Loading…
The EstroGene Database Reveals Diverse Temporal, Context-Dependent, and Bidirectional Estrogen Receptor Regulomes in Breast Cancer
As one of the most successful cancer therapeutic targets, estrogen receptor-α (ER/ESR1) has been extensively studied over the past few decades. Sequencing technological advances have enabled genome-wide analysis of ER action. However, comparison of individual studies is limited by different experime...
Saved in:
| Published in: | Cancer research (Chicago, Ill.) Ill.), 2023-08, Vol.83 (16), p.2656-2674 |
|---|---|
| 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-c412t-59636264ceaecd8b59b3782486b255f92cc57ab551f71f43d7fa182f466c8443 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c412t-59636264ceaecd8b59b3782486b255f92cc57ab551f71f43d7fa182f466c8443 |
| container_end_page | 2674 |
| container_issue | 16 |
| container_start_page | 2656 |
| container_title | Cancer research (Chicago, Ill.) |
| container_volume | 83 |
| creator | Li, Zheqi Li, Tianqin Yates, Megan E Wu, Yang Ferber, Amanda Chen, Lyuqin Brown, Daniel D Carroll, Jason S Sikora, Matthew J Tseng, George C Oesterreich, Steffi Lee, Adrian V |
| description | As one of the most successful cancer therapeutic targets, estrogen receptor-α (ER/ESR1) has been extensively studied over the past few decades. Sequencing technological advances have enabled genome-wide analysis of ER action. However, comparison of individual studies is limited by different experimental designs, and few meta-analyses are available. Here, we established the EstroGene database through unified processing of data from 246 experiments including 136 transcriptomic, cistromic, and epigenetic datasets focusing on estradiol (E2)-triggered ER activation across 19 breast cancer cell lines. A user-friendly browser (https://estrogene.org/) was generated for multiomic data visualization involving gene inquiry under user-defined experimental conditions and statistical thresholds. Notably, annotation of metadata associated with public datasets revealed a considerable lack of experimental details. Comparison of independent RNA-seq or ER ChIP-seq data with the same design showed large variability and only strong effects could be consistently detected. Temporal estrogen response metasignatures were defined, and the association of E2 response rate with temporal transcriptional factors, chromatin accessibility, and heterogeneity of ER expression was evaluated. Unexpectedly, harmonizing 146 E2-induced transcriptomic datasets uncovered a subset of genes harboring bidirectional E2 regulation, which was linked to unique transcriptional factors and highly associated with immune surveillance in the clinical setting. Furthermore, the context dependent E2 response programs were characterized in MCF7 and T47D cell lines, the two most frequently used models in the EstroGene database. Collectively, the EstroGene database provides an informative and practical resource to the cancer research community to uniformly evaluate key reproducible features of ER regulomes and unravels modes of ER signaling.
A resource database integrating 246 publicly available ER profiling datasets facilitates meta-analyses and identifies estrogen response temporal signatures, a bidirectional program, and model-specific biases. |
| doi_str_mv | 10.1158/0008-5472.CAN-23-0539 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10527051</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2822707987</sourcerecordid><originalsourceid>FETCH-LOGICAL-c412t-59636264ceaecd8b59b3782486b255f92cc57ab551f71f43d7fa182f466c8443</originalsourceid><addsrcrecordid>eNpVkctu1DAUhi0EokPhEUBesmhKfIudFWozpUWqQEKztxznZGqU2MH2jMqWJ8ejKSMqL-wj_-c_lw-h96S-JESoT3Vdq0pwSS-7q28VZVUtWPsCrYhgqpKci5doddKcoTcp_SyhILV4jc6YpOUIuUJ_Ng-Ab1KO4RY84LXJpjcJ8A_Yg5kSXrs9xBJvYF5CNNMF7oLP8JirNSzgB_D5Ahs_4Gs3uAg2u-DNdHTcgi8-FpYcYnlsd1OYIWHn8XUEkzLujLcQ36JXYykF757uc7T5crPp7qr777dfu6v7ynJCcyXahjW04RYM2EH1ou2ZVJSrpqdCjC21VkjTC0FGSUbOBjkaoujIm8Yqztk5-ny0XXb9DIMtnZd59BLdbOJvHYzTz3-8e9DbsNdlZVSWzRWHj08OMfzaQcp6dsnCNBkPYZc0VbQIZatkkYqj1MaQUoTxVIfU-sBPH9joAxtd-GnK9IFfyfvwf5OnrH_A2F9Tjpik</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2822707987</pqid></control><display><type>article</type><title>The