Search of reference biomarkers reflecting orbital tissue remodeling in the course of Graves' orbitopathy
Graves' orbitopathy (GO) is a complication in Graves' disease (GD) that causes disfigurement and sometimes blindness. The pathogenesis of GO remains unknown, while its symptoms demonstrate dependence between the thyroid gland and the orbit. The ongoing inflammatory process in retrobulbar t...
Gespeichert in:
| Veröffentlicht in: | Folia histochemica et cytobiologica 2020-01, Vol.1 (1), p.37-45 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 45 |
|---|---|
| container_issue | 1 |
| container_start_page | 37 |
| container_title | Folia histochemica et cytobiologica |
| container_volume | 1 |
| creator | Pawlowski, Przemyslaw Poplawska, Izabela Mysliwiec, Janusz Dik, Willem A Eckstein, Anja Berchner-Pfannschmidt, Utta Milewski, Robert Lawicki, Slawomir Dzieciol-Anikiej, Zofia Rejdak, Robert Reszec, Joanna |
| description | Graves' orbitopathy (GO) is a complication in Graves' disease (GD) that causes disfigurement and sometimes blindness. The pathogenesis of GO remains unknown, while its symptoms demonstrate dependence between the thyroid gland and the orbit. The ongoing inflammatory process in retrobulbar tissue results in its remodeling characterized by increased volume of the orbital contents involving adipose tissue, with fibrosis and adipogenesis as predominant features. This study was aimed at the immunohistochemical verification of potential contribution and correlation between orbital expressions of IGF-1R, CD34, Foxp-3, PPAR-γ and CD4, CD68, TGF-β, FGF-β in severe and mild (long-lasting) GO.
Forty-one orbital tissue specimens - 22 patients with severe GO, 9 patients with mild GO and 10 patients undergoing blepharoplasty as a control group - were processed by routine immunohistochemistry.
Increased IGF-1R, CD34 and Foxp-3 expression was found in both severe and mild GO, yet a significant correlation between CD34 and CD4, CD68, TGF-β, FGF-β expressions was observed in long-lasting GO.
CD34 expression is proposed to be the marker of orbital tissue remodeling in the course of mild GO. |
| doi_str_mv | 10.5603/FHC.a2020.0003 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2377686252</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2395874528</sourcerecordid><originalsourceid>FETCH-LOGICAL-c351t-a28f15f62288e9f8d120ab720f5538160f7662d63cb0c16d1452d1757c16d65c3</originalsourceid><addsrcrecordid>eNp9kc1P3DAQxa2qFSyUa48oUg9wSRjb8UeOaFV2K63EofRsOc6kG5qNFzupxH-Pwy4cOPRkjef3nmbmEfKNQiEk8Ju79bKwDBgUAMA_kQXVlcqF5PQzWQDjVa4F6FNyFuMjQJKU9IScckZVQsoF2f5CG9w2820WsMWAg8Os7vzOhr8Y4vzZoxu74U_mQ92Nts_GLsYJU2fnG-znTjdk4xYz56cQcbZaBfsP49VB4vd23D5_JV9a20e8OL7n5Pfdj4flOt_cr34ubze544KOuWW6paKVjGmNVasbysDWikErBNdUQqukZI3krgZHZUNLwRqqhJoLKRw_J9cH333wTxPG0ey66LDv7YB-ioZxpaSWTLCEfv-APqYNhjSdYbJiioMqy_9SvBJapQl0oooD5YKPMV3N7EOXjvhsKJg5KZOSMq9JmTmpJLg82k71Dpt3_C0a_gJCjIzZ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2395874528</pqid></control><display><type>article</type><title>Search of reference biomarkers reflecting orbital tissue remodeling in the course of Graves' orbitopathy</title><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>Pawlowski, Przemyslaw ; Poplawska, Izabela ; Mysliwiec, Janusz ; Dik, Willem A ; Eckstein, Anja ; Berchner-Pfannschmidt, Utta ; Milewski, Robert ; Lawicki, Slawomir ; Dzieciol-Anikiej, Zofia ; Rejdak, Robert ; Reszec, Joanna</creator><creatorcontrib>Pawlowski, Przemyslaw ; Poplawska, Izabela ; Mysliwiec, Janusz ; Dik, Willem A ; Eckstein, Anja ; Berchner-Pfannschmidt, Utta ; Milewski, Robert ; Lawicki, Slawomir ; Dzieciol-Anikiej, Zofia ; Rejdak, Robert ; Reszec, Joanna</creatorcontrib><description>Graves' orbitopathy (GO) is a complication in Graves' disease (GD) that causes disfigurement and sometimes blindness. The pathogenesis of GO remains unknown, while its symptoms demonstrate dependence between the thyroid gland and the orbit. The ongoing inflammatory process in retrobulbar tissue results in its remodeling characterized by increased volume of the orbital contents involving adipose tissue, with fibrosis and adipogenesis as predominant features. This study was aimed at the immunohistochemical verification of potential contribution and correlation between orbital expressions of IGF-1R, CD34, Foxp-3, PPAR-γ and CD4, CD68, TGF-β, FGF-β in severe and mild (long-lasting) GO.
