Sensitive and quantitative determination of short-chain fatty acids in human serum using liquid chromatography mass spectrometry
Short-chain fatty acids (SCFAs) are increasingly being monitored to elucidate the link between gut health and disease. These metabolites are routinely measured in faeces, but their determination in serum is more challenging due to their low concentrations. A method for the determination of eight SCF...
Gespeichert in:
| Veröffentlicht in: | Analytical and bioanalytical chemistry 2021-10, Vol.413 (25), p.6333-6342 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 6342 |
|---|---|
| container_issue | 25 |
| container_start_page | 6333 |
| container_title | Analytical and bioanalytical chemistry |
| container_volume | 413 |
| creator | Shafaei, Armaghan Vamathevan, Veronica Pandohee, Jessica Lawler, Nathan G. Broadhurst, David Boyce, Mary C. |
| description | Short-chain fatty acids (SCFAs) are increasingly being monitored to elucidate the link between gut health and disease. These metabolites are routinely measured in faeces, but their determination in serum is more challenging due to their low concentrations. A method for the determination of eight SCFAs in serum is described here. High-resolution mass spectrometry and gas chromatography were used to identify the presence of isomeric interferences, which were then overcome through a combination of chromatographic separation and judicious choice of MS fragment ion. The SCFAs were derivatised to form 3-nitrophenylhydrazones before being separated on a reversed-phase column and then detected using liquid chromatography tandem mass spectrometry (LC-QQQ-MS). The LODs and LOQs of SCFAs using this method were in the range 1 to 7 ng mL
−1
and 3 to 19 ng mL
−1
, respectively. The recovery of the SCFAs in serum ranged from 94 to 114% over the three concentration ranges tested. |
| doi_str_mv | 10.1007/s00216-021-03589-w |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_gale_infotracmisc_A677855083</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A677855083</galeid><sourcerecordid>A677855083</sourcerecordid><originalsourceid>FETCH-LOGICAL-c607t-7731551254a83d54d352e6822e67c481bf610f684dc0e1421f2cad12f2d004303</originalsourceid><addsrcrecordid>eNp9Uk1rFTEUDaLY9ukfcCEBN26m5jtxI5SiVii4UNchTTIzKTPJe0mm5e386eb11VcrIoGb3HvPOckNB4BXGJ1ihOS7ghDBomuhQ5Sr993tE3CMBVYdERw9PZwZOQInpVwjhLnC4jk4oowqghE7Bj-_-VhCDTcemujgZjGxhmruCs5Xn-cQW5YiTD0sY8q1s6MJEfam1i00NrgCWzous4mw-LzMcCkhDnAKmyU4aMecZlPTkM163MLZlALL2tvayr7m7QvwrDdT8S_v9xX48enj9_OL7vLr5y_nZ5edFUjWTkqKOceEM6Oo48xRTrxQpAVpmcJXvcCoF4o5izxmBPfEGodJTxxCjCK6Ah_2uuvlavbO-lizmfQ6h9nkrU4m6MedGEY9pButmJJtNYG39wI5bRZfqp5DsX6aTPRpKZpwgRSlHLMGffMX9DotObbxGkoq0d4rxQNqMJPXIfap3Wt3ovpMSKk43-mtwOk_UG05Pwebou9Dqz8ikD3B5lRK9v1hRoz0zjd67xvdgr7zjb5tpNd__s6B8tsoDUD3gNJacfD5YaT_yP4CNNvP3A</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2578648176</pqid></control><display><type>article</type><title>Sensitive and quantitative determination of short-chain fatty acids in human serum using liquid chromatography mass spectrometry</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Shafaei, Armaghan ; Vamathevan, Veronica ; Pandohee, Jessica ; Lawler, Nathan G. ; Broadhurst, David ; Boyce, Mary C.</creator><creatorcontrib>Shafaei, Armaghan ; Vamathevan, Veronica ; Pandohee, Jessica ; Lawler, Nathan G. ; Broadhurst, David ; Boyce, Mary C.</creatorcontrib><description>Short-chain fatty acids (SCFAs) are increasingly being monitored to elucidate the link between gut health and disease. These metabolites are routinely measured in faeces, but their determination in serum is more challenging due to their low concentrations. A method for the determination of eight SCFAs in serum is described here. High-resolution mass spectrometry and gas chromatography were used to identify the presence of isomeric interferences, which were then overcome through a combination of chromatographic separation and judicious choice of MS fragment ion. The SCFAs were derivatised to form 3-nitrophenylhydrazones before being separated on a reversed-phase column and then detected using liquid chromatography tandem mass spectrometry (LC-QQQ-MS). The LODs and LOQs of SCFAs using this method were in the range 1 to 7 ng mL
