Choroidal structural analysis in eyes with diabetic retinopathy and diabetic macular edema-A novel OCT based imaging biomarker
To evaluate structural changes in the choroid among patients with diabetic macular edema (DME), with varying grades of diabetic retinopathy (DR), using enhance depth imaging spectral domain optical coherence tomography (EDI SD-OCT) scans. A cross-sectional study was conducted on 82 eyes with DR and...
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| creator | Gupta, Chanda Tan, Roy Mishra, Chitaranjan Khandelwal, Neha Raman, Rajiv Kim, Ramasamy Agrawal, Rupesh Sen, Parveen |
| description | To evaluate structural changes in the choroid among patients with diabetic macular edema (DME), with varying grades of diabetic retinopathy (DR), using enhance depth imaging spectral domain optical coherence tomography (EDI SD-OCT) scans.
A cross-sectional study was conducted on 82 eyes with DR and DME and 86 healthy control eyes. Eyes with DME were classified according to the severity of DR as per the international DR severity scale. Sub foveal choroidal thickness (SFCT)was obtained using EDI SD-OCT scans. These scans were binarized into luminal and stromal areas, to derive the choroidal vascularity index (CVI). CVI and SFCT were analyzed between the study and control group using paired-T test. Tukey's test was used to correlate the differences in CVI and SFCT between different grades of DR. Further analysis was done to look for the effect of DR severity and type of DME on CVI as well as SFCT using correlation coefficient and linear regression analysis.
SFCT was significantly increased in eyes with DME as compared to the controls (334.47±51.81μm vs 284.53±56.45μm, p |
| doi_str_mv | 10.1371/journal.pone.0207435 |
| format | Article |
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A cross-sectional study was conducted on 82 eyes with DR and DME and 86 healthy control eyes. Eyes with DME were classified according to the severity of DR as per the international DR severity scale. Sub foveal choroidal thickness (SFCT)was obtained using EDI SD-OCT scans. These scans were binarized into luminal and stromal areas, to derive the choroidal vascularity index (CVI). CVI and SFCT were analyzed between the study and control group using paired-T test. Tukey's test was used to correlate the differences in CVI and SFCT between different grades of DR. Further analysis was done to look for the effect of DR severity and type of DME on CVI as well as SFCT using correlation coefficient and linear regression analysis.
SFCT was significantly increased in eyes with DME as compared to the controls (334.47±51.81μm vs 284.53±56.45μm, p<0.001), and showed an ascending trend with worsening of DR, though this difference was not statistically significant [mild non-proliferative diabetic retinopathy (NPDR) = 304.33±40.39μm, moderate NPDR = 327.81±47.39μm, severe NPDR = 357.72±62.65μm, proliferative DR (PDR) = 334.59±47.4μm, p-0.09]. CVI was significantly decreased in DME with DR eyes as compared to controls (63.89±1.89 vs 67.51±2.86, p<0.001). CVI was also significantly decreased with worsening DR (mild NPDR = 66.38±0.3, moderate NPDR = 65.28±0.37, severe NPDR = 63.50±0.47, PDR = 61.27±0.9, p<0.001).
SFCT and CVI are dynamic parameters that are affected by DME. Unlike CVI, SFCT is also affected by ocular and systemic factors like edema and hypertension. CVI may be a more accurate surrogate marker for DME and DR and can potentially be used to monitor the progression of DR.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0207435</identifier><identifier>PMID: 30533048</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Biological markers ; Biology and Life Sciences ; Biomarkers ; Choroid ; Choroid - diagnostic imaging ; Choroid - pathology ; Correlation analysis ; Correlation coefficient ; Correlation coefficients ; Cross-Sectional Studies ; Cystoid macular edema ; Development and progression ; Diabetes ; Diabetes mellitus ; Diabetic retinopathy ; Diabetic Retinopathy - diagnostic imaging ; Diabetic Retinopathy - pathology ; Diagnosis ; Direct reduction ; Edema ; Eye ; Eye (anatomy) ; Female ; Health aspects ; Humans ; Hypertension ; Macular degeneration ; Macular Edema - complications ; Macular Edema - diagnostic imaging ; Macular Edema - pathology ; Male ; Medical imaging ; Medical research ; Medicine and Health Sciences ; Middle Aged ; Optical Coherence Tomography ; Optical tomography ; Population ; Regression analysis ; Retina ; Retinopathy ; Statistical analysis ; Structural analysis ; Studies ; Tomography ; Tomography, Optical Coherence</subject><ispartof>PloS one, 2018-12, Vol.13 (12), p.e0207435-e0207435</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Gupta et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 Gupta et al 2018 Gupta et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-2f71f3761e4b53a64b63ab46e0d53ae34b9711f5991c64a47c0ed20d2689ed203</citedby><cites>FETCH-LOGICAL-c692t-2f71f3761e4b53a64b63ab46e0d53ae34b9711f5991c64a47c0ed20d2689ed203</cites><orcidid>0000-0001-9533-6591 ; 0000-0003-2256-9380</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/PMC6289408/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289408/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30533048$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gupta, Chanda</creatorcontrib><creatorcontrib>Tan, Roy</creatorcontrib><creatorcontrib>Mishra, Chitaranjan</creatorcontrib><creatorcontrib>Khandelwal, Neha</creatorcontrib><creatorcontrib>Raman, Rajiv</creatorcontrib><creatorcontrib>Kim, Ramasamy</creatorcontrib><creatorcontrib>Agrawal, Rupesh</creatorcontrib><creatorcontrib>Sen, Parveen</creatorcontrib><title>Choroidal structural analysis in eyes with diabetic retinopathy and diabetic macular edema-A novel OCT based imaging biomarker</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>To evaluate structural changes in the choroid among patients with diabetic macular edema (DME), with varying grades of diabetic retinopathy (DR), using enhance depth imaging spectral domain optical coherence tomography (EDI SD-OCT) scans.
A cross-sectional study was conducted on 82 eyes with DR and DME and 86 healthy control eyes. Eyes with DME were classified according to the severity of DR as per the international DR severity scale. Sub foveal choroidal thickness (SFCT)was obtained using EDI SD-OCT scans. These scans were binarized into luminal and stromal areas, to derive the choroidal vascularity index (CVI). CVI and SFCT were analyzed between the study and control group using paired-T test. Tukey's test was used to correlate the differences in CVI and SFCT between different grades of DR. Further analysis was done to look for the effect of DR severity and type of DME on CVI as well as SFCT using correlation coefficient and linear regression analysis.
SFCT was significantly increased in eyes with DME as compared to the controls (334.47±51.81μm vs 284.53±56.45μm, p<0.001), and showed an ascending trend with worsening of DR, though this difference was not statistically significant [mild non-proliferative diabetic retinopathy (NPDR) = 304.33±40.39μm, moderate NPDR = 327.81±47.39μm, severe NPDR = 357.72±62.65μm, proliferative DR (PDR) = 334.59±47.4μm, p-0.09]. CVI was significantly decreased in DME with DR eyes as compared to controls (63.89±1.89 vs 67.51±2.86, p<0.001). CVI was also significantly decreased with worsening DR (mild NPDR = 66.38±0.3, moderate NPDR = 65.28±0.37, severe NPDR = 63.50±0.47, PDR = 61.27±0.9, p<0.001).
SFCT and CVI are dynamic parameters that are affected by DME. Unlike CVI, SFCT is also affected by ocular and systemic factors like edema and hypertension. CVI may be a more accurate surrogate marker for DME and DR and can potentially be used to monitor the progression of DR.</description><subject>Biological markers</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Choroid</subject><subject>Choroid - diagnostic imaging</subject><subject>Choroid - pathology</subject><subject>Correlation analysis</subject><subject>Correlation coefficient</subject><subject>Correlation coefficients</subject><subject>Cross-Sectional Studies</subject><subject>Cystoid macular edema</subject><subject>Development and progression</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetic retinopathy</subject><subject>Diabetic Retinopathy - diagnostic imaging</subject><subject>Diabetic Retinopathy - pathology</subject><subject>Diagnosis</subject><subject>Direct reduction</subject><subject>Edema</subject><subject>Eye</subject><subject>Eye (anatomy)</subject><subject>Female</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Macular degeneration</subject><subject>Macular Edema - complications</subject><subject>Macular Edema - diagnostic imaging</subject><subject>Macular Edema - pathology</subject><subject>Male</subject><subject>Medical imaging</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Middle Aged</subject><subject>Optical Coherence Tomography</subject><subject>Optical tomography</subject><subject>Population</subject><subject>Regression analysis</subject><subject>Retina</subject><subject>Retinopathy</subject><subject>Statistical analysis</subject><subject>Structural analysis</subject><subject>Studies</subject><subject>Tomography</subject><subject>Tomography, Optical