Structure-Function Based Molecular Relationships in Ewing’s Sarcoma
Ewing’s Sarcoma Oncogene (ews) on chromosome 22q12 is encoding a ubiquitously expressed RNA-binding protein (EWS) with unknown function that is target of tumor-specific chromosomal translocations in Ewing’s sarcoma family of tumors. A model of transcription complex was proposed in which the heterodi...
Gespeichert in:
| Veröffentlicht in: | BioMed research international 2015-01, Vol.2015 (2015), p.1-15 |
|---|---|
| 1. Verfasser: | |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 15 |
|---|---|
| container_issue | 2015 |
| container_start_page | 1 |
| container_title | BioMed research international |
| container_volume | 2015 |
| creator | Todorova, Roumiana |
| description | Ewing’s Sarcoma Oncogene (ews) on chromosome 22q12 is encoding a ubiquitously expressed RNA-binding protein (EWS) with unknown function that is target of tumor-specific chromosomal translocations in Ewing’s sarcoma family of tumors. A model of transcription complex was proposed in which the heterodimer Rpb4/7 binds to EAD, connecting it to Core RNA Pol II. The DNA-binding domain, provided by EFP, is bound to the promoter. Rpb4/7 binds RNA, stabilizing the transcription complex. The complex Rpb4/7 can stabilize the preinitiation complexes by converting the conformation of RNA Pol II. EWS may change its conformation, so that NTD becomes accessible. Two different mechanisms of interaction between EWS and RNA Pol II are proposed: (I) an intermolecular EWS-EWS interaction between two molecules, pushing conformation from “closed” to “open” state, or (II) an intramolecular interaction inside the molecule of EWS, pushing conformation of the molecule from “closed” to “open” state. The modified forms of EWS may interact with Pol II subunits hsRpb5 and hsRpb7. The EWS and EFPs binding partners are described schematically in a model, an attempt to link the transcription with the splicing. The proposed model helps to understand the functional molecular interactions in cancer, to find new partners and ways to treat cancer. |
| doi_str_mv | 10.1155/2015/798426 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4320925</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A458163348</galeid><sourcerecordid>A458163348</sourcerecordid><originalsourceid>FETCH-LOGICAL-c594t-55818e9cc6a350205420997e72c8412202a680f6b2d752ffb8c2102802a4c8313</originalsourceid><addsrcrecordid>eNqNkctKAzEUhoMoKurKvQy4EWU098lsBJVWhYrgZR3SNNNGpklNZhR3voav55OYoVovK7NJyPn4cvIfALYRPESIsSMMETsqSkExXwLrmCCac0TR8uJMyBrYivEBpiUQhyVfBWuYcSEI5-ugd9uEVjdtMHm_dbqx3mWnKppRduVro9tahezG1KorxImdxcy6rPds3fj99S1mtypoP1WbYKVSdTRbn_sGuO_37s4u8sH1-eXZySDXrKRNzphAwpRac0UYxJBRDMuyMAXWgiKMIVZcwIoP8ahguKqGQmMEsUj3VAuCyAY4nntn7XBqRtq4JqhazoKdqvAivbLyd8XZiRz7J0lJegmzJNj7FAT_2JrYyKmN2tS1csa3USLOU0-wSOn8A4VECMQ6dPcP-uDb4FISiWJJhwtIvqmxqo20rvKpRd1J5QlNyXBCaOc6mFM6-BiDqRa_Q1B2I5fdyOV85Ine-RnIgv0acAL258DEupF6tv-zmYSYSv2AGS94QT4APca6IQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1650072703</pqid></control><display><type>article</type><title>Structure-Function Based Molecular Relationships in Ewing’s Sarcoma</title><source>MEDLINE</source><source>PubMed Central Open Access</source><source>Wiley-Blackwell Open Access Titles</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Todorova, Roumiana</creator><contributor>Obradovic, Zoran</contributor><creatorcontrib>Todorova, Roumiana ; Obradovic, Zoran</creatorcontrib><description>Ewing’s Sarcoma Oncogene (ews) on chromosome 22q12 is encoding a ubiquitously expressed RNA-binding protein (EWS) with unknown function that is target of tumor-specific chromosomal translocations in Ewing’s sarcoma family of tumors. A model of transcription complex was proposed in which the heterodimer Rpb4/7 binds to EAD, connecting it to Core RNA Pol II. The DNA-binding domain, provided by EFP, is bound to the promoter. Rpb4/7 binds RNA, stabilizing the transcription complex. The complex Rpb4/7 can stabilize the preinitiation complexes by converting the conformation of RNA Pol II. EWS