{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T06:35:53Z","timestamp":1778826953289,"version":"3.51.4"},"reference-count":50,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T00:00:00Z","timestamp":1564617600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T00:00:00Z","timestamp":1564617600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing","doi-asserted-by":"publisher","award":["cstc2015shmszx120086"],"award-info":[{"award-number":["cstc2015shmszx120086"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873972"],"award-info":[{"award-number":["81873972"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873980"],"award-info":[{"award-number":["81873980"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81572080"],"award-info":[{"award-number":["81572080"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","award":["2018ZX10732202"],"award-info":[{"award-number":["2018ZX10732202"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Analytica Chimica Acta"],"published-print":{"date-parts":[[2019,8]]},"DOI":"10.1016\/j.aca.2019.03.055","type":"journal-article","created":{"date-parts":[[2019,3,31]],"date-time":"2019-03-31T23:36:41Z","timestamp":1554075401000},"page":"129-136","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":11,"special_numbering":"C","title":["One-step discrimination of BCR\/ABLp210 transcript isoforms directly from RNA extraction with fusion-triggered rolling circle amplification"],"prefix":"10.1016","volume":"1067","author":[{"given":"Nini","family":"Luo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianfeng","family":"Xia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lutan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lizhen","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yangli","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shijia","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1921-9761","authenticated-orcid":false,"given":"Wei","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.aca.2019.03.055_bib1","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1182\/blood.V65.5.1039.1039","article-title":"Chronic myelogenous leukemia: recent advances","volume":"65","author":"Champlin","year":"1985","journal-title":"Blood"},{"key":"10.1016\/j.aca.2019.03.055_bib2","doi-asserted-by":"crossref","first-page":"7071","DOI":"10.1093\/nar\/14.17.7071","article-title":"Molecular analysis of both translocation products of a Philadelphia-positive CML patient","volume":"14","author":"de Klein","year":"1986","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.aca.2019.03.055_bib3","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1042\/CS20040336","article-title":"Chronic myeloid leukaemia: stem cell derived but progenitor cell driven","volume":"109","author":"Marley","year":"2005","journal-title":"Clin. Sci. (Lond.)"},{"key":"10.1016\/j.aca.2019.03.055_bib4","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S1525-1578(10)60454-0","article-title":"Clinical applications of BCR-ABL molecular testing in acute leukemia","volume":"5","author":"Nashed","year":"2003","journal-title":"J.\u00a0Mol. Diagn."},{"key":"10.1016\/j.aca.2019.03.055_bib5","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1093\/bioinformatics\/btt028","article-title":"Genome Fusion Detection: a novel method to detect fusion genes from SNP-array data","volume":"29","author":"Thieme","year":"2013","journal-title":"Bioinformatics"},{"key":"10.1016\/j.aca.2019.03.055_bib6","doi-asserted-by":"crossref","first-page":"112","DOI":"10.5045\/br.2017.52.2.112","article-title":"Evaluation of a new flow cytometry based method for detection of BCR-ABL1 fusion protein in chronic myeloid leukemia","volume":"52","author":"Dasgupta","year":"2017","journal-title":"Blood Res."},{"key":"10.1016\/j.aca.2019.03.055_bib7","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1182\/blood.V88.7.2375.bloodjournal8872375","article-title":"The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype","volume":"88","author":"Melo","year":"1996","journal-title":"Blood"},{"key":"10.1016\/j.aca.2019.03.055_bib8","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.bios.2012.05.010","article-title":"Chitosan encapsulated quantum dots platform for leukemia detection","volume":"38","author":"Sharma","year":"2012","journal-title":"Biosens. Bioelectron."