Loading…

Systematic Review and Meta-analysis on the Association of Occupational Exposure to Free Crystalline Silica and Rheumatoid Arthritis

Key messages • Occupational exposure to free crystalline silica and tobacco smoking are associated with an increased risk rheumatoid arthritis, with the evidence of an interaction in seropositive subjects . • Further studies in the field are needed to support such association We carried out a system...

Full description

Saved in:
Bibliographic Details
Published in:Clinical reviews in allergy & immunology 2022-04, Vol.62 (2), p.333-345
Main Authors: Morotti, A., Sollaku, I., Franceschini, F., Cavazzana, I., Fredi, M., Sala, E., De Palma, G.
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-c572t-b41789eda05b035c061ed2a0084af4c82f651b813defedcd1c815737344ec2753
cites cdi_FETCH-LOGICAL-c572t-b41789eda05b035c061ed2a0084af4c82f651b813defedcd1c815737344ec2753
container_end_page 345
container_issue 2
container_start_page 333
container_title Clinical reviews in allergy & immunology
container_volume 62
creator Morotti, A.
Sollaku, I.
Franceschini, F.
Cavazzana, I.
Fredi, M.
Sala, E.
De Palma, G.
description Key messages • Occupational exposure to free crystalline silica and tobacco smoking are associated with an increased risk rheumatoid arthritis, with the evidence of an interaction in seropositive subjects . • Further studies in the field are needed to support such association We carried out a systematic search for all published epidemiological studies concerning the association between occupational exposure to free crystalline silica (FCS) and subsequent development of rheumatoid arthritis (RA). A meta-analysis was conducted on relevant studies. We searched PubMed and Embase, search engines, for original articles published (from 1960 to November 2019) in any language. In addition, we also searched reference lists of included studies manually for additional relevant articles. Finally, twelve studies were included in the meta-analysis (seven case-control cases and five cohort studies). The odds risks and 95% confidence interval (CI) were calculated using a random effect meta-analysis. A primary meta-analysis (using a random effect model)—regarding RA risk in subjects exposed to FCS—yelled to an overall OR of 1.94 (95% CI 1.46–2.58). We also conducted three further meta-analysis, taking into account the presence of autoantibodies (anti-RF or anti-ACPA) and smoking habits and found a significant association between FCS and RA in both seropositive and seronegative subjects (OR 1.74, 95% CI 1.35–2.25 and OR 1.23, 95% CI 1.06–1.4, respectively) and in seropositive subjects which were smokers (OR 3.30, 95% CI 2.40–4.54). The studies that have investigated the association between RA and occupatational exposure to FCS are still scarce and the heterogeneity between the studies remains high. Some critical limitations have been identified within studies, among which, the methods for assessing exposure stand out. Although with due caution, our results confirm the hypothesis of an association between occupational exposure to FCS and RA development. There was an interaction between FCS and tobacco smoking in RA seropositive workers.
