Compatibility of intravitreally applied epidermal growth factor and amphiregulin

Introduction To examine the compatibility of intravitreally injected epidermal growth factor (EGF) and amphiregulin as EGF family member. Methods Four rabbits (age: 4 months; body weight: 2.5 kg) received three intravitreal injections of EGF (100 ng) uniocularly in monthly intervals and underwent oc...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:International ophthalmology 2021-06, Vol.41 (6), p.2053-2063
Hauptverfasser: Bikbov, Mukharram M., Khalimov, Timur A., Cerrada-Gimenez, Marc, Ragauskas, Symantas, Kalesnykas, Giedrius, Jonas, Jost B.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 2063
container_issue 6
container_start_page 2053
container_title International ophthalmology
container_volume 41
creator Bikbov, Mukharram M.
Khalimov, Timur A.
Cerrada-Gimenez, Marc
Ragauskas, Symantas
Kalesnykas, Giedrius
Jonas, Jost B.
description Introduction To examine the compatibility of intravitreally injected epidermal growth factor (EGF) and amphiregulin as EGF family member. Methods Four rabbits (age: 4 months; body weight: 2.5 kg) received three intravitreal injections of EGF (100 ng) uniocularly in monthly intervals and underwent ocular photography, tonometry, biometry, and optical coherence tomography. After sacrificing the rabbits, the globes were histomorphometrically examined. In a second study part, eyes of 22 guinea pigs (age: 2–3 weeks) received two intravitreal administrations of amphiregulin (10 ng) or phosphate buffered solution (PBS) in 10-day interval, or were left untouched. Ten days after the second injection, the guinea pigs were sacrificed, the enucleated eyes underwent histological and immune-histological examinations. Results The rabbit eyes with EGF injections versus the contralateral untouched eyes did not show significant differences in intraocular pressure (7.5 ± 2.4 mmHg vs. 6.8 ± 2.2 mmHg; P  = 0.66), retinal thickness (158 ± 5 µm vs. 158 ± 3 µm; P  = 1.0), cell counts in the retinal ganglion cell layer (3.3 ± 1.7 cells/150 µm vs. 3.0 ± 1.4 cells/150 µm; P  = 0.83), inner nuclear layer (46.4 ± 23.2 cells/150 µm vs. 39.6 ± 6.4 cells/150 µm; P  = 0.61), and outer nuclear layer (215 ± 108 cells/150 µm vs. 202 ± 47 cells/150 µm; P  = 0.83), or any apoptotic retinal cells. The guinea pig eyes injected with amphiregulin versus eyes with PBS injections did not differ ( P  = 0.72) in the degree of microglial activation, and both groups did not differ from untouched eyes in number of apoptotic retinal cells and retinal gliosis. Conclusions Intravitreal applications of EGF (100 ng) in rabbits nor intravitreal applications of amphiregulin (10 ng) in guinea pigs led to intraocular specific inflammation or any observed intraocular destructive effect. The findings support the notion of a compatibility of intraocular applied EGF and amphiregulin.
doi_str_mv 10.1007/s10792-021-01761-w
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8172503</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2536114817</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-51c7949759cbc3df906094b06e16375517bdba44fa9541cc2ac1f405bb5975023</originalsourceid><addsrcrecordid>eNp9kc1v1DAQxS0EotvCP8ABReLCJTDjT3xBQisoSJXgAGfLcZxdV04c7KSr_e9x2VI-DpzmML_3Zp4eIc8QXiGAel0QlKYtUGwBlcT28IBsUCjWUsngIdkAStEKBXhGzku5BgCttHxMzhhTyKjgG_Jlm8bZLqELMSzHJg1NmJZsb8KSvY3x2Nh5jsH3jZ9D7_NoY7PL6bDsm8G6JeXGTn1jx3kfst-tMUxPyKPBxuKf3s0L8u3D-6_bj-3V58tP23dXreOKL61ApzTXSmjXOdYPGiRo3oH0KJkSAlXXd5bzwWrB0TlqHQ4cRNeJKgLKLsjbk--8dqPvnb99O5o5h9Hmo0k2mL83U9ibXboxb1BRAawavLwzyOn76stixlCcj9FOPq3FVAiplPVURV_8g16nNU81XqWYROTVtFL0RLmcSsl-uH8GwdwWZk6FmVqY-VmYOVTR8z9j3Et-NVQBdgJKXU07n3_f_o_tD-Ovopc</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2536114817</pqid></control><display><type>article</type><title>Compatibility of intravitreally applied epidermal growth factor and amphiregulin</title><source>SpringerLink Journals - AutoHoldings</source><creator>Bikbov, Mukharram M. ; Khalimov, Timur A. ; Cerrada-Gimenez, Marc ; Ragauskas, Symantas ; Kalesnykas, Giedrius ; Jonas, Jost B.</creator><creatorcontrib>Bikbov, Mukharram M. ; Khalimov, Timur A. ; Cerrada-Gimenez, Marc ; Ragauskas, Symantas ; Kalesnykas, Giedrius ; Jonas, Jost B.