejoul","year":"2020","journal-title":"J. Thorac. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1111\/cyt.12982","article-title":"PD-L1 and beyond: Immuno-oncology in cytopathology","volume":"32","author":"Iaccarino","year":"2021","journal-title":"Cytopathology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"668612","DOI":"10.3389\/fmed.2021.668612","article-title":"PD-L1 in Cytological Samples: A Review and a Practical Approach","volume":"8","author":"Tejerina","year":"2021","journal-title":"Front. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.lungcan.2020.01.010","article-title":"Cytology for PD-L1 testing: A systematic review","volume":"141","author":"Gosney","year":"2020","journal-title":"Lung Cancer"},{"key":"ref_20","first-page":"1","article-title":"PD-L1 Testing in Cytological Non-Small Cell Lung Cancer Specimens: A Comparison with Biopsies and Review of the Literature","volume":"2021","author":"Mansour","year":"2021","journal-title":"Acta Cytol."},{"key":"ref_21","unstructured":"Agilent (2021, July 05). PD-L1 IHC 28-8 pharmDx Interpretation Manual. Available online: https:\/\/www.agilent.com\/cs\/library\/usermanuals\/public\/29111_pd-l1-ihc-28-8-interpretation-manual.pdf."},{"key":"ref_22","unstructured":"Altman, D.G. (1991). Practical Statistics for Medical Research, Chapman and Hall\/CRC. [1st ed.]."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1002\/cncy.21578","article-title":"Cytopathology meets basic science: Cytopathology Help Desk","volume":"123","author":"Vigliar","year":"2015","journal-title":"Cancer Cytopathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1159\/000496030","article-title":"Role of Immunocytochemistry in the Cytological Diagnosis of Pulmonary Tumors","volume":"64","author":"Metovic","year":"2020","journal-title":"Acta Cytol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"384","DOI":"10.4187\/respcare.01274","article-title":"Diagnostic Accuracy of Endobronchial Ultrasound Guided Transbronchial Needle Aspiration in Mediastinal Lymphadenopathy: A Systematic Review and Meta-analysis","volume":"57","author":"Chandra","year":"2012","journal-title":"Respir. Care"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1016\/j.ejca.2013.02.008","article-title":"Combined endobronchial and endoscopic ultrasound-guided fine needle aspiration for mediastinal lymph node staging of lung cancer: A meta-analysis","volume":"49","author":"Zhang","year":"2013","journal-title":"Eur. J. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1097\/MCP.0000000000000264","article-title":"Malignant pleural effusions because of lung cancer","volume":"22","author":"Porcel","year":"2016","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1159\/000489769","article-title":"Cell Block in Cytological Diagnostics: Review of Preparatory Techniques","volume":"62","author":"Krogerus","year":"2018","journal-title":"Acta Cytol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1159\/000498889","article-title":"The Role of Ancillary Techniques in Pulmonary Cytopathology","volume":"64","author":"Zhou","year":"2020","journal-title":"Acta Cytol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1159\/000497187","article-title":"Overview of Molecular Testing of Cytology Specimens","volume":"64","author":"Huang","year":"2020","journal-title":"Acta Cytol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.jasc.2018.02.003","article-title":"PD-L1 testing using the clone 22C3 pharmDx kit for selection of patients with non\u2013small cell lung cancer to receive immune checkpoint inhibitor therapy: Are cytology cell blocks a viable option?","volume":"7","author":"Torous","year":"2018","journal-title":"J. Am. Soc. Cytopathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1111\/resp.13614","article-title":"PD-L1 detection in histology specimens and matched pleural fluid cell blocks of patients with NSCLC","volume":"24","author":"Grosu","year":"2019","journal-title":"Respirology"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zou, Y., Xu, L., Tang, Q., You, Q., Wang, X., Ding, W., Zhao, J., and Ren, G. (2020). Cytology cell blocks from malignant pleural effusion are good candidates for PD-L1 detection in advanced NSCLC compared with matched histology samples. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-06851-z"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.lungcan.2015.01.016","article-title":"Clinicopathological analysis of PD-L1 and PD-L2 expression in pulmonary squamous cell carcinoma: Comparison with tumor-infiltrating T cells and the status of oncogenic drivers","volume":"88","author":"Kim","year":"2015","journal-title":"Lung Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1093\/annonc\/mdw289","article-title":"Temporal and spatial discordance of programmed cell death-ligand 1 expression and lymphocyte tumor infiltration between paired primary lesions and brain metastases in lung cancer","volume":"27","author":"Mansfield","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_36","first-page":"4223","article-title":"Discrepancy in Programmed Cell Death-Ligand 1 Between Primary and Metastatic Non-small Cell Lung Cancer","volume":"37","author":"Takamori","year":"2017","journal-title":"Anticancer. Res. Int. J. Cancer Res. Treat."