may change its conformation, so that NTD becomes accessible. Two different mechanisms of interaction between EWS and RNA Pol II are proposed: (I) an intermolecular EWS-EWS interaction between two molecules, pushing conformation from “closed” to “open” state, or (II) an intramolecular interaction inside the molecule of EWS, pushing conformation of the molecule from “closed” to “open” state. The modified forms of EWS may interact with Pol II subunits hsRpb5 and hsRpb7. The EWS and EFPs binding partners are described schematically in a model, an attempt to link the transcription with the splicing. The proposed model helps to understand the functional molecular interactions in cancer, to find new partners and ways to treat cancer.</description><identifier>ISSN: 2314-6133</identifier><identifier>EISSN: 2314-6141</identifier><identifier>DOI: 10.1155/2015/798426</identifier><identifier>PMID: 25688366</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Binding proteins ; Biomedical research ; Chromosomes ; Deoxyribonucleic acid ; DNA ; Ewing's sarcoma ; Gene expression ; Genetic aspects ; Health aspects ; Humans ; Melanoma ; Methods ; Models, Molecular ; Oncogene Proteins, Fusion - genetics ; Oncogene Proteins, Fusion - metabolism ; Pathogenesis ; Physiological aspects ; Proteins ; Review ; RNA polymerase ; RNA sequencing ; RNA-Binding Protein EWS - genetics ; RNA-Binding Protein EWS - metabolism ; RNA-Binding Proteins - genetics ; RNA-Binding Proteins - metabolism ; Sarcoma, Ewing - genetics ; Sarcoma, Ewing - metabolism ; Skin cancer ; Transcription factors ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Tumors</subject><ispartof>BioMed research international, 2015-01, Vol.2015 (2015), p.1-15</ispartof><rights>Copyright © 2015 Roumiana Todorova.</rights><rights>COPYRIGHT 2015 John Wiley & Sons, Inc.</rights><rights>Copyright © 2015 Roumiana Todorova. Roumiana Todorova et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright © 2015 Roumiana Todorova. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c594t-55818e9cc6a350205420997e72c8412202a680f6b2d752ffb8c2102802a4c8313</citedby><cites>FETCH-LOGICAL-c594t-55818e9cc6a350205420997e72c8412202a680f6b2d752ffb8c2102802a4c8313</cites><orcidid>0000-0001-9982-2052</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/PMC4320925/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320925/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25688366$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Obradovic, Zoran</contributor><creatorcontrib>Todorova, Roumiana</creatorcontrib><title>Structure-Function Based Molecular Relationships in Ewing’s Sarcoma</title><title>BioMed research international</title><addtitle>Biomed Res Int</addtitle><description>Ewing’s Sarcoma Oncogene (ews) on chromosome 22q12 is encoding a ubiquitously expressed RNA-binding protein (EWS) with unknown function that is target of tumor-specific chromosomal translocations in Ewing’s sarcoma family of tumors. A model of transcription complex was proposed in which the heterodimer Rpb4/7 binds to EAD, connecting it to Core RNA Pol II. The DNA-binding domain, provided by EFP, is bound to the promoter. Rpb4/7 binds RNA, stabilizing the transcription complex. The complex Rpb4/7 can stabilize the preinitiation complexes by converting the conformation of RNA Pol II. EWS may change its conformation, so that NTD becomes accessible. Two different mechanisms of interaction between EWS and RNA Pol II are proposed: (I) an intermolecular EWS-EWS interaction between two molecules, pushing conformation from “closed” to “open” state, or (II) an intramolecular interaction inside the molecule of EWS, pushing conformation of the molecule from “closed” to “open” state. The modified forms of EWS may interact with Pol II subunits hsRpb5 and hsRpb7. The EWS and EFPs binding partners are described schematically in a model, an attempt to link the transcription with the splicing. The proposed model helps to understand the functional molecular interactions in cancer, to find new partners and ways to treat cancer.