Loading…
A comprehensive meta-analysis of association between genetic variants of GDF5 and osteoarthritis of the knee, hip and hand
Objective A number of studies have reported an association of GDF5 with osteoarthritis (OA) but have produced some divergent findings and their interpretation may not be straightforward. Methods We investigated the association between GDF5 and OA using meta-analytic techniques, combining all publish...
Saved in:
Published in: | Inflammation research 2015-06, Vol.64 (6), p.405-414 |
---|---|
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-c442t-665c5203994901178506685223f3e6fbb6a94310a8a56f4761e59cb418ef554a3 |
---|---|
cites | cdi_FETCH-LOGICAL-c442t-665c5203994901178506685223f3e6fbb6a94310a8a56f4761e59cb418ef554a3 |
container_end_page | 414 |
container_issue | 6 |
container_start_page | 405 |
container_title | Inflammation research |
container_volume | 64 |
creator | Zhang, Rui Yao, Jianfeng Xu, Peng Ji, Baohu Luck, James V. Chin, Brian Lu, Shemin Kelsoe, John R. Ma, Jie |
description | Objective
A number of studies have reported an association of GDF5 with osteoarthritis (OA) but have produced some divergent findings and their interpretation may not be straightforward.
Methods
We investigated the association between GDF5 and OA using meta-analytic techniques, combining all published data up to Nov 2014. 16 independent samples from 11 research teams contributed data on SNP rs143383 (located in the 5’-UTR of GDF5) and knee, hip, and hand OA. The total number of cases and controls for this marker was 7,965 and 12,747 for knee OA, 6,363 and 9,727 for hip OA, and 4,335 and 5,991 for hand OA, respectively. The ORs for each OA phenotype were synthesized using random-effects models or fixed-effects models depending on the test of between-study heterogeneity.
Results
Using a random-effect model, a significant difference was identified between patients with knee OA and controls for the T-allele of rs143383 (Subtotal OR = 1.18, 95 % CI=1.10–1.27, P=1.84 × 10
-6
). For hand OA, a moderate association was also observed (Subtotal OR = 1.09, 95 % CI = 1.02–1.16, P = 0.01) for SNP rs143383 in the combined population. However, non-statistically significant summary OR of hip OA was found in both combined studies (Subtotal OR = 1.22, 95 % CI = 0.97–1.53, P = 0.09) and European studies (Subtotal OR = 1.16, 95 % CI = 0.91–1.48, P = 0.23).
Conclusions
Our results demonstrate that SNP rs143383 of GDF5 is a compelling risk factor for both knee and hand OA, and provide further support for GDF5 in the etiology of OA. Further efforts to identify functional variants of GDF5 in in vitro and in vivo will be required. |
doi_str_mv | 10.1007/s00011-015-0818-9 |
format | article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1680959624</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1680959624</sourcerecordid><originalsourceid>FETCH-LOGICAL-c442t-665c5203994901178506685223f3e6fbb6a94310a8a56f4761e59cb418ef554a3</originalsourceid><addsrcrecordid>eNp1kU1PHSEUhklTU63tD3DTkLjpQizfF5bGVmti4sYm3RFmPONg78AVuDb66-U61hiTboDkPOeFw4PQHqOHjNLFt0IpZYxQpgg1zBD7Du0wySmx1Px-386UCyKMoNvoYyk3jTbc8A9omytjpWJ8Bz0c4T5NqwwjxBLuAE9QPfHRL-9LKDgN2JeS-uBrSBF3UP8CRHwNEWro8Z3Pwcf6xJ1-P1HYxyucSoXkcx1zqHNEHQH_iQAHeAyrJ2Zsyye0Nfhlgc_P-y76dfLj8vgnOb84PTs-Oie9lLwSrVWvOBXWStumXRhFtTaKczEI0EPXaW-lYNQbr_QgF5qBsn0nmYFBKenFLvo6565yul1DqW4KpYfl0kdI6-KYNtQqq7ls6P4b9Catc_uMDWUtZ6K9plFspvqcSskwuFUOk8_3jlG3EeNmMa6JcRsxzraeL8_J626Cq5eOfyYawGegtFK8hvzq6v-mPgKGEpcV</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1699213665</pqid></control><display><type>article</type><title>A comprehensive meta-analysis of association between genetic variants of GDF5 and osteoarthritis of the knee, hip and hand</title><source>Springer Nature</source><creator>Zhang, Rui ; Yao, Jianfeng ; Xu, Peng ; Ji, Baohu ; Luck, James V. ; Chin, Brian ; Lu, Shemin ; Kelsoe, John R. ; Ma, Jie</creator><creatorcontrib>Zhang, Rui ; Yao, Jianfeng ; Xu, Peng ; Ji, Baohu ; Luck, James V. ; Chin, Brian ; Lu, Shemin ; Kelsoe, John R. ; Ma, Jie</creatorcontrib><description>Objective
A number of studies have reported an association of GDF5 with osteoarthritis (OA) but have produced some divergent findings and their interpretation may not be straightforward.