EstroGene Database Reveals Diverse Temporal, Context-Dependent, and Bidirectional Estrogen Receptor Regulomes in Breast Cancer</title><source>Electronic Journals Library</source><creator>Li, Zheqi ; Li, Tianqin ; Yates, Megan E ; Wu, Yang ; Ferber, Amanda ; Chen, Lyuqin ; Brown, Daniel D ; Carroll, Jason S ; Sikora, Matthew J ; Tseng, George C ; Oesterreich, Steffi ; Lee, Adrian V</creator><creatorcontrib>Li, Zheqi ; Li, Tianqin ; Yates, Megan E ; Wu, Yang ; Ferber, Amanda ; Chen, Lyuqin ; Brown, Daniel D ; Carroll, Jason S ; Sikora, Matthew J ; Tseng, George C ; Oesterreich, Steffi ; Lee, Adrian V</creatorcontrib><description>As one of the most successful cancer therapeutic targets, estrogen receptor-α (ER/ESR1) has been extensively studied over the past few decades. Sequencing technological advances have enabled genome-wide analysis of ER action. However, comparison of individual studies is limited by different experimental designs, and few meta-analyses are available. Here, we established the EstroGene database through unified processing of data from 246 experiments including 136 transcriptomic, cistromic, and epigenetic datasets focusing on estradiol (E2)-triggered ER activation across 19 breast cancer cell lines. A user-friendly browser (https://estrogene.org/) was generated for multiomic data visualization involving gene inquiry under user-defined experimental conditions and statistical thresholds. Notably, annotation of metadata associated with public datasets revealed a considerable lack of experimental details. Comparison of independent RNA-seq or ER ChIP-seq data with the same design showed large variability and only strong effects could be consistently detected. Temporal estrogen response metasignatures were defined, and the association of E2 response rate with temporal transcriptional factors, chromatin accessibility, and heterogeneity of ER expression was evaluated. Unexpectedly, harmonizing 146 E2-induced transcriptomic datasets uncovered a subset of genes harboring bidirectional E2 regulation, which was linked to unique transcriptional factors and highly associated with immune surveillance in the clinical setting. Furthermore, the context dependent E2 response programs were characterized in MCF7 and T47D cell lines, the two most frequently used models in the EstroGene database. Collectively, the EstroGene database provides an informative and practical resource to the cancer research community to uniformly evaluate key reproducible features of ER regulomes and unravels modes of ER signaling.
A resource database integrating 246 publicly available ER profiling datasets facilitates meta-analyses and identifies estrogen response temporal signatures, a bidirectional program, and model-specific biases.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.CAN-23-0539</identifier><identifier>PMID: 37272757</identifier><language>eng</language><publisher>United States</publisher><subject>Breast Neoplasms - metabolism ; Cell Line, Tumor ; Databases, Genetic ; Estradiol - pharmacology ; Estrogen Receptor alpha - genetics ; Estrogen Receptor alpha - metabolism ; Estrogens ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Receptors, Estrogen - genetics ; Receptors, Estrogen - metabolism</subject><ispartof>Cancer research (Chicago, Ill.), 2023-08, Vol.83 (16), p.2656-2674</ispartof><rights>2023 American Association for Cancer Research.