doi_str_mv 10.1007/s12016-021-08846-5
format article
fullrecord <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8994741</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A700054555</galeid><sourcerecordid>A700054555</sourcerecordid><originalsourceid>FETCH-LOGICAL-c572t-b41789eda05b035c061ed2a0084af4c82f651b813defedcd1c815737344ec2753</originalsourceid><addsrcrecordid>eNp9Uk1vEzEUXCEQLYU_wAFZQuK2xZ9r54IURS0gFVVq4Ww53rdZV951sL2FnPnjOEkpiYSQD_Z7nhl77Kmq1wSfE4zl-0QoJk2NKamxUrypxZPqlAgxK61GPj1Yn1QvUrrDmGLFZs-rE8YaQRinp9Wv203KMJjsLLqBewc_kBlb9AWyqc1o_Ca5hMKIcg9onlKwrkBLHTp0be203lXGo4uf65CmCCgHdBkB0CIWYeO9GwHdOu-s2Qnf9DCV04Jr0TzmPrrs0svqWWd8glcP81n17fLi6-JTfXX98fNiflVbIWmul5xINYPWYLHETFjcEGipwVhx03GraFdMLRVhLXTQ2pZYRYRkknEOlkrBzqoPe931tBwKAsYcjdfr6AYTNzoYp493RtfrVbjXajbjkpMi8PZBIIbvE6Ss78IUi_2kacNVwyiWB6iV8aDd2IUiZgeXrJ5LjLHgQmwvc_4PVBktDM6GETpX-keEdweEHozPfQp-2n5AOgbSPdDGkFKE7tEhwXobHL0Pji7B0bvg6C3pzeHbPFL-JKUA2B6Qyta4gvjX-39kfwPF1s6u</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2648632071</pqid></control><display><type>article</type><title>Systematic Review and Meta-analysis on the Association of Occupational Exposure to Free Crystalline Silica and Rheumatoid Arthritis</title><source>Springer Nature</source><creator>Morotti, A. ; Sollaku, I. ; Franceschini, F. ; Cavazzana, I. ; Fredi, M. ; Sala, E. ; De Palma, G.</creator><creatorcontrib>Morotti, A. ; Sollaku, I. ; Franceschini, F. ; Cavazzana, I. ; Fredi, M. ; Sala, E. ; De Palma, G.</creatorcontrib><description>Key messages • Occupational exposure to free crystalline silica and tobacco smoking are associated with an increased risk rheumatoid arthritis, with the evidence of an interaction in seropositive subjects . • Further studies in the field are needed to support such association We carried out a systematic search for all published epidemiological studies concerning the association between occupational exposure to free crystalline silica (FCS) and subsequent development of rheumatoid arthritis (RA). A meta-analysis was conducted on relevant studies. We searched PubMed and Embase, search engines, for original articles published (from 1960 to November 2019) in any language. In addition, we also searched reference lists of included studies manually for additional relevant articles. Finally, twelve studies were included in the meta-analysis (seven case-control cases and five cohort studies). The odds risks and 95% confidence interval (CI) were calculated using a random effect meta-analysis. A primary meta-analysis (using a random effect model)—regarding RA risk in subjects exposed to FCS—yelled to an overall OR of 1.94 (95% CI 1.46–2.58). We also conducted three further meta-analysis, taking into account the presence of autoantibodies (anti-RF or anti-ACPA) and smoking habits and found a significant association between FCS and RA in both seropositive and seronegative subjects (OR 1.74, 95% CI 1.35–2.25 and OR 1.23, 95% CI 1.06–1.4, respectively) and in seropositive subjects which were smokers (OR 3.30, 95% CI 2.40–4.54). The studies that have investigated the association between RA and occupatational exposure to FCS are still scarce and the heterogeneity between the studies remains high. Some critical limitations have been identified within studies, among which, the methods for assessing exposure stand out. Although with due caution, our results confirm the hypothesis of an association between occupational exposure to FCS and RA development. There was an interaction between FCS and tobacco smoking in RA seropositive workers.</description><identifier>ISSN: 1559-0267</identifier><identifier>ISSN: 1080-0549</identifier><identifier>EISSN: 1559-0267</identifier><identifier>DOI: 10.1007/s12016-021-08846-5</identifier><identifier>PMID: 33651342</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Allergology ; Analysis ; Arthritis ; Arthritis, Rheumatoid - etiology ; Autoantibodies ; Autoimmunity ; B cells ; Epidemiology ; Humans ; Immunology ; Internal Medicine ; Internet/Web search services ; Medicine ; Medicine &amp; Public Health ; Meta-analysis ; Occupational exposure ; Occupational Exposure - adverse effects ; Occupational health and safety ; Rheumatoid arthritis ; Rheumatoid factor ; Risk Factors ; Silica ; Silicon Dioxide - adverse effects ; Smoking ; Tobacco smoking</subject><ispartof>Clinical reviews in allergy &amp; immunology, 2022-04, Vol.62 (2), p.333-345</ispartof><rights>The Author(s) 2021</rights><rights>2021. The Author(s).