Methods
We investigated the association between GDF5 and OA using meta-analytic techniques, combining all published data up to Nov 2014. 16 independent samples from 11 research teams contributed data on SNP rs143383 (located in the 5’-UTR of GDF5) and knee, hip, and hand OA. The total number of cases and controls for this marker was 7,965 and 12,747 for knee OA, 6,363 and 9,727 for hip OA, and 4,335 and 5,991 for hand OA, respectively. The ORs for each OA phenotype were synthesized using random-effects models or fixed-effects models depending on the test of between-study heterogeneity.
Results
Using a random-effect model, a significant difference was identified between patients with knee OA and controls for the T-allele of rs143383 (Subtotal OR = 1.18, 95 % CI=1.10–1.27, P=1.84 × 10
-6
). For hand OA, a moderate association was also observed (Subtotal OR = 1.09, 95 % CI = 1.02–1.16, P = 0.01) for SNP rs143383 in the combined population. However, non-statistically significant summary OR of hip OA was found in both combined studies (Subtotal OR = 1.22, 95 % CI = 0.97–1.53, P = 0.09) and European studies (Subtotal OR = 1.16, 95 % CI = 0.91–1.48, P = 0.23).
Conclusions
Our results demonstrate that SNP rs143383 of GDF5 is a compelling risk factor for both knee and hand OA, and provide further support for GDF5 in the etiology of OA. Further efforts to identify functional variants of GDF5 in in vitro and in vivo will be required.</description><identifier>ISSN: 1023-3830</identifier><identifier>EISSN: 1420-908X</identifier><identifier>DOI: 10.1007/s00011-015-0818-9</identifier><identifier>PMID: 25894512</identifier><language>eng</language><publisher>Basel: Springer Basel</publisher><subject>Allergology ; Biomedical and Life Sciences ; Biomedicine ; Dermatology ; Gene Frequency ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Growth Differentiation Factor 5 - genetics ; Growth Differentiation Factor 5 - physiology ; Hand ; Humans ; Immunology ; Neurology ; Original Research Paper ; Osteoarthritis - epidemiology ; Osteoarthritis - genetics ; Osteoarthritis - metabolism ; Osteoarthritis, Hip - epidemiology ; Osteoarthritis, Hip - genetics ; Osteoarthritis, Hip - metabolism ; Osteoarthritis, Knee - epidemiology ; Osteoarthritis, Knee - genetics ; Osteoarthritis, Knee - metabolism ; Pharmacology/Toxicology ; Rheumatology</subject><ispartof>Inflammation research, 2015-06, Vol.64 (6), p.405-414</ispartof><rights>Springer Basel 2015</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-665c5203994901178506685223f3e6fbb6a94310a8a56f4761e59cb418ef554a3</citedby><cites>FETCH-LOGICAL-c442t-665c5203994901178506685223f3e6fbb6a94310a8a56f4761e59cb418ef554a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25894512$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Rui</creatorcontrib><creatorcontrib>Yao, Jianfeng</creatorcontrib><creatorcontrib>Xu, Peng</creatorcontrib><creatorcontrib>Ji, Baohu</creatorcontrib><creatorcontrib>Luck, James V.</creatorcontrib><creatorcontrib>Chin, Brian</creatorcontrib><creatorcontrib>Lu, Shemin</creatorcontrib><creatorcontrib>Kelsoe, John R.</creatorcontrib><creatorcontrib>Ma, Jie</creatorcontrib><title>A comprehensive meta-analysis of association between genetic variants of GDF5 and osteoarthritis of the knee, hip and hand</title><title>Inflammation research</title><addtitle>Inflamm. Res</addtitle><addtitle>Inflamm Res</addtitle><description>Objective
A number of studies have reported an association of GDF5 with osteoarthritis (OA) but have produced some divergent findings and their interpretation may not be straightforward.
