Loading…
DNA methylation at IL32 in juvenile idiopathic arthritis
Juvenile idiopathic arthritis (JIA) is the most common autoimmune rheumatic disease of childhood. We recently showed that DNA methylation at the gene encoding the pro-inflammatory cytokine interleukin-32 ( IL32 ) is reduced in JIA CD4+ T cells. To extend this finding, we measured IL32 methylation in...
Saved in:
| Published in: | Scientific reports 2015-06, Vol.5 (1), p.11063-11063, Article 11063 |
|---|---|
| Main Authors: | , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c438t-b8579e1b7a93eb23f32e1adf9a2233586aaa5fa4423953cd1c3bd2307d3c97283 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c438t-b8579e1b7a93eb23f32e1adf9a2233586aaa5fa4423953cd1c3bd2307d3c97283 |
| container_end_page | 11063 |
| container_issue | 1 |
| container_start_page | 11063 |
| container_title | Scientific reports |
| container_volume | 5 |
| creator | Meyer, Braydon Chavez, Raul A. Munro, Jane E. Chiaroni-Clarke, Rachel C. Akikusa, Jonathan D. Allen, Roger C. Craig, Jeffrey M. Ponsonby, Anne-Louise Saffery, Richard Ellis, Justine A. |
| description | Juvenile idiopathic arthritis (JIA) is the most common autoimmune rheumatic disease of childhood. We recently showed that DNA methylation at the gene encoding the pro-inflammatory cytokine interleukin-32 (
IL32
) is reduced in JIA CD4+ T cells. To extend this finding, we measured
IL32
methylation in CD4+ T-cells from an additional sample of JIA cases and age- and sex-matched controls and found a reduction in methylation associated with JIA consistent with the prior data (combined case-control dataset: 25.0% vs 37.7%, p = 0.0045). Further, JIA was associated with reduced
IL32
methylation in CD8+ T cells (15.2% vs 25.5%, p = 0.034), suggesting disease-associated changes to a T cell precursor. Additionally, we measured regional SNPs, along with CD4+ T cell expression of total
IL32
and the γ and β isoforms. Several SNPs were associated with methylation. Two SNPs were also associated with JIA and we found evidence of interaction such that methylation was only associated with JIA in minor allele carriers (e.g. rs10431961 p
interaction
= 0.011). Methylation at one measured CpG was inversely correlated with total
IL32
expression (Spearman r = −0.73, p = 0.0009), but this was not a JIA-associated CpG. Overall, our data further confirms that reduced
IL32
methylation is associated with JIA and that SNPs play an interactive role. |
| doi_str_mv | 10.1038/srep11063 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4603785</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1687654910</sourcerecordid><originalsourceid>FETCH-LOGICAL-c438t-b8579e1b7a93eb23f32e1adf9a2233586aaa5fa4423953cd1c3bd2307d3c97283</originalsourceid><addsrcrecordid>eNplkU1LAzEQhoMotlQP_gFZ8KJCNckkm-QiiJ-Fohc9h-xutk3Z7tYkK_jvjVRL1bnMwDy88_EidETwBcEgL4O3K0JwDjtoSDHjYwqU7m7VA3QYwgKn4FQxovbRgOaYCyHYEMnbp-tsaeP8ozHRdW1mYjaZAs1cmy36d9u6xmauct3KxLkrM-Pj3LvowgHaq00T7OF3HqHX-7uXm8fx9PlhcnM9HZcMZBwXkgtlSSGMAltQqIFaYqpaGUoBuMyNMbw2jFFQHMqKlFBUFLCooFSCShihq7Xuqi-WtiptG71p9Mq7pfEfujNO_-60bq5n3btmOQYheRI4_Rbw3VtvQ9RLF0rbNKa1XR80yaXIOVPpmSN08gdddL1v03maSKV4jgkjiTpbU6XvQvp-vVmGYP1lid5Yktjj7e035I8BCThfAyG12pn1WyP_qX0CW-eT6A</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1899560141</pqid></control><display><type>article</type><title>DNA methylation at IL32 in juvenile idiopathic arthritis</title><source>Publicly Available Content Database</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>Springer Nature - nature.com Journals - Fully Open Access</source><creator>Meyer, Braydon ; Chavez, Raul A. ; Munro, Jane E. ; Chiaroni-Clarke, Rachel C. ; Akikusa, Jonathan D. ; Allen, Roger C. ; Craig, Jeffrey M. ; Ponsonby, Anne-Louise ; Saffery, Richard ; Ellis, Justine A.</creator><creatorcontrib>Meyer, Braydon ; Chavez, Raul A. ; Munro, Jane E. ; Chiaroni-Clarke, Rachel C. ; Akikusa, Jonathan D. ; Allen, Roger C. ; Craig, Jeffrey M. ; Ponsonby, Anne-Louise ; Saffery, Richard ; Ellis, Justine A.</creatorcontrib><description>Juvenile idiopathic arthritis (JIA) is the most common autoimmune rheumatic disease of childhood. We recently showed that DNA methylation at the gene encoding the pro-inflammatory cytokine interleukin-32 (
