Identification and Validation a Necroptosis‑related Prognostic Signature and Associated Regulatory Axis in Stomach Adenocarcinoma
Gastric cancer (GC) ranks fifth in global cancer incidence and third in cancer-related mortality. The prognosis of GC patients was poor. Necroptosis is a type of regulated cell death mediated by RIP1, RIP3, and MLKL. Necroptosis was found to be involved in antitumor immunity in the cancer immunother...
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| description | Gastric cancer (GC) ranks fifth in global cancer incidence and third in cancer-related mortality. The prognosis of GC patients was poor. Necroptosis is a type of regulated cell death mediated by RIP1, RIP3, and MLKL. Necroptosis was found to be involved in antitumor immunity in the cancer immunotherapy.
LASSO Cox regression analysis was performed to construct a prognostic signature. Bioinformatics analysis was performed to construct a lncRNA-miRNA-mRNA regulatory axis. qRT-PCR was performed to verify the expression and prognosis of hub gene in STAD.
Most of necroptosis regulators were upregulated, while the mRNA level of TLR3, ALDH2, and NDRG2 was downregulated in STAD versus gastric tissues. The genetic mutation and copy number variation of necroptosis regulator in STAD were also summarized. GO and KEGG pathways analysis revealed that these necroptosis regulators were mainly involved in programmed necrotic cell death and TNF signaling pathway. A necroptosis‑related prognostic signature based on four genes (EZH2, PGAM5, TLR4, and TRAF2) had a good performance in predicting the prognosis of STAD patients. We also identified lncRNA SNHG1/miR-21-5p/TLR4 regulatory axis in the progression in STAD. Verification study suggested that the hub gene TLR4 upregulated in STAD and correlated with a poor overall survival. Moreover, Cox regression analysis revealed that TLR4 expression and clinical stage were independent factors affecting the prognosis of STAD patients.
We performed a comprehensive bioinformatics analysis and identified a necroptosis‑related prognostic signature and a lncRNA SNHG1/miR-21-5p/TLR4 regulatory axis in STAD. Further study should be performed to confirm our result. |
| doi_str_mv | 10.2147/OTT.S342613 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8648279</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A690357191</galeid><sourcerecordid>A690357191</sourcerecordid><originalsourceid>FETCH-LOGICAL-c591t-b896c980daaf52c0fe1f225837e8f40c8dd38101bb974c7a80dac9314ab4da903</originalsourceid><addsrcrecordid>eNptkt1qFDEUxwdRbK1eeS8DghRk13xNJrkRhlK1UKy4q7chk2RmU2aTbZIReyf4BL6iT2KmXZddkVwkOfmd_8n5KIrnEMwRJPWbq-VyvsAEUYgfFMcQ1mxGOQYP985HxZMYrwGglCHyuDjChDFAET8ufl5o45LtrJLJeldKp8uvcrB6ey0_GhX8Jvlo4-8fv4IZZDK6_BR873xMVpUL2zuZxmDufJsYvbJ3zGfTj5n24bZsvttYWlcukl9LtSqbHNQrGZR12fC0eNTJIZpn2_2k-PLufHn2YXZ59f7irLmcqYrDNGsZp4ozoKXsKqRAZ2CHUMVwbVhHgGJaYwYBbFteE1XLiVQcQyJboiUH-KR4e6-7Gdu10SonHuQgNsGuZbgVXlpx-OLsSvT-m2CUMFTzLHC6FQj-ZjQxibWNygyDdMaPUSCKMGCgrib05T_otR-Dy-llCgJOMM3wjurlYIR1nc9x1SQqGpp_XNWQw0zN_0Plpc3aKu9MZ7P9wOHVnsPKyCGtoh_GqaXxEHx9D-YexxhMtysGBGIaLpGHS2yHK9Mv9uu3Y_9OE_4DXebMIw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2610943662</pqid></control><display><type>article</type><title>Identification and Validation a Necroptosis‑related Prognostic Signature and Associated Regulatory Axis in Stomach Adenocarcinoma</title><source>Taylor & Francis Open Access</source><source>DOVE Medical Press Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central Open Access</source><source>PubMed Central</source><creator>Wang, Ning ; Liu, Dingsheng</creator><creatorcontrib>Wang, Ning ; Liu, Dingsheng</creatorcontrib><description>Gastric cancer (GC) ranks fifth in global cancer incidence and third in cancer-related mortality. The prognosis of GC patients was poor. Necroptosis is a type of regulated cell death mediated by RIP1, RIP3, and MLKL. Necroptosis was found to be involved in antitumor immunity in the cancer immunotherapy.