Methods
We investigated the association between GDF5 and OA using meta-analytic techniques, combining all published data up to Nov 2014. 16 independent samples from 11 research teams contributed data on SNP rs143383 (located in the 5’-UTR of GDF5) and knee, hip, and hand OA. The total number of cases and controls for this marker was 7,965 and 12,747 for knee OA, 6,363 and 9,727 for hip OA, and 4,335 and 5,991 for hand OA, respectively. The ORs for each OA phenotype were synthesized using random-effects models or fixed-effects models depending on the test of between-study heterogeneity.
Results
Using a random-effect model, a significant difference was identified between patients with knee OA and controls for the T-allele of rs143383 (Subtotal OR = 1.18, 95 % CI=1.10–1.27, P=1.84 × 10
-6
). For hand OA, a moderate association was also observed (Subtotal OR = 1.09, 95 % CI = 1.02–1.16, P = 0.01) for SNP rs143383 in the combined population. However, non-statistically significant summary OR of hip OA was found in both combined studies (Subtotal OR = 1.22, 95 % CI = 0.97–1.53, P = 0.09) and European studies (Subtotal OR = 1.16, 95 % CI = 0.91–1.48, P = 0.23).
Conclusions
Our results demonstrate that SNP rs143383 of GDF5 is a compelling risk factor for both knee and hand OA, and provide further support for GDF5 in the etiology of OA. Further efforts to identify functional variants of GDF5 in in vitro and in vivo will be required.</description><subject>Allergology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Dermatology</subject><subject>Gene Frequency</subject><subject>Genetic Predisposition to Disease</subject><subject>Genome-Wide Association Study</subject><subject>Growth Differentiation Factor 5 - genetics</subject><subject>Growth Differentiation Factor 5 - physiology</subject><subject>Hand</subject><subject>Humans</subject><subject>Immunology</subject><subject>Neurology</subject><subject>Original Research Paper</subject><subject>Osteoarthritis - epidemiology</subject><subject>Osteoarthritis - genetics</subject><subject>Osteoarthritis - metabolism</subject><subject>Osteoarthritis, Hip - epidemiology</subject><subject>Osteoarthritis, Hip - genetics</subject><subject>Osteoarthritis, Hip - metabolism</subject><subject>Osteoarthritis, Knee - epidemiology</subject><subject>Osteoarthritis, Knee - genetics</subject><subject>Osteoarthritis, Knee - metabolism</subject><subject>Pharmacology/Toxicology</subject><subject>Rheumatology</subject><issn>1023-3830</issn><issn>1420-908X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNp1kU1PHSEUhklTU63tD3DTkLjpQizfF5bGVmti4sYm3RFmPONg78AVuDb66-U61hiTboDkPOeFw4PQHqOHjNLFt0IpZYxQpgg1zBD7Du0wySmx1Px-386UCyKMoNvoYyk3jTbc8A9omytjpWJ8Bz0c4T5NqwwjxBLuAE9QPfHRL-9LKDgN2JeS-uBrSBF3UP8CRHwNEWro8Z3Pwcf6xJ1-P1HYxyucSoXkcx1zqHNEHQH_iQAHeAyrJ2Zsyye0Nfhlgc_P-y76dfLj8vgnOb84PTs-Oie9lLwSrVWvOBXWStumXRhFtTaKczEI0EPXaW-lYNQbr_QgF5qBsn0nmYFBKenFLvo6565yul1DqW4KpYfl0kdI6-KYNtQqq7ls6P4b9Catc_uMDWUtZ6K9plFspvqcSskwuFUOk8_3jlG3EeNmMa6JcRsxzraeL8_J626Cq5eOfyYawGegtFK8hvzq6v-mPgKGEpcV</recordid><startdate>20150601</startdate><enddate>20150601</enddate><creator>Zhang, Rui</creator><creator>Yao, Jianfeng</creator><creator>Xu, Peng</creator><creator>Ji, Baohu</creator><creator>Luck, James V.</creator><creator>Chin, Brian</creator><creator>Lu, Shemin</creator><creator>Kelsoe, John R.