{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:06:17Z","timestamp":1790816777995,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T00:00:00Z","timestamp":1623974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003385","name":"Georg-August-Universit\u00e4t G\u00f6ttingen","doi-asserted-by":"publisher","award":["1403720"],"award-info":[{"award-number":["1403720"]}],"id":[{"id":"10.13039\/501100003385","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["STR 638\/3-1"],"award-info":[{"award-number":["STR 638\/3-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis, most frequently presenting as microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA). Acute tubular injury with the presence of tubulitis was previously reported to be of prognostic value in ANCA glomerulonephritis (GN). In particular, distinct tubular injury lesions were associated with the deterioration of kidney function at AAV disease onset, as well as renal resistance to treatment, and higher risk of progression to composite outcome in patients with AAV. To expand our knowledge regarding distinct tubular lesions in AAV, we aimed to describe acute tubular injury patterns in association with glomerular lesions in ANCA GN by systematic histological scoring. Methods: A total number of 48 renal biopsies with confirmed renal involvement of AAV admitted to the University Medical Center G\u00f6ttingen from 2015 to 2020 were retrospectively examined. By systematic scoring of tubular injury lesions, the association between clinical parameters, laboratory markers, and histopathological findings was explored. Results: We have shown that cellular casts in renal biopsies were frequently observed in the majority of cases with ANCA GN. Furthermore, we showed that tubular epithelial simplification with dilatation correlated with MPA and MPO subtypes, C3c hypocomplementemia, severe renal involvement, and uACR. Red blood cell (RBC) casts were associated with increased levels of C-reactive protein (CRP), leukocyturia, and hematuria. Finally, we found that hyaline casts were associated with an increased fraction of glomeruli with global glomerular sclerosis. Conclusions: Acute tubular injury patterns were correlated with active ANCA GN, whereas tubular injury lesions reflecting the later stages of kidney disease correlated with chronic glomerular lesions. These results suggest an interplay between different renal compartments.<\/jats:p>","DOI":"10.3390\/jcm10122682","type":"journal-article","created":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T04:10:47Z","timestamp":1623989447000},"page":"2682","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Systematic Scoring of Tubular Injury Patterns Reveals Interplay between Distinct Tubular and Glomerular Lesions in ANCA-Associated Glomerulonephritis"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2843-3567","authenticated-orcid":false,"given":"Samy","family":"Hakroush","sequence":"first","affiliation":[{"name":"Institute of Pathology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9sir\u00e9e","family":"Tampe","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Rheumatology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6065-5680","authenticated-orcid":false,"given":"Peter","family":"Korsten","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Rheumatology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Str\u00f6bel","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4357-9863","authenticated-orcid":false,"given":"Bj\u00f6rn","family":"Tampe","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Rheumatology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/art.37715","article-title":"2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides","volume":"65","author":"Jennette","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1053\/j.ajkd.2015.03.025","article-title":"Characteristics and Outcomes of Granulomatosis with Polyangiitis (Wegener) and Microscopic Polyangiitis Requiring Renal Replacement Therapy: Results From the European Renal Association\u2014European Dialysis and Transplant Association Registry","volume":"66","author":"Hruskova","year":"2015","journal-title":"Am. J. Kidney Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1046\/j.1523-1755.1999.00758.x","article-title":"Kidney biopsy as a predictor for renal outcome in ANCA-associated necrotizing glomerulonephritis","volume":"56","author":"Bajema","year":"1999","journal-title":"Kidney Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1046\/j.1523-1755.2002.00605.x","article-title":"Determinants of outcome in ANCA-associated glomerulonephritis: A prospective clinico-histopathological analysis of 96 