},{"key":"10.1016\/j.aca.2019.03.055_bib9","doi-asserted-by":"crossref","first-page":"3712","DOI":"10.1093\/nar\/gkf451","article-title":"Antiproliferative effect in chronic myeloid leukaemia cells by antisense peptide nucleic acids","volume":"30","author":"Rapozzi","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.aca.2019.03.055_bib10","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1182\/blood.V92.7.2450","article-title":"Regulation of the c-jun gene in p210 BCR-ABL transformed cells corresponds with activity of JNK, the c-jun N-terminal kinase","volume":"92","author":"Burgess","year":"1998","journal-title":"Blood"},{"key":"10.1016\/j.aca.2019.03.055_bib11","doi-asserted-by":"crossref","first-page":"4504","DOI":"10.1128\/MCB.16.8.4504","article-title":"Cellular transformation and malignancy induced by ras require c-jun","volume":"16","author":"Johnson","year":"1996","journal-title":"Mol. Cell Biol."},{"key":"10.1016\/j.aca.2019.03.055_bib12","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1101\/gad.7.7b.1309","article-title":"A\u00a0null mutation at the c-jun locus causes embryonic lethality and retarded cell growth in culture","volume":"7","author":"Johnson","year":"1993","journal-title":"Genes Dev."},{"key":"10.1016\/j.aca.2019.03.055_bib13","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1093\/emboj\/18.5.1367","article-title":"Transcriptional regulation of the cyclin D1 promoter by STAT5: its involvement in cytokine-dependent growth of hematopoietic cells","volume":"18","author":"Matsumura","year":"1999","journal-title":"EMBO J."},{"key":"10.1016\/j.aca.2019.03.055_bib14","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1182\/blood.V93.4.1338","article-title":"GCKR links the Bcr-Abl oncogene and Ras to the stress-activated protein kinase pathway","volume":"93","author":"Shi","year":"1999","journal-title":"Blood"},{"key":"10.1016\/j.aca.2019.03.055_bib15","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1158\/1078-0432.CCR-10-1613","article-title":"Molecular pathways: BCR-ABL","volume":"18","author":"Cilloni","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.aca.2019.03.055_bib16","doi-asserted-by":"crossref","first-page":"3343","DOI":"10.1182\/blood.V96.10.3343","article-title":"The molecular biology of chronic myeloid leukemia","volume":"96","author":"Deininger","year":"2000","journal-title":"Blood"},{"key":"10.1016\/j.aca.2019.03.055_bib17","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1182\/blood-2008-03-144790","article-title":"Molecular biology of bcr-abl1-positive chronic myeloid leukemia","volume":"113","author":"Quintas-Cardama","year":"2009","journal-title":"Blood"},{"key":"10.1016\/j.aca.2019.03.055_bib18","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/nrc2147","article-title":"Chronic myeloid leukaemia as a model of disease evolution in human cancer","volume":"7","author":"Melo","year":"2007","journal-title":"Nat. Rev. Canc."},{"key":"10.1016\/j.aca.2019.03.055_bib19","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1056\/NEJMra020777","article-title":"Chronic myeloid leukemia--advances in biology and new approaches to treatment","volume":"349","author":"Goldman","year":"2003","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.aca.2019.03.055_bib20","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1182\/blood.V78.5.1155.1155","article-title":"Does the breakpoint within the major breakpoint cluster region (M-bcr) influence the duration of the chronic phase in chronic myeloid leukemia? An analytical comparison of current literature","volume":"78","author":"Mills","year":"1991","journal-title":"Blood"},{"key":"10.1016\/j.aca.2019.03.055_bib21","doi-asserted-by":"crossref","first-page":"6041","DOI":"10.1200\/JCO.2009.25.0779","article-title":"Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet","volume":"27","author":"Baccarani","year":"2009","journal-title":"J.\u00a0Clin. Oncol."},{"key":"10.1016\/j.aca.2019.03.055_bib22","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.trsl.2006.07.002","article-title":"Comprehensive analysis of BCR-ABL transcript types in Korean CML patients using a newly developed multiplex RT-PCR","volume":"148","author":"Goh","year":"2006","journal-title":"Transl. Res."},{"key":"10.1016\/j.aca.2019.03.055_bib23","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/0092-8674(84)90077-1","article-title":"Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22","volume":"36","author":"Groffen","year":"1984","journal-title":"Cell"},{"key":"10.1016\/j.aca.2019.03.055_bib24","doi-asserted-by":"crossref","first-page":"108","DOI":"10.6026\/97320630010108","article-title":"Differences in structural elements of bcr-abl oncoprotein isoforms in chronic myelogenous leukemia","volume":"10","author":"Hai","year":"2014","journal-title":"Bioinformation"},{"key":"10.1016\/j.aca.2019.03.055_bib25","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1111\/j.1365-2141.1995.tb08362.x","article-title":"Analysis of molecular breakpoint and m-RNA transcripts in a prospective randomized trial of interferon in chronic myeloid leukaemia: no correlation with clinical features, cytogenetic response, duration of chronic phase, or survival","volume":"89","author":"Shepherd","year":"1995","journal-title":"Br. J. Haematol."