</creator><creator>Ma, Jie</creator><general>Springer Basel</general><general>Springer Nature B.V</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>3V.</scope><scope>7QL</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20150601</creationdate><title>A comprehensive meta-analysis of association between genetic variants of GDF5 and osteoarthritis of the knee, hip and hand</title><author>Zhang, Rui ; Yao, Jianfeng ; Xu, Peng ; Ji, Baohu ; Luck, James V. ; Chin, Brian ; Lu, Shemin ; Kelsoe, John R. ; Ma, Jie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-665c5203994901178506685223f3e6fbb6a94310a8a56f4761e59cb418ef554a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Allergology</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Dermatology</topic><topic>Gene Frequency</topic><topic>Genetic Predisposition to Disease</topic><topic>Genome-Wide Association Study</topic><topic>Growth Differentiation Factor 5 - genetics</topic><topic>Growth Differentiation Factor 5 - physiology</topic><topic>Hand</topic><topic>Humans</topic><topic>Immunology</topic><topic>Neurology</topic><topic>Original Research Paper</topic><topic>Osteoarthritis - epidemiology</topic><topic>Osteoarthritis - genetics</topic><topic>Osteoarthritis - metabolism</topic><topic>Osteoarthritis, Hip - epidemiology</topic><topic>Osteoarthritis, Hip - genetics</topic><topic>Osteoarthritis, Hip - metabolism</topic><topic>Osteoarthritis, Knee - epidemiology</topic><topic>Osteoarthritis, Knee - genetics</topic><topic>Osteoarthritis, Knee - metabolism</topic><topic>Pharmacology/Toxicology</topic><topic>Rheumatology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Rui</creatorcontrib><creatorcontrib>Yao, Jianfeng</creatorcontrib><creatorcontrib>Xu, Peng</creatorcontrib><creatorcontrib>Ji, Baohu</creatorcontrib><creatorcontrib>Luck, James V.</creatorcontrib><creatorcontrib>Chin, Brian</creatorcontrib><creatorcontrib>Lu, Shemin</creatorcontrib><creatorcontrib>Kelsoe, John R.</creatorcontrib><creatorcontrib>Ma, Jie</creatorcontrib><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>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection (Proquest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</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</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</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>MEDLINE - Academic</collection><jtitle>Inflammation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Rui</au><au>Yao, Jianfeng</au><au>Xu, Peng</au><au>Ji, Baohu</au><au>Luck, James V.</au><au>Chin, Brian</au><au>Lu, Shemin</au><au>Kelsoe, John R.</au><au>Ma, Jie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A comprehensive meta-analysis of association between genetic variants of GDF5 and osteoarthritis of the knee, hip and hand</atitle><jtitle>Inflammation research</jtitle><stitle>Inflamm. Res</stitle><addtitle>Inflamm Res</addtitle><date>2015-06-01</date><risdate>2015</risdate><volume>64</volume><issue>6</issue><spage>405</spage><epage>414</epage><pages>405-414</pages><issn>1023-3830</issn><eissn>1420-908X</eissn><abstract>Objective
A number of studies have reported an association of GDF5 with osteoarthritis (OA) but have produced some divergent findings and their interpretation may not be straightforward.