</rights><rights>COPYRIGHT 2022 Springer</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-c572t-b41789eda05b035c061ed2a0084af4c82f651b813defedcd1c815737344ec2753</citedby><cites>FETCH-LOGICAL-c572t-b41789eda05b035c061ed2a0084af4c82f651b813defedcd1c815737344ec2753</cites><orcidid>0000-0001-9821-3060</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33651342$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Morotti, A.</creatorcontrib><creatorcontrib>Sollaku, I.</creatorcontrib><creatorcontrib>Franceschini, F.</creatorcontrib><creatorcontrib>Cavazzana, I.</creatorcontrib><creatorcontrib>Fredi, M.</creatorcontrib><creatorcontrib>Sala, E.</creatorcontrib><creatorcontrib>De Palma, G.</creatorcontrib><title>Systematic Review and Meta-analysis on the Association of Occupational Exposure to Free Crystalline Silica and Rheumatoid Arthritis</title><title>Clinical reviews in allergy &amp; immunology</title><addtitle>Clinic Rev Allerg Immunol</addtitle><addtitle>Clin Rev Allergy Immunol</addtitle><description>Key messages • Occupational exposure to free crystalline silica and tobacco smoking are associated with an increased risk rheumatoid arthritis, with the evidence of an interaction in seropositive subjects . • Further studies in the field are needed to support such association We carried out a systematic search for all published epidemiological studies concerning the association between occupational exposure to free crystalline silica (FCS) and subsequent development of rheumatoid arthritis (RA). A meta-analysis was conducted on relevant studies. We searched PubMed and Embase, search engines, for original articles published (from 1960 to November 2019) in any language. In addition, we also searched reference lists of included studies manually for additional relevant articles. Finally, twelve studies were included in the meta-analysis (seven case-control cases and five cohort studies). The odds risks and 95% confidence interval (CI) were calculated using a random effect meta-analysis. A primary meta-analysis (using a random effect model)—regarding RA risk in subjects exposed to FCS—yelled to an overall OR of 1.94 (95% CI 1.46–2.58). We also conducted three further meta-analysis, taking into account the presence of autoantibodies (anti-RF or anti-ACPA) and smoking habits and found a significant association between FCS and RA in both seropositive and seronegative subjects (OR 1.74, 95% CI 1.35–2.25 and OR 1.23, 95% CI 1.06–1.4, respectively) and in seropositive subjects which were smokers (OR 3.30, 95% CI 2.40–4.54). The studies that have investigated the association between RA and occupatational exposure to FCS are still scarce and the heterogeneity between the studies remains high. Some critical limitations have been identified within studies, among which, the methods for assessing exposure stand out. Although with due caution, our results confirm the hypothesis of an association between occupational exposure to FCS and RA development. There was an interaction between FCS and tobacco smoking in RA seropositive workers.</description><subject>Allergology</subject><subject>Analysis</subject><subject>Arthritis</subject><subject>Arthritis, Rheumatoid - etiology</subject><subject>Autoantibodies</subject><subject>Autoimmunity</subject><subject>B cells</subject><subject>Epidemiology</subject><subject>Humans</subject><subject>Immunology</subject><subject>Internal Medicine</subject><subject>Internet/Web search services</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Meta-analysis</subject><subject>Occupational exposure</subject><subject>Occupational Exposure - adverse effects</subject><subject>Occupational health and safety</subject><subject>Rheumatoid arthritis</subject><subject>Rheumatoid