</description><subject>Binding proteins</subject><subject>Biomedical research</subject><subject>Chromosomes</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Ewing's sarcoma</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Melanoma</subject><subject>Methods</subject><subject>Models, Molecular</subject><subject>Oncogene Proteins, Fusion - genetics</subject><subject>Oncogene Proteins, Fusion - metabolism</subject><subject>Pathogenesis</subject><subject>Physiological aspects</subject><subject>Proteins</subject><subject>Review</subject><subject>RNA polymerase</subject><subject>RNA sequencing</subject><subject>RNA-Binding Protein EWS - genetics</subject><subject>RNA-Binding Protein EWS - metabolism</subject><subject>RNA-Binding Proteins - genetics</subject><subject>RNA-Binding Proteins - metabolism</subject><subject>Sarcoma, Ewing - genetics</subject><subject>Sarcoma, Ewing - metabolism</subject><subject>Skin cancer</subject><subject>Transcription factors</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Tumors</subject><issn>2314-6133</issn><issn>2314-6141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>RHX</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>eNqNkctKAzEUhoMoKurKvQy4EWU098lsBJVWhYrgZR3SNNNGpklNZhR3voav55OYoVovK7NJyPn4cvIfALYRPESIsSMMETsqSkExXwLrmCCac0TR8uJMyBrYivEBpiUQhyVfBWuYcSEI5-ugd9uEVjdtMHm_dbqx3mWnKppRduVro9tahezG1KorxImdxcy6rPds3fj99S1mtypoP1WbYKVSdTRbn_sGuO_37s4u8sH1-eXZySDXrKRNzphAwpRac0UYxJBRDMuyMAXWgiKMIVZcwIoP8ahguKqGQmMEsUj3VAuCyAY4nntn7XBqRtq4JqhazoKdqvAivbLyd8XZiRz7J0lJegmzJNj7FAT_2JrYyKmN2tS1csa3USLOU0-wSOn8A4VECMQ6dPcP-uDb4FISiWJJhwtIvqmxqo20rvKpRd1J5QlNyXBCaOc6mFM6-BiDqRa_Q1B2I5fdyOV85Ine-RnIgv0acAL258DEupF6tv-zmYSYSv2AGS94QT4APca6IQ</recordid><startdate>20150101</startdate><enddate>20150101</enddate><creator>Todorova, Roumiana</creator><general>Hindawi Publishing Corporation</general><general>John Wiley & Sons, Inc</general><general>Hindawi Limited</general><scope>ADJCN</scope><scope>AHFXO</scope><scope>RHU</scope><scope>RHW</scope><scope>RHX</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>7QL</scope><scope>7QO</scope><scope>7T7</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>CWDGH</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>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9982-2052</orcidid></search><sort><creationdate>20150101</creationdate><title>Structure-Function Based Molecular Relationships in Ewing’s Sarcoma</title><author>Todorova, Roumiana</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c594t-55818e9cc6a350205420997e72c8412202a680f6b2d752ffb8c2102802a4c8313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Binding proteins</topic><topic>Biomedical research</topic><topic>Chromosomes</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Ewing's sarcoma</topic><topic>Gene expression</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Melanoma</topic><topic>Methods</topic><topic>Models, Molecular</topic><topic>Oncogene Proteins, Fusion - genetics</topic><topic>Oncogene Proteins, Fusion - metabolism</topic><topic>Pathogenesis</topic><topic>Physiological aspects</topic><topic>Proteins</topic><topic>Review</topic><topic>RNA polymerase</topic><topic>RNA sequencing</topic><topic>RNA-Binding Protein EWS - genetics</topic><topic>RNA-Binding Protein EWS - metabolism</topic><topic>RNA-Binding Proteins - genetics</topic><topic>RNA-Binding Proteins - metabolism</topic><topic>Sarcoma, Ewing - genetics</topic><topic>Sarcoma, Ewing - metabolism</topic><topic>Skin cancer</topic><topic>Transcription factors</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Todorova, Roumiana</creatorcontrib><collection>الدوريات العلمية والإحصائية - e-Marefa Academic and Statistical Periodicals</collection><collection>معرفة - المحتوى العربي الأكاديمي المتكامل - e-Marefa Academic Complete</collection><collection>Hindawi Publishing Complete</collection><collection>Hindawi Publishing Subscription Journals</collection><collection>Hindawi Publishing Open Access 