Prognostic value of isocitrate dehydrogenase mutations in myelodysplastic syndromes: a retrospective cohort study and meta-analysis
Recent genomic sequencing efforts have identified a number of recurrent mutations in myelodysplastic syndromes (MDS) that may contribute to disease progression and overall survival, including mutations in isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2). Pretreatment bone marrow (BM) samples were a...
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| creator | Jin, Jie Hu, Chao Yu, Mengxia Chen, Feifei Ye, Li Yin, Xiufeng Zhuang, Zhengping Tong, Hongyan |
| description | Recent genomic sequencing efforts have identified a number of recurrent mutations in myelodysplastic syndromes (MDS) that may contribute to disease progression and overall survival, including mutations in isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2).
Pretreatment bone marrow (BM) samples were acquired from mononuclear cells in 146 adult patients with de novo MDS from January 2006 to June 2013. Polymerase chain reaction (PCR) and direct sequencing were performed on exon 4 of IDH1/2 genes and mutation status was correlated with overall survival (OS) and leukemia-free survival (LFS). We then performed a meta-analysis combining previously published and current studies to explore the effect of IDH mutations on OS and LFS in MDS.
In our study, somatic mutations of either IDH gene were discovered in 11 MDS patients (7.53%) and were significantly correlated with poorer OS (P = 0.007). IDH mutations were specifically associated with a poorer OS in the intermediate-1 risk group by the International Prognostic Scoring System (IPSS) (P = 0.039). In addition, we discovered decitabine achieved a better therapeutic effect compared to other treatments in IDH mutation-positive patients (P = 0.023). We identified six previous studies of IDH mutations in MDS. A meta-analysis of these studies included 111 MDS patients IDH mutations and 1671 MDS patients with wild-type IDH1/2. The hazard ratios (HRs) of OS and LFS for patients with IDH mutations were 1.62 (95% CI, 1.27-2.09) and 2.21 (95% CI, 1.48-3.30), respectively.
The results from our study and the meta-analysis provide firm evidence that IDH mutations are significantly associated with poorer clinical outcomes in MDS. Identification of IDH mutations may be pivotal for better risk stratification in MDS patients and improving IPSS score. Additionally, hypomethylating agents may be an effective treatment option for MDS patients with IDH mutations. |
| doi_str_mv | 10.1371/journal.pone.0100206 |
| format | Article |
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Pretreatment bone marrow (BM) samples were acquired from mononuclear cells in 146 adult patients with de novo MDS from January 2006 to June 2013. Polymerase chain reaction (PCR) and direct sequencing were performed on exon 4 of IDH1/2 genes and mutation status was correlated with overall survival (OS) and leukemia-free survival (LFS). We then performed a meta-analysis combining previously published and current studies to explore the effect of IDH mutations on OS and LFS in MDS.
In our study, somatic mutations of either IDH gene were discovered in 11 MDS patients (7.53%) and were significantly correlated with poorer OS (P = 0.007). IDH mutations were specifically associated with a poorer OS in the intermediate-1 risk group by the International Prognostic Scoring System (IPSS) (P = 0.039). In addition, we discovered decitabine achieved a better therapeutic effect compared to other treatments in IDH mutation-positive patients (P = 0.023). We identified six previous studies of IDH mutations in MDS. A meta-analysis of these studies included 111 MDS patients IDH mutations and 1671 MDS patients with wild-type IDH1/2. The hazard ratios (HRs) of OS and LFS for patients with IDH mutations were 1.62 (95% CI, 1.27-2.09) and 2.21 (95% CI, 1.48-3.30), respectively.
