{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:48:02Z","timestamp":1790228882427,"version":"4.1.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2020,2,28]],"date-time":"2020-02-28T00:00:00Z","timestamp":1582848000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,2,28]],"date-time":"2020-02-28T00:00:00Z","timestamp":1582848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001702","name":"AO Foundation","doi-asserted-by":"publisher","award":["AO-Germany Research fellowship 2016 (Ren\u00e9 D.\u00a0Verboket)"],"award-info":[{"award-number":["AO-Germany Research fellowship 2016 (Ren\u00e9 D.\u00a0Verboket)"]}],"id":[{"id":"10.13039\/501100001702","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Trauma Emerg Surg"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Introduction<\/jats:title>\n                <jats:p>Cell-based therapy by bone marrow mononuclear cells (BMC) in a large-sized bone defect has already shown improved vascularization and new bone formation. First clinical trials are already being conducted. BMC were isolated from bone marrow aspirate and given back to patients in combination with a scaffold within some hours. However, the optimal concentration of BMC has not yet been determined for bone healing. With this study, we want to determine the optimal dosage of the BMC in the bone defect to support bone healing.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Material and methods<\/jats:title>\n                <jats:p>Scaffolds with increasing BMC concentrations were inserted into a 5\u00a0mm femoral defect, cell concentrations of 2\u2009\u00d7\u200910<jats:sup>6<\/jats:sup> BMC\/mL, 1\u2009\u00d7\u200910<jats:sup>7<\/jats:sup> BMC\/mL and 2\u2009\u00d7\u200910<jats:sup>7<\/jats:sup> BMC\/mL were used. Based on the initial cell number used to colonize the scaffolds, the groups are designated 1\u2009\u00d7\u200910<jats:sup>6<\/jats:sup>, 5\u2009\u00d7\u200910<jats:sup>6<\/jats:sup> and 1\u2009\u00d7\u200910<jats:sup>7<\/jats:sup> group. Bone healing was assessed biomechanically, radiologically (\u00b5CT), and histologically after 8 weeks healing time.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Improved bone healing parameters were noted in the 1\u2009\u00d7\u200910<jats:sup>6<\/jats:sup> and 5\u2009\u00d7\u200910<jats:sup>6<\/jats:sup> BMC groups. A significantly higher BMD was observed in the 1\u2009\u00d7\u200910<jats:sup>6<\/jats:sup> BMC group compared to the other groups. Histologically, a significantly increased bone growth in the defect area was observed in group 5\u2009\u00d7\u200910<jats:sup>6<\/jats:sup> BMC. This finding could be supported radiologically.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>It was shown that the effective dose of BMC for bone defect healing ranges from 2\u2009\u00d7\u200910<jats:sup>6<\/jats:sup> BMC\/mL to 1\u2009\u00d7\u200910<jats:sup>7<\/jats:sup> BMC\/mL. This concentration range seems to be the therapeutic window for BMC-supported therapy of large bone defects. However, further studies are necessary to clarify the exact BMC-dose dependent mechanisms of bone defect healing and to determine the therapeutically effective range more precisely.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00068-020-01331-2","type":"journal-article","created":{"date-parts":[[2020,2,28]],"date-time":"2020-02-28T18:03:46Z","timestamp":1582913026000},"page":"265-276","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Determination of the effective dose of bone marrow mononuclear cell therapy for bone healing in vivo"],"prefix":"10.1007","volume":"46","author":[{"given":"Maren","family":"Janko","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"P\u00f6llinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Schaible","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlene","family":"Bellen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Schr\u00f6der","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Heilani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Fremdling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Marzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Nau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Henrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1086-4016","authenticated-orcid":false,"given":"Ren\u00e9 