Methods
We investigated the association between GDF5 and OA using meta-analytic techniques, combining all published data up to Nov 2014. 16 independent samples from 11 research teams contributed data on SNP rs143383 (located in the 5’-UTR of GDF5) and knee, hip, and hand OA. The total number of cases and controls for this marker was 7,965 and 12,747 for knee OA, 6,363 and 9,727 for hip OA, and 4,335 and 5,991 for hand OA, respectively. The ORs for each OA phenotype were synthesized using random-effects models or fixed-effects models depending on the test of between-study heterogeneity.
Results
Using a random-effect model, a significant difference was identified between patients with knee OA and controls for the T-allele of rs143383 (Subtotal OR = 1.18, 95 % CI=1.10–1.27, P=1.84 × 10
-6
). For hand OA, a moderate association was also observed (Subtotal OR = 1.09, 95 % CI = 1.02–1.16, P = 0.01) for SNP rs143383 in the combined population. However, non-statistically significant summary OR of hip OA was found in both combined studies (Subtotal OR = 1.22, 95 % CI = 0.97–1.53, P = 0.09) and European studies (Subtotal OR = 1.16, 95 % CI = 0.91–1.48, P = 0.23).
Conclusions
Our results demonstrate that SNP rs143383 of GDF5 is a compelling risk factor for both knee and hand OA, and provide further support for GDF5 in the etiology of OA. Further efforts to identify functional variants of GDF5 in in vitro and in vivo will be required.</abstract><cop>Basel</cop><pub>Springer Basel</pub><pmid>25894512</pmid><doi>10.1007/s00011-015-0818-9</doi><tpages>10</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1023-3830 |
ispartof | Inflammation research, 2015-06, Vol.64 (6), p.405-414 |
issn | 1023-3830 1420-908X |
language | eng |
recordid | cdi_proquest_miscellaneous_1680959624 |
source | Springer Nature |
subjects | Allergology Biomedical and Life Sciences Biomedicine Dermatology Gene Frequency Genetic Predisposition to Disease Genome-Wide Association Study Growth Differentiation Factor 5 - genetics Growth Differentiation Factor 5 - physiology Hand Humans Immunology Neurology Original Research Paper Osteoarthritis - epidemiology Osteoarthritis - genetics Osteoarthritis - metabolism Osteoarthritis, Hip - epidemiology Osteoarthritis, Hip - genetics Osteoarthritis, Hip - metabolism Osteoarthritis, Knee - epidemiology Osteoarthritis, Knee - genetics Osteoarthritis, Knee - metabolism Pharmacology/Toxicology Rheumatology |
title | A comprehensive meta-analysis of association between genetic variants of GDF5 and osteoarthritis of the knee, hip and hand |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-20T02%3A53%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20comprehensive%20meta-analysis%20of%20association%20between%20genetic%20variants%20of%20GDF5%20and%20osteoarthritis%20of%20the%20knee,%20hip%20and%20hand&rft.jtitle=Inflammation%20research&rft.au=Zhang,%20Rui&rft.date=2015-06-01&rft.volume=64&rft.issue=6&rft.spage=405&rft.epage=414&rft.pages=405-414&rft.issn=1023-3830&rft.eissn=1420-908X&rft_id=info:doi/10.1007/s00011-015-0818-9&rft_dat=%3Cproquest_cross%3E1680959624%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c442t-665c5203994901178506685223f3e6fbb6a94310a8a56f4761e59cb418ef554a3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1699213665&rft_id=info:pmid/25894512&rfr_iscdi=true |