Development of a novel immune-related genes prognostic signature for osteosarcoma
Immune-related genes (IRGs) are responsible for osteosarcoma (OS) initiation and development. We aimed to develop an optimal IRGs-based signature to assess of OS prognosis. Sample gene expression profiles and clinical information were downloaded from the Therapeutically Applicable Research to Genera...
Gespeichert in:
Veröffentlicht in: | Scientific reports 2020-10, Vol.10 (1), p.18402, Article 18402 |
---|---|
Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | |
---|---|
container_issue | 1 |
container_start_page | 18402 |
container_title | Scientific reports |
container_volume | 10 |
creator | Wu, Zuo-long Deng, Ya-jun Zhang, Guang-zhi Ren, En-hui Yuan, Wen-hua Xie, Qi-qi |
description | Immune-related genes (IRGs) are responsible for osteosarcoma (OS) initiation and development. We aimed to develop an optimal IRGs-based signature to assess of OS prognosis. Sample gene expression profiles and clinical information were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Genotype-Tissue Expression (GTEx) databases. IRGs were obtained from the ImmPort database. R software was used to screen differentially expressed IRGs (DEIRGs) and functional correlation analysis. DEIRGs were analyzed by univariate Cox regression and iterative LASSO Cox regression analysis to develop an optimal prognostic signature, and the signature was further verified by independent cohort (GSE39055) and clinical correlation analysis. The analyses yielded 604 DEIRGs and 10 hub IRGs. A prognostic signature consisting of 13 IRGs was constructed, which strikingly correlated with OS overall survival and distant metastasis (p |
doi_str_mv | 10.1038/s41598-020-75573-w |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmed_primary_33110201</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2471528168</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-9e81d74d923db76c5bc720e8d3896ad7ab76d69d83b602446509f4215707a8463</originalsourceid><addsrcrecordid>eNqNkU1rFTEYhQex2NL2D7iQgBtBRvM5STaC3LYqFETQdchk3hlTZpJrMtNL_725nXqtLsRsEt4855CTU1XPCX5DMFNvMydCqxpTXEshJKt3T6oTirmoKaP06aPzcXWe8w0uS1DNiX5WHTNGSFGSk-rLBdzCGLcThBnFHlkUYhkgP01LgDrBaGfo0AABMtqmOISYZ-9Q9kOw85IA9TGhMoOYbXJxsmfVUW_HDOcP-2n17ery6-Zjff35w6fN--vaccnnWoMineSdpqxrZeNE6yTFoDqmdGM7acuwa3SnWNtgynkjsO45JUJiaRVv2Gn1bvXdLu0EnSsBkh3NNvnJpjsTrTd_3gT_3Qzx1kihiaC8GLx6MEjxxwJ5NpPPDsbRBohLNpQLQSRReo--_Au9iUsKJV6hZHFTpFGFoivlUsw5QX94DMFmX5pZSzPl6819aWZXRC8exzhIflVUALUCO2hjn52H4OCAlVYbIphkcl-w2vjZzj6GTVzCXKSv_19aaLbSuRBhgPQ75D_e_xMo1MPM</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2471528168</pqid></control><display><type>article</type><title>Development of a novel immune-related genes prognostic signature for osteosarcoma</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Springer Nature OA Free Journals</source><source>Nature Free</source><source>Web of Science - Science Citation Index Expanded - 2020<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /></source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Wu, Zuo-long ; Deng, Ya-jun ; Zhang, Guang-zhi ; Ren, En-hui ; Yuan, Wen-hua ; Xie, Qi-qi</creator><creatorcontrib>Wu, Zuo-long ; Deng, Ya-jun ; Zhang, Guang-zhi ; Ren, En-hui ; Yuan, Wen-hua ; Xie, Qi-qi</creatorcontrib><description>Immune-related genes (IRGs) are responsible for osteosarcoma (OS) initiation and development. We aimed to develop an optimal IRGs-based signature to assess of OS prognosis. Sample gene expression profiles and clinical information were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Genotype-Tissue Expression (GTEx) databases. IRGs were obtained from the ImmPort database. R software was used to screen differentially expressed IRGs (DEIRGs) and functional correlation analysis. DEIRGs were analyzed by univariate Cox regression and iterative LASSO Cox regression analysis to develop an optimal prognostic signature, and the signature was further verified by independent cohort (GSE39055) and clinical correlation analysis. The analyses yielded 604 DEIRGs and 