D.","family":"Verboket","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,28]]},"reference":[{"key":"1331_CR1","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.ocl.2009.07.006","volume":"41","author":"JD Conway","year":"2010","unstructured":"Conway JD. Autograft and nonunions: morbidity with intramedullary bone graft versus iliac crest bone graft. Orthop Clin North Am. 2010;41:75\u201384 (table of contents).","journal-title":"Orthop Clin North Am"},{"key":"1331_CR2","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1089\/ten.tec.2008.0385","volume":"15","author":"D Henrich","year":"2009","unstructured":"Henrich D, Seebach C, Kaehling C, Scherzed A, Wilhelm K, Tewksbury R, et al. Simultaneous cultivation of human endothelial-like differentiated precursor cells and human marrow stromal cells on beta-tricalcium phosphate. Tissue Eng Part C Methods. 2009;15:551\u201360.","journal-title":"Tissue Eng Part C Methods"},{"key":"1331_CR3","doi-asserted-by":"publisher","first-page":"1961","DOI":"10.1089\/ten.tea.2009.0715","volume":"16","author":"C Seebach","year":"2010","unstructured":"Seebach C, Henrich D, Kahling C, Wilhelm K, Tami AE, Alini M, et al. Endothelial progenitor cells and mesenchymal stem cells seeded onto beta-TCP granules enhance early vascularization and bone healing in a critical-sized bone defect in rats. Tissue Eng Part A. 2010;16:1961\u201370.","journal-title":"Tissue Eng Part A"},{"key":"1331_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2012\/652034","volume":"2012","author":"Y Wang","year":"2012","unstructured":"Wang Y, Han Z-B, Song Y-P, Han ZC. Safety of mesenchymal stem cells for clinical application. Stem Cells Int. 2012;2012:1\u20134.","journal-title":"Stem Cells Int"},{"key":"1331_CR5","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1016\/j.exphem.2012.05.003","volume":"40","author":"CR Jenkins","year":"2012","unstructured":"Jenkins CR, Shevchuk OO, Giambra V, Lam SH, Carboni JM, Gottardis MM, et al. IGF signaling contributes to malignant transformation of hematopoietic progenitors by the MLL-AF9 oncoprotein. Exp Hematol. 2012;40:715\u20136.","journal-title":"Exp Hematol"},{"key":"1331_CR6","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1111\/j.1538-7836.2008.03214.x","volume":"7","author":"JD Pearson","year":"2009","unstructured":"Pearson JD. Endothelial progenitor cells\u2014hype or hope? J Thromb Haemost. 2009;7:255\u201362.","journal-title":"J Thromb Haemost"},{"key":"1331_CR7","first-page":"729","volume":"9","author":"R Verboket","year":"2018","unstructured":"Verboket R, Leiblein M, Seebach C, Nau C, Janko M, Bellen M, et al. Autologous cell-based therapy for treatment of large bone defects: from bench to bedside. Eur J Trauma Emerg Surg. 2018;9:729\u2013817.","journal-title":"Eur J Trauma Emerg Surg."},{"key":"1331_CR8","first-page":"762407","volume":"2015","author":"D Henrich","year":"2015","unstructured":"Henrich D, Verboket R, Schaible A, Kontradowitz K, Oppermann E, Brune JC, et al. Characterization of bone marrow mononuclear cells on biomaterials for bone tissue engineering in vitro. Biomed Res Int. 2015;2015:762407\u201312.","journal-title":"Biomed Res Int"},{"key":"1331_CR9","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1186\/s12967-016-1066-7","volume":"14","author":"C Seebach","year":"2016","unstructured":"Seebach C, Henrich D, Meier S, Nau C, Bonig H, Marzi I. Safety and feasibility of cell-based therapy of autologous bone marrow-derived mononuclear cells in plate-stabilized proximal humeral fractures in humans. J Transl Med. 2016;14:314.","journal-title":"J Transl Med."