{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:38:05Z","timestamp":1790393885783,"version":"4.1.0"},"reference-count":68,"publisher":"Frontiers Media SA","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 NS082902"],"award-info":[{"award-number":["R21 NS082902"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009797","name":"Barrow Neurological Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009797","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"DOI":"10.3389\/fncel.2017.00287","type":"journal-article","created":{"date-parts":[[2017,9,22]],"date-time":"2017-09-22T08:25:41Z","timestamp":1506068741000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":31,"title":["Distinctive Roles for \u03b17*- and \u03b19*-Nicotinic Acetylcholine Receptors in Inflammatory and Autoimmune Responses in the Murine Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis"],"prefix":"10.3389","volume":"11","author":[{"given":"Qiang","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Whiteaker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara J.","family":"Morley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu-Dong","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald J.","family":"Lukas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2017,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1084\/jem.20040131","article-title":"CD24 controls expansion and persistence of autoreactive T cells in the central nervous system during experimental autoimmune encephalomyelitis","volume":"200","author":"Bai","year":"2004","journal-title":"J. Exp. Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11064-010-0252-x","article-title":"Central and peripheral cytokines mediate immune-brain connectivity","volume":"36","author":"Besedovsky","year":"2011","journal-title":"Neurochem. Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.neuron.2009.09.001","article-title":"Immune proteins in brain development and synaptic plasticity","volume":"64","author":"Boulanger","year":"2009","journal-title":"Neuron"},{"key":"B4","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1189\/jlb.0906544","article-title":"Nicotine and serotonin in immune regulation and inflammatory processes: a perspective","volume":"81","author":"Clo\u00ebz-Tayarani","year":"2007","journal-title":"J. Leukoc. Biol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1056\/NEJM200108023450506","article-title":"Autoimmune diseases","volume":"345","author":"Davidson","year":"2001","journal-title":"N Engl J. Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1016\/0092-8674(94)90555-x","article-title":"\u03b19: an acetylcholine receptor with novel pharmacological properties expressed in rat cochlear hair cells","volume":"79","author":"Elgoyhen","year":"1994","journal-title":"Cell"},{"key":"B7","doi-asserted-by":"publisher","first-page":"644","DOI":"10.2174\/138945012800399008","article-title":"The yin and yang of non-neuronal \u03b17-nicotinic receptors in inflammation and autoimmunity","volume":"13","author":"Filippini","year":"2012","journal-title":"Curr. Drug Targets"},{"key":"B8","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1038\/nrneurol.2012.200","article-title":"Neuroprotection and repair in multiple sclerosis","volume":"8","author":"Franklin","year":"2012","journal-title":"Nat. Rev. Neurol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1254\/jphs.fm0070109","article-title":"Basic and clinical aspects of non-neuronal acetylcholine: expression of an independent, non-neuronal cholinergic system in lymphocytes and its clinical significance in immunotherapy","volume":"106","author":"Fujii","year":"2008","journal-title":"J. Pharmacol. Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"359","DOI":"10.2174\/1568007023339184","article-title":"Regulation of nicotinic acetylcholine receptor numbers and function by chronic nicotine exposure","volume":"1","author":"Gentry","year":"2002","journal-title":"Curr. Drug Targets CNS Neurol. Disord."},{"key":"B11","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1124\/jpet.102.041756","article-title":"Effects of prolonged nicotinic ligand exposure on function of heterologously expressed, human \u03b14\u03b22- and \u03b14\u03b24-nicotinic acetylcholine receptors","volume":"304","author":"Gentry","year":"2003","journal-title":"J. Pharmacol. Exper. Ther."},{"key":"B12","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1016\/j.lfs.2012.10.004","article-title":"The non-neuronal cholinergic system: basic science, therapeutic implications and new perspectives","volume":"91","author":"Grando","year":"2012","journal-title":"Life Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e16149","DOI":"10.1371\/journal.pone.0016149","article-title":"Smoking and multiple sclerosis: an updated meta-analysis","volume":"6","author":"Handel","year":"2011","journal-title":"PLoS One"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1907","DOI":"10.1084\/jem.20092749","article-title":"Central nervous system (CNS)-resident natural killer cells suppress Th17 responses and CNS autoimmune pathology","volume":"207","author":"Hao","year":"2010","journal-title":"J. Exp. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e57495","DOI":"10.1371\/journal.pone.0057495","article-title":"Nicotinic receptor \u03b22 determines NK cell-dependent metastasis in a murine model of metastatic lung cancer","volume":"8","author":"Hao","year":"2013","journal-title":"PLoS One"},{"key":"B16","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.expneurol.2010.09.020","article-title":"Attenuation of CNS inflammatory responses by nicotine involves \u03b17 and non-\u03b17 nicotinic receptors","volume":"227","author":"Hao","year":"2011","journal-title":"Exp. Neurol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1212\/WNL.0b013e3181b59c40","article-title":"Tobacco smoking, but not Swedish snuff use, increases the risk of multiple sclerosis","volume":"73","author":"Hedstr\u00f6m","year":"2009","journal-title":"Neurology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1177\/1352458512471879","article-title":"Nicotine might have a protective effect in the etiology of multiple sclerosis","volume":"19","author":"Hedstr\u00f6m","year":"2013","journal-title":"Mult. Scler."},{"key":"B19","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1096\/fj.05-5465com","article-title":"The neuronal chemokine CX3CL1\/fractalkine selectively recruits NK cells that modify experimental autoimmune encephalomyelitis within the central nervous system","volume":"20","author":"Huang","year":"2006","journal-title":"FASEB J."},{"key":"B20","doi-asserted-by":"publisher","first-page":"4705","DOI":"10.1021\/jm040219e","article-title":"Neuronal nicotinic acetylcholine receptors: structural revelations, target identifications, and therapeutic inspirations","volume":"48","author":"Jensen","year":"2005","journal-title":"J. Med. Chem."},{"key":"B21","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/j.tins.2005.04.010","article-title":"Why doesn\u2019t nicotinic ACh receptor immunoreactivity knock out?","volume":"28","author":"Jones","year":"2005","journal-title":"Trends Neurosci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2314","DOI":"10.1016\/j.lfs.2007.02.036","article-title":"Expression and function of genes encoding cholinergic components in murine immune cells","volume":"80","author":"Kawashima","year":"2007","journal-title":"Life Sci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1016\/j.biocel.2010.12.003","article-title":"Differential involvement of \u03b14\u03b22, \u03b17 and \u03b19\u03b110 nicotinic acetylcholine receptors in B lymphocyte activation in vitro","volume":"43","author":"Koval","year":"2011","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/s0165-5728(02)00220-5","article-title":"Differential expression of nicotinic acetylcholine receptor subunits in fetal and neonatal mouse thymus","volume":"130","author":"Kuo","year":"2002","journal-title":"J. Neuroimmunol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jns.2013.05.010","article-title":"Pathology and disease mechanisms in different stages of multiple sclerosis","volume":"333","author":"Lassmann","year":"2013","journal-title":"J. Neurol. Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"349","DOI":"10.2174\/18715281113129990053","article-title":"Anti-inflammatory treatments for chronic diseases: a review","volume":"12","author":"Laveti","year":"2013","journal-title":"Inflamm. Allergy Drug Targets"},{"key":"B27","doi-asserted-by":"publisher","first-page":"E396","DOI":"10.1073\/pnas.1612930114","article-title":"Astrocyte-derived interleukin-15 exacerbates ischemic brain injury via propagation of cellular immunity","volume":"114","author":"Li","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"B28","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1523\/JNEUROSCI.3952-08.2009","article-title":"A novel nicotinic acetylcholine receptor subtype in basal forebrain cholinergic neurons with high sensitivity to amyloid peptides","volume":"29","author":"Liu","year":"2009","journal-title":"J. Neurosci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1016\/j.immuni.2017.02.015","article-title":"Brain ischemia suppresses immunity in the periphery and brain via different neurogenic innervations","volume":"46","author":"Liu","year":"2017","journal-title":"Immunity"},{"key":"B31","doi-asserted-by":"publisher","first-page":"7253","DOI":"10.1523\/jneurosci.3235-12.2013","article-title":"A novel nicotinic mechanism underlies \u03b2-amyloid-induced neuronal hyperexcitation","volume":"33","author":"Liu","year":"2013","journal-title":"J. Neurosci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1134","DOI":"10.1111\/j.1471-4159.1991.tb11403.x","article-title":"Effects of chronic nicotinic ligand exposure on functional activity of nicotinic acetylcholine receptors expressed by cells of the PC12 rat pheochromocytoma or the TE671\/RD human clonal line","volume":"56","author":"Lukas","year":"1991","journal-title":"J. Neurochem."},{"key":"B33","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1111\/j.1749-6632.1995.tb17471.x","article-title":"Diversity and patterns of regulation of nicotinic receptor subtypes","volume":"757","author":"Lukas","year":"1995","journal-title":"Ann. N Y Acad. Sci."