10 hub IRGs. A prognostic signature consisting of 13 IRGs was constructed, which strikingly correlated with OS overall survival and distant metastasis (p < 0.05, p < 0.01), and clinical subgroup showed that the signature’s prognostic ability was independent of clinicopathological factors. Univariate and multivariate Cox regression analyses also supported its prognostic value. In conclusion, we developed an IRGs signature that is a prognostic indicator in OS patients, and the signature might serve as potential prognostic indicator to identify outcome of OS and facilitate personalized management of the high-risk patients.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-75573-w</identifier><identifier>PMID: 33110201</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/114 ; 631/250 ; 631/337 ; 631/67 ; 692/53 ; Biomarkers, Tumor - genetics ; Bone cancer ; Cohort Studies ; Correlation analysis ; Female ; Gene expression ; Gene Expression Regulation, Neoplastic ; Genotypes ; Humanities and Social Sciences ; Humans ; Kaplan-Meier Estimate ; Male ; Medical prognosis ; Metastases ; multidisciplinary ; Multidisciplinary Sciences ; Osteosarcoma ; Osteosarcoma - genetics ; Osteosarcoma - immunology ; Osteosarcoma - pathology ; Prognosis ; Regression analysis ; Risk groups ; Sarcoma ; Science ; Science & Technology ; Science & Technology - Other Topics ; Science (multidisciplinary)</subject><ispartof>Scientific reports, 2020-10, Vol.10 (1), p.18402, Article 18402</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>20</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000615373700008</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c474t-9e81d74d923db76c5bc720e8d3896ad7ab76d69d83b602446509f4215707a8463</citedby><cites>FETCH-LOGICAL-c474t-9e81d74d923db76c5bc720e8d3896ad7ab76d69d83b602446509f4215707a8463</cites><orcidid>0000-0001-7731-4241 ; 0000-0003-4099-5287</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/PMC7591524/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591524/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,2118,27933,27934,28257,41129,42198,51585,53800,53802</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33110201$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Zuo-long</creatorcontrib><creatorcontrib>Deng, Ya-jun</creatorcontrib><creatorcontrib>Zhang, Guang-zhi</creatorcontrib><creatorcontrib>Ren, En-hui</creatorcontrib><creatorcontrib>Yuan, Wen-hua</creatorcontrib><creatorcontrib>Xie, Qi-qi</creatorcontrib><title>Development of a novel immune-related genes prognostic signature for osteosarcoma</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>SCI REP-UK</addtitle><addtitle>Sci Rep</addtitle><description>Immune-related genes (IRGs) are responsible for osteosarcoma (OS) initiation and development. We aimed to develop an optimal IRGs-based signature to assess of OS prognosis. Sample gene expression profiles and clinical information were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Genotype-Tissue Expression (GTEx) databases. IRGs were obtained from the ImmPort database. R software was used to screen differentially expressed IRGs (DEIRGs) and functional correlation analysis. DEIRGs were analyzed by univariate Cox regression and iterative LASSO Cox regression analysis to develop an optimal prognostic signature, and the signature was further verified by independent cohort (GSE39055) and clinical correlation analysis. The analyses yielded 604 DEIRGs and 10 hub IRGs. A prognostic signature consisting of 13 IRGs was constructed, which strikingly correlated with OS overall survival and distant metastasis (p < 0.05, p < 0.01), and clinical subgroup showed that the signature’s prognostic ability was independent of clinicopathological factors. Univariate and multivariate Cox regression analyses also supported its prognostic value. In conclusion, we developed an IRGs signature that is a prognostic indicator in OS patients, and the signature might serve as potential prognostic indicator to identify outcome of OS and facilitate personalized management of the high-risk patients.