The results from our study and the meta-analysis provide firm evidence that IDH mutations are significantly associated with poorer clinical outcomes in MDS. Identification of IDH mutations may be pivotal for better risk stratification in MDS patients and improving IPSS score. Additionally, hypomethylating agents may be an effective treatment option for MDS patients with IDH mutations.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0100206</identifier><identifier>PMID: 24936872</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>5-aza-2'-deoxycytidine ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Analysis ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Bone marrow ; Cancer therapies ; Cell cycle ; Cohort analysis ; Dehydrogenases ; Deoxyribonucleic acid ; Development and progression ; Disorders ; DNA ; DNA methylation ; Enzymes ; Female ; Follow-Up Studies ; Gene sequencing ; Hematology ; Hospitals ; Humans ; Hypoxia ; IDH gene ; Isocitrate dehydrogenase ; Isocitrate Dehydrogenase - genetics ; Leukemia ; Leukocytes (mononuclear) ; Male ; Medical prognosis ; Medical research ; Medicine ; Medicine and Health Sciences ; Meta-analysis ; Middle Aged ; Mutation ; Mutation - genetics ; Myelodysplastic syndrome ; Myelodysplastic syndromes ; Myelodysplastic Syndromes - drug therapy ; Myelodysplastic Syndromes - genetics ; Myelodysplastic Syndromes - mortality ; Oxidoreductases ; Pathogenesis ; Patients ; Polymerase chain reaction ; Prognosis ; Reagents ; Retrospective Studies ; Survival ; Survival Rate ; Young Adult</subject><ispartof>PloS one, 2014-06, Vol.9 (6), p.e100206-e100206</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Jin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Jin et al 2014 Jin et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-1d2f296931b3f986e2644df687a18ced95f052926420a7b994564752edf78b4f3</citedby><cites>FETCH-LOGICAL-c758t-1d2f296931b3f986e2644df687a18ced95f052926420a7b994564752edf78b4f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4061070/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4061070/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2929,23871,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24936872$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Zuo, Zhuang</contributor><creatorcontrib>Jin, Jie</creatorcontrib><creatorcontrib>Hu, Chao</creatorcontrib><creatorcontrib>Yu, Mengxia</creatorcontrib><creatorcontrib>Chen, Feifei</creatorcontrib><creatorcontrib>Ye, Li</creatorcontrib><creatorcontrib>Yin, Xiufeng</creatorcontrib><creatorcontrib>Zhuang, Zhengping</creatorcontrib><creatorcontrib>Tong, Hongyan</creatorcontrib><title>Prognostic value of isocitrate dehydrogenase mutations in myelodysplastic syndromes: a retrospective cohort study and meta-analysis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Recent genomic sequencing efforts have identified a number of recurrent mutations in myelodysplastic syndromes (MDS) that may contribute to disease progression and overall survival, including mutations in isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2).
Pretreatment bone marrow (BM) samples were acquired from mononuclear cells in 146 adult patients with de novo MDS from January 2006 to June 2013. Polymerase chain reaction (PCR) and direct sequencing were performed on exon 4 of IDH1/2 genes and mutation status was correlated with overall survival (OS) and leukemia-free survival (LFS). We then performed a meta-analysis combining previously published and current studies to explore the effect of IDH mutations on OS and LFS in MDS.
In our study, somatic mutations of either IDH gene were discovered in 11 MDS patients (7.53%) and were significantly correlated with poorer OS (P = 0.007). IDH mutations were specifically associated with a poorer OS in the intermediate-1 risk group by the International Prognostic Scoring System (IPSS) (P = 0.039). In addition, we discovered decitabine achieved a better therapeutic effect compared to other treatments in IDH mutation-positive patients (P = 0.023). We identified six previous studies of IDH mutations in MDS. A meta-analysis of these studies included 111 MDS patients IDH mutations and 1671 MDS patients with wild-type IDH1/2. The hazard ratios (HRs) of OS and LFS for patients with IDH mutations were 1.62 (95% CI, 1.27-2.09) and 2.21 (95% CI, 1.48-3.30), respectively.
