{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:28:37Z","timestamp":1772252917076,"version":"3.50.1"},"reference-count":64,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T00:00:00Z","timestamp":1634256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>Background: The outflow tract of crocodilians resembles that of birds and mammals as ventricular septation is complete. The arterial anatomy, however, presents with a pulmonary trunk originating from the right ventricular cavum, and two aortas originating from either the right or left ventricular cavity. Mixing of blood in crocodilians cannot occur at the ventricular level as in other reptiles but instead takes place at the aortic root level by a shunt, the foramen of Panizza, the opening of which is guarded by two facing semilunar leaflets of both bicuspid aortic valves. Methods: Developmental stages of Alligator mississipiensis, Crocodilus niloticus and Caiman latirostris were studied histologically. Results and Conclusions: The outflow tract septation complex can be divided into two components. The aorto-pulmonary septum divides the pulmonary trunk from both aortas, whereas the interaortic septum divides the systemic from the visceral aorta. Neural crest cells are most likely involved in the formation of both components. Remodeling of the endocardial cushions and both septa results in the formation of bicuspid valves in all three arterial trunks. The foramen of Panizza originates intracardially as a channel in the septal endocardial cushion.<\/jats:p>","DOI":"10.3390\/jcdd8100132","type":"journal-article","created":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T13:35:47Z","timestamp":1634304947000},"page":"132","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Ventricular Septation and Outflow Tract Development in Crocodilians Result in Two Aortas with Bicuspid Semilunar Valves"],"prefix":"10.3390","volume":"8","author":[{"given":"Robert E.","family":"Poelmann","sequence":"first","affiliation":[{"name":"Sylvius Laboratory, Department of Animal Sciences and Health, Institute of Biology, University of Leiden, Sylvi-usweg 72, 2333BE Leiden, The Netherlands"},{"name":"Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, P.O. Box 9600, 2300RC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana C.","family":"Gittenberger-de Groot","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, P.O. Box 9600, 2300RC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charissa","family":"Goerdajal","sequence":"additional","affiliation":[{"name":"Sylvius Laboratory, Department of Animal Sciences and Health, Institute of Biology, University of Leiden, Sylvi-usweg 72, 2333BE Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nimrat","family":"Grewal","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Leiden University Medical Center, Albinusdreef 2, P.O. Box 9600, 2300RC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Merijn A. G.","family":"De Bakker","sequence":"additional","affiliation":[{"name":"Sylvius Laboratory, Department of Animal Sciences and Health, Institute of Biology, University of Leiden, Sylvi-usweg 72, 2333BE Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael K.","family":"Richardson","sequence":"additional","affiliation":[{"name":"Sylvius Laboratory, Department of Animal Sciences and Health, Institute of Biology, University of Leiden, Sylvi-usweg 72, 2333BE Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1146\/annurev-physiol-012110-142145","article-title":"Heart valve structure and function in development and disease","volume":"73","author":"Hinton","year":"2011","journal-title":"Annu. Rev. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.carpath.2019.03.002","article-title":"The role of hemodynamics in bicuspid aortopathy: A histopathologic study","volume":"41","author":"Grewal","year":"2019","journal-title":"Cardiovasc Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1001\/jama.2011.1286","article-title":"Incidence of aortic complications in patients with bicuspid aortic valves","volume":"306","author":"Michelena","year":"2011","journal-title":"JAMA"},{"key":"ref_4","first-page":"248","article-title":"Embryonic Development of the Bicuspid Aortic Valve","volume":"2","author":"Martin","year":"2015","journal-title":"J. Cardiovasc. Dev. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.ydbio.2011.07.037","article-title":"GATA5 interacts with GATA4 and GATA6 in outflow tract development","volume":"358","author":"Laforest","year":"2011","journal-title":"Dev. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"dev151944","DOI":"10.1242\/dev.151944","article-title":"Krox20 defines a subpopulation of cardiac neural crest cells contributing to arterial valves and bicuspid aortic valve","volume":"145","author":"Odelin","year":"2018","journal-title":"Development"},{"key":"ref_7","first-page":"17","article-title":"Evidence of Aortopathy in Mice with Haploinsufficiency of Notch1 in Nos3-Null Background","volume":"2","author":"Koenig","year":"2015","journal-title":"J. Cardiovasc. Dev. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1002\/dvdy.21097","article-title":"Woodrow Benson. BMP and FGF regulatory pathways in semilunar valve precursor cells","volume":"236","author":"Zhao","year":"2007","journal-title":"Dev. Dyn."},{"key":"ref_9","first-page":"56","article-title":"Increased Hemodynamic Load in Early Embryonic Stages Alters Endocardial to Mesenchymal Transition","volume":"8","author":"Midgett","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"dmm034637","DOI":"10.1242\/dmm.034637","article-title":"Bicuspid aortic valve formation: Nos3 mutation leads to abnormal lineage patterning of neural crest cells and the second heart field","volume":"11","author":"Peterson","year":"2018","journal-title":"Dis. Model Mech."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.pcad.2020.06.008","article-title":"Embryonic development of bicuspid aortic valves","volume":"63","year":"2020","journal-title":"Prog. Cardiovasc. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Poelmann, R.E., and Gittenberger-de Groot, A.C. (2018). Hemodynamics in Cardiac Development. J. Cardiovasc. Dev. Dis., 5.","DOI":"10.20944\/preprints201809.0313.v1"},{"key":"ref_13","unstructured":"Oscar, H. (1906). Die Entwicklung des Blutgef\u00e4sssystems. Handbuch der Vergleichenden and Experimentellen Entwicklungslehre der Wirbeltiere, Fischer Jena."},{"key":"ref_14","first-page":"298","article-title":"Note on the Reptilian Heart","volume":"53","author":"Goodrich","year":"1919","journal-title":"J. Anat."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1007\/s00415-013-7028-6","article-title":"Bartolomeo Panizza (1785\u20131867)","volume":"261","author":"Sandrone","year":"2014","journal-title":"J. Neurol."},{"key":"ref_16","first-page":"67","article-title":"Note sur le systeme circulatoire des Crocodiliens","volume":"21","author":"Poelman","year":"1854","journal-title":"Bull. Acad. Belg."},{"key":"ref_17","first-page":"R875","article-title":"Flow dynamics of the crocodilian heart","volume":"256","author":"Axelsson","year":"1989","journal-title":"Am. J. Physiol."},{"key":"ref_18","first-page":"R1133","article-title":"Central vascular flow patterns in the alligator Alligator mississipiensis","volume":"269","author":"Malvin","year":"1995","journal-title":"Am. J. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1111\/brv.12572","article-title":"Cardiovascular shunting in vertebrates: A practical integration of competing hypotheses","volume":"95","author":"Burggren","year":"2020","journal-title":"Biol. Rev. Camb. Philos. Soc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13227-017-0072-z","article-title":"Outflow tract sep-tation and the aortic arch system in reptiles: Lessons for understanding the mammalian heart","volume":"8","author":"Poelmann","year":"2017","journal-title":"Evodevo"},{"key":"ref_21","first-page":"69","article-title":"Reproductive biology and embryology of the crocodilians","volume":"Volume 14","author":"Gans","year":"1985","journal-title":"Biology of the Reptilia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1111\/j.1748-1716.1991.tb09187.x","article-title":"Gut blood flow in the estuarine crocodile, Crocodylus porosus","volume":"142","author":"Axelsson","year":"1991","journal-title":"Acta Physiol. Scand."},{"key":"ref_23","first-page":"6","article-title":"Description de quelques reptiles nouveaux a Madagascar en 1870","volume":"15","author":"Grandidier","year":"1872","journal-title":"Ann. Des Sci. Nat. Cinquieme Ser. Zologie Et Paleontol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4199","DOI":"10.1111\/j.1365-294X.2011.05245.x","article-title":"An ancient icon reveals new mysteries: Mummy DNA resurrects a cryptic species within the Nile crocodile","volume":"20","author":"Hekkala","year":"2011","journal-title":"Mol. Ecol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"a037226","DOI":"10.1101\/cshperspect.a037226","article-title":"Reptiles as a Model System to Study Heart Development","volume":"12","author":"Jensen","year":"2020","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1006\/dbio.1998.8860","article-title":"Cardiac neural crest cells provide new insight into septation of the cardiac outflow tract: Aortic sac to ventricular septal closure","volume":"196","author":"Waldo","year":"1998","journal-title":"Dev. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/0167-5273(89)90270-2","article-title":"The outflow tract of the heart--embryologic and morphologic correlations","volume":"22","author":"Bartelings","year":"1989","journal-title":"Int. J. Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1126\/science.6844926","article-title":"Neural crest cells contribute to normal aorticopulmonary septation","volume":"220","author":"Kirby","year":"1983","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6771","DOI":"10.1038\/s41598-017-06964-9","article-title":"Regulation of Sema3c and the Interaction between Cardiac Neural Crest and Second Heart Field during Outflow Tract Development","volume":"7","author":"Kodo","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.celrep.2017.01.002","article-title":"Temporally Distinct Six2-Positive Second Heart Field Progenitors Regulate Mammalian Heart Development and Disease","volume":"18","author":"Zhou","year":"2017","journal-title":"Cell Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1002\/dvdy.24641","article-title":"Intercalated cushion cells within the cardiac outflow tract are derived from the myocardial troponin T type 2 (Tnnt2) Cre lineage","volume":"247","author":"Mifflin","year":"2018","journal-title":"Dev. Dyn."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Henderson, D.J., Eley, L., and Chaudhry, B. (2020). New Concepts in the Development and Malformation of the Arterial Valves. Cardiovasc. Dev. Dis., 7.","DOI":"10.3390\/jcdd7040038"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/(SICI)1097-0177(199807)212:3<373::AID-AJA5>3.0.CO;2-E","article-title":"Neural crest cells in outflow tract septation of the embry-onic chicken heart: Differentiation and apoptosis","volume":"212","author":"Poelmann","year":"1998","journal-title":"Dev. Dyn."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Stefanovic, S., Etchevers, H.C., and Zaffran, S. (2021). Outflow Tract Formation-Embryonic Origins of Conotruncal Congenital Heart Disease. J. Cardiovasc. Dev. Dis., 8.","DOI":"10.3390\/jcdd8040042"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"609","DOI":"10.4161\/cam.4.4.13489","article-title":"Factors controlling cardiac neural crest cell migration","volume":"4","author":"Kirby","year":"2010","journal-title":"Cell Adh. Migr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1161\/01.RES.82.2.221","article-title":"Neural crest cell contribu-tion to the developing circulatory system: Implications for vascular morphology?","volume":"82","author":"Bergwerff","year":"1998","journal-title":"Circ. Res."},{"key":"ref_37","first-page":"413","article-title":"Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development","volume":"9","author":"Baardman","year":"2016","journal-title":"Dis. Model Mech."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/BF00321897","article-title":"Distribution of the neural crest cells in the heart of birds: A three dimen-sional analysis","volume":"180","author":"Sumida","year":"1989","journal-title":"Anat. Embryol. (Berl.)"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1242\/dev.124.2.505","article-title":"Pax3 is required for cardiac neural crest migration in the mouse: Evidence from the splotch (Sp2H) mutant","volume":"124","author":"Conway","year":"1997","journal-title":"Development"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1161\/ATVBAHA.117.309599","article-title":"Smooth Muscle Cells Derived From Second Heart Field and Cardiac Neural Crest Reside in Spatially Distinct Domains in the Media of the Ascending Aor-ta-Brief Report","volume":"37","author":"Sawada","year":"2017","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Gittenberger-de Groot, A.C., Peterson, J.C., Wisse, L.J., Roest, A.A.W., Poelmann, R.E., B\u00f6kenkamp, R., Elzenga, N.J., Hazekamp, M., Bartelings, M.M., and Jongbloed, M.R.M. (2020). Pulmonary ductal coarctation and left pulmonary artery interruption; pathology and role of neural crest and second heart field during development. PLoS ONE, 15.","DOI":"10.1101\/2020.01.17.910224"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ydbio.2007.09.023","article-title":"Myocardium at the base of the aorta and pulmonary trunk is prefigured in the outflow tract of the heart and in subdomains of the second heart field","volume":"313","author":"Bajolle","year":"2008","journal-title":"Dev. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1002\/ar.a.10099","article-title":"Spatiotemporally separated cardiac neural crest subpopulations that target the outflow tract septum and pharyngeal arch arteries","volume":"275","author":"Boot","year":"2003","journal-title":"Anat. Rec. A Discov. Mol. Cell Evol. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/j.0021-8782.2004.00326.x","article-title":"Formation of cartilaginous foci in the central fibrous body of the heart in Syrian hamsters (Mesocricetus auratus)","volume":"205","author":"Guerrero","year":"2004","journal-title":"J. Anat."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1046\/j.1469-7580.2000.19630485.x","article-title":"Bones in the heart skeleton of the otter (Lutra lutra)","volume":"196","author":"Egerbacher","year":"2000","journal-title":"J. Anat."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.22192\/ijarbs.2017.04.05.001","article-title":"The cardiac skeleton of the Egyptian Water buffalo (Bubalus bubalis)","volume":"4","author":"Daghash","year":"2017","journal-title":"Int. J. Adv. Res. Biol. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/s12565-013-0199-5","article-title":"Inner ventricular structures and valves of the heart in white rhinoceros (Ceratotherium simum)","volume":"89","author":"Erdogan","year":"2014","journal-title":"Anat. Sci. Int."