−1
and 3 to 19 ng mL
−1
, respectively. The recovery of the SCFAs in serum ranged from 94 to 114% over the three concentration ranges tested.</description><identifier>ISSN: 1618-2642</identifier><identifier>EISSN: 1618-2650</identifier><identifier>DOI: 10.1007/s00216-021-03589-w</identifier><identifier>PMID: 34382104</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Analysis ; Analytical Chemistry ; Biochemistry ; Blood Chemical Analysis - methods ; Characterization and Evaluation of Materials ; Chemistry ; Chemistry and Materials Science ; Chromatography ; Chromatography, Liquid - methods ; Fatty acids ; Fatty Acids, Volatile - blood ; Food Science ; Gas chromatography ; Humans ; Identification and classification ; Laboratory Medicine ; Liquid chromatography ; Low concentrations ; Mass spectrometry ; Mass Spectrometry - methods ; Mass spectroscopy ; Metabolites ; Monitoring/Environmental Analysis ; Reproducibility of Results ; Research Paper ; Scientific imaging ; Sensitivity and Specificity ; Spectroscopy</subject><ispartof>Analytical and bioanalytical chemistry, 2021-10, Vol.413 (25), p.6333-6342</ispartof><rights>The Author(s) 2021</rights><rights>2021. The Author(s).</rights><rights>COPYRIGHT 2021 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-c607t-7731551254a83d54d352e6822e67c481bf610f684dc0e1421f2cad12f2d004303</citedby><cites>FETCH-LOGICAL-c607t-7731551254a83d54d352e6822e67c481bf610f684dc0e1421f2cad12f2d004303</cites><orcidid>0000-0002-4908-8061</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/s00216-021-03589-w$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00216-021-03589-w$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34382104$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shafaei, Armaghan</creatorcontrib><creatorcontrib>Vamathevan, Veronica</creatorcontrib><creatorcontrib>Pandohee, Jessica</creatorcontrib><creatorcontrib>Lawler, Nathan G.</creatorcontrib><creatorcontrib>Broadhurst, David</creatorcontrib><creatorcontrib>Boyce, Mary C.</creatorcontrib><title>Sensitive and quantitative determination of short-chain fatty acids in human serum using liquid chromatography mass spectrometry</title><title>Analytical and bioanalytical chemistry</title><addtitle>Anal Bioanal Chem</addtitle><addtitle>Anal Bioanal Chem</addtitle><description>Short-chain fatty acids (SCFAs) are increasingly being monitored to elucidate the link between gut health and disease. These metabolites are routinely measured in faeces, but their determination in serum is more challenging due to their low concentrations. A method for the determination of eight SCFAs in serum is described here. High-resolution mass spectrometry and gas chromatography were used to identify the presence of isomeric interferences, which were then overcome through a combination of chromatographic separation and judicious choice of MS fragment ion. The SCFAs were derivatised to form 3-nitrophenylhydrazones before being separated on a reversed-phase column and then detected using liquid chromatography tandem mass spectrometry (LC-QQQ-MS). The LODs and LOQs of SCFAs using this method were in the range 1 to 7 ng mL
−1
and 3 to 19 ng mL
−1
, respectively. The recovery of the SCFAs in serum ranged from 94 to 114% over the three concentration ranges tested.