Loading…

Hashimoto’s Thyroiditis Minimizes Lymph Node Metastasis in BRAF Mutant Papillary Thyroid Carcinomas

Hashimoto’s thyroiditis (HT) (autoimmune thyroiditis) is a clinicopathological entity associated with chronic lymphocytic infiltration resulting in hypothyroidism. HT is a double-edged sword that increases the risk of papillary thyroid cancer (PTC), yet it serves as a protective factor for PTC progr...

Full description

Saved in:
Bibliographic Details
Published in:Biomedicines 2022-08, Vol.10 (8), p.2051
Main Authors: Issa, Peter P., Omar, Mahmoud, Buti, Yusef, Issa, Chad P., Chabot, Bert, Carnabatu, Christopher J., Munshi, Ruhul, Hussein, Mohammad, Aboueisha, Mohamed, Shama, Mohamed, Corsetti, Ralph L., Toraih, Eman, Kandil, Emad
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-c479t-bf4d2bb096ff9e8c22629fcb4e80bad318b8e1b62d5f49ef4ee5b6f160be01613
cites cdi_FETCH-LOGICAL-c479t-bf4d2bb096ff9e8c22629fcb4e80bad318b8e1b62d5f49ef4ee5b6f160be01613
container_end_page
container_issue 8
container_start_page 2051
container_title Biomedicines
container_volume 10
creator Issa, Peter P.
Omar, Mahmoud
Buti, Yusef
Issa, Chad P.
Chabot, Bert
Carnabatu, Christopher J.
Munshi, Ruhul
Hussein, Mohammad
Aboueisha, Mohamed
Shama, Mohamed
Corsetti, Ralph L.
Toraih, Eman
Kandil, Emad
description Hashimoto’s thyroiditis (HT) (autoimmune thyroiditis) is a clinicopathological entity associated with chronic lymphocytic infiltration resulting in hypothyroidism. HT is a double-edged sword that increases the risk of papillary thyroid cancer (PTC), yet it serves as a protective factor for PTC progression. BRAF mutation in PTCs is associated with rapid cell growth, aggressive tumor characteristics, and higher mortality rates. Here, we aimed to analyze the influence of HT in patients with PTCs and its effect on lymph node metastasis (LNM) in BRAF mutant tumors. Adults diagnosed with PTC between 2008 and January 2021 were retrospectively included. A total of 427 patients, 128 of whom had underlying HT, were included. The HT group had significantly higher rates of microcarcinoma (49.2% vs. 37.5%, p = 0.025) and less lateral LNM (8.6% vs. 17.1%, p = 0.024). Interestingly, BRAF-mutated PTCs were found to have significantly less overall LNM (20.9% vs. 51%, p = 0.001), central LNM (25.6% vs. 45.1%, p = 0.040) and lateral LNM (9.3% vs. 29.4%, p = 0.010) in patients with HT when compared to those without underlying HT. HT was found to be an independent protective predictor of overall and lateral LNM. Altogether, HT was able to neutralize the effect of BRAF mutation and was determined to be an independent protective factor against LNM. Specifically, our work may influence treatment-aggressiveness decision making for endocrinologists, oncologists and surgeons alike.