LASSO Cox regression analysis was performed to construct a prognostic signature. Bioinformatics analysis was performed to construct a lncRNA-miRNA-mRNA regulatory axis. qRT-PCR was performed to verify the expression and prognosis of hub gene in STAD.
Most of necroptosis regulators were upregulated, while the mRNA level of TLR3, ALDH2, and NDRG2 was downregulated in STAD versus gastric tissues. The genetic mutation and copy number variation of necroptosis regulator in STAD were also summarized. GO and KEGG pathways analysis revealed that these necroptosis regulators were mainly involved in programmed necrotic cell death and TNF signaling pathway. A necroptosis‑related prognostic signature based on four genes (EZH2, PGAM5, TLR4, and TRAF2) had a good performance in predicting the prognosis of STAD patients. We also identified lncRNA SNHG1/miR-21-5p/TLR4 regulatory axis in the progression in STAD. Verification study suggested that the hub gene TLR4 upregulated in STAD and correlated with a poor overall survival. Moreover, Cox regression analysis revealed that TLR4 expression and clinical stage were independent factors affecting the prognosis of STAD patients.
We performed a comprehensive bioinformatics analysis and identified a necroptosis‑related prognostic signature and a lncRNA SNHG1/miR-21-5p/TLR4 regulatory axis in STAD. Further study should be performed to confirm our result.</description><identifier>ISSN: 1178-6930</identifier><identifier>EISSN: 1178-6930</identifier><identifier>DOI: 10.2147/OTT.S342613</identifier><identifier>PMID: 34880629</identifier><language>eng</language><publisher>New Zealand: Dove Medical Press Limited</publisher><subject>Adenocarcinoma ; Aldehyde dehydrogenase ; Apoptosis ; Bioinformatics ; Biomarkers ; Cancer immunotherapy ; Cancer therapies ; Cell death ; China ; Copy number ; Development and progression ; Gastric cancer ; Gene expression ; Gene mutations ; Genes ; Genomes ; Health aspects ; Immunotherapy ; Medical prognosis ; Medical research ; Medicine, Experimental ; Metastasis ; MicroRNA ; miRNA ; Mortality ; mRNA ; Mutation ; Necroptosis ; Non-coding RNA ; Ontology ; Original Research ; Patients ; Prognosis ; Regression analysis ; Signal transduction ; Stomach cancer ; TLR3 protein ; TLR4 protein ; Toll-like receptors ; TRAF2 protein ; Tumor necrosis factor</subject><ispartof>OncoTargets and therapy, 2021-01, Vol.14, p.5373-5383</ispartof><rights>2021 Wang and Liu.</rights><rights>COPYRIGHT 2021 Dove Medical Press Limited</rights><rights>2021. This work is licensed under https://creativecommons.org/licenses/by-nc/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 Wang and Liu. 2021 Wang and Liu.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c591t-b896c980daaf52c0fe1f225837e8f40c8dd38101bb974c7a80dac9314ab4da903</citedby><cites>FETCH-LOGICAL-c591t-b896c980daaf52c0fe1f225837e8f40c8dd38101bb974c7a80dac9314ab4da903</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8648279/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8648279/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,882,3849,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34880629$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Ning</creatorcontrib><creatorcontrib>Liu, Dingsheng</creatorcontrib><title>Identification and Validation a Necroptosis‑related Prognostic Signature and Associated Regulatory Axis in Stomach Adenocarcinoma</title><title>OncoTargets and therapy</title><addtitle>Onco Targets Ther</addtitle><description>Gastric cancer (GC) ranks fifth in global cancer incidence and third in cancer-related mortality. The prognosis of GC patients was poor. Necroptosis is a type of regulated cell death mediated by RIP1, RIP3, and MLKL. Necroptosis was found to be involved in antitumor immunity in the cancer immunotherapy.
LASSO Cox regression analysis was performed to construct a prognostic signature. Bioinformatics analysis was performed to construct a lncRNA-miRNA-mRNA regulatory axis. qRT-PCR was performed to verify the expression and prognosis of hub gene in STAD.