},{"key":"B34","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/978-3-662-40279-5_7","article-title":"Neuronal nicotinic acetylcholine receptors","volume-title":"The Nicotinic Acetylcholine Receptors: Current Views and Future Trends","author":"Lukas","year":"1998"},{"key":"B35","first-page":"27","article-title":"Recent developments in nicotinic acetylcholine receptor biology","volume-title":"Biological and Biophysical Aspects of Ligand-Gated Ion Channel Receptor Superfamilies","author":"Lukas","year":"2006"},{"key":"B36","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/S0031-6997(24)01406-6","article-title":"International Union of Pharmacology. XX. Current status of the nomenclature for nicotinic acetylcholine receptors and their subunits","volume":"51","author":"Lukas","year":"1999","journal-title":"Pharmacol. Rev."},{"key":"B37","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1002\/(sici)1098-2299(199607\/08)38:3\/4<136::aid-ddr2>3.0.co;2-n","article-title":"Regulation by nicotine of its own receptors","volume":"38","author":"Lukas","year":"1996","journal-title":"Drug Dev. Res."},{"key":"B38","doi-asserted-by":"publisher","first-page":"6518","DOI":"10.4049\/jimmunol.167.11.6518","article-title":"Involvement of nicotinic acetylcholine receptors in suppression of antimicrobial activity and cytokine responses of alveolar macrophages to Legionella pneumophila infection by nicotine","volume":"167","author":"Matsunaga","year":"2001","journal-title":"J. Immunol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1007\/s00213-006-0441-0","article-title":"Guidelines on nicotine dose selection for in vivo research","volume":"190","author":"Matta","year":"2007","journal-title":"Psychopharmacology (Berl)"},{"key":"B40","doi-asserted-by":"publisher","first-page":"2915","DOI":"10.4049\/jimmunol.169.6.2915","article-title":"Murine fetal thymus organ cultures treated with nicotine exhibit a reduction in mature thymocytes and expanded populations of immature thymocytes","volume":"169","author":"Middlebrook","year":"2002","journal-title":"J. Immunol."},{"key":"B41","article-title":"Effects of nicotine exposure on developing murine and human thymocytes in fetal thumus organ culture","volume-title":"FASEB Conference on Neuroimmunology","author":"Middlebrook","year":"2000"},{"key":"B42","doi-asserted-by":"publisher","first-page":"516","DOI":"10.3389\/fnins.2017.00516","article-title":"Generation and characterization of \u03b19 and \u03b110 nicotinic acetylcholine receptor subunit knockout mice on a C57Bl\/6J background","volume":"11","author":"Morley","year":"","journal-title":"Front. Neurosci."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1002\/cne.24131","article-title":"Nicotinic acetylcholine receptors regulate vestibular afferent gain and activation timing","volume":"525","author":"Morley","year":"","journal-title":"J. Comp. Neurol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1111\/j.1471-4159.2007.04498.x","article-title":"Evaluating the suitability of nicotinic acetylcholine receptor antibodies for standard immunodetection procedures","volume":"102","author":"Moser","year":"2007","journal-title":"J. Neurochem."},{"key":"B46","doi-asserted-by":"publisher","first-page":"203","DOI":"10.2174\/187152808785748155","article-title":"Therapeutic benefits of regulating inflammation in autoimmunity","volume":"7","author":"Nikoopour","year":"2008","journal-title":"Inflamm. Allergy Drug Targets"},{"key":"B47","doi-asserted-by":"publisher","first-page":"6681","DOI":"10.4049\/jimmunol.0902212","article-title":"Activation of the cholinergic anti-inflammatory system by nicotine attenuates neuroinflammation via suppression of Th1 and Th17 responses","volume":"183","author":"Nizri","year":"2009","journal-title":"J. Immunol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1038\/aps.2009.67","article-title":"Nicotine and inflammatory neurological disorders","volume":"30","author":"Piao","year":"2009","journal-title":"Acta Pharmacol. Sin."},{"key":"B49","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.pneurobio.2007.12.005","article-title":"It is not \u201ceither\/or\u201d: activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood","volume":"84","author":"Picciotto","year":"2008","journal-title":"Prog. Neurobiol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1111\/j.1600-065X.2012.01126.x","article-title":"Mechanisms regulating regional localization of inflammation during CNS autoimmunity","volume":"248","author":"Pierson","year":"2012","journal-title":"Immunol. Rev."},{"key":"B51","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1038\/gene.2010.72","article-title":"Plasticity of the murine spleen T-cell cholinergic receptors and their role in in vitro differentiation of naive CD4 T cells toward the Th1, Th2 and Th17 lineages","volume":"12","author":"Qian","year":"2011","journal-title":"Genes Immun."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1177\/1352458512470862","article-title":"Smoking as a risk factor for multiple sclerosis","volume":"19","author":"Salzer","year":"2013","journal-title":"Mult. Scler."},{"key":"B53","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/s0304-3940(99)00259-1","article-title":"Diversity of mRNA expression for muscarinic acetylcholine receptor subtypes and neuronal nicotinic acetylcholine receptor subunits in human mononuclear leukocytes and leukemic cell lines","volume":"266","author":"Sato","year":"1999","journal-title":"Neurosci. Lett."