{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T03:10:24Z","timestamp":1788491424358,"version":"build-2803163510"},"reference-count":60,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2017,8,9]],"date-time":"2017-08-09T00:00:00Z","timestamp":1502236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cognitive impairment and behavioral disparities are the distinctive baseline features to investigate in most animal models of neurodegenerative disease. However, neuronal complications are multifactorial and demand a suitable animal model to investigate their underlying basal mechanisms. By contrast, the numerous existing neurodegenerative studies have utilized various animal strains, leading to factual disparity. Choosing an optimal mouse strain for preliminary assessment of neuronal complications is therefore imperative. In this study, we systematically compared the behavioral, cognitive, cholinergic, and inflammatory impairments of outbred ICR and inbred C57BL\/6 mice strains subject to scopolamine-induced amnesia. We then extended this study to the sub-strains C57BL\/6N and C57BL\/6J, where in addition to the above-mentioned parameters, their endogenous antioxidant levels and cAMP response-element binding protein (CREB)\/brain-derived neurotrophic factor (BDNF) protein expression were also evaluated. Compared with the ICR strain, the scopolamine-inflicted C57BL\/6 strains exhibited a substantial reduction of spontaneous alternation and an approximately two-fold increase in inflammatory protein expression, compared to the control group. Among the sub-strains, scopolamine-treated C57BL\/6N strains exhibited declined step-through latency, elevated acetylcholinesterase (AChE) activity and inflammatory protein expression, associated with reduced endogenous antioxidant levels and p-CREB\/BDNF expression, compared to the control and tacrine-treated groups. This indicates that the C57BL\/6N strains exhibit significantly enhanced scopolamine-induced neuronal impairment compared to the other evaluated strains.<\/jats:p>","DOI":"10.3390\/ijms18081735","type":"journal-article","created":{"date-parts":[[2017,8,9]],"date-time":"2017-08-09T10:54:56Z","timestamp":1502276096000},"page":"1735","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Comparative Studies on Behavioral, Cognitive and Biomolecular Profiling of ICR, C57BL\/6 and Its Sub-Strains Suitable for Scopolamine-Induced Amnesic Models"],"prefix":"10.3390","volume":"18","author":[{"given":"Govindarajan","family":"Karthivashan","sequence":"first","affiliation":[{"name":"Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 27478, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-Young","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 27478, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3244-9334","authenticated-orcid":false,"given":"Joon-Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 27478, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duk-Yeon","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 27478, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8584-6854","authenticated-orcid":false,"given":"Palanivel","family":"Ganesan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 27478, Korea"},{"name":"Nanotechnology Research Center, Department of Applied Life Science, College of Biomedical and Health Science, Konkuk University, Chungju 27478, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7041-1524","authenticated-orcid":false,"given":"Dong-Kug","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 27478, Korea"},{"name":"Nanotechnology Research Center, Department of Applied Life Science, College of Biomedical and Health Science, Konkuk University, Chungju 27478, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/nature20411","article-title":"Ageing, neurodegeneration and brain rejuvenation","volume":"539","year":"2016","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S82","DOI":"10.1590\/1516-4446-2013-1157","article-title":"Animal models of neurodegenerative diseases","volume":"35","author":"Ribeiro","year":"2013","journal-title":"Rev. Bras. Psiquiatr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.trci.2016.07.001","article-title":"Alzheimer\u2019s drug-development pipeline: 2016","volume":"2","author":"Cummings","year":"2016","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1126\/science.6338589","article-title":"Alzheimer\u2019s disease: A disorder of cortical cholinergic innervation","volume":"219","author":"Coyle","year":"1983","journal-title":"Science"},{"key":"ref_5","first-page":"12","article-title":"Mitochondrial Dysfunction Contributes to the Pathogenesis of Alzheimer\u2019s Disease","volume":"2015","author":"Jara","year":"2015","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"a006171","DOI":"10.1101\/cshperspect.a006171","article-title":"The Neuropsychological Profile of Alzheimer Disease","volume":"2","author":"Weintraub","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1038\/nm1113-1355","article-title":"Small nanobody drugs win big backing from pharma","volume":"19","author":"Williams","year":"2013","journal-title":"Nat. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/nrd3439","article-title":"Trial watch: Phase II failures: 2008\u20132010","volume":"10","author":"Arrowsmith","year":"2011","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_9","first-page":"5","article-title":"Animal models in translational medicine: Validation and prediction","volume":"2","author":"Denayer","year":"2014","journal-title":"New Horiz. Transl. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3389\/fnagi.2011.00008","article-title":"The Hippocampal Neuroproteome with Aging and Cognitive Decline: Past Progress and Future Directions","volume":"3","author":"VanGuilder","year":"2011","journal-title":"Front. Aging Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5368","DOI":"10.1523\/JNEUROSCI.6251-09.2010","article-title":"Brain-derived neurotrophic factor is associated with age-related decline in hippocampal volume","volume":"30","author":"Erickson","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"More, S.V., Kumar, H., Cho, D.-Y., Yun, Y.-S., and Choi, D.-K. (2016). Toxin-Induced Experimental Models of Learning and Memory Impairment. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17091447"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.5114\/aoms.2015.56342","article-title":"Brain-derived neurotrophic factor and its clinical implications","volume":"11","author":"Bathina","year":"2015","journal-title":"Arch. Med. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s13311-014-0327-5","article-title":"Synaptic Therapy in Alzheimer\u2019s disease: A CREB-centric Approach","volume":"12","author":"Teich","year":"2015","journal-title":"Neurotherapeutics"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chen, S.D., Wu, C.L., Hwang, W.C., and Yang, D.I. (2017). More Insight into BDNF against Neurodegeneration: Anti-Apoptosis, Anti-Oxidation, and Suppression of Autophagy. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18030545"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"P9","DOI":"10.1186\/1750-1326-8-S1-P9","article-title":"CYP2E1 and Parkinson\u2019s disease in a MPTP-induced C57BL\/6 mouse model","volume":"8","author":"Basaran","year":"2013","journal-title":"Mol. Neurodegener."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"22405","DOI":"10.1038\/srep22405","article-title":"Fermented Sipjeondaebo-tang Alleviates Memory Deficits and Loss of Hippocampal Neurogenesis in Scopolamine-induced Amnesia in Mice","volume":"6","author":"Park","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.pnpbp.2014.03.006","article-title":"Estrogen levels modify scopolamine-induced amnesia in gonadally intact rats","volume":"53","author":"Sousa","year":"2014","journal-title":"Prog. Neuro Psychopharmacol. Biol. Psychiatr."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Falsafi, S.K., Deli, A., H\u00f6ger, H., Pollak, A., and Lubec, G. (2012). Scopolamine Administration Modulates Muscarinic, Nicotinic and NMDA Receptor Systems. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0032082"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9748","DOI":"10.1038\/srep09748","article-title":"Scopolamine effects on functional brain connectivity: A pharmacological model of Alzheimer\u2019s disease","volume":"5","author":"Bajo","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1159\/000026546","article-title":"Tacrine treatment of Alzheimer\u2019s disease: Many expectations, few certainties","volume":"38","author":"Malaguarnera","year":"1998","journal-title":"Neuropsychobiology"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Qizilbash, N., Birks, J., Lopez-Arrieta, J., Lewington, S., and Szeto, S. (2000). Tacrine for Alzheimer\u2019s disease. Cochrane Database Syst. Rev., Cd000202.","DOI":"10.1002\/14651858.CD000202"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1538\/expanim.58.141","article-title":"Genetic differences among C57BL\/6 substrains","volume":"58","author":"Mekada","year":"2009","journal-title":"Exp. Anim."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3649","DOI":"10.1002\/jnr.22155","article-title":"Serotonin transporter, 5-HT1A receptor, and behavior in DBA\/2J mice in comparison with four inbred mouse strains","volume":"87","author":"Popova","year":"2009","journal-title":"J. Neurosci. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s00213-008-1215-7","article-title":"Effects of adolescent fluoxetine treatment on fear-, anxiety- or stress-related behaviors in C57BL\/6J or BALB\/cJ mice","volume":"200","author":"Norcross","year":"2008","journal-title":"Psychopharmacology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2510","DOI":"10.3390\/ijms10062510","article-title":"Trends in the Molecular Pathogenesis and Clinical Therapeutics of Common Neurodegenerative Disorders","volume":"10","author":"Choonara","year":"2009","journal-title":"Int. J. Mol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2015). 2015 Alzheimer\u2019s disease facts and figures. Alzheimer\u2019s Dement., 11, 332\u2013384.","DOI":"10.1016\/j.jalz.2015.02.003"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1586\/14737175.8.11.1703","article-title":"Cholinergic system during the progression of Alzheimer\u2019s disease: Therapeutic implications","volume":"8","author":"Mufson","year":"2008","journal-title":"Expert Rev. Neurother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.bbr.2009.12.048","article-title":"The Cholinergic System and Parkinson Disease","volume":"221","author":"Bohnen","year":"2011","journal-title":"Behav. Brain Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/0006-8993(96)00427-1","article-title":"Role of dorsal hippocampus in acquisition, consolidation and retrieval of rat\u2019s passive avoidance response: A tetrodotoxin functional inactivation study","volume":"730","author":"Lorenzini","year":"1996","journal-title":"Brain Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.ejphar.2010.09.001","article-title":"Neuroprotective effects of chlorogenic acid on scopolamine-induced amnesia via anti-acetylcholinesterase and anti-oxidative activities in mice","volume":"649","author":"Kwon","year":"2010","journal-title":"Eur. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.nlm.2006.11.005","article-title":"The ameliorating effect of oroxylin A on scopolamine-induced memory impairment in mice","volume":"87","author":"Kim","year":"2007","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1007\/BF00212843","article-title":"Attenuation of scopolamine-induced impairment of spontaneous alternation behaviour by antagonist but not inverse agonist and agonist \u03b2-carbolines","volume":"94","author":"Sarter","year":"1988","journal-title":"Psychopharmacology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.bbr.2010.11.037","article-title":"The cholinergic system and hippocampal plasticity","volume":"221","author":"Drever","year":"2011","journal-title":"Behav. Brain Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1177\/0891988704267463","article-title":"Role of cholinesterase inhibitors in Parkinson\u2019s disease and dementia with Lewy bodies","volume":"17","author":"Aarsland","year":"2004","journal-title":"J. Geriatr. Psychiatr. Neurol."},{"key":"ref_36","first-page":"46","article-title":"Cholinergic receptor alterations in the cerebral cortex of spinal cord injured rat","volume":"10","author":"Chinthu","year":"2017","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.bbr.2010.11.047","article-title":"The cholinergic system and neostriatal memory functions","volume":"221","author":"Havekes","year":"2011","journal-title":"Behav. Brain Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4033","DOI":"10.1007\/s00213-015-4012-0","article-title":"Cross-site strain comparison of pharmacological deficits in the touchscreen visual discrimination test","volume":"232","author":"Mohler","year":"2015","journal-title":"Psychopharmacology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1111\/j.1601-183X.2006.00284.x","article-title":"Strain specificity and cholinergic modulation of visuospatial attention in three inbred mouse strains","volume":"6","author":"Pattij","year":"2007","journal-title":"Genes Brain Behav."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"821","DOI":"10.2174\/1381612805666230111212056","article-title":"Brain inflammation in Alzheimer disease and the therapeutic implications","volume":"5","author":"McGeer","year":"1999","journal-title":"Curr. Pharm. Des."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.cbi.2015.09.016","article-title":"N-palmitoyl serotonin alleviates scopolamine-induced memory impairment via regulation of cholinergic and antioxidant systems, and expression of BDNF and p-CREB in mice","volume":"242","author":"Min","year":"2015","journal-title":"Chem. Biol. Interact."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/hipo.20356","article-title":"Differential involvement of the dorsal hippocampus in passive avoidance in C57bl\/6J and DBA\/2J mice","volume":"18","author":"Baarendse","year":"2008","journal-title":"Hippocampus"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/nn1209","article-title":"Prefrontal cortex and decision making in a mixed-strategy game","volume":"7","author":"Barraclough","year":"2004","journal-title":"Nat. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S0074-7742(07)82016-2","article-title":"Oxidative stress and the pathogenesis of neurodegenerative disorders","volume":"82","author":"Reynolds","year":"2007","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2174\/187152708783885156","article-title":"Alzheimer disease and the role of free radicals in the pathogenesis of the disease","volume":"7","author":"Moreira","year":"2008","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"8590578","DOI":"10.1155\/2016\/8590578","article-title":"The Role of Reactive Oxygen Species in the Pathogenesis of Alzheimer\u2019s Disease, Parkinson\u2019s Disease, and Huntington\u2019s Disease: A Mini Review","volume":"2016","author":"Manoharan","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"7792","DOI":"10.3390\/molecules15117792","article-title":"Nutraceutical antioxidants as novel neuroprotective agents","volume":"15","author":"Kelsey","year":"2010","journal-title":"Molecules"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1155\/2012\/428010","article-title":"Mechanism of Oxidative Stress in Neurodegeneration","volume":"2012","author":"Gandhi","year":"2012","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.biopha.2003.11.004","article-title":"Neurodegenerative diseases and oxidative stress","volume":"58","author":"Emerit","year":"2004","journal-title":"Biomed. Pharmacother."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"484613","DOI":"10.1155\/2013\/484613","article-title":"Role of redox signaling in neuroinflammation and neurodegenerative diseases","volume":"2013","author":"Hsieh","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.brainres.2016.09.013","article-title":"Brain damage resulting from postnatal hypoxic-ischemic brain injury is reduced in C57BL\/6J mice as compared to C57BL\/6N mice","volume":"1650","author":"Wolf","year":"2016","journal-title":"Brain Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.freeradbiomed.2013.05.049","article-title":"A spontaneous mutation in the nicotinamide nucleotide transhydrogenase gene of C57BL\/6J mice results in mitochondrial redox abnormalities","volume":"63","author":"Ronchi","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.bbabio.2006.03.010","article-title":"Mitochondrial NADPH, transhydrogenase and disease","volume":"1757","author":"Rydstrom","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1254\/jphs.91.267","article-title":"Brain-derived neurotrophic factor\/TrkB signaling in memory processes","volume":"91","author":"Yamada","year":"2003","journal-title":"J. Pharmacol. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/ng882","article-title":"Disruption of CREB function in brain leads to neurodegeneration","volume":"31","author":"Mantamadiotis","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/nrneurol.2009.54","article-title":"Brain-derived neurotrophic factor in neurodegenerative diseases","volume":"5","author":"Zuccato","year":"2009","journal-title":"Nat. Rev. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1002\/ptr.3596","article-title":"Kalopanaxsaponins A and B isolated from Kalopanax pictus ameliorate memory deficits in mice","volume":"26","author":"Joh","year":"2012","journal-title":"Phytother. Res. PTR"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"9651","DOI":"10.1038\/srep09651","article-title":"Hippocampal memory enhancing activity of pine needle extract against scopolamine-induced amnesia in a mouse model","volume":"5","author":"Lee","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1111\/j.1471-4159.2008.05864.x","article-title":"The CREB\/CRE transcriptional pathway: Protection against oxidative stress-mediated neuronal cell death","volume":"108","author":"Lee","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1271\/bbb.120247","article-title":"Cognitive enhancing effects of \u03b1 asarone in amnesic mice by influencing cholinergic and antioxidant defense mechanisms","volume":"76","author":"Kumar","year":"2012","journal-title":"Biosci. Biotechnol. Biochem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/8\/1735\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:41:56Z","timestamp":1760208116000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/8\/1735"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,9]]},"references-count":60,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2017,8]]}},"alternative-id":["ijms18081735"],"URL":"https:\/\/doi.org\/10.3390\/ijms18081735","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,9]]}}}