</creatorcontrib><description>Introduction To examine the compatibility of intravitreally injected epidermal growth factor (EGF) and amphiregulin as EGF family member. Methods Four rabbits (age: 4 months; body weight: 2.5 kg) received three intravitreal injections of EGF (100 ng) uniocularly in monthly intervals and underwent ocular photography, tonometry, biometry, and optical coherence tomography. After sacrificing the rabbits, the globes were histomorphometrically examined. In a second study part, eyes of 22 guinea pigs (age: 2–3 weeks) received two intravitreal administrations of amphiregulin (10 ng) or phosphate buffered solution (PBS) in 10-day interval, or were left untouched. Ten days after the second injection, the guinea pigs were sacrificed, the enucleated eyes underwent histological and immune-histological examinations. Results The rabbit eyes with EGF injections versus the contralateral untouched eyes did not show significant differences in intraocular pressure (7.5 ± 2.4 mmHg vs. 6.8 ± 2.2 mmHg; P  = 0.66), retinal thickness (158 ± 5 µm vs. 158 ± 3 µm; P  = 1.0), cell counts in the retinal ganglion cell layer (3.3 ± 1.7 cells/150 µm vs. 3.0 ± 1.4 cells/150 µm; P  = 0.83), inner nuclear layer (46.4 ± 23.2 cells/150 µm vs. 39.6 ± 6.4 cells/150 µm; P  = 0.61), and outer nuclear layer (215 ± 108 cells/150 µm vs. 202 ± 47 cells/150 µm; P  = 0.83), or any apoptotic retinal cells. The guinea pig eyes injected with amphiregulin versus eyes with PBS injections did not differ ( P  = 0.72) in the degree of microglial activation, and both groups did not differ from untouched eyes in number of apoptotic retinal cells and retinal gliosis. Conclusions Intravitreal applications of EGF (100 ng) in rabbits nor intravitreal applications of amphiregulin (10 ng) in guinea pigs led to intraocular specific inflammation or any observed intraocular destructive effect. The findings support the notion of a compatibility of intraocular applied EGF and amphiregulin.</description><identifier>ISSN: 0165-5701</identifier><identifier>EISSN: 1573-2630</identifier><identifier>DOI: 10.1007/s10792-021-01761-w</identifier><identifier>PMID: 33713254</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Amphiregulin ; Apoptosis ; Body weight ; Compatibility ; Epidermal growth factor ; Eye ; Eye (anatomy) ; Gliosis ; Growth factors ; Guinea pigs ; Inflammation ; Intraocular pressure ; Medicine ; Medicine &amp; Public Health ; Ophthalmology ; Original Paper ; Photography ; Rabbits ; Retina ; Retinal cells</subject><ispartof>International ophthalmology, 2021-06, Vol.41 (6), p.2053-2063</ispartof><rights>The Author(s) 2021</rights><rights>The Author(s) 2021. 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>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-51c7949759cbc3df906094b06e16375517bdba44fa9541cc2ac1f405bb5975023</citedby><cites>FETCH-LOGICAL-c474t-51c7949759cbc3df906094b06e16375517bdba44fa9541cc2ac1f405bb5975023</cites><orcidid>0000-0003-2972-5227</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10792-021-01761-w$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10792-021-01761-w$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33713254$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bikbov, Mukharram M.</creatorcontrib><creatorcontrib>Khalimov, Timur A.</creatorcontrib><creatorcontrib>Cerrada-Gimenez, Marc</creatorcontrib><creatorcontrib>Ragauskas, Symantas</creatorcontrib><creatorcontrib>Kalesnykas, Giedrius</creatorcontrib><creatorcontrib>Jonas, Jost B.</creatorcontrib><title>Compatibility of intravitreally applied epidermal growth factor and amphiregulin</title><title>International ophthalmology</title><addtitle>Int Ophthalmol</addtitle><addtitle>Int Ophthalmol</addtitle><description>Introduction To examine the compatibility of intravitreally injected epidermal growth factor (EGF) and amphiregulin as EGF family member. Methods Four rabbits (age: 4 months; body weight: 2.5 kg) received three intravitreal injections of EGF (100 ng) uniocularly in monthly intervals and underwent ocular photography, tonometry, biometry, and optical coherence tomography. After sacrificing the rabbits, the globes were histomorphometrically examined. In a second study part, eyes of 22 guinea pigs (age: 2–3 weeks) received two intravitreal administrations of amphiregulin (10 ng) or phosphate buffered solution (PBS) in 10-day interval, or were left untouched. Ten days after the second injection, the guinea