},{"key":"B54","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.neuron.2009.09.044","article-title":"MHC class I: an unexpected role in neuronal plasticity","volume":"64","author":"Shatz","year":"2009","journal-title":"Neuron"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1730","DOI":"10.4049\/jimmunol.182.3.1730","article-title":"Nicotinic attenuation of central nervous system inflammation and autoimmunity","volume":"182","author":"Shi","year":"2009","journal-title":"J. Immunol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1046\/j.1471-4159.2004.02347.x","article-title":"Cholinergic modulation of microglial activation by \u03b17 nicotinic receptors","volume":"89","author":"Shytle","year":"2004","journal-title":"J. Neurochem."},{"key":"B57","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/icb.2013.1","article-title":"Differential modulation of experimental autoimmune encephalomyelitis by \u03b19*- and \u03b22*-nicotinic acetylcholine receptors","volume":"91","author":"Simard","year":"2013","journal-title":"Immunol. Cell Biol."},{"key":"B58","first-page":"1328","article-title":"Acetylcholine receptors in the retinas of the \u03b17 nicotinic acetylcholine receptor knockout mouse","volume":"20","author":"Smith","year":"2014","journal-title":"Mol. Vis."},{"key":"B59","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1038\/nrd2927","article-title":"Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system","volume":"8","author":"Taly","year":"2009","journal-title":"Nat. Rev. Drug Discov."},{"key":"B60","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1038\/nri2566","article-title":"Reflex control of immunity","volume":"9","author":"Tracey","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1038\/nrd1797","article-title":"The vagus nerve and the nicotinic anti-inflammatory pathway","volume":"4","author":"Ulloa","year":"2005","journal-title":"Nat. Rev. Drug Discov."},{"key":"B62","doi-asserted-by":"publisher","first-page":"485781","DOI":"10.1155\/2012\/485781","article-title":"Positive and negative regulation of cellular immune responses in physiologic conditions and diseases","volume":"2012","author":"Vigan\u00f2","year":"2012","journal-title":"Clin. Dev. Immunol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.neuro.2015.12.017","article-title":"Prenatal cigarette smoke exposure effects on apoptotic and nicotinic acetylcholine receptor expression in the infant mouse brainstem","volume":"53","author":"Vivekanandarajah","year":"2016","journal-title":"Neurotoxicology"},{"key":"B64","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.ijdevneu.2015.09.007","article-title":"Postnatal nicotine effects on the expression of nicotinic acetylcholine receptors in the developing piglet hippocampus and brainstem","volume":"47","author":"Vivekanandarajah","year":"2015","journal-title":"Int. J. Dev. Neurosci."},{"key":"B66","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1038\/nature01339","article-title":"Nicotinic acetylcholine receptor \u03b17 subunit is an essential regulator of inflammation","volume":"421","author":"Wang","year":"2003","journal-title":"Nature"},{"key":"B65","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1124\/jpet.110.169961","article-title":"Stimulation of \u03b17 nicotinic acetylcholine receptor by nicotine increases suppressive capacity of naturally occurring CD4+CD25+ regulatory T cells in mice in vitro","volume":"335","author":"Wang","year":"2010","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B67","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1038\/nature01325","article-title":"Inflammation and therapeutic vaccination in CNS diseases","volume":"420","author":"Weiner","year":"2002","journal-title":"Nature"},{"key":"B68","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1038\/nm0798-770","article-title":"The viral triggering of autoimmune disease","volume":"4","author":"Wekerle","year":"1998","journal-title":"Nat. Med."},{"key":"B69","doi-asserted-by":"publisher","first-page":"1558","DOI":"10.1038\/bjp.2008.185","article-title":"Acetylcholine beyond neurons: the non-neuronal cholinergic system in humans","volume":"154","author":"Wessler","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1007\/s002130000382","article-title":"A comparison of the abuse liability and dependence potential of nicotine patch, gum, spray and inhaler","volume":"149","author":"West","year":"2000","journal-title":"Psychopharmacology (Berl)"}],"container-title":["Frontiers in Cellular Neuroscience"],"original-title":[],"link":[{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fncel.2017.00287\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T21:25:00Z","timestamp":1750886700000},"score":1,"resource":{"primary":{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fncel.2017.00287\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,22]]},"references-count":68,"alternative-id":["10.3389\/fncel.2017.00287"],"URL":"https:\/\/doi.org\/10.3389\/fncel.2017.00287","relation":{},"ISSN":["1662-5102"],"issn-type":[{"value":"1662-5102","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,22]]},"article-number":"287"}}