</description><subject>631/114</subject><subject>631/250</subject><subject>631/337</subject><subject>631/67</subject><subject>692/53</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Bone cancer</subject><subject>Cohort Studies</subject><subject>Correlation analysis</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genotypes</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Metastases</subject><subject>multidisciplinary</subject><subject>Multidisciplinary Sciences</subject><subject>Osteosarcoma</subject><subject>Osteosarcoma - genetics</subject><subject>Osteosarcoma - immunology</subject><subject>Osteosarcoma - pathology</subject><subject>Prognosis</subject><subject>Regression analysis</subject><subject>Risk groups</subject><subject>Sarcoma</subject><subject>Science</subject><subject>Science & Technology</subject><subject>Science & Technology - Other Topics</subject><subject>Science (multidisciplinary)</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>AOWDO</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkU1rFTEYhQex2NL2D7iQgBtBRvM5STaC3LYqFETQdchk3hlTZpJrMtNL_725nXqtLsRsEt4855CTU1XPCX5DMFNvMydCqxpTXEshJKt3T6oTirmoKaP06aPzcXWe8w0uS1DNiX5WHTNGSFGSk-rLBdzCGLcThBnFHlkUYhkgP01LgDrBaGfo0AABMtqmOISYZ-9Q9kOw85IA9TGhMoOYbXJxsmfVUW_HDOcP-2n17ery6-Zjff35w6fN--vaccnnWoMineSdpqxrZeNE6yTFoDqmdGM7acuwa3SnWNtgynkjsO45JUJiaRVv2Gn1bvXdLu0EnSsBkh3NNvnJpjsTrTd_3gT_3Qzx1kihiaC8GLx6MEjxxwJ5NpPPDsbRBohLNpQLQSRReo--_Au9iUsKJV6hZHFTpFGFoivlUsw5QX94DMFmX5pZSzPl6819aWZXRC8exzhIflVUALUCO2hjn52H4OCAlVYbIphkcl-w2vjZzj6GTVzCXKSv_19aaLbSuRBhgPQ75D_e_xMo1MPM</recordid><startdate>20201027</startdate><enddate>20201027</enddate><creator>Wu, Zuo-long</creator><creator>Deng, Ya-jun</creator><creator>Zhang, Guang-zhi</creator><creator>Ren, En-hui</creator><creator>Yuan, Wen-hua</creator><creator>Xie, Qi-qi</creator><general>Nature Publishing Group UK</general><general>NATURE PORTFOLIO</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</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>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7731-4241</orcidid><orcidid>https://orcid.org/0000-0003-4099-5287</orcidid></search><sort><creationdate>20201027</creationdate><title>Development of a novel immune-related genes prognostic signature for osteosarcoma</title><author>Wu, Zuo-long ; Deng, Ya-jun ; Zhang, Guang-zhi ; Ren, En-hui ; Yuan, Wen-hua ; Xie, Qi-qi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-9e81d74d923db76c5bc720e8d3896ad7ab76d69d83b602446509f4215707a8463</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>631/114</topic><topic>631/250</topic><topic>631/337</topic><topic>631/67</topic><topic>692/53</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Bone cancer</topic><topic>Cohort Studies</topic><topic>Correlation analysis</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genotypes</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Kaplan-Meier Estimate</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Metastases</topic><topic>multidisciplinary</topic><topic>Multidisciplinary Sciences</topic><topic>Osteosarcoma</topic><topic>Osteosarcoma - genetics</topic><topic>Osteosarcoma - immunology</topic><topic>Osteosarcoma - pathology</topic><topic>Prognosis</topic><topic>Regression analysis</topic><topic>Risk groups</topic><topic>Sarcoma</topic><topic>Science</topic><topic>Science & Technology</topic><topic>Science & Technology - Other Topics</topic><topic>Science (multidisciplinary)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Zuo-long</creatorcontrib><creatorcontrib>Deng, Ya-jun</creatorcontrib><creatorcontrib>Zhang, Guang-zhi</creatorcontrib><creatorcontrib>Ren, En-hui</creatorcontrib><creatorcontrib>Yuan, Wen-hua</creatorcontrib><creatorcontrib>Xie, Qi-qi</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</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>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 Edition)</collection><collection>ProQuest Central UK/Ireland</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 