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>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Advanced Technologies & Aerospace Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Middle East & Africa Database</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</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>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>BioMed research international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Todorova, Roumiana</au><au>Obradovic, Zoran</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structure-Function Based Molecular Relationships in Ewing’s Sarcoma</atitle><jtitle>BioMed research international</jtitle><addtitle>Biomed Res Int</addtitle><date>2015-01-01</date><risdate>2015</risdate><volume>2015</volume><issue>2015</issue><spage>1</spage><epage>15</epage><pages>1-15</pages><issn>2314-6133</issn><eissn>2314-6141</eissn><abstract>Ewing’s Sarcoma Oncogene (ews) on chromosome 22q12 is encoding a ubiquitously expressed RNA-binding protein (EWS) with unknown function that is target of tumor-specific chromosomal translocations in Ewing’s sarcoma family of tumors. A model of transcription complex was proposed in which the heterodimer Rpb4/7 binds to EAD, connecting it to Core RNA Pol II. The DNA-binding domain, provided by EFP, is bound to the promoter. Rpb4/7 binds RNA, stabilizing the transcription complex. The complex Rpb4/7 can stabilize the preinitiation complexes by converting the conformation of RNA Pol II. EWS may change its conformation, so that NTD becomes accessible. Two different mechanisms of interaction between EWS and RNA Pol II are proposed: (I) an intermolecular EWS-EWS interaction between two molecules, pushing conformation from “closed” to “open” state, or (II) an intramolecular interaction inside the molecule of EWS, pushing conformation of the molecule from “closed” to “open” state. The modified forms of EWS may interact with Pol II subunits hsRpb5 and hsRpb7. The EWS and EFPs binding partners are described schematically in a model, an attempt to link the transcription with the splicing. The proposed model helps to understand the functional molecular interactions in cancer, to find new partners and ways to treat cancer.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>25688366</pmid><doi>10.1155/2015/798426</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0001-9982-2052</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2314-6133 |
| ispartof | BioMed research international, 2015-01, Vol.2015 (2015), p.1-15 |
| issn | 2314-6133 2314-6141 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4320925 |
| source | MEDLINE; PubMed Central Open Access; Wiley-Blackwell Open Access Titles; PubMed Central; Alma/SFX Local Collection |
| subjects | Binding proteins Biomedical research Chromosomes Deoxyribonucleic acid DNA Ewing's sarcoma Gene expression Genetic aspects Health aspects Humans Melanoma Methods Models, Molecular Oncogene Proteins, Fusion - genetics Oncogene Proteins, Fusion - metabolism Pathogenesis Physiological aspects Proteins Review RNA polymerase RNA sequencing RNA-Binding Protein EWS - genetics RNA-Binding Protein EWS - metabolism RNA-Binding Proteins - genetics RNA-Binding Proteins - metabolism Sarcoma, Ewing - genetics Sarcoma, Ewing - metabolism Skin cancer Transcription factors Transcription Factors - genetics Transcription Factors - metabolism Tumors |
| title | Structure-Function Based Molecular Relationships in Ewing’s Sarcoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T01%3A45%3A40IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Structure-Function%20Based%20Molecular%20Relationships%20in%20Ewing%E2%80%99s%20Sarcoma&rft.jtitle=BioMed%20research%20international&rft.au=Todorova,%20Roumiana&rft.date=2015-01-01&rft.volume=2015&rft.issue=2015&rft.spage=1&rft.epage=15&rft.pages=1-15&rft.issn=2314-6133&rft.eissn=2314-6141&rft_id=info:doi/10.1155/2015/798426&rft_dat=%3Cgale_pubme%3EA458163348%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1650072703&rft_id=info:pmid/25688366&rft_galeid=A458163348&rfr_iscdi=true |