{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:06:10Z","timestamp":1791219970804,"version":"4.1.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2018,8,4]],"date-time":"2018-08-04T00:00:00Z","timestamp":1533340800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Ministry of Education, Science, and Culture, Tokyo, Japan"},{"name":"Grants-in-Aid for Scientific Research","award":["25461135"],"award-info":[{"award-number":["25461135"]}]},{"name":"Grants-in-Aid for Scientific Research","award":["23790863"],"award-info":[{"award-number":["23790863"]}]},{"name":"Grants-in-Aid for Scientific Research","award":["23790861"],"award-info":[{"award-number":["23790861"]}]},{"name":"Ministry of Health Labor and Welfare"},{"name":"Health Science Research Grants"},{"name":"Research on Translational Research"},{"name":"Intractable Diseases, and Nanomedicine"},{"name":"Intractable Diseases Overcome Research Project"},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"JST CREST","award":["JPMJCR17H5"],"award-info":[{"award-number":["JPMJCR17H5"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,2,1]]},"DOI":"10.1093\/cvr\/cvy200","type":"journal-article","created":{"date-parts":[[2018,8,2]],"date-time":"2018-08-02T07:32:25Z","timestamp":1533195145000},"page":"419-431","source":"Crossref","is-referenced-by-count":108,"title":["Peroxisome proliferator-activated receptor-gamma targeting nanomedicine promotes cardiac healing after acute myocardial infarction by skewing monocyte\/macrophage polarization in preclinical animal models"],"prefix":"10.1093","volume":"115","author":[{"given":"Masaki","family":"Tokutome","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1, Maidashi, Higashi-ku, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Matoba","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1, Maidashi, Higashi-ku, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Nakano","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1, Maidashi, Higashi-ku, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arihide","family":"Okahara","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1, Maidashi, Higashi-ku, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1, Maidashi, Higashi-ku, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Ichiro","family":"Koga","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Research, Development, and Translational Medicine, Center for Disruptive Cardiovascular Medicine, Kyushu University, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaku","family":"Nakano","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Research, Development, and Translational Medicine, Center for Disruptive Cardiovascular Medicine, Kyushu University, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Tsutsui","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1, Maidashi, Higashi-ku, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensuke","family":"Egashira","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1, Maidashi, Higashi-ku, Fukuoka, Japan"},{"name":"Department of Cardiovascular Research, Development, and Translational Medicine, Center for Disruptive Cardiovascular Medicine, Kyushu University, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,8,3]]},"reference":[{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B1","first-page":"e38","article-title":"Heart disease and stroke statistics\u20142016 update","volume":"133","author":"Mozaffarian","year":"2016","journal-title":"Circulation"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B2","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1056\/NEJMoa1208200","article-title":"Door-to-balloon time and mortality among patients undergoing primary PCI","volume":"369","author":"Menees","year":"2013","journal-title":"N Engl J Med"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B3","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1056\/NEJMra071667","article-title":"Myocardial reperfusion injury","volume":"357","author":"Yellon","year":"2007","journal-title":"N Engl J Med"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B4","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1172\/JCI62874","article-title":"Myocardial ischemia-reperfusion injury: a neglected therapeutic target","volume":"123","author":"Hausenloy","year":"2013","journal-title":"J Clin Invest"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B5","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1161\/CIRCRESAHA.111.243170","article-title":"Inflammation in myocardial diseases","volume":"110","author":"Marchant","year":"2012","journal-title":"Circ Res"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B6","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1161\/CIRCULATIONAHA.113.001878","article-title":"Pathological ventricular remodeling: mechanisms: part 1 of 2","volume":"128","author":"Burchfield","year":"2013","journal-title":"Circulation"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B7","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/S0735-1097(02)02136-8","article-title":"The