},{"key":"1331_CR10","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1161\/CIRCHEARTFAILURE.108.843243","volume":"3","author":"B Assmus","year":"2010","unstructured":"Assmus B, Rolf A, Erbs S, Els\u00e4sser A, Haberbosch W, Hambrecht R, et al. Clinical outcome 2 years after intracoronary administration of bone marrow-derived progenitor cells in acute myocardial infarction. Circ Heart Fail. 2010;3:89\u201396.","journal-title":"Circ Heart Fail"},{"issue":"Suppl 2","key":"1331_CR11","doi-asserted-by":"publisher","first-page":"S62","DOI":"10.1016\/S0020-1383(10)70012-7","volume":"41","author":"D Henrich","year":"2010","unstructured":"Henrich D, Seebach C, Sterlepper E, Tauchmann C, Marzi I, Frank J. RIA reamings and hip aspirate: a comparative evaluation of osteoprogenitor and endothelial progenitor cells. Injury. 2010;41(Suppl 2):S62\u2013S6868.","journal-title":"Injury"},{"key":"1331_CR12","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.3109\/14653249.2011.605118","volume":"13","author":"Z Ku\u00e7i","year":"2011","unstructured":"Ku\u00e7i Z, Ku\u00e7i S, Zircher S, Koller S, Schubert R, Bonig H, et al. Mesenchymal stromal cells derived from CD271+ bone marrow mononuclear cells exert potent allosuppressive properties. Cytotherapy. 2011;13:1193\u2013204.","journal-title":"Cytotherapy"},{"issue":"7","key":"1331_CR13","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1080\/09537104.2018.1530346","volume":"30","author":"R Verboket","year":"2019","unstructured":"Verboket R, Herrera-Vizcaino C, Thorwart K, Booms P, Bellen M, Al-Maawi S, Sader R, Marzi I, Henrich D, Ghanaati S. Influence of concentration and preparation of platelet rich fibrin on human bone marrow mononuclear cells (in vitro). Platelets. 2019;30(7):861\u201370.","journal-title":"Platelets"},{"key":"1331_CR14","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1089\/ten.tea.2014.0410","volume":"21","author":"C Seebach","year":"2015","unstructured":"Seebach C, Henrich D, Schaible A, Relja B, Jugold M, Bonig H, et al. Cell-based therapy by implanted human bone marrow-derived mononuclear cells improved bone healing of large bone defects in rats. Tissue Eng Part A. 2015;21:1565\u201378.","journal-title":"Tissue Eng Part A"},{"key":"1331_CR15","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1089\/ten.tea.2015.0030","volume":"22","author":"C Nau","year":"2016","unstructured":"Nau C, Henrich D, Seebach C, Schr\u00f6der K, Fitzsimmons S-J, Hankel S, et al. Treatment of large bone defects with a vascularized periosteal flap in combination with biodegradable scaffold seeded with bone marrow-derived mononuclear cells: an experimental study in rats. Tissue Eng Part A. 2016;22:133\u201341.","journal-title":"Tissue Eng Part A"},{"key":"1331_CR16","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1161\/01.RES.0000264508.47717.6b","volume":"100","author":"B Assmus","year":"2007","unstructured":"Assmus B, Fischer-Rasokat U, Honold J, Seeger FH, Fichtlscherer S, Tonn T, et al. Transcoronary transplantation of functionally competent BMCs is associated with a decrease in natriuretic peptide serum levels and improved survival of patients with chronic post-infarction heart failure: results of the TOPCARE-CHD Registry. Circ Res. 2007;100:1234\u201341.","journal-title":"Circ Res"},{"key":"1331_CR17","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1089\/tec.2007.0234","volume":"14","author":"I Drosse","year":"2008","unstructured":"Drosse I, Volkmer E, Seitz S, Seitz H, Penzkofer R, Zahn K, et al. Validation of a femoral critical size defect model for orthotopic evaluation of bone healing: a biomechanical, veterinary and trauma surgical perspective. Tissue Eng Part C Methods. 2008;14:79\u201388.","journal-title":"Tissue Eng Part C Methods."},{"key":"1331_CR18","doi-asserted-by":"publisher","DOI":"10.1007\/s00068-019-01296-x","author":"RD Verboket","year":"2020","unstructured":"Verboket RD, Leiblein M, Janko M, Schaible A, Brune JC, et al. From two stages to one: acceleration of the induced membrane (Masquelet) technique using human acellular dermis for the treatment of non-infectious large bone defects. Eur J Trauma Emerg Surg. 2020. https:\/\/doi.org\/10.1007\/s00068-019-01296-x.","journal-title":"Eur J Trauma Emerg Surg."