A portable optical-fibre-based surface plasmon resonance biosensor for the detection of therapeutic antibodies in human serum
Different lines of evidence indicate that monitoring the blood levels of therapeutic antibodies, characterized by high inter-individual variability, can help to optimize clinical decision making, improving patient outcomes and reducing costs with these expensive treatments. A surface plasmon resonan...
Gespeichert in:
| Veröffentlicht in: | Scientific reports 2020-07, Vol.10 (1), p.11154-11154, Article 11154 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 11154 |
|---|---|
| container_issue | 1 |
| container_start_page | 11154 |
| container_title | Scientific reports |
| container_volume | 10 |
| creator | Zeni, Luigi Perri, Chiara Cennamo, Nunzio Arcadio, Francesco D’Agostino, Girolamo Salmona, Mario Beeg, Marten Gobbi, Marco |
| description | Different lines of evidence indicate that monitoring the blood levels of therapeutic antibodies, characterized by high inter-individual variability, can help to optimize clinical decision making, improving patient outcomes and reducing costs with these expensive treatments. A surface plasmon resonance (SPR)-based immunoassay has recently been shown to allow highly reliable and robust monitoring of serum concentrations of infliximab, with significant advantages over classical ELISA. The next level of advancement would be the availability of compact and transportable SPR devices suitable for easy, fast and cheap point-of-care analysis. Here we report the data obtained with recently developed, cost-effective, optical-fibre-based SPR sensors (SPR-POF), which allow the construction of a compact miniaturized system for remote sensing. We carried out an extensive characterization of infliximab binding to an anti-infliximab antibody immobilized on the SPR-POF sensor surface. The present proof-of-principle studies demonstrate the feasibility of the proposed SPR-POF platform for the specific detection of infliximab, in both buffer and human serum, and pave the way for further technological improvements. |
| doi_str_mv | 10.1038/s41598-020-68050-x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7341820</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2420903434</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-3ee796706bc7be696d2ddc781efd4da47809031dc945be5a842e1ca43d1ec9263</originalsourceid><addsrcrecordid>eNp9kU1rFjEQxxdRbKn9Ah4k4MVLNG_7dhFK0VYoeNFzyMtsn5TdZM1kpT343c3jU2v1YCAkzPzmn5n8m-YlZ285k8M7VLwdB8oEo93AWkZvnzTHgqmWCinE00f3o-YU8YbV1YpR8fF5cyRFJzsl1XHz44ysKRdjZyBpLcGZmU7BZqDWIHiCW56MA7LOBpcUSQZM0cQasSEhREyZTHWXHRAPBVwJlUrTPpDNCluVJCaWYJMPgCREstsWEwlC3pYXzbPJzAin9-dJ8_Xjhy_nl_Tq88Wn87Mr6lSvCpUA_dj1rLOut9CNnRfeu37gMHnljeoHNjLJvRtVa6E1gxLAnVHSc3BjnfWkeX_QXTe7gHcQSzazXnNYTL7TyQT9dyaGnb5O33UvFR8EqwJv7gVy-rYBFr0EdDDPJkLaUAsluOqYlG1FX_-D3qQtxzrento3Wj--UuJAuZwQM0wPzXCm9wbrg8G6Gqx_Gaxva9Grx2M8lPy2swLyAGBNxWvIf97-j-xPqFO0ow</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2420903434</pqid></control><display><type>article</type><title>A portable optical-fibre-based surface plasmon resonance biosensor for the detection of therapeutic antibodies in human serum</title><source>MEDLINE</source><source>Nature Free</source><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><source>Springer Nature OA Free Journals</source><creator>Zeni, Luigi ; Perri, Chiara ; Cennamo, Nunzio ; Arcadio, Francesco ; D’Agostino, Girolamo ; Salmona, Mario ; Beeg, Marten ; Gobbi, Marco</creator><creatorcontrib>Zeni, Luigi ; Perri, Chiara ; Cennamo, Nunzio ; Arcadio, Francesco ; D’Agostino, Girolamo ; Salmona, Mario ; Beeg, Marten ; Gobbi, Marco</creatorcontrib><description>Different lines of evidence indicate that monitoring the blood levels of therapeutic antibodies, characterized by high inter-individual variability, can help to optimize clinical decision making, improving patient outcomes and reducing costs with these expensive treatments. A surface plasmon resonance (SPR)-based immunoassay has recently been shown to allow highly reliable and robust monitoring of serum concentrations of infliximab, with significant advantages over classical ELISA. The next level of advancement would be the availability of compact and transportable SPR devices suitable for easy, fast and cheap point-of-care analysis. Here we report the data obtained with recently developed, cost-effective, optical-fibre-based SPR sensors (SPR-POF), which allow the construction of a compact miniaturized system for remote sensing. We carried out an extensive characterization of infliximab binding to an anti-infliximab antibody immobilized on the SPR-POF sensor surface. The present proof-of-principle studies demonstrate the feasibility of the proposed SPR-POF platform for the specific detection of infliximab, in both buffer and human serum, and pave the way for further technological improvements.