Forty-one orbital tissue specimens - 22 patients with severe GO, 9 patients with mild GO and 10 patients undergoing blepharoplasty as a control group - were processed by routine immunohistochemistry.
Increased IGF-1R, CD34 and Foxp-3 expression was found in both severe and mild GO, yet a significant correlation between CD34 and CD4, CD68, TGF-β, FGF-β expressions was observed in long-lasting GO.
CD34 expression is proposed to be the marker of orbital tissue remodeling in the course of mild GO.</description><identifier>ISSN: 0239-8508</identifier><identifier>EISSN: 1897-5631</identifier><identifier>DOI: 10.5603/FHC.a2020.0003</identifier><identifier>PMID: 32176314</identifier><language>eng</language><publisher>Poland: Wydawnictwo Via Medica</publisher><subject>Adipogenesis ; Adipose tissue ; Biomarkers ; Blindness ; Body fat ; CD34 antigen ; CD4 antigen ; Connective tissue ; Fibroblast growth factors ; Fibroblasts ; Fibrosis ; Graves disease ; Histology ; Immunohistochemistry ; Immunology ; Inflammation ; Insulin-like growth factors ; Ophthalmology ; Pathogenesis ; Peroxisome proliferator-activated receptors ; Signs and symptoms ; Steroids ; Studies ; Surgery ; Thyroid ; Thyroid diseases ; Thyroid gland</subject><ispartof>Folia histochemica et cytobiologica, 2020-01, Vol.1 (1), p.37-45</ispartof><rights>2020. This work is published under https://creativecommons.org/licenses/by-nc-nd/4.0 (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020. This work is published under https://creativecommons.org/licenses/by-nc-nd/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>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c351t-a28f15f62288e9f8d120ab720f5538160f7662d63cb0c16d1452d1757c16d65c3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32176314$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pawlowski, Przemyslaw</creatorcontrib><creatorcontrib>Poplawska, Izabela</creatorcontrib><creatorcontrib>Mysliwiec, Janusz</creatorcontrib><creatorcontrib>Dik, Willem A</creatorcontrib><creatorcontrib>Eckstein, Anja</creatorcontrib><creatorcontrib>Berchner-Pfannschmidt, Utta</creatorcontrib><creatorcontrib>Milewski, Robert</creatorcontrib><creatorcontrib>Lawicki, Slawomir</creatorcontrib><creatorcontrib>Dzieciol-Anikiej, Zofia</creatorcontrib><creatorcontrib>Rejdak, Robert</creatorcontrib><creatorcontrib>Reszec, Joanna</creatorcontrib><title>Search of reference biomarkers reflecting orbital tissue remodeling in the course of Graves' orbitopathy</title><title>Folia histochemica et cytobiologica</title><addtitle>Folia Histochem Cytobiol</addtitle><description>Graves' orbitopathy (GO) is a complication in Graves' disease (GD) that causes disfigurement and sometimes blindness. The pathogenesis of GO remains unknown, while its symptoms demonstrate dependence between the thyroid gland and the orbit. The ongoing inflammatory process in retrobulbar tissue results in its remodeling characterized by increased volume of the orbital contents involving adipose tissue, with fibrosis and adipogenesis as predominant features. This study was aimed at the immunohistochemical verification of potential contribution and correlation between orbital expressions of IGF-1R, CD34, Foxp-3, PPAR-γ and CD4, CD68, TGF-β, FGF-β in severe and mild (long-lasting) GO.
Forty-one orbital tissue specimens - 22 patients with severe GO, 9 patients with mild GO and 10 patients undergoing blepharoplasty as a control group - were processed by routine immunohistochemistry.
Increased IGF-1R, CD34 and Foxp-3 expression was found in both severe and mild GO, yet a significant correlation between CD34 and CD4, CD68, TGF-β, FGF-β expressions was observed in long-lasting GO.