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/ar.1091790204","article-title":"The sheep heart: Coronary and conduction system anatomy with special reference to the presence of an os cordis","volume":"179","author":"Frink","year":"1974","journal-title":"Anat. Rec."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"9417","DOI":"10.1038\/s41598-020-66345-7","article-title":"Discovery of os cordis in the cardiac skeleton of chimpanzees (Pan troglodytes)","volume":"10","author":"Baiker","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1111\/joa.12661","article-title":"Sequential segmental analysis of the crocodilian heart","volume":"231","author":"Cook","year":"2017","journal-title":"J. Anat."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1002\/ar.1091250302","article-title":"Circulation in the reptilian heart (Caiman sclerops)","volume":"125","author":"White","year":"1956","journal-title":"Anat. Rec."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1002\/ar.1092400211","article-title":"Cartilago cordis in serpents","volume":"240","author":"Young","year":"1994","journal-title":"Anat. Rec."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1002\/jmor.10134","article-title":"Formation of cartilage in the heart of the Spanish terrapin, Mauremys leprosa (Reptilia, Chelonia)","volume":"258","author":"Guerrero","year":"2003","journal-title":"J. Morphol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/ahe.12195","article-title":"His-tology and Immunohistochemistry of the Cardiac Ventricular Structure in the Green Turtle (Chelonia mydas)","volume":"45","author":"Braz","year":"2016","journal-title":"Anat. Histol. Embryol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e1900334","DOI":"10.1002\/biot.201900334","article-title":"Mammalian Pericardium-Based Bioprosthetic Materials in Xenotransplantation and Tissue Engineering","volume":"15","author":"Grebenik","year":"2020","journal-title":"Biotechnol. J."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Grewal, N., Gittenberger-de Groot, A.C., Thusen, J.V., Wisse, L.J., Bartelings, M.M., DeRuiter, M.C., Klautz RJ, M., and Poelmann, R.E. (2020). The Development of the Ascending Aortic Wall in Tricuspid and Bicuspid Aortic Valve: A Process from Matu-ration to Degeneration. J. Clin. Med., 9.","DOI":"10.3390\/jcm9040908"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"dmm044990","DOI":"10.1242\/dmm.044990","article-title":"Disturbed nitric oxide signalling gives rise to congenital bicuspid aortic valve and aortopathy","volume":"13","author":"Peterson","year":"2020","journal-title":"Dis. Model Mech."},{"key":"ref_58","first-page":"87","article-title":"Sulla struttura del cuore e sulla circolazione del sangue del Crocodilus lucius","volume":"70","author":"Panizza","year":"1833","journal-title":"Biblioteca Italiana"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1161\/01.RES.77.1.1","article-title":"Molecular regulation of atrioventricular valvuloseptal morphogenesis","volume":"77","author":"Eisenberg","year":"1995","journal-title":"Circ. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S0074-7696(05)43005-3","article-title":"Cell biology of cardiac cushion development","volume":"243","author":"Person","year":"2005","journal-title":"Int. Rev. Cytol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"jeb201079","DOI":"10.1242\/jeb.201079","article-title":"Does the left aorta provide proton-rich blood to the gut when crocodilians digest a meal?","volume":"222","author":"Conner","year":"2019","journal-title":"J. Exp. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/35022652","article-title":"An actively controlled heart valve","volume":"406","author":"Franklin","year":"2000","journal-title":"Nature"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1242\/jeb.205.13.1843","article-title":"Delayed depolarization of the cog-wheel valve and pulmonary-to-systemic shunting in alligators","volume":"205","author":"Syme","year":"2002","journal-title":"J. Exp. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1242\/jeb.199.2.359","article-title":"Dynamic anatomical study of cardiac shunting in croco-diles using high-resolution angioscopy","volume":"199","author":"Axelsson","year":"1996","journal-title":"J. Exp. Biol."}],"container-title":["Journal of Cardiovascular Development and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2308-3425\/8\/10\/132\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:15:11Z","timestamp":1760166911000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2308-3425\/8\/10\/132"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,15]]},"references-count":64,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["jcdd8100132"],"URL":"https:\/\/doi.org\/10.3390\/jcdd8100132","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints202108.0157.v1","asserted-by":"object"}]},"ISSN":["2308-3425"],"issn-type":[{"value":"2308-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,15]]}}}