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-59636264ceaecd8b59b3782486b255f92cc57ab551f71f43d7fa182f466c8443</citedby><cites>FETCH-LOGICAL-c412t-59636264ceaecd8b59b3782486b255f92cc57ab551f71f43d7fa182f466c8443</cites><orcidid>0000-0003-2567-8283 ; 0000-0002-5932-1592 ; 0000-0002-2537-6923 ; 0000-0002-0432-5035 ; 0000-0003-2915-7442 ; 0000-0003-3643-0080 ; 0000-0001-9917-514X ; 0000-0002-7410-9514 ; 0000-0002-6541-5309 ; 0000-0002-0173-268X ; 0000-0003-1213-640X ; 0000-0002-5447-1014</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,786,790,891,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37272757$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Zheqi</creatorcontrib><creatorcontrib>Li, Tianqin</creatorcontrib><creatorcontrib>Yates, Megan E</creatorcontrib><creatorcontrib>Wu, Yang</creatorcontrib><creatorcontrib>Ferber, Amanda</creatorcontrib><creatorcontrib>Chen, Lyuqin</creatorcontrib><creatorcontrib>Brown, Daniel D</creatorcontrib><creatorcontrib>Carroll, Jason S</creatorcontrib><creatorcontrib>Sikora, Matthew J</creatorcontrib><creatorcontrib>Tseng, George C</creatorcontrib><creatorcontrib>Oesterreich, Steffi</creatorcontrib><creatorcontrib>Lee, Adrian V</creatorcontrib><title>The EstroGene Database Reveals Diverse Temporal, Context-Dependent, and Bidirectional Estrogen Receptor Regulomes in Breast Cancer</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>As one of the most successful cancer therapeutic targets, estrogen receptor-α (ER/ESR1) has been extensively studied over the past few decades. Sequencing technological advances have enabled genome-wide analysis of ER action. However, comparison of individual studies is limited by different experimental designs, and few meta-analyses are available. Here, we established the EstroGene database through unified processing of data from 246 experiments including 136 transcriptomic, cistromic, and epigenetic datasets focusing on estradiol (E2)-triggered ER activation across 19 breast cancer cell lines. A user-friendly browser (https://estrogene.org/) was generated for multiomic data visualization involving gene inquiry under user-defined experimental conditions and statistical thresholds. Notably, annotation of metadata associated with public datasets revealed a considerable lack of experimental details. Comparison of independent RNA-seq or ER ChIP-seq data with the same design showed large variability and only strong effects could be consistently detected. Temporal estrogen response metasignatures were defined, and the association of E2 response rate with temporal transcriptional factors, chromatin accessibility, and heterogeneity of ER expression was evaluated. Unexpectedly, harmonizing 146 E2-induced transcriptomic datasets uncovered a subset of genes harboring bidirectional E2 regulation, which was linked to unique transcriptional factors and highly associated with immune surveillance in the clinical setting. Furthermore, the context dependent E2 response programs were characterized in MCF7 and T47D cell lines, the two most frequently used models in the EstroGene database. Collectively, the EstroGene database provides an informative and practical resource to the cancer research community to uniformly evaluate key reproducible features of ER regulomes and unravels modes of ER signaling.
A resource database integrating 246 publicly available ER profiling datasets facilitates meta-analyses and identifies estrogen response temporal signatures, a bidirectional program, and model-specific biases.</description><subject>Breast Neoplasms - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Databases, Genetic</subject><subject>Estradiol - pharmacology</subject><subject>Estrogen Receptor alpha - genetics</subject><subject>Estrogen Receptor alpha - metabolism</subject><subject>Estrogens</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Receptors, Estrogen - genetics</subject><subject>Receptors, Estrogen - metabolism</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNpVkctu1DAUhi0EokPhEUBesmhKfIudFWozpUWqQEKztxznZGqU2MH2jMqWJ8ejKSMqL-wj_-c_lw-h96S-JESoT3Vdq0pwSS-7q28VZVUtWPsCrYhgqpKci5doddKcoTcp_SyhILV4jc6YpOUIuUJ_Ng-Ab1KO4RY84LXJpjcJ8A_Yg5kSXrs9xBJvYF5CNNMF7oLP8JirNSzgB_D5Ahs_4Gs3uAg2u-DNdHTcgi8-FpYcYnlsd1OYIWHn8XUEkzLujLcQ36JXYykF757uc7T5crPp7qr777dfu6v7ynJCcyXahjW04RYM2EH1ou2ZVJSrpqdCjC21VkjTC0FGSUbOBjkaoujIm8Yqztk5-ny0XXb9DIMtnZd59BLdbOJvHYzTz3-8e9DbsNdlZVSWzRWHj08OMfzaQcp6dsnCNBkPYZc0VbQIZatkkYqj1MaQUoTxVIfU-sBPH9joAxtd-GnK9IFfyfvwf5OnrH_A2F9Tjpik</recordid><startdate>20230815</startdate><enddate>20230815</enddate><creator>Li, Zheqi</creator><creator>Li, Tianqin</creator><creator>Yates, Megan