Coherence</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk99v0zAQxyMEYmPwHyCwhITgocWOHSd5QaoqflSaVAkGr9bFdhKPNO5sZ9AX_nbcNRsN2gOyFF_sz319d_YlyXOC54Tm5N2lHVwP3Xxrez3HKc4ZzR4kp6Sk6YynmD48sk-SJ95fYpzRgvPHyQmNFsWsOE1-L1vrrFHQIR_cIMPgoglReOeNR6ZHeqc9-mlCi5SBSgcjkYvf3m4htLuIqr8bG5BDBw5ppTcwW6DeXusOrZcXqAKvFTIbaEzfoMrYDbgf2j1NHtXQef1snM-Sbx8_XCw_z87Xn1bLxflM8jINs7TOSU1zTjSrMgqcVZxCxbjGKv5qyqoyJ6TOypJIzoDlEmuVYpXyotwb9Cx5edDddtaLsXRepCRjPGVlWUZidSCUhUuxdTFUtxMWjLhZsK4R4GKOnRY55ITiGFGaV0ynBLJYaKlkXRQsy5WKWu_H04Zqo5XUfYhVnYhOd3rTisZeC54WJcNFFHgzCjh7NWgfxMZ4qbsOem2Hm7gzwgmnPKKv_kHvz26kGogJmL628Vy5FxWLjGeUZHm515rfQ8URr9PI-M5qE9cnDm8nDpEJ-ldoYPBerL5--X92_X3Kvj5iWw1daL3thmBs76cgO4DSWe-dru-KTLDYt8ltNcS-TcTYJtHtxfEF3Tnd9gX9A40iDZc</recordid><startdate>20181211</startdate><enddate>20181211</enddate><creator>Gupta, Chanda</creator><creator>Tan, Roy</creator><creator>Mishra, Chitaranjan</creator><creator>Khandelwal, Neha</creator><creator>Raman, Rajiv</creator><creator>Kim, Ramasamy</creator><creator>Agrawal, Rupesh</creator><creator>Sen, Parveen</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</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>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-9533-6591</orcidid><orcidid>https://orcid.org/0000-0003-2256-9380</orcidid></search><sort><creationdate>20181211</creationdate><title>Choroidal structural analysis in eyes with diabetic retinopathy and diabetic macular edema-A novel OCT based imaging biomarker</title><author>Gupta, Chanda ; Tan, Roy ; Mishra, Chitaranjan ; Khandelwal, Neha ; Raman, Rajiv ; Kim, Ramasamy ; Agrawal, Rupesh ; Sen, Parveen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-2f71f3761e4b53a64b63ab46e0d53ae34b9711f5991c64a47c0ed20d2689ed203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Biological markers</topic><topic>Biology and Life Sciences</topic><topic>Biomarkers</topic><topic>Choroid</topic><topic>Choroid - diagnostic imaging</topic><topic>Choroid - pathology</topic><topic>Correlation analysis</topic><topic>Correlation coefficient</topic><topic>Correlation coefficients</topic><topic>Cross-Sectional Studies</topic><topic>Cystoid macular edema</topic><topic>Development and progression</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetic retinopathy</topic><topic>Diabetic Retinopathy - diagnostic imaging</topic><topic>Diabetic Retinopathy - pathology</topic><topic>Diagnosis</topic><topic>Direct reduction</topic><topic>Edema</topic><topic>Eye</topic><topic>Eye (anatomy)</topic><topic>Female</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Macular degeneration</topic><topic>Macular Edema - complications</topic><topic>Macular Edema - diagnostic imaging</topic><topic>Macular Edema - pathology</topic><topic>Male</topic><topic>Medical imaging</topic><topic>Medical research</topic><topic>Medicine and Health Sciences</topic><topic>Middle Aged</topic><topic>Optical Coherence Tomography</topic><topic>Optical tomography</topic><topic>Population</topic><topic>Regression analysis</topic><topic>Retina</topic><topic>Retinopathy</topic><topic>Statistical analysis</topic><topic>Structural analysis</topic><topic>Studies</topic><topic>Tomography</topic><topic>Tomography, Optical Coherence</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gupta, Chanda</creatorcontrib><creatorcontrib>Tan, Roy</creatorcontrib><creatorcontrib>Mishra, Chitaranjan</creatorcontrib><creatorcontrib>Khandelwal, Neha</creatorcontrib><creatorcontrib>Raman, Rajiv</creatorcontrib><creatorcontrib>Kim, Ramasamy</creatorcontrib><creatorcontrib>Agrawal, Rupesh</creatorcontrib><creatorcontrib>Sen, Parveen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database (ProQuest)</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>ProQuest - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gupta, Chanda</au><au>Tan, Roy</au><au>Mishra, Chitaranjan</au><au>Khandelwal, Neha</au><au>Raman, Rajiv</au><au>Kim, Ramasamy</au><au>Agrawal, Rupesh</au><au>Sen, Parveen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Choroidal structural analysis in eyes with diabetic retinopathy and diabetic macular edema-A novel OCT based imaging biomarker</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2018-12-11</date><risdate>2018</risdate><volume>13</volume><issue>12</issue><spage>e0207435</spage><epage>e0207435</epage><pages>e0207435-e0207435</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>To evaluate structural changes in the choroid among patients with diabetic macular edema (DME), with varying grades of diabetic retinopathy (DR), using enhance depth imaging spectral domain optical coherence tomography (EDI SD-OCT) scans.