Most of necroptosis regulators were upregulated, while the mRNA level of TLR3, ALDH2, and NDRG2 was downregulated in STAD versus gastric tissues. The genetic mutation and copy number variation of necroptosis regulator in STAD were also summarized. GO and KEGG pathways analysis revealed that these necroptosis regulators were mainly involved in programmed necrotic cell death and TNF signaling pathway. A necroptosis‑related prognostic signature based on four genes (EZH2, PGAM5, TLR4, and TRAF2) had a good performance in predicting the prognosis of STAD patients. We also identified lncRNA SNHG1/miR-21-5p/TLR4 regulatory axis in the progression in STAD. Verification study suggested that the hub gene TLR4 upregulated in STAD and correlated with a poor overall survival. Moreover, Cox regression analysis revealed that TLR4 expression and clinical stage were independent factors affecting the prognosis of STAD patients.
We performed a comprehensive bioinformatics analysis and identified a necroptosis‑related prognostic signature and a lncRNA SNHG1/miR-21-5p/TLR4 regulatory axis in STAD. Further study should be performed to confirm our result.</description><subject>Adenocarcinoma</subject><subject>Aldehyde dehydrogenase</subject><subject>Apoptosis</subject><subject>Bioinformatics</subject><subject>Biomarkers</subject><subject>Cancer immunotherapy</subject><subject>Cancer therapies</subject><subject>Cell death</subject><subject>China</subject><subject>Copy number</subject><subject>Development and progression</subject><subject>Gastric cancer</subject><subject>Gene expression</subject><subject>Gene mutations</subject><subject>Genes</subject><subject>Genomes</subject><subject>Health aspects</subject><subject>Immunotherapy</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Medicine, Experimental</subject><subject>Metastasis</subject><subject>MicroRNA</subject><subject>miRNA</subject><subject>Mortality</subject><subject>mRNA</subject><subject>Mutation</subject><subject>Necroptosis</subject><subject>Non-coding RNA</subject><subject>Ontology</subject><subject>Original Research</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Regression analysis</subject><subject>Signal transduction</subject><subject>Stomach cancer</subject><subject>TLR3 protein</subject><subject>TLR4 protein</subject><subject>Toll-like receptors</subject><subject>TRAF2 protein</subject><subject>Tumor necrosis factor</subject><issn>1178-6930</issn><issn>1178-6930</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</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>eNptkt1qFDEUxwdRbK1eeS8DghRk13xNJrkRhlK1UKy4q7chk2RmU2aTbZIReyf4BL6iT2KmXZddkVwkOfmd_8n5KIrnEMwRJPWbq-VyvsAEUYgfFMcQ1mxGOQYP985HxZMYrwGglCHyuDjChDFAET8ufl5o45LtrJLJeldKp8uvcrB6ey0_GhX8Jvlo4-8fv4IZZDK6_BR873xMVpUL2zuZxmDufJsYvbJ3zGfTj5n24bZsvttYWlcukl9LtSqbHNQrGZR12fC0eNTJIZpn2_2k-PLufHn2YXZ59f7irLmcqYrDNGsZp4ozoKXsKqRAZ2CHUMVwbVhHgGJaYwYBbFteE1XLiVQcQyJboiUH-KR4e6-7Gdu10SonHuQgNsGuZbgVXlpx-OLsSvT-m2CUMFTzLHC6FQj-ZjQxibWNygyDdMaPUSCKMGCgrib05T_otR-Dy-llCgJOMM3wjurlYIR1nc9x1SQqGpp_XNWQw0zN_0Plpc3aKu9MZ7P9wOHVnsPKyCGtoh_GqaXxEHx9D-YexxhMtysGBGIaLpGHS2yHK9Mv9uu3Y_9OE_4DXebMIw</recordid><startdate>20210101</startdate><enddate>20210101</enddate><creator>Wang, Ning</creator><creator>Liu, Dingsheng</creator><general>Dove Medical Press Limited</general><general>Taylor & Francis Ltd</general><general>Dove</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</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>GUQSH</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20210101</creationdate><title>Identification and Validation a Necroptosis‑related Prognostic Signature and Associated Regulatory Axis in Stomach Adenocarcinoma</title><author>Wang, Ning ; Liu, Dingsheng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c591t-b896c980daaf52c0fe1f225837e8f40c8dd38101bb974c7a80dac9314ab4da903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adenocarcinoma</topic><topic>Aldehyde dehydrogenase</topic><topic>Apoptosis</topic><topic>Bioinformatics</topic><topic>Biomarkers</topic><topic>Cancer immunotherapy</topic><topic>Cancer therapies</topic><topic>Cell death</topic><topic>China</topic><topic>Copy number</topic><topic>Development and progression</topic><topic>Gastric cancer</topic><topic>Gene expression</topic><topic>Gene mutations</topic><topic>Genes</topic><topic>Genomes</topic><topic>Health