E</creator><creator>Wu, Yang</creator><creator>Ferber, Amanda</creator><creator>Chen, Lyuqin</creator><creator>Brown, Daniel D</creator><creator>Carroll, Jason S</creator><creator>Sikora, Matthew J</creator><creator>Tseng, George C</creator><creator>Oesterreich, Steffi</creator><creator>Lee, Adrian V</creator><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>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2567-8283</orcidid><orcidid>https://orcid.org/0000-0002-5932-1592</orcidid><orcidid>https://orcid.org/0000-0002-2537-6923</orcidid><orcidid>https://orcid.org/0000-0002-0432-5035</orcidid><orcidid>https://orcid.org/0000-0003-2915-7442</orcidid><orcidid>https://orcid.org/0000-0003-3643-0080</orcidid><orcidid>https://orcid.org/0000-0001-9917-514X</orcidid><orcidid>https://orcid.org/0000-0002-7410-9514</orcidid><orcidid>https://orcid.org/0000-0002-6541-5309</orcidid><orcidid>https://orcid.org/0000-0002-0173-268X</orcidid><orcidid>https://orcid.org/0000-0003-1213-640X</orcidid><orcidid>https://orcid.org/0000-0002-5447-1014</orcidid></search><sort><creationdate>20230815</creationdate><title>The EstroGene Database Reveals Diverse Temporal, Context-Dependent, and Bidirectional Estrogen Receptor Regulomes in Breast Cancer</title><author>Li, Zheqi ; Li, Tianqin ; Yates, Megan E ; Wu, Yang ; Ferber, Amanda ; Chen, Lyuqin ; Brown, Daniel D ; Carroll, Jason S ; Sikora, Matthew J ; Tseng, George C ; Oesterreich, Steffi ; Lee, Adrian V</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-59636264ceaecd8b59b3782486b255f92cc57ab551f71f43d7fa182f466c8443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Breast Neoplasms - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Databases, Genetic</topic><topic>Estradiol - pharmacology</topic><topic>Estrogen Receptor alpha - genetics</topic><topic>Estrogen Receptor alpha - metabolism</topic><topic>Estrogens</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Receptors, Estrogen - genetics</topic><topic>Receptors, Estrogen - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Zheqi</creatorcontrib><creatorcontrib>Li, Tianqin</creatorcontrib><creatorcontrib>Yates, Megan E</creatorcontrib><creatorcontrib>Wu, Yang</creatorcontrib><creatorcontrib>Ferber, Amanda</creatorcontrib><creatorcontrib>Chen, Lyuqin</creatorcontrib><creatorcontrib>Brown, Daniel D</creatorcontrib><creatorcontrib>Carroll, Jason S</creatorcontrib><creatorcontrib>Sikora, Matthew J</creatorcontrib><creatorcontrib>Tseng, George C</creatorcontrib><creatorcontrib>Oesterreich, Steffi</creatorcontrib><creatorcontrib>Lee, Adrian V</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Zheqi</au><au>Li, Tianqin</au><au>Yates, Megan E</au><au>Wu, Yang</au><au>Ferber, Amanda</au><au>Chen, Lyuqin</au><au>Brown, Daniel D</au><au>Carroll, Jason S</au><au>Sikora, Matthew J</au><au>Tseng, George C</au><au>Oesterreich, Steffi</au><au>Lee, Adrian V</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The EstroGene Database Reveals Diverse Temporal, Context-Dependent, and Bidirectional Estrogen Receptor Regulomes in Breast Cancer</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2023-08-15</date><risdate>2023</risdate><volume>83</volume><issue>16</issue><spage>2656</spage><epage>2674</epage><pages>2656-2674</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>As one of the most successful cancer therapeutic targets, estrogen receptor-α (ER/ESR1) has been extensively studied over the past few decades. Sequencing technological advances have enabled genome-wide analysis of ER action. However, comparison of individual studies is limited by different experimental designs, and few meta-analyses are available. Here, we established the EstroGene database through unified processing