Korea</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>Access via ProQuest (Open Access)</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 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>Wu, Zuo-long</au><au>Deng, Ya-jun</au><au>Zhang, Guang-zhi</au><au>Ren, En-hui</au><au>Yuan, Wen-hua</au><au>Xie, Qi-qi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development of a novel immune-related genes prognostic signature for osteosarcoma</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><stitle>SCI REP-UK</stitle><addtitle>Sci Rep</addtitle><date>2020-10-27</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>18402</spage><pages>18402-</pages><artnum>18402</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Immune-related genes (IRGs) are responsible for osteosarcoma (OS) initiation and development. We aimed to develop an optimal IRGs-based signature to assess of OS prognosis. Sample gene expression profiles and clinical information were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Genotype-Tissue Expression (GTEx) databases. IRGs were obtained from the ImmPort database. R software was used to screen differentially expressed IRGs (DEIRGs) and functional correlation analysis. DEIRGs were analyzed by univariate Cox regression and iterative LASSO Cox regression analysis to develop an optimal prognostic signature, and the signature was further verified by independent cohort (GSE39055) and clinical correlation analysis. The analyses yielded 604 DEIRGs and 10 hub IRGs. A prognostic signature consisting of 13 IRGs was constructed, which strikingly correlated with OS overall survival and distant metastasis (p < 0.05, p < 0.01), and clinical subgroup showed that the signature’s prognostic ability was independent of clinicopathological factors. Univariate and multivariate Cox regression analyses also supported its prognostic value. In conclusion, we developed an IRGs signature that is a prognostic indicator in OS patients, and the signature might serve as potential prognostic indicator to identify outcome of OS and facilitate personalized management of the high-risk patients.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>33110201</pmid><doi>10.1038/s41598-020-75573-w</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-7731-4241</orcidid><orcidid>https://orcid.org/0000-0003-4099-5287</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 2045-2322 |
ispartof | Scientific reports, 2020-10, Vol.10 (1), p.18402, Article 18402 |
issn | 2045-2322 2045-2322 |
language | eng |
recordid | cdi_pubmed_primary_33110201 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Springer Nature OA Free Journals; Nature Free; Web of Science - Science Citation Index Expanded - 2020<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" />; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
subjects | 631/114 631/250 631/337 631/67 692/53 Biomarkers, Tumor - genetics Bone cancer Cohort Studies Correlation analysis Female Gene expression Gene Expression Regulation, Neoplastic Genotypes Humanities and Social Sciences Humans Kaplan-Meier Estimate Male Medical prognosis Metastases multidisciplinary Multidisciplinary Sciences Osteosarcoma Osteosarcoma - genetics Osteosarcoma - immunology Osteosarcoma - pathology Prognosis Regression analysis Risk groups Sarcoma Science Science & Technology Science & Technology - Other Topics Science (multidisciplinary) |
title | Development of a novel immune-related genes prognostic signature for osteosarcoma |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-03T12%3A03%3A15IST&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=Development%20of%20a%20novel%20immune-related%20genes%20prognostic%20signature%20for%20osteosarcoma&rft.jtitle=Scientific%20reports&rft.au=Wu,%20Zuo-long&rft.date=2020-10-27&rft.volume=10&rft.issue=1&rft.spage=18402&rft.pages=18402-&rft.artnum=18402&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/s41598-020-75573-w&rft_dat=%3Cproquest_pubme%3E2471528168%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2471528168&rft_id=info:pmid/33110201&rfr_iscdi=true |