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-68050-x</identifier><identifier>PMID: 32636434</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>639/624 ; 639/624/1107/510 ; 639/624/1107/527 ; Acids ; Antibodies ; Antibodies - blood ; Antibodies - therapeutic use ; Biosensing Techniques - instrumentation ; Biosensing Techniques - methods ; Biosensors ; Blood & organ donations ; Blood levels ; Clinical decision making ; Decision making ; Enzyme-Linked Immunosorbent Assay ; Feasibility studies ; Gold ; Humanities and Social Sciences ; Humans ; Infliximab ; ISO standards ; Laboratories ; Ligands ; Monoclonal antibodies ; multidisciplinary ; Optical Fibers ; Polymers ; Remote sensing ; Remote Sensing Technology - instrumentation ; Remote Sensing Technology - methods ; Reproducibility of Results ; Resonance ; Science ; Science (multidisciplinary) ; Sensitivity and Specificity ; Sensors ; Surface plasmon resonance ; Surface Plasmon Resonance - instrumentation ; Surface Plasmon Resonance - methods ; Tumor necrosis factor-α</subject><ispartof>Scientific reports, 2020-07, Vol.10 (1), p.11154-11154, Article 11154</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. 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-c474t-3ee796706bc7be696d2ddc781efd4da47809031dc945be5a842e1ca43d1ec9263</citedby><cites>FETCH-LOGICAL-c474t-3ee796706bc7be696d2ddc781efd4da47809031dc945be5a842e1ca43d1ec9263</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/PMC7341820/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341820/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32636434$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zeni, Luigi</creatorcontrib><creatorcontrib>Perri, Chiara</creatorcontrib><creatorcontrib>Cennamo, Nunzio</creatorcontrib><creatorcontrib>Arcadio, Francesco</creatorcontrib><creatorcontrib>D’Agostino, Girolamo</creatorcontrib><creatorcontrib>Salmona, Mario</creatorcontrib><creatorcontrib>Beeg, Marten</creatorcontrib><creatorcontrib>Gobbi, Marco</creatorcontrib><title>A portable optical-fibre-based surface plasmon resonance biosensor for the detection of therapeutic antibodies in human serum</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Different lines of evidence indicate that monitoring the blood levels of therapeutic antibodies, characterized by high inter-individual variability, can help to optimize clinical decision making, improving patient outcomes and reducing costs with these expensive treatments. A surface plasmon resonance (SPR)-based immunoassay has recently been shown to allow highly reliable and robust monitoring of serum concentrations of infliximab, with significant advantages over classical ELISA. The next level of advancement would be the availability of compact and transportable SPR devices suitable for easy, fast and cheap point-of-care analysis. Here we report the data obtained with recently developed, cost-effective, optical-fibre-based SPR sensors (SPR-POF), which allow the construction of a compact miniaturized system for remote sensing. We carried out an extensive characterization of infliximab binding to an anti-infliximab antibody immobilized on the SPR-POF sensor surface. The present proof-of-principle studies demonstrate the feasibility of the proposed SPR-POF platform for the specific detection of infliximab, in both buffer and human serum, and pave the way for further technological improvements.