CD34 expression is proposed to be the marker of orbital tissue remodeling in the course of mild GO.</description><subject>Adipogenesis</subject><subject>Adipose tissue</subject><subject>Biomarkers</subject><subject>Blindness</subject><subject>Body fat</subject><subject>CD34 antigen</subject><subject>CD4 antigen</subject><subject>Connective tissue</subject><subject>Fibroblast growth factors</subject><subject>Fibroblasts</subject><subject>Fibrosis</subject><subject>Graves disease</subject><subject>Histology</subject><subject>Immunohistochemistry</subject><subject>Immunology</subject><subject>Inflammation</subject><subject>Insulin-like growth factors</subject><subject>Ophthalmology</subject><subject>Pathogenesis</subject><subject>Peroxisome proliferator-activated receptors</subject><subject>Signs and symptoms</subject><subject>Steroids</subject><subject>Studies</subject><subject>Surgery</subject><subject>Thyroid</subject><subject>Thyroid diseases</subject><subject>Thyroid gland</subject><issn>0239-8508</issn><issn>1897-5631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kc1P3DAQxa2qFSyUa48oUg9wSRjb8UeOaFV2K63EofRsOc6kG5qNFzupxH-Pwy4cOPRkjef3nmbmEfKNQiEk8Ju79bKwDBgUAMA_kQXVlcqF5PQzWQDjVa4F6FNyFuMjQJKU9IScckZVQsoF2f5CG9w2820WsMWAg8Os7vzOhr8Y4vzZoxu74U_mQ92Nts_GLsYJU2fnG-znTjdk4xYz56cQcbZaBfsP49VB4vd23D5_JV9a20e8OL7n5Pfdj4flOt_cr34ubze544KOuWW6paKVjGmNVasbysDWikErBNdUQqukZI3krgZHZUNLwRqqhJoLKRw_J9cH333wTxPG0ey66LDv7YB-ioZxpaSWTLCEfv-APqYNhjSdYbJiioMqy_9SvBJapQl0oooD5YKPMV3N7EOXjvhsKJg5KZOSMq9JmTmpJLg82k71Dpt3_C0a_gJCjIzZ</recordid><startdate>20200101</startdate><enddate>20200101</enddate><creator>Pawlowski, Przemyslaw</creator><creator>Poplawska, Izabela</creator><creator>Mysliwiec, Janusz</creator><creator>Dik, Willem A</creator><creator>Eckstein, Anja</creator><creator>Berchner-Pfannschmidt, Utta</creator><creator>Milewski, Robert</creator><creator>Lawicki, Slawomir</creator><creator>Dzieciol-Anikiej, Zofia</creator><creator>Rejdak, Robert</creator><creator>Reszec, Joanna</creator><general>Wydawnictwo Via Medica</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>4T-</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TO</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BYOGL</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20200101</creationdate><title>Search of reference biomarkers reflecting orbital tissue remodeling in the course of Graves' orbitopathy</title><author>Pawlowski, Przemyslaw ; Poplawska, Izabela ; Mysliwiec, Janusz ; Dik, Willem A ; Eckstein, Anja ; Berchner-Pfannschmidt, Utta ; Milewski, Robert ; Lawicki, Slawomir ; Dzieciol-Anikiej, Zofia ; Rejdak, Robert ; Reszec, Joanna</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c351t-a28f15f62288e9f8d120ab720f5538160f7662d63cb0c16d1452d1757c16d65c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adipogenesis</topic><topic>Adipose tissue</topic><topic>Biomarkers</topic><topic>Blindness</topic><topic>Body fat</topic><topic>CD34 antigen</topic><topic>CD4 antigen</topic><topic>Connective tissue</topic><topic>Fibroblast growth factors</topic><topic>Fibroblasts</topic><topic>Fibrosis</topic><topic>Graves disease</topic><topic>Histology</topic><topic>Immunohistochemistry</topic><topic>Immunology</topic><topic>Inflammation</topic><topic>Insulin-like growth factors</topic><topic>Ophthalmology</topic><topic>Pathogenesis</topic><topic>Peroxisome proliferator-activated receptors</topic><topic>Signs and symptoms</topic><topic>Steroids</topic><topic>Studies</topic><topic>Surgery</topic><topic>Thyroid</topic><topic>Thyroid diseases</topic><topic>Thyroid gland</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pawlowski, Przemyslaw</creatorcontrib><creatorcontrib>Poplawska, Izabela</creatorcontrib><creatorcontrib>Mysliwiec, Janusz</creatorcontrib><creatorcontrib>Dik, Willem A</creatorcontrib><creatorcontrib>Eckstein, Anja</creatorcontrib><creatorcontrib>Berchner-Pfannschmidt, Utta</creatorcontrib><creatorcontrib>Milewski, Robert</creatorcontrib><creatorcontrib>Lawicki, Slawomir</creatorcontrib><creatorcontrib>Dzieciol-Anikiej, Zofia</creatorcontrib><creatorcontrib>Rejdak, Robert</creatorcontrib><creatorcontrib>Reszec, Joanna</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Docstoc</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</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>ProQuest