pigs were sacrificed, the enucleated eyes underwent histological and immune-histological examinations. Results The rabbit eyes with EGF injections versus the contralateral untouched eyes did not show significant differences in intraocular pressure (7.5 ± 2.4 mmHg vs. 6.8 ± 2.2 mmHg; P  = 0.66), retinal thickness (158 ± 5 µm vs. 158 ± 3 µm; P  = 1.0), cell counts in the retinal ganglion cell layer (3.3 ± 1.7 cells/150 µm vs. 3.0 ± 1.4 cells/150 µm; P  = 0.83), inner nuclear layer (46.4 ± 23.2 cells/150 µm vs. 39.6 ± 6.4 cells/150 µm; P  = 0.61), and outer nuclear layer (215 ± 108 cells/150 µm vs. 202 ± 47 cells/150 µm; P  = 0.83), or any apoptotic retinal cells. The guinea pig eyes injected with amphiregulin versus eyes with PBS injections did not differ ( P  = 0.72) in the degree of microglial activation, and both groups did not differ from untouched eyes in number of apoptotic retinal cells and retinal gliosis. Conclusions Intravitreal applications of EGF (100 ng) in rabbits nor intravitreal applications of amphiregulin (10 ng) in guinea pigs led to intraocular specific inflammation or any observed intraocular destructive effect. The findings support the notion of a compatibility of intraocular applied EGF and amphiregulin.</description><subject>Amphiregulin</subject><subject>Apoptosis</subject><subject>Body weight</subject><subject>Compatibility</subject><subject>Epidermal growth factor</subject><subject>Eye</subject><subject>Eye (anatomy)</subject><subject>Gliosis</subject><subject>Growth factors</subject><subject>Guinea pigs</subject><subject>Inflammation</subject><subject>Intraocular pressure</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Ophthalmology</subject><subject>Original Paper</subject><subject>Photography</subject><subject>Rabbits</subject><subject>Retina</subject><subject>Retinal cells</subject><issn>0165-5701</issn><issn>1573-2630</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kc1v1DAQxS0EotvCP8ABReLCJTDjT3xBQisoSJXgAGfLcZxdV04c7KSr_e9x2VI-DpzmML_3Zp4eIc8QXiGAel0QlKYtUGwBlcT28IBsUCjWUsngIdkAStEKBXhGzku5BgCttHxMzhhTyKjgG_Jlm8bZLqELMSzHJg1NmJZsb8KSvY3x2Nh5jsH3jZ9D7_NoY7PL6bDsm8G6JeXGTn1jx3kfst-tMUxPyKPBxuKf3s0L8u3D-6_bj-3V58tP23dXreOKL61ApzTXSmjXOdYPGiRo3oH0KJkSAlXXd5bzwWrB0TlqHQ4cRNeJKgLKLsjbk--8dqPvnb99O5o5h9Hmo0k2mL83U9ibXboxb1BRAawavLwzyOn76stixlCcj9FOPq3FVAiplPVURV_8g16nNU81XqWYROTVtFL0RLmcSsl-uH8GwdwWZk6FmVqY-VmYOVTR8z9j3Et-NVQBdgJKXU07n3_f_o_tD-Ovopc</recordid><startdate>20210601</startdate><enddate>20210601</enddate><creator>Bikbov, Mukharram M.</creator><creator>Khalimov, Timur A.</creator><creator>Cerrada-Gimenez, Marc</creator><creator>Ragauskas, Symantas</creator><creator>Kalesnykas, Giedrius</creator><creator>Jonas, Jost B.</creator><general>Springer Netherlands</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7T7</scope><scope>7TK</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><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2972-5227</orcidid></search><sort><creationdate>20210601</creationdate><title>Compatibility of intravitreally applied epidermal growth factor and amphiregulin</title><author>Bikbov, Mukharram M. ; Khalimov, Timur A. ; Cerrada-Gimenez, Marc ; Ragauskas, Symantas ; Kalesnykas, Giedrius ; Jonas, Jost B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-51c7949759cbc3df906094b06e16375517bdba44fa9541cc2ac1f405bb5975023</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Amphiregulin</topic><topic>Apoptosis</topic><topic>Body weight</topic><topic>Compatibility</topic><topic>Epidermal growth factor</topic><topic>Eye</topic><topic>Eye (anatomy)</topic><topic>Gliosis</topic><topic>Growth factors</topic><topic>Guinea pigs</topic><topic>Inflammation</topic><topic>Intraocular pressure</topic><topic>Medicine</topic><topic>Medicine &amp; Public Health</topic><topic>Ophthalmology</topic><topic>Original Paper</topic><topic>Photography</topic><topic>Rabbits</topic><topic>Retina</topic><topic>Retinal cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bikbov, Mukharram M.</creatorcontrib><creatorcontrib>Khalimov, Timur A.</creatorcontrib><creatorcontrib>Cerrada-Gimenez, Marc</creatorcontrib><creatorcontrib>Ragauskas, Symantas</creatorcontrib><creatorcontrib>Kalesnykas, Giedrius</creatorcontrib><creatorcontrib>Jonas, Jost B.