},{"key":"1331_CR19","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.injury.2015.10.079","volume":"47","author":"C Nau","year":"2016","unstructured":"Nau C, Seebach C, Trumm A, Schaible A, Kontradowitz K, Meier S, et al. Alteration of Masquelet\u2019s induced membrane characteristics by different kinds of antibiotic enriched bone cement in a critical size defect model in the rat\u2019s femur. Injury. 2016;47:325\u201334.","journal-title":"Injury"},{"key":"1331_CR20","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1089\/ten.tea.2017.0479","volume":"25","author":"M Janko","year":"2018","unstructured":"Janko M, Dietz K, Rachor J, Sahm J, Schr\u00f6der K, Schaible A, et al. Improvement of bone healing by neutralization of microRNA-335-5p, but not by neutralization of microRNA-92A in bone marrow mononuclear cells transplanted into a large femur defect of the rat. Tissue Eng Part A. 2018;25:55\u201368.","journal-title":"Tissue Eng Part A"},{"key":"1331_CR21","doi-asserted-by":"publisher","first-page":"60","DOI":"10.3109\/10520298609110708","volume":"61","author":"W Garvey","year":"1986","unstructured":"Garvey W, Fathi A, Bigelow F, Carpenter B, Jimenez C. Improved Movat pentachrome stain. Stain Technol. 1986;61:60\u20132.","journal-title":"Stain Technol"},{"key":"1331_CR22","doi-asserted-by":"publisher","first-page":"4550","DOI":"10.1016\/j.biomaterials.2004.11.032","volume":"26","author":"T Hisatome","year":"2005","unstructured":"Hisatome T, Yasunaga Y, Yanada S, Tabata Y, Ikada Y, Ochi M. Neovascularization and bone regeneration by implantation of autologous bone marrow mononuclear cells. Biomaterials. 2005;26:4550\u20136.","journal-title":"Biomaterials"},{"key":"1331_CR23","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/j.jbspin.2009.04.002","volume":"76","author":"Y Sun","year":"2009","unstructured":"Sun Y, Feng Y, Zhang C. The effect of bone marrow mononuclear cells on vascularization and bone regeneration in steroid-induced osteonecrosis of the femoral head. Joint Bone Spine. 2009;76:685\u201390.","journal-title":"Joint Bone Spine"},{"key":"1331_CR24","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1016\/j.jacc.2009.10.059","volume":"55","author":"B Assmus","year":"2010","unstructured":"Assmus B, Tonn T, Seeger FH, Yoon C-H, Leistner D, Klotsche J, et al. Red blood cell contamination of the final cell product impairs the efficacy of autologous bone marrow mononuclear cell therapy. J Am Coll Cardiol. 2010;55:1385\u201394.","journal-title":"J Am Coll Cardiol"},{"key":"1331_CR25","doi-asserted-by":"publisher","first-page":"3009","DOI":"10.1161\/01.CIR.0000043246.74879.CD","volume":"106","author":"B Assmus","year":"2002","unstructured":"Assmus B. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation. 2002;106:3009\u2013177.","journal-title":"Circulation"},{"key":"1331_CR26","doi-asserted-by":"publisher","first-page":"e87642","DOI":"10.1371\/journal.pone.0087642","volume":"9","author":"K Eldesoqi","year":"2014","unstructured":"Eldesoqi K, Henrich D, El-Kady AM, Arbid MS, Abd El-Hady BM, Marzi I, et al. Safety evaluation of a bioglass-polylactic acid composite scaffold seeded with progenitor cells in a rat skull critical-size bone defect. PLoS ONE. 2014;9:e87642.","journal-title":"PLoS ONE"},{"issue":"3","key":"1331_CR27","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1002\/term.2484","volume":"12","author":"M Janko","year":"2018","unstructured":"Janko M, Sahm J, Schaible A, Brune JC, Bellen M, Schr\u00f6der K, et al. Comparison of three different types of scaffolds preseeded with human bone marrow mononuclear cells on the bone healing in a femoral critical size defect model of the athymic rat. J Tissue Eng Regen Med. 2018;12(3):653\u201366.","journal-title":"J Tissue Eng Regen Med"},{"key":"1331_CR28","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/j.tibtech.2013.04.003","volume":"31","author":"E Anitua","year":"2013","unstructured":"Anitua E, Prado R, Orive G. Endogenous morphogens and fibrin bioscaffolds for stem cell therapeutics. Trends Biotechnol. 