},{"key":"10.1016\/j.aca.2019.03.055_bib26","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1016\/S0959-8049(00)00128-3","article-title":"The possible influences of B2A2 and B3A2 BCR\/ABL protein structure on thrombopoiesis in chronic myeloid leukaemia","volume":"36","author":"Perego","year":"2000","journal-title":"Eur. J. Cancer"},{"key":"10.1016\/j.aca.2019.03.055_bib27","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.3324\/haematol.2009.009134","article-title":"Chronic myeloid leukemia patients with the e13a2 BCR-ABL fusion transcript have inferior responses to imatinib compared to patients with the e14a2 transcript","volume":"94","author":"Lucas","year":"2009","journal-title":"Haematologica"},{"key":"10.1016\/j.aca.2019.03.055_bib28","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.3324\/haematol.2013.096537","article-title":"Distinct characteristics of e13a2 versus e14a2 BCR-ABL1 driven chronic myeloid leukemia under first-line therapy with imatinib","volume":"99","author":"Hanfstein","year":"2014","journal-title":"Haematologica"},{"key":"10.1016\/j.aca.2019.03.055_bib29","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1002\/ajh.24774","article-title":"The BCR-ABL1 transcript type influences response and outcome in Philadelphia chromosome-positive chronic myeloid leukemia patients treated frontline with imatinib","volume":"92","author":"Castagnetti","year":"2017","journal-title":"Am. J. Hematol."},{"key":"10.1016\/j.aca.2019.03.055_bib30","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1182\/blood-2015-10-674242","article-title":"Impact of BCR-ABL transcript type on outcome in patients with chronic-phase CML treated with tyrosine kinase inhibitors","volume":"127","author":"Jain","year":"2016","journal-title":"Blood"},{"key":"10.1016\/j.aca.2019.03.055_bib31","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1111\/ejh.12597","article-title":"Gender and BCR-ABL transcript type are correlated with molecular response to imatinib treatment in patients with chronic myeloid leukemia","volume":"96","author":"Lin","year":"2016","journal-title":"Eur. J. Haematol."},{"key":"10.1016\/j.aca.2019.03.055_bib32","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.jmoldx.2014.01.002","article-title":"ChildSeq-RNA: a next-generation sequencing-based diagnostic assay to identify known fusion transcripts in childhood sarcomas","volume":"16","author":"Qadir","year":"2014","journal-title":"J.\u00a0Mol. Diagn."},{"key":"10.1016\/j.aca.2019.03.055_bib33","doi-asserted-by":"crossref","first-page":"30722","DOI":"10.1038\/srep30722","article-title":"A\u00a0simple, rapid, low-cost technique for naked-eye detection of urine-isolated TMPRSS2:ERG gene fusion RNA","volume":"6","author":"Koo","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.aca.2019.03.055_bib34","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1593\/neo.06283","article-title":"Three-color FISH analysis of TMPRSS2\/ERG fusions in prostate cancer indicates that genomic microdeletion of chromosome 21 is associated with rearrangement","volume":"8","author":"Yoshimoto","year":"2006","journal-title":"Neoplasia"},{"key":"10.1016\/j.aca.2019.03.055_bib35","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.celrep.2013.12.002","article-title":"FuseFISH: robust detection of transcribed gene fusions in single cells","volume":"6","author":"Semrau","year":"2014","journal-title":"Cell Rep."},{"key":"10.1016\/j.aca.2019.03.055_bib36","doi-asserted-by":"crossref","first-page":"e23","DOI":"10.1093\/nar\/gkl1097","article-title":"Dry-reagent disposable dipstick test for visual screening of seven leukemia-related chromosomal translocations","volume":"35","author":"Kalogianni","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.aca.2019.03.055_bib37","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.talanta.2015.09.010","article-title":"A\u00a0colorimetric biosensor for detection of attomolar microRNA with a functional nucleic acid-based amplification machine","volume":"146","author":"Li","year":"2016","journal-title":"Talanta"},{"key":"10.1016\/j.aca.2019.03.055_bib38","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.aca.2017.11.016","article-title":"Highly sensitive MicroRNA 146a detection using a gold nanoparticle-based CTG repeat probing system and isothermal amplification","volume":"999","author":"Le","year":"2018","journal-title":"Anal. Chim. Acta"},{"key":"10.1016\/j.aca.2019.03.055_bib39","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.aca.2016.09.019","article-title":"G-quadruplex fluorescent probe-mediated real-time rolling circle amplification strategy for highly sensitive microRNA detection","volume":"943","author":"Jiang","year":"2016","journal-title":"Anal. Chim. Acta"},{"key":"10.1016\/j.aca.2019.03.055_bib40","doi-asserted-by":"crossref","first-page":"7137","DOI":"10.1021\/acs.analchem.6b01192","article-title":"Novel one-tube-one-step real-time methodology for rapid transcriptomic biomarker detection: signal amplification by ternary initiation complexes","volume":"88","author":"Fujita","year":"2016","journal-title":"Anal. Chem."