doi_str_mv 10.3390/biomedicines10082051
format article
fullrecord <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_9c52084ef8a446f796e3896c4b7680ad</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_9c52084ef8a446f796e3896c4b7680ad</doaj_id><sourcerecordid>2706109489</sourcerecordid><originalsourceid>FETCH-LOGICAL-c479t-bf4d2bb096ff9e8c22629fcb4e80bad318b8e1b62d5f49ef4ee5b6f160be01613</originalsourceid><addsrcrecordid>eNptkt9qFDEUxoNYbFn7Bl4MeOPN1vybTHIj1MX-gV0rUq9DkjnpZpmZrMmMsL3qa_h6PolZt4oVQyAnOT--fHwchF4RfMaYwm9tiD20wYUBMsFYUlyTZ-iEUtrMFa7V87_qY3Sa8waXpQiThL9Ax0yUS63ECYIrk9ehj2P88fA9V7frXYqhDWPI1SoMoQ_3kKvlrt-uq4-xhWoFo8lll34Yqvefzy-q1TSaYaw-mW3oOpN2v0WqhUnFYOxNfomOvOkynD6eM_Tl4sPt4mq-vLm8Xpwv5443apxbz1tqLVbCewXSUSqo8s5ykNialhFpJRAraFt7rsBzgNoKTwS2gIkgbIauD7ptNBu9TaEvfnQ0Qf96iOlOmzQG14FWrqZYcvDScC58owQwqYTjthESl89m6N1BazvZkrWDYUymeyL6tDOEtb6L37TiuJZsb-bNo0CKXyfIo-5DdlAyGiBOWdMGNwKThuGCvv4H3cQpDSWqPSUIVlyqQvED5VLMOYH_Y4ZgvR8L_b-xYD8Bu9ivTw</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2706109489</pqid></control><display><type>article</type><title>Hashimoto’s Thyroiditis Minimizes Lymph Node Metastasis in BRAF Mutant Papillary Thyroid Carcinomas</title><source>PubMed Central Free</source><source>Publicly Available Content (ProQuest)</source><creator>Issa, Peter P. ; Omar, Mahmoud ; Buti, Yusef ; Issa, Chad P. ; Chabot, Bert ; Carnabatu, Christopher J. ; Munshi, Ruhul ; Hussein, Mohammad ; Aboueisha, Mohamed ; Shama, Mohamed ; Corsetti, Ralph L. ; Toraih, Eman ; Kandil, Emad</creator><creatorcontrib>Issa, Peter P. ; Omar, Mahmoud ; Buti, Yusef ; Issa, Chad P. ; Chabot, Bert ; Carnabatu, Christopher J. ; Munshi, Ruhul ; Hussein, Mohammad ; Aboueisha, Mohamed ; Shama, Mohamed ; Corsetti, Ralph L. ; Toraih, Eman ; Kandil, Emad</creatorcontrib><description>Hashimoto’s thyroiditis (HT) (autoimmune thyroiditis) is a clinicopathological entity associated with chronic lymphocytic infiltration resulting in hypothyroidism. HT is a double-edged sword that increases the risk of papillary thyroid cancer (PTC), yet it serves as a protective factor for PTC progression. BRAF mutation in PTCs is associated with rapid cell growth, aggressive tumor characteristics, and higher mortality rates. Here, we aimed to analyze the influence of HT in patients with PTCs and its effect on lymph node metastasis (LNM) in BRAF mutant tumors. Adults diagnosed with PTC between 2008 and January 2021 were retrospectively included. A total of 427 patients, 128 of whom had underlying HT, were included. The HT group had significantly higher rates of microcarcinoma (49.2% vs. 37.5%, p = 0.025) and less lateral LNM (8.6% vs. 17.1%, p = 0.024). Interestingly, BRAF-mutated PTCs were found to have significantly less overall LNM (20.9% vs. 51%, p = 0.001), central LNM (25.6% vs. 45.1%, p = 0.040) and lateral LNM (9.3% vs. 29.4%, p = 0.010) in patients with HT when compared to those without underlying HT. HT was found to be an independent protective predictor of overall and lateral LNM. Altogether, HT was able to neutralize the effect of BRAF mutation and was determined to be an independent protective factor against LNM. Specifically, our work may influence treatment-aggressiveness decision making for endocrinologists, oncologists and surgeons alike.</description><identifier>ISSN: 2227-9059</identifier><identifier>EISSN: 2227-9059</identifier><identifier>DOI: 10.3390/biomedicines10082051</identifier><identifier>PMID: 36009596</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Biopsy ; Decision making ; Hashimoto’s thyroiditis ; Hypothyroidism ; lymph node metastasis ; Lymph nodes ; Lymphatic system ; Medical prognosis ; Metastases ; Metastasis ; Mutants ; Mutation ; Papillary thyroid cancer ; Papillary thyroid carcinoma ; Patients ; protective factor ; risk factor ; Thyroid cancer ; Thyroidectomy ; Thyroiditis ; Tumors</subject><ispartof>Biomedicines, 2022-08, Vol.10 (8), p.2051</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 by the authors. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c479t-bf4d2bb096ff9e8c22629fcb4e80bad318b8e1b62d5f49ef4ee5b6f160be01613</citedby><cites>FETCH-LOGICAL-c479t-bf4d2bb096ff9e8c22629fcb4e80bad318b8e1b62d5f49ef4ee5b6f160be01613</cites><orcidid>0000-0002-5248-3142 ; 0000-0001-9267-3787</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2706109489/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2706109489?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids></links><search><creatorcontrib>Issa, Peter P.</creatorcontrib><creatorcontrib>Omar, Mahmoud</creatorcontrib><creatorcontrib>Buti, Yusef</creatorcontrib><creatorcontrib>Issa, Chad P.</creatorcontrib><creatorcontrib>Chabot, Bert</creatorcontrib><creatorcontrib>Carnabatu, Christopher J.</creatorcontrib><creatorcontrib>Munshi, Ruhul</creatorcontrib><creatorcontrib>Hussein, Mohammad</creatorcontrib><creatorcontrib>Aboueisha, Mohamed</creatorcontrib><creatorcontrib>Shama, Mohamed</creatorcontrib><creatorcontrib>Corsetti, Ralph L.</creatorcontrib><creatorcontrib>Toraih, Eman</creatorcontrib><creatorcontrib>Kandil, Emad</creatorcontrib><title>Hashimoto’s Thyroiditis Minimizes Lymph Node Metastasis in BRAF Mutant Papillary Thyroid Carcinomas</title><title>Biomedicines</title><description>Hashimoto’s thyroiditis (HT) (autoimmune thyroiditis) is a clinicopathological entity associated with chronic lymphocytic infiltration resulting in hypothyroidism. HT is a double-edged sword that increases the risk of papillary thyroid cancer (PTC), yet it serves as a protective factor for PTC progression. BRAF mutation in PTCs is associated with rapid cell growth, aggressive tumor characteristics, and higher mortality rates. Here, we aimed to analyze the influence of HT in patients with PTCs and its effect on lymph node metastasis (LNM) in BRAF mutant tumors. Adults diagnosed with PTC between 2008 and January 2021 were retrospectively included. A total of 427 patients, 128 of whom had underlying HT, were included. The HT group had significantly higher rates of microcarcinoma (49.2% vs. 37.5%, p = 0.025) and less lateral LNM (8.6% vs. 17.1%, p = 0.024). Interestingly, BRAF-mutated PTCs were found to have significantly less overall LNM (20.9% vs. 51%, p = 0.001), central LNM (25.6% vs. 45.1%, p = 0.040) and lateral LNM (9.3% vs. 29.4%, p = 0.010) in patients with HT when compared to those without underlying HT. HT was found to be an independent protective predictor of overall and lateral LNM. Altogether, HT was able to neutralize the effect of BRAF mutation and was determined to be an independent protective factor against LNM. Specifically, our work may influence treatment-aggressiveness decision making for endocrinologists, oncologists and surgeons alike.</description><subject>Biopsy</subject><subject>Decision making</subject><subject>Hashimoto’s thyroiditis</subject><subject>Hypothyroidism</subject><subject>lymph node metastasis</subject><subject>Lymph nodes</subject><subject>Lymphatic system</subject><subject>Medical prognosis</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mutants</subject><subject>Mutation</subject><subject>Papillary thyroid cancer</subject><subject>Papillary thyroid carcinoma</subject><subject>Patients</subject><subject>protective factor</subject><subject>risk factor</subject><subject>Thyroid