of data from 246 experiments including 136 transcriptomic, cistromic, and epigenetic datasets focusing on estradiol (E2)-triggered ER activation across 19 breast cancer cell lines. A user-friendly browser (https://estrogene.org/) was generated for multiomic data visualization involving gene inquiry under user-defined experimental conditions and statistical thresholds. Notably, annotation of metadata associated with public datasets revealed a considerable lack of experimental details. Comparison of independent RNA-seq or ER ChIP-seq data with the same design showed large variability and only strong effects could be consistently detected. Temporal estrogen response metasignatures were defined, and the association of E2 response rate with temporal transcriptional factors, chromatin accessibility, and heterogeneity of ER expression was evaluated. Unexpectedly, harmonizing 146 E2-induced transcriptomic datasets uncovered a subset of genes harboring bidirectional E2 regulation, which was linked to unique transcriptional factors and highly associated with immune surveillance in the clinical setting. Furthermore, the context dependent E2 response programs were characterized in MCF7 and T47D cell lines, the two most frequently used models in the EstroGene database. Collectively, the EstroGene database provides an informative and practical resource to the cancer research community to uniformly evaluate key reproducible features of ER regulomes and unravels modes of ER signaling.
A resource database integrating 246 publicly available ER profiling datasets facilitates meta-analyses and identifies estrogen response temporal signatures, a bidirectional program, and model-specific biases.</abstract><cop>United States</cop><pmid>37272757</pmid><doi>10.1158/0008-5472.CAN-23-0539</doi><tpages>19</tpages><orcidid>https://orcid.org/0000-0003-2567-8283</orcidid><orcidid>https://orcid.org/0000-0002-5932-1592</orcidid><orcidid>https://orcid.org/0000-0002-2537-6923</orcidid><orcidid>https://orcid.org/0000-0002-0432-5035</orcidid><orcidid>https://orcid.org/0000-0003-2915-7442</orcidid><orcidid>https://orcid.org/0000-0003-3643-0080</orcidid><orcidid>https://orcid.org/0000-0001-9917-514X</orcidid><orcidid>https://orcid.org/0000-0002-7410-9514</orcidid><orcidid>https://orcid.org/0000-0002-6541-5309</orcidid><orcidid>https://orcid.org/0000-0002-0173-268X</orcidid><orcidid>https://orcid.org/0000-0003-1213-640X</orcidid><orcidid>https://orcid.org/0000-0002-5447-1014</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0008-5472 |
| ispartof | Cancer research (Chicago, Ill.), 2023-08, Vol.83 (16), p.2656-2674 |
| issn | 0008-5472 1538-7445 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10527051 |
| source | Electronic Journals Library |
| subjects | Breast Neoplasms - metabolism Cell Line, Tumor Databases, Genetic Estradiol - pharmacology Estrogen Receptor alpha - genetics Estrogen Receptor alpha - metabolism Estrogens Female Gene Expression Regulation, Neoplastic Humans Receptors, Estrogen - genetics Receptors, Estrogen - metabolism |
| title | The EstroGene Database Reveals Diverse Temporal, Context-Dependent, and Bidirectional Estrogen Receptor Regulomes in Breast Cancer |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-23T05%3A26%3A44IST&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=The%20EstroGene%20Database%20Reveals%20Diverse%20Temporal,%20Context-Dependent,%20and%20Bidirectional%20Estrogen%20Receptor%20Regulomes%20in%20Breast%20Cancer&rft.jtitle=Cancer%20research%20(Chicago,%20Ill.)&rft.au=Li,%20Zheqi&rft.date=2023-08-15&rft.volume=83&rft.issue=16&rft.spage=2656&rft.epage=2674&rft.pages=2656-2674&rft.issn=0008-5472&rft.eissn=1538-7445&rft_id=info:doi/10.1158/0008-5472.CAN-23-0539&rft_dat=%3Cproquest_pubme%3E2822707987%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c412t-59636264ceaecd8b59b3782486b255f92cc57ab551f71f43d7fa182f466c8443%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2822707987&rft_id=info:pmid/37272757&rfr_iscdi=true |