},{"key":"10.1016\/j.aca.2019.03.055_bib41","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1471-2407-4-25","article-title":"Association of HLA Class I and Class II genes with bcr-abl transcripts in leukemia patients with t(9;22) (q34;q11)","volume":"4","author":"Mundhada","year":"2004","journal-title":"BMC Canc."},{"key":"10.1016\/j.aca.2019.03.055_bib42","doi-asserted-by":"crossref","first-page":"16134","DOI":"10.1021\/bi048634w","article-title":"Efficient silencing of bcr\/abl oncogene by single- and double-stranded siRNAs targeted against b2a2 transcripts","volume":"43","author":"Rapozzi","year":"2004","journal-title":"Biochemistry"},{"key":"10.1016\/j.aca.2019.03.055_bib43","doi-asserted-by":"crossref","first-page":"16636","DOI":"10.1002\/anie.201708964","article-title":"A\u00a0thermophilic tetramolecular G-quadruplex\/hemin DNAzyme","volume":"56","author":"Guo","year":"2017","journal-title":"Angew Chem. Int. Ed. Engl."},{"key":"10.1016\/j.aca.2019.03.055_bib44","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1021\/ja309588h","article-title":"Thioflavin T as an efficient inducer and selective fluorescent sensor for the human telomeric G-quadruplex DNA","volume":"135","author":"Mohanty","year":"2013","journal-title":"J.\u00a0Am. Chem. Soc."},{"key":"10.1016\/j.aca.2019.03.055_bib45","doi-asserted-by":"crossref","first-page":"11612","DOI":"10.1093\/nar\/gku833","article-title":"Selective recognition of parallel and anti-parallel thrombin-binding aptamer G-quadruplexes by different fluorescent dyes","volume":"42","author":"Zhao","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.aca.2019.03.055_bib46","doi-asserted-by":"crossref","first-page":"e65","DOI":"10.1093\/nar\/gku111","article-title":"Thioflavin T as a fluorescence light-up probe for G4 formation","volume":"42","author":"Renaud de la Faverie","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.aca.2019.03.055_bib47","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1002\/anie.201309388","article-title":"Toehold-initiated rolling circle amplification for visualizing individual microRNAs in situ in single cells","volume":"53","author":"Deng","year":"2014","journal-title":"Angew Chem. Int. Ed. Engl."},{"key":"10.1016\/j.aca.2019.03.055_bib48","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1182\/asheducation-2015.1.257","article-title":"Molecular monitoring in CML and the prospects for treatment-free remissions","author":"Deininger","year":"2015","journal-title":"Hematology"},{"key":"10.1016\/j.aca.2019.03.055_bib49","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1016\/j.mayocp.2015.08.010","article-title":"Diagnosis and treatment of chronic myeloid leukemia in 2015","volume":"90","author":"Thompson","year":"2015","journal-title":"Mayo Clin. Proc."},{"key":"10.1016\/j.aca.2019.03.055_bib50","doi-asserted-by":"crossref","first-page":"984","DOI":"10.6004\/jnccn.2009.0065","article-title":"NCCN clinical practice guidelines in oncology: chronic myelogenous leukemia","volume":"7","author":"O'Brien","year":"2009","journal-title":"J.\u00a0Natl. Compr. Cancer Netw."}],"container-title":["Analytica Chimica Acta"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0003267019303733?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0003267019303733?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T02:42:06Z","timestamp":1778640126000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0003267019303733"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8]]},"references-count":50,"alternative-id":["S0003267019303733"],"URL":"https:\/\/doi.org\/10.1016\/j.aca.2019.03.055","relation":{},"ISSN":["0003-2670"],"issn-type":[{"value":"0003-2670","type":"print"}],"subject":[],"published":{"date-parts":[[2019,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"One-step discrimination of BCR\/ABLp210 transcript isoforms directly from RNA extraction with fusion-triggered rolling circle amplification","name":"articletitle","label":"Article Title"},{"value":"Analytica Chimica Acta","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.aca.2019.03.055","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}