</description><subject>639/624</subject><subject>639/624/1107/510</subject><subject>639/624/1107/527</subject><subject>Acids</subject><subject>Antibodies</subject><subject>Antibodies - blood</subject><subject>Antibodies - therapeutic use</subject><subject>Biosensing Techniques - instrumentation</subject><subject>Biosensing Techniques - methods</subject><subject>Biosensors</subject><subject>Blood & organ donations</subject><subject>Blood levels</subject><subject>Clinical decision making</subject><subject>Decision making</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Feasibility studies</subject><subject>Gold</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Infliximab</subject><subject>ISO standards</subject><subject>Laboratories</subject><subject>Ligands</subject><subject>Monoclonal antibodies</subject><subject>multidisciplinary</subject><subject>Optical Fibers</subject><subject>Polymers</subject><subject>Remote sensing</subject><subject>Remote Sensing Technology - instrumentation</subject><subject>Remote Sensing Technology - methods</subject><subject>Reproducibility of Results</subject><subject>Resonance</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Sensitivity and Specificity</subject><subject>Sensors</subject><subject>Surface plasmon resonance</subject><subject>Surface Plasmon Resonance - instrumentation</subject><subject>Surface Plasmon Resonance - methods</subject><subject>Tumor necrosis factor-α</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kU1rFjEQxxdRbKn9Ah4k4MVLNG_7dhFK0VYoeNFzyMtsn5TdZM1kpT343c3jU2v1YCAkzPzmn5n8m-YlZ285k8M7VLwdB8oEo93AWkZvnzTHgqmWCinE00f3o-YU8YbV1YpR8fF5cyRFJzsl1XHz44ysKRdjZyBpLcGZmU7BZqDWIHiCW56MA7LOBpcUSQZM0cQasSEhREyZTHWXHRAPBVwJlUrTPpDNCluVJCaWYJMPgCREstsWEwlC3pYXzbPJzAin9-dJ8_Xjhy_nl_Tq88Wn87Mr6lSvCpUA_dj1rLOut9CNnRfeu37gMHnljeoHNjLJvRtVa6E1gxLAnVHSc3BjnfWkeX_QXTe7gHcQSzazXnNYTL7TyQT9dyaGnb5O33UvFR8EqwJv7gVy-rYBFr0EdDDPJkLaUAsluOqYlG1FX_-D3qQtxzrento3Wj--UuJAuZwQM0wPzXCm9wbrg8G6Gqx_Gaxva9Grx2M8lPy2swLyAGBNxWvIf97-j-xPqFO0ow</recordid><startdate>20200707</startdate><enddate>20200707</enddate><creator>Zeni, Luigi</creator><creator>Perri, Chiara</creator><creator>Cennamo, Nunzio</creator><creator>Arcadio, Francesco</creator><creator>D’Agostino, Girolamo</creator><creator>Salmona, Mario</creator><creator>Beeg, Marten</creator><creator>Gobbi, Marco</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</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>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</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>20200707</creationdate><title>A portable optical-fibre-based surface plasmon resonance biosensor for the detection of therapeutic antibodies in human serum</title><author>Zeni, Luigi ; Perri, Chiara ; Cennamo, Nunzio ; Arcadio, Francesco ; D’Agostino, Girolamo ; Salmona, Mario ; Beeg, Marten ; Gobbi, Marco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-3ee796706bc7be696d2ddc781efd4da47809031dc945be5a842e1ca43d1ec9263</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>639/624</topic><topic>639/624/1107/510</topic><topic>639/624/1107/527</topic><topic>Acids</topic><topic>Antibodies</topic><topic>Antibodies - blood</topic><topic>Antibodies - therapeutic use</topic><topic>Biosensing Techniques - instrumentation</topic><topic>Biosensing Techniques - methods</topic><topic>Biosensors</topic><topic>Blood & organ donations</topic><topic>Blood levels</topic><topic>Clinical decision making</topic><topic>Decision making</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Feasibility studies</topic><topic>Gold</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Infliximab</topic><topic>ISO standards</topic><topic>Laboratories</topic><topic>Ligands</topic><topic>Monoclonal antibodies</topic><topic>multidisciplinary</topic><topic>Optical Fibers</topic><topic>Polymers</topic><topic>Remote sensing</topic><topic>Remote Sensing Technology - instrumentation</topic><topic>Remote Sensing Technology - methods</topic><topic>Reproducibility of Results</topic><topic>Resonance</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Sensitivity and Specificity</topic><topic>Sensors</topic><topic>Surface plasmon resonance</topic><topic>Surface Plasmon Resonance - instrumentation</topic><topic>Surface Plasmon Resonance - methods</topic><topic>Tumor necrosis factor-α</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zeni, Luigi</creatorcontrib><creatorcontrib>Perri, Chiara</creatorcontrib><creatorcontrib>Cennamo, Nunzio</creatorcontrib><creatorcontrib>Arcadio, Francesco</creatorcontrib><creatorcontrib>D’Agostino, Girolamo</creatorcontrib><creatorcontrib>Salmona, Mario</creatorcontrib><creatorcontrib>Beeg, Marten</creatorcontrib><creatorcontrib>Gobbi, Marco</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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</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 