</description><subject>Analysis</subject><subject>Analytical Chemistry</subject><subject>Biochemistry</subject><subject>Blood Chemical Analysis - methods</subject><subject>Characterization and Evaluation of Materials</subject><subject>Chemistry</subject><subject>Chemistry and Materials Science</subject><subject>Chromatography</subject><subject>Chromatography, Liquid - methods</subject><subject>Fatty acids</subject><subject>Fatty Acids, Volatile - blood</subject><subject>Food Science</subject><subject>Gas chromatography</subject><subject>Humans</subject><subject>Identification and classification</subject><subject>Laboratory Medicine</subject><subject>Liquid chromatography</subject><subject>Low concentrations</subject><subject>Mass spectrometry</subject><subject>Mass Spectrometry - methods</subject><subject>Mass spectroscopy</subject><subject>Metabolites</subject><subject>Monitoring/Environmental Analysis</subject><subject>Reproducibility of Results</subject><subject>Research Paper</subject><subject>Scientific imaging</subject><subject>Sensitivity and Specificity</subject><subject>Spectroscopy</subject><issn>1618-2642</issn><issn>1618-2650</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9Uk1rFTEUDaLY9ukfcCEBN26m5jtxI5SiVii4UNchTTIzKTPJe0mm5e386eb11VcrIoGb3HvPOckNB4BXGJ1ihOS7ghDBomuhQ5Sr993tE3CMBVYdERw9PZwZOQInpVwjhLnC4jk4oowqghE7Bj-_-VhCDTcemujgZjGxhmruCs5Xn-cQW5YiTD0sY8q1s6MJEfam1i00NrgCWzous4mw-LzMcCkhDnAKmyU4aMecZlPTkM163MLZlALL2tvayr7m7QvwrDdT8S_v9xX48enj9_OL7vLr5y_nZ5edFUjWTkqKOceEM6Oo48xRTrxQpAVpmcJXvcCoF4o5izxmBPfEGodJTxxCjCK6Ah_2uuvlavbO-lizmfQ6h9nkrU4m6MedGEY9pButmJJtNYG39wI5bRZfqp5DsX6aTPRpKZpwgRSlHLMGffMX9DotObbxGkoq0d4rxQNqMJPXIfap3Wt3ovpMSKk43-mtwOk_UG05Pwebou9Dqz8ikD3B5lRK9v1hRoz0zjd67xvdgr7zjb5tpNd__s6B8tsoDUD3gNJacfD5YaT_yP4CNNvP3A</recordid><startdate>20211001</startdate><enddate>20211001</enddate><creator>Shafaei, Armaghan</creator><creator>Vamathevan, Veronica</creator><creator>Pandohee, Jessica</creator><creator>Lawler, Nathan G.</creator><creator>Broadhurst, David</creator><creator>Boyce, Mary C.</creator><general>Springer Berlin Heidelberg</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>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8BQ</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>AFKRA</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>F28</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H8D</scope><scope>H8G</scope><scope>HCIFZ</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KB.</scope><scope>KR7</scope><scope>L7M</scope><scope>LK8</scope><scope>L~C</scope><scope>L~D</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PDBOC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-4908-8061</orcidid></search><sort><creationdate>20211001</creationdate><title>Sensitive and quantitative determination of short-chain fatty acids in human serum using liquid chromatography mass spectrometry</title><author>Shafaei, Armaghan ; Vamathevan, Veronica ; Pandohee, Jessica ; Lawler, Nathan G. ; Broadhurst, David ; Boyce, Mary C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c607t-7731551254a83d54d352e6822e67c481bf610f684dc0e1421f2cad12f2d004303</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Analysis</topic><topic>Analytical Chemistry</topic><topic>Biochemistry</topic><topic>Blood Chemical Analysis - methods</topic><topic>Characterization and Evaluation of Materials</topic><topic>Chemistry</topic><topic>Chemistry and Materials Science</topic><topic>Chromatography</topic><topic>Chromatography, Liquid - methods</topic><topic>Fatty acids</topic><topic>Fatty Acids, Volatile - blood</topic><topic>Food Science</topic><topic>Gas chromatography</topic><topic>Humans</topic><topic>Identification and classification</topic><topic>Laboratory Medicine</topic><topic>Liquid chromatography</topic><topic>Low concentrations</topic><topic>Mass spectrometry</topic><topic>Mass Spectrometry - methods</topic><topic>Mass spectroscopy</topic><topic>Metabolites</topic><topic>Monitoring/Environmental Analysis</topic><topic>Reproducibility of Results</topic><topic>Research Paper</topic><topic>Scientific imaging</topic><topic>Sensitivity and Specificity</topic><topic>Spectroscopy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shafaei, Armaghan</creatorcontrib><creatorcontrib>Vamathevan, Veronica</creatorcontrib><creatorcontrib>Pandohee, Jessica</creatorcontrib><creatorcontrib>Lawler, Nathan G.</creatorcontrib><creatorcontrib>Broadhurst, David</creatorcontrib><creatorcontrib>Boyce, Mary C.