Pharma Collection</collection><collection>Technology Research Database</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>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</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>East Europe, Central Europe Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</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>Research Library Prep</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>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</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>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Folia histochemica et cytobiologica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pawlowski, Przemyslaw</au><au>Poplawska, Izabela</au><au>Mysliwiec, Janusz</au><au>Dik, Willem A</au><au>Eckstein, Anja</au><au>Berchner-Pfannschmidt, Utta</au><au>Milewski, Robert</au><au>Lawicki, Slawomir</au><au>Dzieciol-Anikiej, Zofia</au><au>Rejdak, Robert</au><au>Reszec, Joanna</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Search of reference biomarkers reflecting orbital tissue remodeling in the course of Graves' orbitopathy</atitle><jtitle>Folia histochemica et cytobiologica</jtitle><addtitle>Folia Histochem Cytobiol</addtitle><date>2020-01-01</date><risdate>2020</risdate><volume>1</volume><issue>1</issue><spage>37</spage><epage>45</epage><pages>37-45</pages><issn>0239-8508</issn><eissn>1897-5631</eissn><abstract>Graves' orbitopathy (GO) is a complication in Graves' disease (GD) that causes disfigurement and sometimes blindness. The pathogenesis of GO remains unknown, while its symptoms demonstrate dependence between the thyroid gland and the orbit. The ongoing inflammatory process in retrobulbar tissue results in its remodeling characterized by increased volume of the orbital contents involving adipose tissue, with fibrosis and adipogenesis as predominant features. This study was aimed at the immunohistochemical verification of potential contribution and correlation between orbital expressions of IGF-1R, CD34, Foxp-3, PPAR-γ and CD4, CD68, TGF-β, FGF-β in severe and mild (long-lasting) GO.
Forty-one orbital tissue specimens - 22 patients with severe GO, 9 patients with mild GO and 10 patients undergoing blepharoplasty as a control group - were processed by routine immunohistochemistry.
Increased IGF-1R, CD34 and Foxp-3 expression was found in both severe and mild GO, yet a significant correlation between CD34 and CD4, CD68, TGF-β, FGF-β expressions was observed in long-lasting GO.
CD34 expression is proposed to be the marker of orbital tissue remodeling in the course of mild GO.</abstract><cop>Poland</cop><pub>Wydawnictwo Via Medica</pub><pmid>32176314</pmid><doi>10.5603/FHC.a2020.0003</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0239-8508 |
| ispartof | Folia histochemica et cytobiologica, 2020-01, Vol.1 (1), p.37-45 |
| issn | 0239-8508 1897-5631 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2377686252 |
| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Adipogenesis Adipose tissue Biomarkers Blindness Body fat CD34 antigen CD4 antigen Connective tissue Fibroblast growth factors Fibroblasts Fibrosis Graves disease Histology Immunohistochemistry Immunology Inflammation Insulin-like growth factors Ophthalmology Pathogenesis Peroxisome proliferator-activated receptors Signs and symptoms Steroids Studies Surgery Thyroid Thyroid diseases Thyroid gland |
| title | Search of reference biomarkers reflecting orbital tissue remodeling in the course of Graves' orbitopathy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-21T19%3A18%3A02IST&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=Search%20of%20reference%20biomarkers%20reflecting%20orbital%20tissue%20remodeling%20in%20the%20course%20of%20Graves'%20orbitopathy&rft.jtitle=Folia%20histochemica%20et%20cytobiologica&rft.au=Pawlowski,%20Przemyslaw&rft.date=2020-01-01&rft.volume=1&rft.issue=1&rft.spage=37&rft.epage=45&rft.pages=37-45&rft.issn=0239-8508&rft.eissn=1897-5631&rft_id=info:doi/10.5603/FHC.a2020.0003&rft_dat=%3Cproquest_cross%3E2395874528%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2395874528&rft_id=info:pmid/32176314&rfr_iscdi=true |