Prognostic value of integrated cytogenetic, somatic variation, and copy number variation analyses in Korean patients with newly diagnosed multiple myeloma
To investigate the prognostic value of gene variants and copy number variations (CNVs) in patients with newly diagnosed multiple myeloma (NDMM), an integrative genomic analysis was performed. Sixty-seven patients with NDMM exhibiting more than 60% plasma cells in the bone marrow aspirate were enroll...
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| Veröffentlicht in: | PloS one 2021-02, Vol.16 (2), p.e0246322 |
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| creator | Lee, Nuri Kim, Sung-Min Lee, Youngeun Jeong, Dajeong Yun, Jiwon Ryu, Sohee Yoon, Sung-Soo Ahn, Yong-Oon Hwang, Sang Mee Lee, Dong Soon |
| description | To investigate the prognostic value of gene variants and copy number variations (CNVs) in patients with newly diagnosed multiple myeloma (NDMM), an integrative genomic analysis was performed.
Sixty-seven patients with NDMM exhibiting more than 60% plasma cells in the bone marrow aspirate were enrolled in the study. Whole-exome sequencing was conducted on bone marrow nucleated cells. Mutation and CNV analyses were performed using the CNVkit and Nexus Copy Number software. In addition, karyotype and fluorescent in situ hybridization were utilized for the integrated analysis.
Eighty-three driver gene mutations were detected in 63 patients with NDMM. The median number of mutations per patient was 2.0 (95% confidence interval [CI] = 2.0-3.0, range = 0-8). MAML2 and BHLHE41 mutations were associated with decreased survival. CNVs were detected in 56 patients (72.7%; 56/67). The median number of CNVs per patient was 6.0 (95% CI = 5.7-7.0; range = 0-16). Among the CNVs, 1q gain, 6p gain, 6q loss, 8p loss, and 13q loss were associated with decreased survival. Additionally, 1q gain and 6p gain were independent adverse prognostic factors. Increased numbers of CNVs and driver gene mutations were associated with poor clinical outcomes. Cluster analysis revealed that patients with the highest number of driver mutations along with 1q gain, 6p gain, and 13q loss exhibited the poorest prognosis.
In addition to the known prognostic factors, the integrated analysis of genetic variations and CNVs could contribute to prognostic stratification of patients with NDMM. |
| doi_str_mv | 10.1371/journal.pone.0246322 |
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Sixty-seven patients with NDMM exhibiting more than 60% plasma cells in the bone marrow aspirate were enrolled in the study. Whole-exome sequencing was conducted on bone marrow nucleated cells. Mutation and CNV analyses were performed using the CNVkit and Nexus Copy Number software. In addition, karyotype and fluorescent in situ hybridization were utilized for the integrated analysis.
Eighty-three driver gene mutations were detected in 63 patients with NDMM. The median number of mutations per patient was 2.0 (95% confidence interval [CI] = 2.0-3.0, range = 0-8). MAML2 and BHLHE41 mutations were associated with decreased survival. CNVs were detected in 56 patients (72.7%; 56/67). The median number of CNVs per patient was 6.0 (95% CI = 5.7-7.0; range = 0-16). Among the CNVs, 1q gain, 6p gain, 6q loss, 8p loss, and 13q loss were associated with decreased survival. Additionally, 1q gain and 6p gain were independent adverse prognostic factors. Increased numbers of CNVs and driver gene mutations were associated with poor clinical outcomes. Cluster analysis revealed that patients with the highest number of driver mutations along with 1q gain, 6p gain, and 13q loss exhibited the poorest prognosis.