IL32
) is reduced in JIA CD4+ T cells. To extend this finding, we measured
IL32
methylation in CD4+ T-cells from an additional sample of JIA cases and age- and sex-matched controls and found a reduction in methylation associated with JIA consistent with the prior data (combined case-control dataset: 25.0% vs 37.7%, p = 0.0045). Further, JIA was associated with reduced
IL32
methylation in CD8+ T cells (15.2% vs 25.5%, p = 0.034), suggesting disease-associated changes to a T cell precursor. Additionally, we measured regional SNPs, along with CD4+ T cell expression of total
IL32
and the γ and β isoforms. Several SNPs were associated with methylation. Two SNPs were also associated with JIA and we found evidence of interaction such that methylation was only associated with JIA in minor allele carriers (e.g. rs10431961 p
interaction
= 0.011). Methylation at one measured CpG was inversely correlated with total
IL32
expression (Spearman r = −0.73, p = 0.0009), but this was not a JIA-associated CpG. Overall, our data further confirms that reduced
IL32
methylation is associated with JIA and that SNPs play an interactive role.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep11063</identifier><identifier>PMID: 26057774</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>45/22 ; 45/41 ; 45/77 ; 45/90 ; 631/208/176/1988 ; 631/208/199 ; 631/208/200 ; Arthritis ; Arthritis, Juvenile - genetics ; CD4 antigen ; CD4-Positive T-Lymphocytes - metabolism ; CD8 antigen ; Children ; CpG islands ; DNA Methylation ; Humanities and Social Sciences ; Humans ; Inflammation ; Interleukins - metabolism ; Isoforms ; Lymphocytes T ; multidisciplinary ; Polymorphism, Single Nucleotide ; Rheumatic diseases ; Science ; Single-nucleotide polymorphism</subject><ispartof>Scientific reports, 2015-06, Vol.5 (1), p.11063-11063, Article 11063</ispartof><rights>The Author(s) 2015</rights><rights>Copyright Nature Publishing Group Jun 2015</rights><rights>Copyright © 2015, Macmillan Publishers Limited 2015 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-b8579e1b7a93eb23f32e1adf9a2233586aaa5fa4423953cd1c3bd2307d3c97283</citedby><cites>FETCH-LOGICAL-c438t-b8579e1b7a93eb23f32e1adf9a2233586aaa5fa4423953cd1c3bd2307d3c97283</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1899560141/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1899560141?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,315,730,783,787,888,25765,27936,27937,37024,37025,44602,53804,53806,75460</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26057774$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Meyer, Braydon</creatorcontrib><creatorcontrib>Chavez, Raul A.</creatorcontrib><creatorcontrib>Munro, Jane E.</creatorcontrib><creatorcontrib>Chiaroni-Clarke, Rachel C.</creatorcontrib><creatorcontrib>Akikusa, Jonathan D.</creatorcontrib><creatorcontrib>Allen, Roger C.</creatorcontrib><creatorcontrib>Craig, Jeffrey M.</creatorcontrib><creatorcontrib>Ponsonby, Anne-Louise</creatorcontrib><creatorcontrib>Saffery, Richard</creatorcontrib><creatorcontrib>Ellis, Justine A.</creatorcontrib><title>DNA methylation at IL32 in juvenile idiopathic arthritis</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Juvenile idiopathic arthritis (JIA) is the most common autoimmune rheumatic disease of childhood. We recently showed that DNA methylation at the gene encoding the pro-inflammatory cytokine interleukin-32 (
IL32
) is reduced in JIA CD4+ T cells. To extend this finding, we measured
IL32
methylation in CD4+ T-cells from an additional sample of JIA cases and age- and sex-matched controls and found a reduction in methylation associated with JIA consistent with the prior data (combined case-control dataset: 25.0% vs 37.7%, p = 0.0045). Further, JIA was associated with reduced