effect of blockade of the CD11\/CD18 integrin receptor on infarct size in patients with acute myocardial infarction treated with direct angioplasty: the results of the HALT-MI study","volume":"40","author":"Faxon","year":"2002","journal-title":"J Am Coll Cardiol"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B8","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1016\/j.amjcard.2013.01.287","article-title":"Effects of interleukin-1 blockade with anakinra on adverse cardiac remodeling and heart failure after acute myocardial infarction [from the Virginia Commonwealth University-Anakinra Remodeling Trial (2) (VCU-ART2) Pilot Study]","volume":"111","author":"Abbate","year":"2013","journal-title":"Am J Cardiol"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B9","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1016\/j.jacc.2010.04.066","article-title":"A new monocyte chemotactic protein-1\/chemokine CC motif ligand-2 competitor limiting neointima formation and myocardial ischemia\/reperfusion injury in mice","volume":"56","author":"Liehn","year":"2010","journal-title":"J Am Coll Cardiol"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B10","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1038\/nbt.1989","article-title":"Therapeutic siRNA silencing in inflammatory monocytes in mice","volume":"29","author":"Leuschner","year":"2011","journal-title":"Nat Biotechnol"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B11","doi-asserted-by":"crossref","first-page":"29601.","DOI":"10.1038\/srep29601","article-title":"Nanoparticle-mediated delivery of Irbesartan induces cardioprotection from myocardial ischemia-reperfusion injury by antagonizing monocyte-mediated inflammation","volume":"6","author":"Nakano","year":"2016","journal-title":"Sci Rep"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B12","doi-asserted-by":"crossref","first-page":"818","DOI":"10.2353\/ajpath.2007.060547","article-title":"Macrophage depletion impairs wound healing and increases left ventricular remodeling after myocardial injury in mice","volume":"170","author":"van Amerongen","year":"2007","journal-title":"Am J Pathol"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B13","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/nm.3159","article-title":"PPAR\u03b3; signaling and metabolism: the good, the bad and the future","volume":"19","author":"Ahmadian","year":"2013","journal-title":"Nat Med"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B14","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.amjcard.2006.11.004","article-title":"Inflammation in diabetes mellitus: role of peroxisome proliferator-activated receptor-\u03b1 and peroxisome proliferator-activated receptor-\u03b3 agonists","volume":"99","author":"Libby","year":"2007","journal-title":"Am J Cardiol"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B15","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1161\/CIRCULATIONAHA.104.475673","article-title":"Peroxisome proliferator activated receptors as transcriptional nodal points and therapeutic targets","volume":"115","author":"Brown","year":"2007","journal-title":"Circulation"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B16","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/j.bbalip.2007.02.013","article-title":"PPARs and molecular mechanisms of transrepression","volume":"1771","author":"Ricote","year":"2007","journal-title":"Biochim Biophys Acta"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B17","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1016\/j.cardiores.2004.12.008","article-title":"Beneficial effects of PPAR-gamma ligands in ischemia-reperfusion injury, inflammation and shock","volume":"65","author":"Abdelrahman","year":"2005","journal-title":"Cardiovasc Res"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B18","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.cmet.2007.06.010","article-title":"PPAR\u03b3 activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties","volume":"6","author":"Bouhlel","year":"2007","journal-title":"Cell Metab"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B19","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1038\/nature05894","article-title":"Macrophage-specific PPAR\u03b3 controls alternative activation and improves insulin resistance","volume":"447","author":"Odegaard","year":"2007","journal-title":"Nature"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B20","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/34178","article-title":"The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation","volume":"391","author":"Ricote","year":"1998","journal-title":"Nature"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B21","doi-asserted-by":"crossref","first-page":"H2436","DOI":"10.1152\/ajpheart.00690.2008","article-title":"Pioglitazone protects