patients","volume":"62","author":"Hauer","year":"2002","journal-title":"Kidney Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1681\/ASN.2005080870","article-title":"Clinical and Histologic Determinants of Renal Outcome in ANCA-Associated Vasculitis: A Prospective Analysis of 100 Patients with Severe Renal Involvement","volume":"17","author":"Hauer","year":"2006","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1093\/oxfordjournals.ndt.a027086","article-title":"The renal histopathology in systemic vasculitis: An international survey study of inter- and intra-observer agreement","volume":"11","author":"Bajema","year":"1996","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1681\/ASN.2010050477","article-title":"Histopathologic Classification of ANCA-Associated Glomerulonephritis","volume":"21","author":"Berden","year":"2010","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.1093\/ndt\/gfr643","article-title":"Re-evaluation of the histopathologic classification of ANCA-associated glomerulonephritis: A study of 121 patients in a single center","volume":"27","author":"Chang","year":"2012","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ellis, C.L., Manno, R.L., Havill, J.P., Racusen, L.C., and Geetha, D. (2013). Validation of the new classification of pauci-immune glomerulonephritis in a United States cohort and its correlation with renal outcome. BMC Nephrol., 14.","DOI":"10.1186\/1471-2369-14-210"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"300","DOI":"10.3109\/14397595.2013.854068","article-title":"Validation of the 2010 histopathological classification of ANCA-associated glomerulonephritis in a Japanese single-center cohort","volume":"24","author":"Togashi","year":"2014","journal-title":"Mod. Rheumatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1097\/01.mnh.0000444818.95496.a4","article-title":"Histopathological classification of antineutrophil cytoplasmic antibody-associated glomerulonephritis: An update","volume":"23","author":"Rahmattulla","year":"2014","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"905","DOI":"10.2215\/CJN.08290813","article-title":"Predictors of Treatment Outcomes in ANCA-Associated Vasculitis with Severe Kidney Failure","volume":"9","author":"Lee","year":"2014","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.humpath.2016.01.015","article-title":"The predictive value of kidney biopsy in renal vasculitis: A multicenter cohort study","volume":"52","author":"Villacorta","year":"2016","journal-title":"Hum. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1016\/j.humpath.2014.02.017","article-title":"Validation of a histopathologic classification scheme for antineutrophil cytoplasmic antibody\u2013associated glomerulonephritis","volume":"45","author":"Nohr","year":"2014","journal-title":"Hum. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.2215\/CJN.01210214","article-title":"The New Histopathologic Classification of ANCA-Associated GN and Its Association with Renal Outcomes in Childhood","volume":"9","author":"Noone","year":"2014","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1093\/ndt\/gfu084","article-title":"ANCA serotype and histopathological classification for the prediction of renal outcome in ANCA-associated glomerulonephritis","volume":"29","author":"Quintana","year":"2014","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1681\/ASN.2012090912","article-title":"Estimating Renal Survival Using the ANCA-Associated GN Classification","volume":"24","author":"Hilhorst","year":"2013","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Iwakiri, T., Fujimoto, S., Kitagawa, K., Furuichi, K., Yamahana, J., Matsuura, Y., Yamashita, A., Uezono, S., Shimao, Y., and Hisanaga, S. (2013). Validation of a newly proposed histopathological classification in Japanese patients with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis. BMC Nephrol., 14.","DOI":"10.1186\/1471-2369-14-125"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1053\/j.ajkd.2013.08.025","article-title":"Histopathologic and Clinical Predictors of Kidney Outcomes in ANCA-Associated Vasculitis","volume":"63","author":"Ford","year":"2014","journal-title":"Am. J. Kidney Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1007\/s00296-014-3041-z","article-title":"Histopathological classification of pauci-immune glomerulonephritis and its impact on outcome","volume":"34","author":"Naidu","year":"2014","journal-title":"Rheumatol. Int."