IL32
methylation in CD8+ T cells (15.2% vs 25.5%, p = 0.034), suggesting disease-associated changes to a T cell precursor. Additionally, we measured regional SNPs, along with CD4+ T cell expression of total
IL32
and the γ and β isoforms. Several SNPs were associated with methylation. Two SNPs were also associated with JIA and we found evidence of interaction such that methylation was only associated with JIA in minor allele carriers (e.g. rs10431961 p
interaction
= 0.011). Methylation at one measured CpG was inversely correlated with total
IL32
expression (Spearman r = −0.73, p = 0.0009), but this was not a JIA-associated CpG. Overall, our data further confirms that reduced
IL32
methylation is associated with JIA and that SNPs play an interactive role.</description><subject>45/22</subject><subject>45/41</subject><subject>45/77</subject><subject>45/90</subject><subject>631/208/176/1988</subject><subject>631/208/199</subject><subject>631/208/200</subject><subject>Arthritis</subject><subject>Arthritis, Juvenile - genetics</subject><subject>CD4 antigen</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>CD8 antigen</subject><subject>Children</subject><subject>CpG islands</subject><subject>DNA Methylation</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Interleukins - metabolism</subject><subject>Isoforms</subject><subject>Lymphocytes T</subject><subject>multidisciplinary</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Rheumatic diseases</subject><subject>Science</subject><subject>Single-nucleotide polymorphism</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNplkU1LAzEQhoMotlQP_gFZ8KJCNckkm-QiiJ-Fohc9h-xutk3Z7tYkK_jvjVRL1bnMwDy88_EidETwBcEgL4O3K0JwDjtoSDHjYwqU7m7VA3QYwgKn4FQxovbRgOaYCyHYEMnbp-tsaeP8ozHRdW1mYjaZAs1cmy36d9u6xmauct3KxLkrM-Pj3LvowgHaq00T7OF3HqHX-7uXm8fx9PlhcnM9HZcMZBwXkgtlSSGMAltQqIFaYqpaGUoBuMyNMbw2jFFQHMqKlFBUFLCooFSCShihq7Xuqi-WtiptG71p9Mq7pfEfujNO_-60bq5n3btmOQYheRI4_Rbw3VtvQ9RLF0rbNKa1XR80yaXIOVPpmSN08gdddL1v03maSKV4jgkjiTpbU6XvQvp-vVmGYP1lid5Yktjj7e035I8BCThfAyG12pn1WyP_qX0CW-eT6A</recordid><startdate>20150609</startdate><enddate>20150609</enddate><creator>Meyer, Braydon</creator><creator>Chavez, Raul A.</creator><creator>Munro, Jane E.</creator><creator>Chiaroni-Clarke, Rachel C.</creator><creator>Akikusa, Jonathan D.</creator><creator>Allen, Roger C.</creator><creator>Craig, Jeffrey M.</creator><creator>Ponsonby, Anne-Louise</creator><creator>Saffery, Richard</creator><creator>Ellis, Justine A.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150609</creationdate><title>DNA methylation at IL32 in juvenile idiopathic arthritis</title><author>Meyer, Braydon ; Chavez, Raul A. ; Munro, Jane E. ; Chiaroni-Clarke, Rachel C. ; Akikusa, Jonathan D. ; Allen, Roger C. ; Craig, Jeffrey M. ; Ponsonby, Anne-Louise ; Saffery, Richard ; Ellis, Justine A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-b8579e1b7a93eb23f32e1adf9a2233586aaa5fa4423953cd1c3bd2307d3c97283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>45/22</topic><topic>45/41</topic><topic>45/77</topic><topic>45/90</topic><topic>631/208/176/1988</topic><topic>631/208/199</topic><topic>631/208/200</topic><topic>Arthritis</topic><topic>Arthritis, Juvenile - genetics</topic><topic>CD4 antigen</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>CD8 antigen</topic><topic>Children</topic><topic>CpG islands</topic><topic>DNA Methylation</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Interleukins - metabolism</topic><topic>Isoforms</topic><topic>Lymphocytes T</topic><topic>multidisciplinary</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Rheumatic diseases</topic><topic>Science</topic><topic>Single-nucleotide polymorphism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Meyer, Braydon</creatorcontrib><creatorcontrib>Chavez, Raul A.</creatorcontrib><creatorcontrib>Munro, Jane E.</creatorcontrib><creatorcontrib>Chiaroni-Clarke, Rachel C.</creatorcontrib><creatorcontrib>Akikusa, Jonathan D.