the myocardium against ischemia-reperfusion injury in eNOS and iNOS knockout mice","volume":"295","author":"Ye","year":"2008","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B22","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.yjmcc.2008.03.004","article-title":"Pioglitazone, a peroxisome proliferator-activated receptor-\u03b3 agonist, attenuates myocardial ischemia\u2013reperfusion injury in mice with metabolic disorders","volume":"44","author":"Honda","year":"2008","journal-title":"J Mol Cell Cardiol"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B23","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1161\/ATVBAHA.108.182584","article-title":"Therapeutic neovascularization by nanotechnology-mediated cell-selective delivery of pitavastatin into the vascular endothelium","volume":"29","author":"Kubo","year":"2009","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B24","doi-asserted-by":"crossref","first-page":"S65","DOI":"10.1161\/CIRCULATIONAHA.107.740613","article-title":"Local delivery of imatinib mesylate (STI571)-incorporated nanoparticle ex vivo suppresses vein graft neointima formation","volume":"118","author":"Kimura","year":"2008","journal-title":"Circulation"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B25","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1161\/HYPERTENSIONAHA.110.157032","article-title":"Nanoparticle-mediated delivery of pitavastatin into lungs ameliorates the development and induces regression of monocrotaline-induced pulmonary artery hypertension","volume":"57","author":"Chen","year":"2011","journal-title":"Hypertension"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B26","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1161\/ATVBAHA.112.253823","article-title":"Nanoparticle-mediated delivery of pioglitazone enhances therapeutic neovascularization in a murine model of hindlimb ischemia","volume":"32","author":"Nagahama","year":"2012","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B27","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1161\/CIRCULATIONAHA.113.002870","article-title":"Nanoparticle-mediated delivery of pitavastatin inhibits atherosclerotic plaque destabilization\/rupture in mice by regulating the recruitment of inflammatory monocytes","volume":"129","author":"Katsuki","year":"2014","journal-title":"Circulation"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B28","doi-asserted-by":"crossref","first-page":"e0132451.","DOI":"10.1371\/journal.pone.0132451","article-title":"A new therapeutic modality for acute myocardial infarction: nanoparticle-mediated delivery of pitavastatin induces cardioprotection from ischemia-reperfusion injury via activation of PI3K\/Akt pathway and anti-inflammation in a rat model","volume":"10","author":"Nagaoka","year":"2015","journal-title":"PLoS One"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B29","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.nantod.2015.06.006","article-title":"Nanoparticle uptake: the phagocyte problem","volume":"10","author":"Gustafson","year":"2015","journal-title":"Nano Today"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B30","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1161\/ATVBAHA.115.307057","article-title":"Pioglitazone-incorporated nanoparticles prevent plaque destabilization and rupture by regulating monocyte\/macrophage differentiation in ApoE\u2212\/\u2212 mice","volume":"36","author":"Nakashiro","year":"2016","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B31","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0939-6411(97)00121-5","article-title":"Properties of a peptide containing dl-lactide\/glycolide copolymer nanospheres prepared by novel emulsion solvent diffusion methods","volume":"45","author":"Kawashima","year":"1998","journal-title":"Eur J Pharm Biopharm"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B32","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1161\/01.RES.0000261924.76669.36","article-title":"Distinct roles of autophagy in the heart during ischemia and reperfusion: roles of AMP-activated protein kinase and beclin 1 in mediating autophagy","volume":"100","author":"Matsui","year":"2007","journal-title":"Circ Res"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B33","doi-asserted-by":"crossref","first-page":"2170","DOI":"10.1161\/CIRCULATIONAHA.110.958033","article-title":"Silent information regulator 1 protects the heart from ischemia\/reperfusion","volume":"122","author":"Hsu","year":"2010","journal-title":"Circulation"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B34","doi-asserted-by":"crossref","first-page":"e0162425","DOI":"10.1371\/journal.pone.0162425","article-title":"A translational study of a new therapeutic approach for acute myocardial infarction: nanoparticle-mediated delivery of pitavastatin into reperfused myocardium reduces ischemia-reperfusion injury in a preclinical porcine