In addition to the known prognostic factors, the integrated analysis of genetic variations and CNVs could contribute to prognostic stratification of patients with NDMM.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0246322</identifier><identifier>PMID: 33544757</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Albumins ; Algorithms ; Anemia ; Biology and Life Sciences ; Blood ; Bone diseases ; Cancer ; Chemical compounds ; Chemotherapy ; Computer programs ; Copy number ; Creatinine ; Cytogenetics ; Cytogenetics - methods ; Data analysis ; Deoxyribonucleic acid ; DNA ; DNA Copy Number Variations - genetics ; Editing ; Exome Sequencing ; Female ; Genetic aspects ; Genetic Testing - methods ; Genetic Variation - genetics ; Genomes ; Hematology ; Hospitals ; Humans ; Hybridization ; Hypercalcemia ; Karyotyping ; L-Lactate dehydrogenase ; Laboratories ; Lactate dehydrogenase ; Lactic acid ; Male ; Malignancy ; Medical prognosis ; Medical research ; Medical schools ; Medicine ; Medicine and Health Sciences ; Methodology ; Middle Aged ; Multiple myeloma ; Multiple Myeloma - diagnosis ; Multiple Myeloma - genetics ; Multiple Myeloma - mortality ; Mutation ; Patients ; Pharmacology ; Plasma ; Polymerase chain reaction ; Prognosis ; Protocol (computers) ; Quality control ; Renal function ; Republic of Korea ; Research and Analysis Methods ; Signs and symptoms ; Software ; Survival Analysis ; Urea ; Visualization</subject><ispartof>PloS one, 2021-02, Vol.16 (2), p.e0246322</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Lee 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>2021 Lee et al 2021 Lee et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-1a988636b5826d47da56ce9a8070e04016fa6c9762fbe98090908dc327001a4d3</citedby><cites>FETCH-LOGICAL-c692t-1a988636b5826d47da56ce9a8070e04016fa6c9762fbe98090908dc327001a4d3</cites><orcidid>0000-0003-2591-7459</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864461/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864461/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33544757$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Nuri</creatorcontrib><creatorcontrib>Kim, Sung-Min</creatorcontrib><creatorcontrib>Lee, Youngeun</creatorcontrib><creatorcontrib>Jeong, Dajeong</creatorcontrib><creatorcontrib>Yun, Jiwon</creatorcontrib><creatorcontrib>Ryu, Sohee</creatorcontrib><creatorcontrib>Yoon, Sung-Soo</creatorcontrib><creatorcontrib>Ahn, Yong-Oon</creatorcontrib><creatorcontrib>Hwang, Sang Mee</creatorcontrib><creatorcontrib>Lee, Dong Soon</creatorcontrib><title>Prognostic value of integrated cytogenetic, somatic variation, and copy number variation analyses in Korean patients with newly diagnosed multiple myeloma</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>To investigate the prognostic value of gene variants and copy number variations (CNVs) in patients with newly diagnosed multiple myeloma (NDMM), an integrative genomic analysis was performed.
Sixty-seven patients with NDMM exhibiting more than 60% plasma cells in the bone marrow aspirate were enrolled in the study. Whole-exome sequencing was conducted on bone marrow nucleated cells. Mutation and CNV analyses were performed using the CNVkit and Nexus Copy Number software. In addition, karyotype and fluorescent in situ hybridization were utilized for the integrated analysis.
Eighty-three driver gene mutations were detected in 63 patients with NDMM. The median number of mutations per patient was 2.0 (95% confidence interval [CI] = 2.0-3.0, range = 0-8). MAML2 and BHLHE41 mutations were associated with decreased survival. CNVs were detected in 56 patients (72.7%; 56/67). The median number of CNVs per patient was 6.0 (95% CI = 5.7-7.0; range = 0-16). Among the CNVs, 1q gain, 6p gain, 6q loss, 8p loss, and 13q loss were associated with decreased survival. Additionally, 1q gain and 6p gain were independent adverse prognostic factors. Increased numbers of CNVs and driver gene mutations were associated with poor clinical outcomes. Cluster analysis revealed that patients with the highest number of driver mutations along with 1q gain, 6p gain, and 13q loss exhibited the poorest prognosis.
In addition to the known prognostic factors, the integrated analysis of genetic variations and CNVs could contribute to prognostic stratification of patients with NDMM.</description><subject>Aged</subject><subject>Albumins</subject><subject>Algorithms</subject><subject>Anemia</subject><subject>Biology and Life Sciences</subject><subject>Blood</subject><subject>Bone diseases</subject><subject>Cancer</subject><subject>Chemical compounds</subject><subject>Chemotherapy</subject><subject>Computer programs</subject><subject>Copy number</subject><subject>Creatinine</subject><subject>Cytogenetics</subject><subject>Cytogenetics - methods</subject><subject>Data analysis</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Copy Number Variations - genetics</subject><subject>Editing</subject><subject>Exome Sequencing</subject><subject>Female</subject><subject>Genetic aspects</subject><subject>Genetic Testing - methods</subject><subject>Genetic Variation - genetics</subject><subject>Genomes</subject><subject>Hematology</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Hybridization</subject><subject>Hypercalcemia</subject><subject>Karyotyping</subject><subject>L-Lactate