The results from our study and the meta-analysis provide firm evidence that IDH mutations are significantly associated with poorer clinical outcomes in MDS. Identification of IDH mutations may be pivotal for better risk stratification in MDS patients and improving IPSS score. Additionally, hypomethylating agents may be an effective treatment option for MDS patients with IDH mutations.</description><subject>5-aza-2'-deoxycytidine</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analysis</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Bone marrow</subject><subject>Cancer therapies</subject><subject>Cell cycle</subject><subject>Cohort analysis</subject><subject>Dehydrogenases</subject><subject>Deoxyribonucleic acid</subject><subject>Development and progression</subject><subject>Disorders</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>Enzymes</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Gene sequencing</subject><subject>Hematology</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>IDH gene</subject><subject>Isocitrate dehydrogenase</subject><subject>Isocitrate Dehydrogenase - genetics</subject><subject>Leukemia</subject><subject>Leukocytes (mononuclear)</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Meta-analysis</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Mutation - genetics</subject><subject>Myelodysplastic syndrome</subject><subject>Myelodysplastic syndromes</subject><subject>Myelodysplastic Syndromes - drug therapy</subject><subject>Myelodysplastic Syndromes - genetics</subject><subject>Myelodysplastic Syndromes - mortality</subject><subject>Oxidoreductases</subject><subject>Pathogenesis</subject><subject>Patients</subject><subject>Polymerase chain reaction</subject><subject>Prognosis</subject><subject>Reagents</subject><subject>Retrospective Studies</subject><subject>Survival</subject><subject>Survival Rate</subject><subject>Young Adult</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk01r3DAQhk1padK0_6C0gkJpD7vVly2rh0II_VgIpPTrKrTSeFeLbW0sOdTn_vFqd52wLjkUH2xGz7yaeT2TZc8JnhMmyLuN77tW1_Otb2GOCcYUFw-yUyIZnRUUs4dH3yfZkxA2GOesLIrH2QnlkhWloKfZn6-dX7U-RGfQja57QL5CLnjjYqcjIAvrwSYEWh0ANX3U0fk2INeiZoDa2yFsa71PD0ObyAbCe6RRB7HzYQsmuhtAxq99F1GIvR2Qbi1qIOqZTuUPwYWn2aNK1wGeje-z7Oenjz8uvswurz4vLs4vZ0bkZZwRSysqC8nIklWyLIAWnNsq9aFJacDKvMI5lSlKsRZLKXlecJFTsJUol7xiZ9nLg-629kGN_gVFZMlLJnMpErE4ENbrjdp2rtHdoLx2ah_w3UrpLvVag7KFEIRazCkxvBSw1EYvIeciFcZlmSetD-Nt_bIBa6BNjtYT0elJ69Zq5W8UxwXBAieBN6NA5697CFE1Lhioa92C71PdORO5ZAzv0Ff_oPd3N1IrnRpwbeXTvWYnqs45KTlNbpWJmt9DpcdC40watsql-CTh7SQhMRF-x5XuQ1CL79_-n736NWVfH7Fr0HVcB1_3-wGcgvwAmjRyoYPqzmSC1W5Xbt1Qu11R466ktBfHP-gu6XY52F_UJhE5</recordid><startdate>20140617</startdate><enddate>20140617</enddate><creator>Jin, Jie</creator><creator>Hu, Chao</creator><creator>Yu, Mengxia</creator><creator>Chen, Feifei</creator><creator>Ye, Li</creator><creator>Yin, Xiufeng</creator><creator>Zhuang, Zhengping</creator><creator>Tong, Hongyan</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140617</creationdate><title>Prognostic value of isocitrate dehydrogenase mutations in myelodysplastic syndromes: a retrospective cohort study and meta-analysis</title><author>Jin, Jie ; Hu, Chao ; Yu, Mengxia ; Chen, Feifei ; Ye, Li ; Yin, Xiufeng ; Zhuang, Zhengping ; Tong, Hongyan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-1d2f296931b3f986e2644df687a18ced95f052926420a7b994564752edf78b4f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>5-aza-2'-deoxycytidine</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Analysis</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Bone marrow</topic><topic>Cancer therapies</topic><topic>Cell cycle</topic><topic>Cohort analysis</topic><topic>Dehydrogenases</topic><topic>Deoxyribonucleic acid</topic><topic>Development and progression</topic><topic>Disorders</topic><topic>DNA</topic><topic>DNA methylation</topic><topic>Enzymes</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Gene sequencing</topic><topic>Hematology</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>IDH gene</topic><topic>Isocitrate dehydrogenase</topic><topic>Isocitrate Dehydrogenase - genetics</topic><topic>Leukemia</topic><topic>Leukocytes (mononuclear)</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Meta-analysis</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Mutation - genetics</topic><topic>Myelodysplastic syndrome</topic><topic>Myelodysplastic syndromes</topic><topic>Myelodysplastic Syndromes - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jin, Jie</au><au>Hu, Chao</au><au>Yu, Mengxia</au><au>Chen, Feifei</au><au>Ye, Li</au><au>Yin, Xiufeng</au><au>Zhuang, Zhengping</au><au>Tong, Hongyan</au><au>Zuo, Zhuang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prognostic value of isocitrate dehydrogenase mutations in myelodysplastic syndromes: a retrospective cohort study and meta-analysis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-06-17</date><risdate>2014</risdate><volume>9</volume><issue>6</issue><spage>e100206</spage><epage>e100206</epage><pages>e100206-e100206</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Recent genomic sequencing efforts have identified a number of recurrent mutations in myelodysplastic syndromes (MDS) that may contribute to disease progression and overall survival, including mutations in isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2).