cancer</subject><subject>Thyroidectomy</subject><subject>Thyroiditis</subject><subject>Tumors</subject><issn>2227-9059</issn><issn>2227-9059</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptkt9qFDEUxoNYbFn7Bl4MeOPN1vybTHIj1MX-gV0rUq9DkjnpZpmZrMmMsL3qa_h6PolZt4oVQyAnOT--fHwchF4RfMaYwm9tiD20wYUBMsFYUlyTZ-iEUtrMFa7V87_qY3Sa8waXpQiThL9Ax0yUS63ECYIrk9ehj2P88fA9V7frXYqhDWPI1SoMoQ_3kKvlrt-uq4-xhWoFo8lll34Yqvefzy-q1TSaYaw-mW3oOpN2v0WqhUnFYOxNfomOvOkynD6eM_Tl4sPt4mq-vLm8Xpwv5443apxbz1tqLVbCewXSUSqo8s5ykNialhFpJRAraFt7rsBzgNoKTwS2gIkgbIauD7ptNBu9TaEvfnQ0Qf96iOlOmzQG14FWrqZYcvDScC58owQwqYTjthESl89m6N1BazvZkrWDYUymeyL6tDOEtb6L37TiuJZsb-bNo0CKXyfIo-5DdlAyGiBOWdMGNwKThuGCvv4H3cQpDSWqPSUIVlyqQvED5VLMOYH_Y4ZgvR8L_b-xYD8Bu9ivTw</recordid><startdate>20220822</startdate><enddate>20220822</enddate><creator>Issa, Peter P.</creator><creator>Omar, Mahmoud</creator><creator>Buti, Yusef</creator><creator>Issa, Chad P.</creator><creator>Chabot, Bert</creator><creator>Carnabatu, Christopher J.</creator><creator>Munshi, Ruhul</creator><creator>Hussein, Mohammad</creator><creator>Aboueisha, Mohamed</creator><creator>Shama, Mohamed</creator><creator>Corsetti, Ralph L.</creator><creator>Toraih, Eman</creator><creator>Kandil, Emad</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>8FE</scope><scope>8FH</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>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-5248-3142</orcidid><orcidid>https://orcid.org/0000-0001-9267-3787</orcidid></search><sort><creationdate>20220822</creationdate><title>Hashimoto’s Thyroiditis Minimizes Lymph Node Metastasis in BRAF Mutant Papillary Thyroid Carcinomas</title><author>Issa, Peter P. ; Omar, Mahmoud ; Buti, Yusef ; Issa, Chad P. ; Chabot, Bert ; Carnabatu, Christopher J. ; Munshi, Ruhul ; Hussein, Mohammad ; Aboueisha, Mohamed ; Shama, Mohamed ; Corsetti, Ralph L. ; Toraih, Eman ; Kandil, Emad</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c479t-bf4d2bb096ff9e8c22629fcb4e80bad318b8e1b62d5f49ef4ee5b6f160be01613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Biopsy</topic><topic>Decision making</topic><topic>Hashimoto’s thyroiditis</topic><topic>Hypothyroidism</topic><topic>lymph node metastasis</topic><topic>Lymph nodes</topic><topic>Lymphatic system</topic><topic>Medical prognosis</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mutants</topic><topic>Mutation</topic><topic>Papillary thyroid cancer</topic><topic>Papillary thyroid carcinoma</topic><topic>Patients</topic><topic>protective factor</topic><topic>risk factor</topic><topic>Thyroid cancer</topic><topic>Thyroidectomy</topic><topic>Thyroiditis</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Issa, Peter P.</creatorcontrib><creatorcontrib>Omar, Mahmoud</creatorcontrib><creatorcontrib>Buti, Yusef</creatorcontrib><creatorcontrib>Issa, Chad P.</creatorcontrib><creatorcontrib>Chabot, Bert</creatorcontrib><creatorcontrib>Carnabatu, Christopher J.</creatorcontrib><creatorcontrib>Munshi, Ruhul</creatorcontrib><creatorcontrib>Hussein, Mohammad</creatorcontrib><creatorcontrib>Aboueisha, Mohamed</creatorcontrib><creatorcontrib>Shama, Mohamed</creatorcontrib><creatorcontrib>Corsetti, Ralph L.</creatorcontrib><creatorcontrib>Toraih, Eman</creatorcontrib><creatorcontrib>Kandil, Emad</creatorcontrib><collection>CrossRef</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Biological Science Collection</collection><collection>ProQuest Biological Science Journals</collection><collection>Publicly Available Content (ProQuest)</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><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Biomedicines</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Issa, Peter P.</au><au>Omar, Mahmoud</au><au>Buti, Yusef</au><au>Issa, Chad P.</au><au>Chabot, Bert</au><au>Carnabatu, Christopher J.