2013;31:364\u201374.","journal-title":"Trends Biotechnol"},{"key":"1331_CR29","doi-asserted-by":"publisher","first-page":"2392","DOI":"10.1002\/jbm.a.34537","volume":"101A","author":"S Mobini","year":"2013","unstructured":"Mobini S, Hoyer B, Solati-Hashjin M, Lode A, Nosoudi N, Samadikuchaksaraei A, et al. Fabrication and characterization of regenerated silk scaffolds reinforced with natural silk fibers for bone tissue engineering. J Biomed Mater Res A. 2013;101A:2392\u2013404.","journal-title":"J Biomed Mater Res A"},{"key":"1331_CR30","doi-asserted-by":"publisher","first-page":"5474","DOI":"10.1016\/j.biomaterials.2005.02.002","volume":"26","author":"V Karageorgiou","year":"2005","unstructured":"Karageorgiou V, Kaplan D. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials. 2005;26:5474\u201391.","journal-title":"Biomaterials"},{"key":"1331_CR31","first-page":"1","volume":"84-A","author":"P St\u00f6rmann","year":"2018","unstructured":"St\u00f6rmann P, Kupsch J, Kontradowitz K, Leiblein M, Verboket R, Seebach C, et al. Cultivation of EPC and co-cultivation with MSC on \u03b2-TCP granules in vitro is feasible without fibronectin coating but influenced by scaffolds\u2019 design. Eur J Trauma Emerg Surg. 2018;84-A:1\u201312.","journal-title":"Eur J Trauma Emerg Surg."},{"key":"1331_CR32","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1016\/j.injury.2010.02.017","volume":"41","author":"C Seebach","year":"2010","unstructured":"Seebach C, Schultheiss J, Wilhelm K, Frank J, Henrich D. Comparison of six bone-graft substitutes regarding to cell seeding efficiency, metabolism and growth behaviour of human mesenchymal stem cells (MSC) in vitro. Injury. 2010;41:731\u20138.","journal-title":"Injury"},{"key":"1331_CR33","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1186\/s13287-018-1034-7","volume":"9","author":"X Wang","year":"2018","unstructured":"Wang X, Wang C, Gou W, Xu X, Wang Y, Wang A, et al. The optimal time to inject bone mesenchymal stem cells for fracture healing in a murine model. Stem Cell Res Ther BioMed Central. 2018;9:272\u2013310.","journal-title":"Stem Cell Res Ther BioMed Central"},{"key":"1331_CR34","doi-asserted-by":"publisher","first-page":"1961","DOI":"10.1089\/ten.tea.2009.0715","volume":"16","author":"C Seebach","year":"2010","unstructured":"Seebach C, Henrich D, K\u00e4hling C, Wilhelm K, Tami AE, Alini M, et al. Endothelial progenitor cells and mesenchymal stem cells seeded onto \u03b2-TCP granules enhance early vascularization and bone healing in a critical-sized bone defect in rats. Tissue Eng Part A. 2010;16:1961\u201370.","journal-title":"Tissue Eng Part A"},{"key":"1331_CR35","doi-asserted-by":"publisher","first-page":"4476","DOI":"10.1016\/j.actbio.2010.07.006","volume":"6","author":"S Ghanaati","year":"2010","unstructured":"Ghanaati S, Barbeck M, Orth C, Willershausen I, Thimm BW, Hoffmann C, et al. Influence of \u03b2-tricalcium phosphate granule size and morphology on tissue reaction in vivo. Acta Biomater. 2010;6:4476\u201387.","journal-title":"Acta Biomater"}],"container-title":["European Journal of Trauma and Emergency Surgery"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00068-020-01331-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00068-020-01331-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00068-020-01331-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T00:05:34Z","timestamp":1614384334000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00068-020-01331-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,28]]},"references-count":35,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,4]]}},"alternative-id":["1331"],"URL":"https:\/\/doi.org\/10.1007\/s00068-020-01331-2","relation":{},"ISSN":["1863-9933","1863-9941"],"issn-type":[{"value":"1863-9933","type":"print"},{"value":"1863-9941","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,28]]},"assertion":[{"value":"8 February 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 February 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 February 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}