model","volume":"11","author":"Ichimura","year":"2016","journal-title":"PLoS One"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B35","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1161\/CIRCRESAHA.107.164384","article-title":"Peroxisome proliferator-activated receptor-\u03b3-mediated effects in the vasculature","volume":"102","author":"Duan","year":"2008","journal-title":"Circ Res"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B36","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/S0002-9440(10)63309-3","article-title":"Targeted deletion of CC chemokine receptor 2 attenuates left ventricular remodeling after experimental myocardial infarction","volume":"165","author":"Kaikita","year":"2004","journal-title":"Am J Pathol"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B37","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1126\/science.1175202","article-title":"Identification of splenic reservoir monocytes and their deployment to inflammatory sites","volume":"325","author":"Swirski","year":"2009","journal-title":"Science"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B38","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1536\/ihj.16-457","article-title":"Nanoparticle-mediated delivery of pitavastatin to monocytes\/macrophages inhibits left ventricular remodeling after acute myocardial infarction by inhibiting monocyte-mediated inflammation","volume":"58","author":"Mao","year":"2017","journal-title":"Int Heart J"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B39","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1111\/j.1365-2567.2012.03619.x","article-title":"Induction of nuclear factor-\u03baB responses by the S100A9 protein is Toll-like receptor-4-dependent","volume":"137","author":"Riva","year":"2012","journal-title":"Immunology"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B40","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ejheart.2007.11.005","article-title":"Up-regulation of PPAR\u03b3 in myocardial infarction","volume":"10","author":"Fliegner","year":"2008","journal-title":"Eur J Heart Fail"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B41","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1161\/CIRCRESAHA.114.303204","article-title":"Ly-6Chigh monocytes depend on Nr4a1 to balance both inflammatory and reparative phases in the infarcted myocardium","volume":"114","author":"Hilgendorf","year":"2014","journal-title":"Circ Res"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B42","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1161\/CIRCRESAHA.111.243162","article-title":"Regulation of the inflammatory response in cardiac repair","volume":"110","author":"Frangogiannis","year":"2012","journal-title":"Circ Res"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B43","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.yjmcc.2007.06.011","article-title":"Differences in inflammation, MMP activation and collagen damage account for gender difference in murine cardiac rupture following myocardial infarction","volume":"43","author":"Fang","year":"2007","journal-title":"J Mol Cell Cardiol"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B44","doi-asserted-by":"crossref","first-page":"H1229","DOI":"10.1152\/ajpheart.00207.2003","article-title":"Targeted deletion of MMP-2 attenuates early LV rupture and late remodeling after experimental myocardial infarction","volume":"285","author":"Hayashidani","year":"2003","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B45","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.cardiores.2004.03.002","article-title":"Inhibition of I\u03baB phosphorylation in cardiomyocytes attenuates myocardial ischemia\/reperfusion injury","volume":"63","author":"Onai","year":"2004","journal-title":"Cardiovasc Res"},{"key":"key\n\t\t\t\t2019020505293985400_cvy200-B46","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1111\/j.1463-1326.2009.01097.x","article-title":"The PPAR-gamma agonist rosiglitazone facilitates Akt rephosphorylation and inhibits apoptosis in cardiomyocytes during hypoxia\/reoxygenation","volume":"11","author":"Kilter","year":"2009","journal-title":"Diabetes Obes Metab"}],"container-title":["Cardiovascular Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/cardiovascres\/article-pdf\/115\/2\/419\/27708709\/cvy200.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,10,21]],"date-time":"2019-10-21T14:58:57Z","timestamp":1571669937000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article\/115\/2\/419\/5066356"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,3]]},"references-count":46,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2018,8,3]]},"published-print":{"date-parts":[[2019,2,1]]}},"URL":"https:\/\/doi.org\/10.1093\/cvr\/cvy200","relation":{},"ISSN":["0008-6363","1755-3245"],"issn-type":[{"value":"0008-6363","type":"print"},{"value":"1755-3245","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,2,1]]},"published":{"date-parts":[[2018,8,3]]}}}