</au><au>Munshi, Ruhul</au><au>Hussein, Mohammad</au><au>Aboueisha, Mohamed</au><au>Shama, Mohamed</au><au>Corsetti, Ralph L.</au><au>Toraih, Eman</au><au>Kandil, Emad</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hashimoto’s Thyroiditis Minimizes Lymph Node Metastasis in BRAF Mutant Papillary Thyroid Carcinomas</atitle><jtitle>Biomedicines</jtitle><date>2022-08-22</date><risdate>2022</risdate><volume>10</volume><issue>8</issue><spage>2051</spage><pages>2051-</pages><issn>2227-9059</issn><eissn>2227-9059</eissn><abstract>Hashimoto’s thyroiditis (HT) (autoimmune thyroiditis) is a clinicopathological entity associated with chronic lymphocytic infiltration resulting in hypothyroidism. HT is a double-edged sword that increases the risk of papillary thyroid cancer (PTC), yet it serves as a protective factor for PTC progression. BRAF mutation in PTCs is associated with rapid cell growth, aggressive tumor characteristics, and higher mortality rates. Here, we aimed to analyze the influence of HT in patients with PTCs and its effect on lymph node metastasis (LNM) in BRAF mutant tumors. Adults diagnosed with PTC between 2008 and January 2021 were retrospectively included. A total of 427 patients, 128 of whom had underlying HT, were included. The HT group had significantly higher rates of microcarcinoma (49.2% vs. 37.5%, p = 0.025) and less lateral LNM (8.6% vs. 17.1%, p = 0.024). Interestingly, BRAF-mutated PTCs were found to have significantly less overall LNM (20.9% vs. 51%, p = 0.001), central LNM (25.6% vs. 45.1%, p = 0.040) and lateral LNM (9.3% vs. 29.4%, p = 0.010) in patients with HT when compared to those without underlying HT. HT was found to be an independent protective predictor of overall and lateral LNM. Altogether, HT was able to neutralize the effect of BRAF mutation and was determined to be an independent protective factor against LNM. Specifically, our work may influence treatment-aggressiveness decision making for endocrinologists, oncologists and surgeons alike.</abstract><cop>Basel</cop><pub>MDPI AG</pub><pmid>36009596</pmid><doi>10.3390/biomedicines10082051</doi><orcidid>https://orcid.org/0000-0002-5248-3142</orcidid><orcidid>https://orcid.org/0000-0001-9267-3787</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 2227-9059
ispartof Biomedicines, 2022-08, Vol.10 (8), p.2051
issn 2227-9059
2227-9059
language eng
recordid cdi_doaj_primary_oai_doaj_org_article_9c52084ef8a446f796e3896c4b7680ad
source PubMed Central Free; Publicly Available Content (ProQuest)
subjects Biopsy
Decision making
Hashimoto’s thyroiditis
Hypothyroidism
lymph node metastasis
Lymph nodes
Lymphatic system
Medical prognosis
Metastases
Metastasis
Mutants
Mutation
Papillary thyroid cancer
Papillary thyroid carcinoma
Patients
protective factor
risk factor
Thyroid cancer
Thyroidectomy
Thyroiditis
Tumors
title Hashimoto’s Thyroiditis Minimizes Lymph Node Metastasis in BRAF Mutant Papillary Thyroid Carcinomas
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-02T19%3A22%3A01IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Hashimoto%E2%80%99s%20Thyroiditis%20Minimizes%20Lymph%20Node%20Metastasis%20in%20BRAF%20Mutant%20Papillary%20Thyroid%20Carcinomas&rft.jtitle=Biomedicines&rft.au=Issa,%20Peter%20P.&rft.date=2022-08-22&rft.volume=10&rft.issue=8&rft.spage=2051&rft.pages=2051-&rft.issn=2227-9059&rft.eissn=2227-9059&rft_id=info:doi/10.3390/biomedicines10082051&rft_dat=%3Cproquest_doaj_%3E2706109489%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c479t-bf4d2bb096ff9e8c22629fcb4e80bad318b8e1b62d5f49ef4ee5b6f160be01613%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2706109489&rft_id=info:pmid/36009596&rfr_iscdi=true