factor</subject><subject>Risk Factors</subject><subject>Silica</subject><subject>Silicon Dioxide - adverse effects</subject><subject>Smoking</subject><subject>Tobacco smoking</subject><issn>1559-0267</issn><issn>1080-0549</issn><issn>1559-0267</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp9Uk1vEzEUXCEQLYU_wAFZQuK2xZ9r54IURS0gFVVq4Ww53rdZV951sL2FnPnjOEkpiYSQD_Z7nhl77Kmq1wSfE4zl-0QoJk2NKamxUrypxZPqlAgxK61GPj1Yn1QvUrrDmGLFZs-rE8YaQRinp9Wv203KMJjsLLqBewc_kBlb9AWyqc1o_Ca5hMKIcg9onlKwrkBLHTp0be203lXGo4uf65CmCCgHdBkB0CIWYeO9GwHdOu-s2Qnf9DCV04Jr0TzmPrrs0svqWWd8glcP81n17fLi6-JTfXX98fNiflVbIWmul5xINYPWYLHETFjcEGipwVhx03GraFdMLRVhLXTQ2pZYRYRkknEOlkrBzqoPe931tBwKAsYcjdfr6AYTNzoYp493RtfrVbjXajbjkpMi8PZBIIbvE6Ss78IUi_2kacNVwyiWB6iV8aDd2IUiZgeXrJ5LjLHgQmwvc_4PVBktDM6GETpX-keEdweEHozPfQp-2n5AOgbSPdDGkFKE7tEhwXobHL0Pji7B0bvg6C3pzeHbPFL-JKUA2B6Qyta4gvjX-39kfwPF1s6u</recordid><startdate>20220401</startdate><enddate>20220401</enddate><creator>Morotti, A.</creator><creator>Sollaku, I.</creator><creator>Franceschini, F.</creator><creator>Cavazzana, I.</creator><creator>Fredi, M.</creator><creator>Sala, E.</creator><creator>De Palma, G.</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><scope>C6C</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>7T5</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</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>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9821-3060</orcidid></search><sort><creationdate>20220401</creationdate><title>Systematic Review and Meta-analysis on the Association of Occupational Exposure to Free Crystalline Silica and Rheumatoid Arthritis</title><author>Morotti, A. ; Sollaku, I. ; Franceschini, F. ; Cavazzana, I. ; Fredi, M. ; Sala, E. ; De Palma, G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c572t-b41789eda05b035c061ed2a0084af4c82f651b813defedcd1c815737344ec2753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Allergology</topic><topic>Analysis</topic><topic>Arthritis</topic><topic>Arthritis, Rheumatoid - etiology</topic><topic>Autoantibodies</topic><topic>Autoimmunity</topic><topic>B cells</topic><topic>Epidemiology</topic><topic>Humans</topic><topic>Immunology</topic><topic>Internal Medicine</topic><topic>Internet/Web search services</topic><topic>Medicine</topic><topic>Medicine &amp; Public Health</topic><topic>Meta-analysis</topic><topic>Occupational exposure</topic><topic>Occupational Exposure - adverse effects</topic><topic>Occupational health and safety</topic><topic>Rheumatoid arthritis</topic><topic>Rheumatoid factor</topic><topic>Risk Factors</topic><topic>Silica</topic><topic>Silicon Dioxide - adverse effects</topic><topic>Smoking</topic><topic>Tobacco smoking</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Morotti, A.</creatorcontrib><creatorcontrib>Sollaku, I.</creatorcontrib><creatorcontrib>Franceschini, F.</creatorcontrib><creatorcontrib>Cavazzana, I.</creatorcontrib><creatorcontrib>Fredi, M.</creatorcontrib><creatorcontrib>Sala, E.</creatorcontrib><creatorcontrib>De Palma, G.</creatorcontrib><collection>SpringerOpen</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>Immunology 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>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>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</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 &amp; Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science 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>PubMed Central (Full Participant titles)</collection><jtitle>Clinical reviews in allergy &amp; immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Morotti, A.</au><au>Sollaku, I.</au><au>Franceschini, F.</au><au>Cavazzana, I.</au><au>Fredi, M.</au><au>Sala, E.