</creatorcontrib><collection>Springer Nature OA/Free Journals</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health &amp; Medical Collection</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 Edition)</collection><collection>ProQuest Central UK/Ireland</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 &amp; Medical Complete (Alumni)</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>International ophthalmology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bikbov, Mukharram M.</au><au>Khalimov, Timur A.</au><au>Cerrada-Gimenez, Marc</au><au>Ragauskas, Symantas</au><au>Kalesnykas, Giedrius</au><au>Jonas, Jost B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Compatibility of intravitreally applied epidermal growth factor and amphiregulin</atitle><jtitle>International ophthalmology</jtitle><stitle>Int Ophthalmol</stitle><addtitle>Int Ophthalmol</addtitle><date>2021-06-01</date><risdate>2021</risdate><volume>41</volume><issue>6</issue><spage>2053</spage><epage>2063</epage><pages>2053-2063</pages><issn>0165-5701</issn><eissn>1573-2630</eissn><abstract>Introduction To examine the compatibility of intravitreally injected epidermal growth factor (EGF) and amphiregulin as EGF family member. Methods Four rabbits (age: 4 months; body weight: 2.5 kg) received three intravitreal injections of EGF (100 ng) uniocularly in monthly intervals and underwent ocular photography, tonometry, biometry, and optical coherence tomography. After sacrificing the rabbits, the globes were histomorphometrically examined. In a second study part, eyes of 22 guinea pigs (age: 2–3 weeks) received two intravitreal administrations of amphiregulin (10 ng) or phosphate buffered solution (PBS) in 10-day interval, or were left untouched. Ten days after the second injection, the guinea pigs were sacrificed, the enucleated eyes underwent histological and immune-histological examinations. Results The rabbit eyes with EGF injections versus the contralateral untouched eyes did not show significant differences in intraocular pressure (7.5 ± 2.4 mmHg vs. 6.8 ± 2.2 mmHg; P  = 0.66), retinal thickness (158 ± 5 µm vs. 158 ± 3 µm; P  = 1.0), cell counts in the retinal ganglion cell layer (3.3 ± 1.7 cells/150 µm vs. 3.0 ± 1.4 cells/150 µm; P  = 0.83), inner nuclear layer (46.4 ± 23.2 cells/150 µm vs. 39.6 ± 6.4 cells/150 µm; P  = 0.61), and outer nuclear layer (215 ± 108 cells/150 µm vs. 202 ± 47 cells/150 µm; P  = 0.83), or any apoptotic retinal cells. The guinea pig eyes injected with amphiregulin versus eyes with PBS injections did not differ ( P  = 0.72) in the degree of microglial activation, and both groups did not differ from untouched eyes in number of apoptotic retinal cells and retinal gliosis. Conclusions Intravitreal applications of EGF (100 ng) in rabbits nor intravitreal applications of amphiregulin (10 ng) in guinea pigs led to intraocular specific inflammation or any observed intraocular destructive effect. The findings support the notion of a compatibility of intraocular applied EGF and amphiregulin.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>33713254</pmid><doi>10.1007/s10792-021-01761-w</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-2972-5227</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0165-5701
ispartof International ophthalmology, 2021-06, Vol.41 (6), p.2053-2063
issn 0165-5701
1573-2630
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8172503
source SpringerLink Journals - AutoHoldings
subjects Amphiregulin
Apoptosis
Body weight
Compatibility
Epidermal growth factor
Eye
Eye (anatomy)
Gliosis
Growth factors
Guinea pigs
Inflammation
Intraocular pressure
Medicine
Medicine & Public Health
Ophthalmology
Original Paper
Photography
Rabbits
Retina
Retinal cells
title Compatibility of intravitreally applied epidermal growth factor and amphiregulin
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-11T04%3A53%3A41IST&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=Compatibility%20of%20intravitreally%20applied%20epidermal%20growth%20factor%20and%20amphiregulin&rft.jtitle=International%20ophthalmology&rft.au=Bikbov,%20Mukharram%20M.&rft.date=2021-06-01&rft.volume=41&rft.issue=6&rft.spage=2053&rft.epage=2063&rft.pages=2053-2063&rft.issn=0165-5701&rft.eissn=1573-2630&rft_id=info:doi/10.1007/s10792-021-01761-w&rft_dat=%3Cproquest_pubme%3E2536114817%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=2536114817&rft_id=info:pmid/33713254&rfr_iscdi=true