aspects</topic><topic>Immunotherapy</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Medicine, Experimental</topic><topic>Metastasis</topic><topic>MicroRNA</topic><topic>miRNA</topic><topic>Mortality</topic><topic>mRNA</topic><topic>Mutation</topic><topic>Necroptosis</topic><topic>Non-coding RNA</topic><topic>Ontology</topic><topic>Original Research</topic><topic>Patients</topic><topic>Prognosis</topic><topic>Regression analysis</topic><topic>Signal transduction</topic><topic>Stomach cancer</topic><topic>TLR3 protein</topic><topic>TLR4 protein</topic><topic>Toll-like receptors</topic><topic>TRAF2 protein</topic><topic>Tumor necrosis factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Ning</creatorcontrib><creatorcontrib>Liu, Dingsheng</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</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 Central UK/Ireland</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 Korea</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>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>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</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 Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>OncoTargets and therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Ning</au><au>Liu, Dingsheng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification and Validation a Necroptosis‑related Prognostic Signature and Associated Regulatory Axis in Stomach Adenocarcinoma</atitle><jtitle>OncoTargets and therapy</jtitle><addtitle>Onco Targets Ther</addtitle><date>2021-01-01</date><risdate>2021</risdate><volume>14</volume><spage>5373</spage><epage>5383</epage><pages>5373-5383</pages><issn>1178-6930</issn><eissn>1178-6930</eissn><abstract>Gastric cancer (GC) ranks fifth in global cancer incidence and third in cancer-related mortality. The prognosis of GC patients was poor. Necroptosis is a type of regulated cell death mediated by RIP1, RIP3, and MLKL. Necroptosis was found to be involved in antitumor immunity in the cancer immunotherapy.
LASSO Cox regression analysis was performed to construct a prognostic signature. Bioinformatics analysis was performed to construct a lncRNA-miRNA-mRNA regulatory axis. qRT-PCR was performed to verify the expression and prognosis of hub gene in STAD.
Most of necroptosis regulators were upregulated, while the mRNA level of TLR3, ALDH2, and NDRG2 was downregulated in STAD versus gastric tissues. The genetic mutation and copy number variation of necroptosis regulator in STAD were also summarized. GO and KEGG pathways analysis revealed that these necroptosis regulators were mainly involved in programmed necrotic cell death and TNF signaling pathway. A necroptosis‑related prognostic signature based on four genes (EZH2, PGAM5, TLR4, and TRAF2) had a good performance in predicting the prognosis of STAD patients. We also identified lncRNA SNHG1/miR-21-5p/TLR4 regulatory axis in the progression in STAD. Verification study suggested that the hub gene TLR4 upregulated in STAD and correlated with a poor overall survival. Moreover, Cox regression analysis revealed that TLR4 expression and clinical stage were independent factors affecting the prognosis of STAD patients.
We performed a comprehensive bioinformatics analysis and identified a necroptosis‑related prognostic signature and a lncRNA SNHG1/miR-21-5p/TLR4 regulatory axis in STAD. Further study should be performed to confirm our result.</abstract><cop>New Zealand</cop><pub>Dove Medical Press Limited</pub><pmid>34880629</pmid><doi>10.2147/OTT.S342613</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| source | Taylor & Francis Open Access; DOVE Medical Press Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; PubMed Central |
| subjects | Adenocarcinoma Aldehyde dehydrogenase Apoptosis Bioinformatics Biomarkers Cancer immunotherapy Cancer therapies Cell death China Copy number Development and progression Gastric cancer Gene expression Gene mutations Genes Genomes Health aspects Immunotherapy Medical prognosis Medical research Medicine, Experimental Metastasis MicroRNA miRNA Mortality mRNA Mutation Necroptosis Non-coding RNA Ontology Original Research Patients Prognosis Regression analysis Signal transduction Stomach cancer TLR3 protein TLR4 protein Toll-like receptors TRAF2 protein Tumor necrosis factor |
| title | Identification and Validation a Necroptosis‑related Prognostic Signature and Associated Regulatory Axis in Stomach Adenocarcinoma |
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