Pretreatment bone marrow (BM) samples were acquired from mononuclear cells in 146 adult patients with de novo MDS from January 2006 to June 2013. Polymerase chain reaction (PCR) and direct sequencing were performed on exon 4 of IDH1/2 genes and mutation status was correlated with overall survival (OS) and leukemia-free survival (LFS). We then performed a meta-analysis combining previously published and current studies to explore the effect of IDH mutations on OS and LFS in MDS.
In our study, somatic mutations of either IDH gene were discovered in 11 MDS patients (7.53%) and were significantly correlated with poorer OS (P = 0.007). IDH mutations were specifically associated with a poorer OS in the intermediate-1 risk group by the International Prognostic Scoring System (IPSS) (P = 0.039). In addition, we discovered decitabine achieved a better therapeutic effect compared to other treatments in IDH mutation-positive patients (P = 0.023). We identified six previous studies of IDH mutations in MDS. A meta-analysis of these studies included 111 MDS patients IDH mutations and 1671 MDS patients with wild-type IDH1/2. The hazard ratios (HRs) of OS and LFS for patients with IDH mutations were 1.62 (95% CI, 1.27-2.09) and 2.21 (95% CI, 1.48-3.30), respectively.
The results from our study and the meta-analysis provide firm evidence that IDH mutations are significantly associated with poorer clinical outcomes in MDS. Identification of IDH mutations may be pivotal for better risk stratification in MDS patients and improving IPSS score. Additionally, hypomethylating agents may be an effective treatment option for MDS patients with IDH mutations.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24936872</pmid><doi>10.1371/journal.pone.0100206</doi><oa>free_for_read</oa></addata></record> |
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| ispartof | PloS one, 2014-06, Vol.9 (6), p.e100206-e100206 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1984839597 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 5-aza-2'-deoxycytidine Adolescent Adult Aged Aged, 80 and over Analysis Antineoplastic Combined Chemotherapy Protocols - therapeutic use Bone marrow Cancer therapies Cell cycle Cohort analysis Dehydrogenases Deoxyribonucleic acid Development and progression Disorders DNA DNA methylation Enzymes Female Follow-Up Studies Gene sequencing Hematology Hospitals Humans Hypoxia IDH gene Isocitrate dehydrogenase Isocitrate Dehydrogenase - genetics Leukemia Leukocytes (mononuclear) Male Medical prognosis Medical research Medicine Medicine and Health Sciences Meta-analysis Middle Aged Mutation Mutation - genetics Myelodysplastic syndrome Myelodysplastic syndromes Myelodysplastic Syndromes - drug therapy Myelodysplastic Syndromes - genetics Myelodysplastic Syndromes - mortality Oxidoreductases Pathogenesis Patients Polymerase chain reaction Prognosis Reagents Retrospective Studies Survival Survival Rate Young Adult |
| title | Prognostic value of isocitrate dehydrogenase mutations in myelodysplastic syndromes: a retrospective cohort study and meta-analysis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-11T18%3A57%3A23IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Prognostic%20value%20of%20isocitrate%20dehydrogenase%20mutations%20in%20myelodysplastic%20syndromes:%20a%20retrospective%20cohort%20study%20and%20meta-analysis&rft.jtitle=PloS%20one&rft.au=Jin,%20Jie&rft.date=2014-06-17&rft.volume=9&rft.issue=6&rft.spage=e100206&rft.epage=e100206&rft.pages=e100206-e100206&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0100206&rft_dat=%3Cgale_plos_%3EA418424758%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1984839597&rft_id=info:pmid/24936872&rft_galeid=A418424758&rft_doaj_id=oai_doaj_org_article_d67712d0421c487ebacabe54786e4985&rfr_iscdi=true |