dehydrogenase</subject><subject>Laboratories</subject><subject>Lactate dehydrogenase</subject><subject>Lactic acid</subject><subject>Male</subject><subject>Malignancy</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Medical schools</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Methodology</subject><subject>Middle Aged</subject><subject>Multiple myeloma</subject><subject>Multiple Myeloma - diagnosis</subject><subject>Multiple Myeloma - genetics</subject><subject>Multiple Myeloma - mortality</subject><subject>Mutation</subject><subject>Patients</subject><subject>Pharmacology</subject><subject>Plasma</subject><subject>Polymerase chain reaction</subject><subject>Prognosis</subject><subject>Protocol (computers)</subject><subject>Quality control</subject><subject>Renal function</subject><subject>Republic of Korea</subject><subject>Research and Analysis Methods</subject><subject>Signs and symptoms</subject><subject>Software</subject><subject>Survival Analysis</subject><subject>Urea</subject><subject>Visualization</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9tu1DAQhiMEoqXwBggsISGQuosdO45zg1RVHCoqFXG6tWaTSdaVYy920rKvwtPidLeli3qBfGHL883_22NPlj1ldM54yd6c-zE4sPOVdzinuZA8z-9l-6zi-UzmlN-_td7LHsV4TmnBlZQPsz3OCyHKotzPfn8OvnM-DqYmF2BHJL4lxg3YBRiwIfV68B06TPFDEn0PGzCYtPDukIBLjF-tiRv7BYa_oRQBu44Ykxr55AOCI6sUQTdEcmmGJXF4adekMTD5J6t-tINZWST9Gm1yepw9aMFGfLKdD7Lv7999O_44Oz37cHJ8dDqrZZUPMwaVUpLLRaFy2YiygULWWIGiJUUqKJMtyLoqZd4usFK0SkM1Nc9LShmIhh9kzze6K-uj3pY16lwoqYQQiibiZEM0Hs71Kpgewlp7MPpqw4dOQ0iFsaglo7LlvC5aVqZctcgFoGSLBkoBTcmS1tut27josalTPQLYHdHdiDNL3fkLXSophJwEXm0Fgv85Yhx0b2KN1oJDP16du2RFJZhK6It_0Ltvt6U6SBcwrvXJt55E9ZEsqCpkISat-R1UGg32pk5_sDVpfyfh9U5CYgb8NXQwxqhPvn75f_bsxy778ha7RLDDMno7Tp8u7oJiA9bBxxiwvSkyo3pqoetq6KmF9LaFUtqz2w90k3TdM_wP5ukY-A</recordid><startdate>20210205</startdate><enddate>20210205</enddate><creator>Lee, Nuri</creator><creator>Kim, Sung-Min</creator><creator>Lee, Youngeun</creator><creator>Jeong, Dajeong</creator><creator>Yun, Jiwon</creator><creator>Ryu, Sohee</creator><creator>Yoon, Sung-Soo</creator><creator>Ahn, Yong-Oon</creator><creator>Hwang, Sang Mee</creator><creator>Lee, Dong Soon</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>AEUYN</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><orcidid>https://orcid.org/0000-0003-2591-7459</orcidid></search><sort><creationdate>20210205</creationdate><title>Prognostic value of integrated cytogenetic, somatic variation, and copy number variation analyses in Korean patients with newly diagnosed multiple myeloma</title><author>Lee, Nuri ; Kim, Sung-Min ; Lee, Youngeun ; Jeong, Dajeong ; Yun, Jiwon ; Ryu, Sohee ; Yoon, Sung-Soo ; Ahn, Yong-Oon ; Hwang, Sang Mee ; Lee, Dong Soon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-1a988636b5826d47da56ce9a8070e04016fa6c9762fbe98090908dc327001a4d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Aged</topic><topic>Albumins</topic><topic>Algorithms</topic><topic>Anemia</topic><topic>Biology and Life Sciences</topic><topic>Blood</topic><topic>Bone diseases</topic><topic>Cancer</topic><topic>Chemical compounds</topic><topic>Chemotherapy</topic><topic>Computer programs</topic><topic>Copy number</topic><topic>Creatinine</topic><topic>Cytogenetics</topic><topic>Cytogenetics - methods</topic><topic>Data analysis</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Copy Number Variations - genetics</topic><topic>Editing</topic><topic>Exome Sequencing</topic><topic>Female</topic><topic>Genetic aspects</topic><topic>Genetic Testing - methods</topic><topic>Genetic Variation - genetics</topic><topic>Genomes</topic><topic>Hematology</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Hybridization</topic><topic>Hypercalcemia</topic><topic>Karyotyping</topic><topic>L-Lactate dehydrogenase</topic><topic>Laboratories</topic><topic>Lactate dehydrogenase</topic><topic>Lactic acid</topic><topic>Male</topic><topic>Malignancy</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Medical schools</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Methodology</topic><topic>Middle Aged</topic><topic>Multiple myeloma</topic><topic>Multiple Myeloma - diagnosis</topic><topic>Multiple Myeloma - genetics</topic><topic>Multiple Myeloma - 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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>Lee, Nuri</au><au>Kim, Sung-Min</au><au>Lee, Youngeun</au><au>Jeong, Dajeong</au><au>Yun, Jiwon</au><au>Ryu, Sohee</au><au>Yoon, Sung-Soo</au><au>Ahn, Yong-Oon</au><au>Hwang, Sang Mee</au><au>Lee, Dong Soon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prognostic value of integrated cytogenetic, somatic variation, and copy number variation analyses in Korean patients with newly diagnosed multiple myeloma</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2021-02-05</date><risdate>2021</risdate><volume>16</volume><issue>2</issue><spage>e0246322</spage><pages>e0246322-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>To investigate the prognostic value of gene variants and copy number variations (CNVs) in patients with newly diagnosed multiple myeloma (NDMM), an integrative genomic analysis was performed.