</creatorcontrib><collection>Springer Nature OA Free Journals</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>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science & Engineering Collection</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>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>SciTech Premium Collection</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>ProQuest Biological Science Collection</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Materials Science Collection</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Analytical and bioanalytical chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shafaei, Armaghan</au><au>Vamathevan, Veronica</au><au>Pandohee, Jessica</au><au>Lawler, Nathan G.</au><au>Broadhurst, David</au><au>Boyce, Mary C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sensitive and quantitative determination of short-chain fatty acids in human serum using liquid chromatography mass spectrometry</atitle><jtitle>Analytical and bioanalytical chemistry</jtitle><stitle>Anal Bioanal Chem</stitle><addtitle>Anal Bioanal Chem</addtitle><date>2021-10-01</date><risdate>2021</risdate><volume>413</volume><issue>25</issue><spage>6333</spage><epage>6342</epage><pages>6333-6342</pages><issn>1618-2642</issn><eissn>1618-2650</eissn><abstract>Short-chain fatty acids (SCFAs) are increasingly being monitored to elucidate the link between gut health and disease. These metabolites are routinely measured in faeces, but their determination in serum is more challenging due to their low concentrations. A method for the determination of eight SCFAs in serum is described here. High-resolution mass spectrometry and gas chromatography were used to identify the presence of isomeric interferences, which were then overcome through a combination of chromatographic separation and judicious choice of MS fragment ion. The SCFAs were derivatised to form 3-nitrophenylhydrazones before being separated on a reversed-phase column and then detected using liquid chromatography tandem mass spectrometry (LC-QQQ-MS). The LODs and LOQs of SCFAs using this method were in the range 1 to 7 ng mL
−1
and 3 to 19 ng mL
−1
, respectively. The recovery of the SCFAs in serum ranged from 94 to 114% over the three concentration ranges tested.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>34382104</pmid><doi>10.1007/s00216-021-03589-w</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-4908-8061</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1618-2642 |
| ispartof | Analytical and bioanalytical chemistry, 2021-10, Vol.413 (25), p.6333-6342 |
| issn | 1618-2642 1618-2650 |
| language | eng |
| recordid | cdi_gale_infotracmisc_A677855083 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Analysis Analytical Chemistry Biochemistry Blood Chemical Analysis - methods Characterization and Evaluation of Materials Chemistry Chemistry and Materials Science Chromatography Chromatography, Liquid - methods Fatty acids Fatty Acids, Volatile - blood Food Science Gas chromatography Humans Identification and classification Laboratory Medicine Liquid chromatography Low concentrations Mass spectrometry Mass Spectrometry - methods Mass spectroscopy Metabolites Monitoring/Environmental Analysis Reproducibility of Results Research Paper Scientific imaging Sensitivity and Specificity Spectroscopy |
| title | Sensitive and quantitative determination of short-chain fatty acids in human serum using liquid chromatography mass spectrometry |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T14%3A36%3A08IST&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=Sensitive%20and%20quantitative%20determination%20of%20short-chain%20fatty%20acids%20in%20human%20serum%20using%20liquid%20chromatography%20mass%20spectrometry&rft.jtitle=Analytical%20and%20bioanalytical%20chemistry&rft.au=Shafaei,%20Armaghan&rft.date=2021-10-01&rft.volume=413&rft.issue=25&rft.spage=6333&rft.epage=6342&rft.pages=6333-6342&rft.issn=1618-2642&rft.eissn=1618-2650&rft_id=info:doi/10.1007/s00216-021-03589-w&rft_dat=%3Cgale_pubme%3EA677855083%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2578648176&rft_id=info:pmid/34382104&rft_galeid=A677855083&rfr_iscdi=true |