</au><au>De Palma, G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Systematic Review and Meta-analysis on the Association of Occupational Exposure to Free Crystalline Silica and Rheumatoid Arthritis</atitle><jtitle>Clinical reviews in allergy &amp; immunology</jtitle><stitle>Clinic Rev Allerg Immunol</stitle><addtitle>Clin Rev Allergy Immunol</addtitle><date>2022-04-01</date><risdate>2022</risdate><volume>62</volume><issue>2</issue><spage>333</spage><epage>345</epage><pages>333-345</pages><issn>1559-0267</issn><issn>1080-0549</issn><eissn>1559-0267</eissn><abstract>Key messages • Occupational exposure to free crystalline silica and tobacco smoking are associated with an increased risk rheumatoid arthritis, with the evidence of an interaction in seropositive subjects . • Further studies in the field are needed to support such association We carried out a systematic search for all published epidemiological studies concerning the association between occupational exposure to free crystalline silica (FCS) and subsequent development of rheumatoid arthritis (RA). A meta-analysis was conducted on relevant studies. We searched PubMed and Embase, search engines, for original articles published (from 1960 to November 2019) in any language. In addition, we also searched reference lists of included studies manually for additional relevant articles. Finally, twelve studies were included in the meta-analysis (seven case-control cases and five cohort studies). The odds risks and 95% confidence interval (CI) were calculated using a random effect meta-analysis. A primary meta-analysis (using a random effect model)—regarding RA risk in subjects exposed to FCS—yelled to an overall OR of 1.94 (95% CI 1.46–2.58). We also conducted three further meta-analysis, taking into account the presence of autoantibodies (anti-RF or anti-ACPA) and smoking habits and found a significant association between FCS and RA in both seropositive and seronegative subjects (OR 1.74, 95% CI 1.35–2.25 and OR 1.23, 95% CI 1.06–1.4, respectively) and in seropositive subjects which were smokers (OR 3.30, 95% CI 2.40–4.54). The studies that have investigated the association between RA and occupatational exposure to FCS are still scarce and the heterogeneity between the studies remains high. Some critical limitations have been identified within studies, among which, the methods for assessing exposure stand out. Although with due caution, our results confirm the hypothesis of an association between occupational exposure to FCS and RA development. There was an interaction between FCS and tobacco smoking in RA seropositive workers.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>33651342</pmid><doi>10.1007/s12016-021-08846-5</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-9821-3060</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1559-0267
ispartof Clinical reviews in allergy & immunology, 2022-04, Vol.62 (2), p.333-345
issn 1559-0267
1080-0549
1559-0267
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8994741
source Springer Nature
subjects Allergology
Analysis
Arthritis
Arthritis, Rheumatoid - etiology
Autoantibodies
Autoimmunity
B cells
Epidemiology
Humans
Immunology
Internal Medicine
Internet/Web search services
Medicine
Medicine & Public Health
Meta-analysis
Occupational exposure
Occupational Exposure - adverse effects
Occupational health and safety
Rheumatoid arthritis
Rheumatoid factor
Risk Factors
Silica
Silicon Dioxide - adverse effects
Smoking
Tobacco smoking
title Systematic Review and Meta-analysis on the Association of Occupational Exposure to Free Crystalline Silica and Rheumatoid Arthritis
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T22%3A05%3A52IST&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=Systematic%20Review%20and%20Meta-analysis%20on%20the%20Association%20of%20Occupational%20Exposure%20to%20Free%20Crystalline%20Silica%20and%20Rheumatoid%20Arthritis&rft.jtitle=Clinical%20reviews%20in%20allergy%20&%20immunology&rft.au=Morotti,%20A.&rft.date=2022-04-01&rft.volume=62&rft.issue=2&rft.spage=333&rft.epage=345&rft.pages=333-345&rft.issn=1559-0267&rft.eissn=1559-0267&rft_id=info:doi/10.1007/s12016-021-08846-5&rft_dat=%3Cgale_pubme%3EA700054555%3C/gale_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c572t-b41789eda05b035c061ed2a0084af4c82f651b813defedcd1c815737344ec2753%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2648632071&rft_id=info:pmid/33651342&rft_galeid=A700054555&rfr_iscdi=true