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"87234","DOI":"10.18632\/oncotarget.20254","article-title":"Concordance of programmed death-ligand 1 expression between primary and metastatic non-small cell lung cancer by immunohistochemistry and RNA in situ hybridization","volume":"8","author":"Kim","year":"2017","journal-title":"Oncotarget"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.lungcan.2019.04.009","article-title":"The metastatic site does not influence PD-L1 expression in advanced non-small cell lung carcinoma","volume":"132","author":"Wang","year":"2019","journal-title":"Lung Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1016\/j.jtho.2020.04.026","article-title":"Programmed Death-Ligand 1 Heterogeneity and Its Impact on Benefit From Immune Checkpoint Inhibitors in NSCLC","volume":"15","author":"Hong","year":"2020","journal-title":"J. Thorac. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s12253-018-0469-6","article-title":"The Clinicopathological and Molecular Associations of PD-L1 Expression in Non-small Cell Lung Cancer: Analysis of a Series of 10,005 Cases Tested with the 22C3 Assay","volume":"26","author":"Evans","year":"2020","journal-title":"Pathol. Oncol. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1016\/j.jtho.2018.05.013","article-title":"PD-L1 Immunohistochemistry Comparability Study in Real-Life Clinical Samples: Results of Blueprint Phase 2 Project","volume":"13","author":"Tsao","year":"2018","journal-title":"J. Thorac. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/cncy.21973","article-title":"Cytologic-histologic correlation of programmed death-ligand 1 immunohistochemistry in lung carcinomas: PD-L1 Staining in Cytology Specimens","volume":"126","author":"Kravets","year":"2018","journal-title":"Cancer Cytopathol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.lungcan.2020.06.002","article-title":"Comprehensive assessment of PD-L1 immunohistochemistry on paired tissue and cytology specimens from non-small cell lung cancer","volume":"146","author":"Orain","year":"2020","journal-title":"Lung Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1002\/dc.24651","article-title":"Interobserver agreement in programmed cell death-ligand 1 immunohistochemistry scoring in nonsmall cell lung carcinoma cytologic specimens","volume":"49","author":"Sinclair","year":"2021","journal-title":"Diagn. Cytopathol."},{"key":"ref_45","first-page":"211","article-title":"Prognostic significance of programmed cell death ligand 1 (pd-l1), cd8 tumor-infiltrating lymphocytes and p53 in non-small cell lung cancer: An immunohistochemical study","volume":"1","author":"Rashed","year":"2017","journal-title":"Turk. J. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.critrevonc.2016.02.001","article-title":"PD-L1 expression in cancer patients receiving anti PD-1\/PD-L1 antibodies: A systematic review and meta-analysis","volume":"100","author":"Gandini","year":"2016","journal-title":"Crit. Rev. Oncol.-Hematol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"10255","DOI":"10.1038\/s41598-017-10925-7","article-title":"PD-L1 expression in lung cancer and its correlation with driver mutations: A meta-analysis","volume":"7","author":"Zhang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"11206","DOI":"10.1038\/s41598-018-29156-5","article-title":"PD-L1 expression in pleural effusions of pulmonary adenocarcinoma and survival prediction: A controlled study by pleural biopsy","volume":"8","author":"Xu","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Velcheti, V., Patwardhan, P.D., Liu, F.X., Chen, X., Cao, X., and Burke, T. (2018). Real-world PD-L1 testing and distribution of PD-L1 tumor expression by immunohistochemistry assay type among patients with metastatic non-small cell lung cancer in the United States. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0206370"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/10\/1927\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:17:27Z","timestamp":1760167047000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/10\/1927"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,18]]},"references-count":49,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["diagnostics11101927"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics11101927","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,18]]}}}