Sixty-seven patients with NDMM exhibiting more than 60% plasma cells in the bone marrow aspirate were enrolled in the study. Whole-exome sequencing was conducted on bone marrow nucleated cells. Mutation and CNV analyses were performed using the CNVkit and Nexus Copy Number software. In addition, karyotype and fluorescent in situ hybridization were utilized for the integrated analysis.
Eighty-three driver gene mutations were detected in 63 patients with NDMM. The median number of mutations per patient was 2.0 (95% confidence interval [CI] = 2.0-3.0, range = 0-8). MAML2 and BHLHE41 mutations were associated with decreased survival. CNVs were detected in 56 patients (72.7%; 56/67). The median number of CNVs per patient was 6.0 (95% CI = 5.7-7.0; range = 0-16). Among the CNVs, 1q gain, 6p gain, 6q loss, 8p loss, and 13q loss were associated with decreased survival. Additionally, 1q gain and 6p gain were independent adverse prognostic factors. Increased numbers of CNVs and driver gene mutations were associated with poor clinical outcomes. Cluster analysis revealed that patients with the highest number of driver mutations along with 1q gain, 6p gain, and 13q loss exhibited the poorest prognosis.
In addition to the known prognostic factors, the integrated analysis of genetic variations and CNVs could contribute to prognostic stratification of patients with NDMM.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33544757</pmid><doi>10.1371/journal.pone.0246322</doi><tpages>e0246322</tpages><orcidid>https://orcid.org/0000-0003-2591-7459</orcidid><oa>free_for_read</oa></addata></record> |
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| language | eng |
| recordid | cdi_plos_journals_2486844480 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Aged Albumins Algorithms Anemia Biology and Life Sciences Blood Bone diseases Cancer Chemical compounds Chemotherapy Computer programs Copy number Creatinine Cytogenetics Cytogenetics - methods Data analysis Deoxyribonucleic acid DNA DNA Copy Number Variations - genetics Editing Exome Sequencing Female Genetic aspects Genetic Testing - methods Genetic Variation - genetics Genomes Hematology Hospitals Humans Hybridization Hypercalcemia Karyotyping L-Lactate dehydrogenase Laboratories Lactate dehydrogenase Lactic acid Male Malignancy Medical prognosis Medical research Medical schools Medicine Medicine and Health Sciences Methodology Middle Aged Multiple myeloma Multiple Myeloma - diagnosis Multiple Myeloma - genetics Multiple Myeloma - mortality Mutation Patients Pharmacology Plasma Polymerase chain reaction Prognosis Protocol (computers) Quality control Renal function Republic of Korea Research and Analysis Methods Signs and symptoms Software Survival Analysis Urea Visualization |
| title | Prognostic value of integrated cytogenetic, somatic variation, and copy number variation analyses in Korean patients with newly diagnosed multiple myeloma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T10%3A23%3A25IST&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%20integrated%20cytogenetic,%20somatic%20variation,%20and%20copy%20number%20variation%20analyses%20in%20Korean%20patients%20with%20newly%20diagnosed%20multiple%20myeloma&rft.jtitle=PloS%20one&rft.au=Lee,%20Nuri&rft.date=2021-02-05&rft.volume=16&rft.issue=2&rft.spage=e0246322&rft.pages=e0246322-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0246322&rft_dat=%3Cgale_plos_%3EA650856548%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=2486844480&rft_id=info:pmid/33544757&rft_galeid=A650856548&rft_doaj_id=oai_doaj_org_article_6106f33c5f174488b24ae61bda74ad71&rfr_iscdi=true |