</creatorcontrib><creatorcontrib>Allen, Roger C.</creatorcontrib><creatorcontrib>Craig, Jeffrey M.</creatorcontrib><creatorcontrib>Ponsonby, Anne-Louise</creatorcontrib><creatorcontrib>Saffery, Richard</creatorcontrib><creatorcontrib>Ellis, Justine A.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Meyer, Braydon</au><au>Chavez, Raul A.</au><au>Munro, Jane E.</au><au>Chiaroni-Clarke, Rachel C.</au><au>Akikusa, Jonathan D.</au><au>Allen, Roger C.</au><au>Craig, Jeffrey M.</au><au>Ponsonby, Anne-Louise</au><au>Saffery, Richard</au><au>Ellis, Justine A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DNA methylation at IL32 in juvenile idiopathic arthritis</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2015-06-09</date><risdate>2015</risdate><volume>5</volume><issue>1</issue><spage>11063</spage><epage>11063</epage><pages>11063-11063</pages><artnum>11063</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Juvenile idiopathic arthritis (JIA) is the most common autoimmune rheumatic disease of childhood. We recently showed that DNA methylation at the gene encoding the pro-inflammatory cytokine interleukin-32 (
IL32
) is reduced in JIA CD4+ T cells. To extend this finding, we measured
IL32
methylation in CD4+ T-cells from an additional sample of JIA cases and age- and sex-matched controls and found a reduction in methylation associated with JIA consistent with the prior data (combined case-control dataset: 25.0% vs 37.7%, p = 0.0045). Further, JIA was associated with reduced
IL32
methylation in CD8+ T cells (15.2% vs 25.5%, p = 0.034), suggesting disease-associated changes to a T cell precursor. Additionally, we measured regional SNPs, along with CD4+ T cell expression of total
IL32
and the γ and β isoforms. Several SNPs were associated with methylation. Two SNPs were also associated with JIA and we found evidence of interaction such that methylation was only associated with JIA in minor allele carriers (e.g. rs10431961 p
interaction
= 0.011). Methylation at one measured CpG was inversely correlated with total
IL32
expression (Spearman r = −0.73, p = 0.0009), but this was not a JIA-associated CpG. Overall, our data further confirms that reduced
IL32
methylation is associated with JIA and that SNPs play an interactive role.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26057774</pmid><doi>10.1038/srep11063</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2045-2322 |
| ispartof | Scientific reports, 2015-06, Vol.5 (1), p.11063-11063, Article 11063 |
| issn | 2045-2322 2045-2322 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4603785 |
| source | Publicly Available Content Database; PubMed Central; Free Full-Text Journals in Chemistry; Springer Nature - nature.com Journals - Fully Open Access |
| subjects | 45/22 45/41 45/77 45/90 631/208/176/1988 631/208/199 631/208/200 Arthritis Arthritis, Juvenile - genetics CD4 antigen CD4-Positive T-Lymphocytes - metabolism CD8 antigen Children CpG islands DNA Methylation Humanities and Social Sciences Humans Inflammation Interleukins - metabolism Isoforms Lymphocytes T multidisciplinary Polymorphism, Single Nucleotide Rheumatic diseases Science Single-nucleotide polymorphism |
| title | DNA methylation at IL32 in juvenile idiopathic arthritis |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-11-11T20%3A40%3A30IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=DNA%20methylation%20at%20IL32%20in%20juvenile%20idiopathic%20arthritis&rft.jtitle=Scientific%20reports&rft.au=Meyer,%20Braydon&rft.date=2015-06-09&rft.volume=5&rft.issue=1&rft.spage=11063&rft.epage=11063&rft.pages=11063-11063&rft.artnum=11063&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/srep11063&rft_dat=%3Cproquest_pubme%3E1687654910%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c438t-b8579e1b7a93eb23f32e1adf9a2233586aaa5fa4423953cd1c3bd2307d3c97283%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1899560141&rft_id=info:pmid/26057774&rfr_iscdi=true |