},{"key":"ref_21","first-page":"56","article-title":"Predictors of renal survival in ANCA-associated vasculitis. Validation of a histopatological classification schema and review of the literature","volume":"33","author":"Moroni","year":"2015","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Andreiana, I., Stancu, S., Avram, A., Taran, L., and Mircescu, G. (2015). ANCA positive crescentic glomerulonephritis outcome in a Central East European cohort: A retrospective study. BMC Nephrol., 16.","DOI":"10.1186\/s12882-015-0091-8"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1093\/ndt\/gfu237","article-title":"Long-term outcome of anti-neutrophil cytoplasm antibody-associated glomerulonephritis: Evaluation of the international histological classification and other prognostic factors","volume":"30","author":"Tanna","year":"2015","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1007\/s10067-016-3195-z","article-title":"Clinical presentation and outcome prediction of clinical, serological, and histopathological classification schemes in ANCA-associated vasculitis with renal involvement","volume":"35","year":"2016","journal-title":"Clin. Rheumatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"i31","DOI":"10.1093\/ndt\/gfv035","article-title":"Twenty-five years of RENHIS: A history of histopathological studies within EUVAS","volume":"30","author":"Ferrario","year":"2015","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.2215\/CJN.04800516","article-title":"Prognostic Value of Histologic Classification of ANCA-Associated Glomerulonephritis","volume":"11","author":"Sriskandarajah","year":"2016","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"304","DOI":"10.3899\/jrheum.160866","article-title":"Histopathological Classification and Renal Outcome in Patients with Antineutrophil Cytoplasmic Antibodies-associated Renal Vasculitis: A Study of 186 Patients and Metaanalysis","volume":"44","author":"Chen","year":"2016","journal-title":"J. Rheumatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1016\/j.kint.2018.07.020","article-title":"Development and validation of a renal risk score in ANCA-associated glomerulonephritis","volume":"94","author":"Brix","year":"2018","journal-title":"Kidney Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1053\/ajkd.2003.50115","article-title":"An index for renal outcome in ANCA-associated glomerulonephritis","volume":"41","author":"Vergunst","year":"2003","journal-title":"Am. J. Kidney Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1136\/annrheumdis-2017-212578","article-title":"Urinary epidermal growth factor predicts renal prognosis in antineutrophil cytoplasmic antibody-associated vasculitis","volume":"77","author":"Wu","year":"2018","journal-title":"Ann. Rheum. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s00795-013-0067-3","article-title":"Renal atrophy after ischemia-reperfusion injury depends on massive tubular apoptosis induced by TNFalpha in the later phase","volume":"47","author":"Adachi","year":"2014","journal-title":"Med. Mol. Morphol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/nrneph.2015.3","article-title":"Mechanisms of maladaptive repair after AKI leading to accelerated kidney ageing and CKD","volume":"11","author":"Ferenbach","year":"2015","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e14000","DOI":"10.14814\/phy2.14000","article-title":"Histological characteristics of Acute Tubular Injury during Delayed Graft Function predict renal function after renal transplantation","volume":"7","author":"Pieters","year":"2019","journal-title":"Physiol. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Hakroush, S., Tampe, D., Korsten, P., Str\u00f6bel, P., Zeisberg, M., and Tampe, B. (2021). Histopathological Findings Predict Renal Recovery in Severe ANCA-Associated Vasculitis Requiring Intensive Care Treatment. Front. Med., 7.","DOI":"10.3389\/fmed.2020.622028"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Hakroush, S., Kluge, I., Str\u00f6bel, P., Korsten, P., Tampe, D., and Tampe, B. (2021). Systematic Histological Scoring Reveals More Prominent Interstitial Inflammation in Myeloperoxidase-ANCA Compared to Proteinase 3-ANCA Glomerulonephritis. J. Clin. Med., 10.","DOI":"10.3390\/jcm10061231"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"27","DOI":"10.55563\/clinexprheumatol\/7eol6d","article-title":"Bowman\u2019s capsule rupture links glomerular damage to tubulointerstitial inflammation in ANCA-associated glomerulonephritis","volume":"39","author":"Hakroush","year":"2021","journal-title":"Clin. Exp. Rheumatol"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Tampe, D., Korsten, P., Str\u00f6bel, P., Hakroush, S., and Tampe, B. (2021). Proteinuria Indicates Decreased Normal Glomeruli in ANCA-Associated Glomerulonephritis Independent of Systemic Disease Activity. J. Clin. Med., 10.","DOI":"10.3390\/jcm10071538"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1136\/ard.2008.101279","article-title":"Modification and validation of the Birmingham Vasculitis Activity Score (version 3)","volume":"68","author":"Mukhtyar","year":"2009","journal-title":"Ann. Rheum. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.1001\/jama.1993.03510240069035","article-title":"A New Simplified Acute Physiology Score (SAPS II) Based on a European\/North American Multicenter Study","volume":"270","author":"Lemeshow","year":"1993","journal-title":"JAMA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/ki.2010.165","article-title":"Normalization of urinary biomarkers to creatinine during changes in glomerular filtration rate","volume":"78","author":"Waikar","year":"2010","journal-title":"Kidney Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1097\/TP.0000000000002366","article-title":"A 2018 Reference Guide to the Banff Classification of Renal Allograft Pathology","volume":"102","author":"Roufosse","year":"2018","journal-title":"Transplantation"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/0014-4800(89)90013-0","article-title":"Tissue injury and repair in the rat kidney after exposure to cisplatin or carboplatin","volume":"51","author":"Nonclercq","year":"1989","journal-title":"Exp. Mol. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1038\/ki.1993.148","article-title":"Morphology of ischemic acute renal failure, normal function, and cyclosporine toxicity in cyclosporine-treated renal allograft recipients","volume":"43","author":"Solez","year":"1993","journal-title":"Kidney Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1097\/00005792-198905000-00005","article-title":"Primary acute renal failure (\u201cacute tubular necrosis\u201d) in the transplanted kidney: Morphology and pathogenesis","volume":"68","author":"Olsen","year":"1989","journal-title":"Medicine"},{"key":"ref_46","first-page":"623","article-title":"Acute renal failure. I. Relative importance of proximal vs. distal tubular injury","volume":"275","author":"Lieberthal","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1681\/ASN.2016090974","article-title":"Unique Transcriptional Programs Identify Subtypes of AKI","volume":"28","author":"Xu","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.autrev.2012.08.006","article-title":"Renal involvement in anti-neutrophil cytoplasmic autoantibody associated vasculitis","volume":"12","author":"Sinico","year":"2013","journal-title":"Autoimmun. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/ki.1979.112","article-title":"Recovery from postischemic acute renal failure in the rat","volume":"16","author":"Finn","year":"1979","journal-title":"Kidney Int."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/ki.1978.85","article-title":"Nephron function of the transplanted rat kidney","volume":"14","author":"Engberg","year":"1978","journal-title":"Kidney Int."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/0002-9343(53)90143-0","article-title":"Correlations of structure and function and mechanisms of recovery in acute tubular necrosis","volume":"15","author":"Oliver","year":"1953","journal-title":"Am. J. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/BF00196151","article-title":"Tubular dilatation in the repair process of ischaemic tubular necrosis","volume":"425","author":"Shimizu","year":"1994","journal-title":"Virchows Arch."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1016\/S0002-9440(10)65239-X","article-title":"A Rat Model of Progressive Chronic Renal Failure Produced by Microembolism","volume":"155","author":"Kimura","year":"1999","journal-title":"Am. J. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/ki.1997.2","article-title":"Understanding the nature of renal disease progression","volume":"51","author":"Remuzzi","year":"1997","journal-title":"Kidney Int."},{"key":"ref_55","first-page":"467","article-title":"Microscopic Polyarteritis: Presentation, Pathology and Prognosis","volume":"56","author":"Winearls","year":"1985","journal-title":"QJM Int. J. Med."},{"key":"ref_56","unstructured":"Beale, L.S. (1869). Kidney Diseases, Urinary Deposits, and Calculous Disorders: Their Nature and Treatment, John Churchill and Sons."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1053\/j.ajkd.2018.07.012","article-title":"Urine Sediment Examination in the Diagnosis and Management of Kidney Disease: Core Curriculum 2019","volume":"73","author":"Cavanaugh","year":"2019","journal-title":"Am. J. Kidney Dis."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/12\/2682\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:18:06Z","timestamp":1760163486000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/12\/2682"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,18]]},"references-count":57,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["jcm10122682"],"URL":"https:\/\/doi.org\/10.3390\/jcm10122682","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,18]]}}}