A cross-sectional study was conducted on 82 eyes with DR and DME and 86 healthy control eyes. Eyes with DME were classified according to the severity of DR as per the international DR severity scale. Sub foveal choroidal thickness (SFCT)was obtained using EDI SD-OCT scans. These scans were binarized into luminal and stromal areas, to derive the choroidal vascularity index (CVI). CVI and SFCT were analyzed between the study and control group using paired-T test. Tukey's test was used to correlate the differences in CVI and SFCT between different grades of DR. Further analysis was done to look for the effect of DR severity and type of DME on CVI as well as SFCT using correlation coefficient and linear regression analysis.
SFCT was significantly increased in eyes with DME as compared to the controls (334.47±51.81μm vs 284.53±56.45μm, p<0.001), and showed an ascending trend with worsening of DR, though this difference was not statistically significant [mild non-proliferative diabetic retinopathy (NPDR) = 304.33±40.39μm, moderate NPDR = 327.81±47.39μm, severe NPDR = 357.72±62.65μm, proliferative DR (PDR) = 334.59±47.4μm, p-0.09]. CVI was significantly decreased in DME with DR eyes as compared to controls (63.89±1.89 vs 67.51±2.86, p<0.001). CVI was also significantly decreased with worsening DR (mild NPDR = 66.38±0.3, moderate NPDR = 65.28±0.37, severe NPDR = 63.50±0.47, PDR = 61.27±0.9, p<0.001).
SFCT and CVI are dynamic parameters that are affected by DME. Unlike CVI, SFCT is also affected by ocular and systemic factors like edema and hypertension. CVI may be a more accurate surrogate marker for DME and DR and can potentially be used to monitor the progression of DR.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>30533048</pmid><doi>10.1371/journal.pone.0207435</doi><tpages>e0207435</tpages><orcidid>https://orcid.org/0000-0001-9533-6591</orcidid><orcidid>https://orcid.org/0000-0003-2256-9380</orcidid><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_2154624999 |
| source | MEDLINE; PLoS_OA刊; PubMed Central; Directory of Open Access Journals; Free Full-Text Journals in Chemistry; EZB Electronic Journals Library |
| subjects | Biological markers Biology and Life Sciences Biomarkers Choroid Choroid - diagnostic imaging Choroid - pathology Correlation analysis Correlation coefficient Correlation coefficients Cross-Sectional Studies Cystoid macular edema Development and progression Diabetes Diabetes mellitus Diabetic retinopathy Diabetic Retinopathy - diagnostic imaging Diabetic Retinopathy - pathology Diagnosis Direct reduction Edema Eye Eye (anatomy) Female Health aspects Humans Hypertension Macular degeneration Macular Edema - complications Macular Edema - diagnostic imaging Macular Edema - pathology Male Medical imaging Medical research Medicine and Health Sciences Middle Aged Optical Coherence Tomography Optical tomography Population Regression analysis Retina Retinopathy Statistical analysis Structural analysis Studies Tomography Tomography, Optical Coherence |
| title | Choroidal structural analysis in eyes with diabetic retinopathy and diabetic macular edema-A novel OCT based imaging biomarker |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T08%3A59%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Choroidal%20structural%20analysis%20in%20eyes%20with%20diabetic%20retinopathy%20and%20diabetic%20macular%20edema-A%20novel%20OCT%20based%20imaging%20biomarker&rft.jtitle=PloS%20one&rft.au=Gupta,%20Chanda&rft.date=2018-12-11&rft.volume=13&rft.issue=12&rft.spage=e0207435&rft.epage=e0207435&rft.pages=e0207435-e0207435&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0207435&rft_dat=%3Cgale_plos_%3EA565315796%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2154624999&rft_id=info:pmid/30533048&rft_galeid=A565315796&rft_doaj_id=oai_doaj_org_article_7a713071f27b4e21a5193cdcf88457dd&rfr_iscdi=true |