Edition)</collection><collection>ProQuest One Sustainability</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>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>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</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>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zeni, Luigi</au><au>Perri, Chiara</au><au>Cennamo, Nunzio</au><au>Arcadio, Francesco</au><au>D’Agostino, Girolamo</au><au>Salmona, Mario</au><au>Beeg, Marten</au><au>Gobbi, Marco</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A portable optical-fibre-based surface plasmon resonance biosensor for the detection of therapeutic antibodies in human serum</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-07-07</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>11154</spage><epage>11154</epage><pages>11154-11154</pages><artnum>11154</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Different lines of evidence indicate that monitoring the blood levels of therapeutic antibodies, characterized by high inter-individual variability, can help to optimize clinical decision making, improving patient outcomes and reducing costs with these expensive treatments. A surface plasmon resonance (SPR)-based immunoassay has recently been shown to allow highly reliable and robust monitoring of serum concentrations of infliximab, with significant advantages over classical ELISA. The next level of advancement would be the availability of compact and transportable SPR devices suitable for easy, fast and cheap point-of-care analysis. Here we report the data obtained with recently developed, cost-effective, optical-fibre-based SPR sensors (SPR-POF), which allow the construction of a compact miniaturized system for remote sensing. We carried out an extensive characterization of infliximab binding to an anti-infliximab antibody immobilized on the SPR-POF sensor surface. The present proof-of-principle studies demonstrate the feasibility of the proposed SPR-POF platform for the specific detection of infliximab, in both buffer and human serum, and pave the way for further technological improvements.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32636434</pmid><doi>10.1038/s41598-020-68050-x</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2045-2322 |
| ispartof | Scientific reports, 2020-07, Vol.10 (1), p.11154-11154, Article 11154 |
| issn | 2045-2322 2045-2322 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7341820 |
| source | MEDLINE; Nature Free; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry; Springer Nature OA Free Journals |
| subjects | 639/624 639/624/1107/510 639/624/1107/527 Acids Antibodies Antibodies - blood Antibodies - therapeutic use Biosensing Techniques - instrumentation Biosensing Techniques - methods Biosensors Blood & organ donations Blood levels Clinical decision making Decision making Enzyme-Linked Immunosorbent Assay Feasibility studies Gold Humanities and Social Sciences Humans Infliximab ISO standards Laboratories Ligands Monoclonal antibodies multidisciplinary Optical Fibers Polymers Remote sensing Remote Sensing Technology - instrumentation Remote Sensing Technology - methods Reproducibility of Results Resonance Science Science (multidisciplinary) Sensitivity and Specificity Sensors Surface plasmon resonance Surface Plasmon Resonance - instrumentation Surface Plasmon Resonance - methods Tumor necrosis factor-α |
| title | A portable optical-fibre-based surface plasmon resonance biosensor for the detection of therapeutic antibodies in human serum |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T04%3A05%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20portable%20optical-fibre-based%20surface%20plasmon%20resonance%20biosensor%20for%20the%20detection%20of%20therapeutic%20antibodies%20in%20human%20serum&rft.jtitle=Scientific%20reports&rft.au=Zeni,%20Luigi&rft.date=2020-07-07&rft.volume=10&rft.issue=1&rft.spage=11154&rft.epage=11154&rft.pages=11154-11154&rft.artnum=11154&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/s41598-020-68050-x&rft_dat=%3Cproquest_pubme%3E2420903434%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2420903434&rft_id=info:pmid/32636434&rfr_iscdi=true |