Towards Control and Oversight of SARS‐CoV‐2 Diagnosis and Monitoring through Multiplexed Quantitative Electroanalytical Immune Response Biosensors
The development of versatile and sensitive biotools to quantify specific SARS‐CoV‐2 immunoglobulins in SARS‐CoV‐2 infected and non‐infected individuals, built on the surface of magnetic microbeads functionalized with nucleocapsid (N) and in‐house expressed recombinant spike (S) proteins is reported....
Gespeichert in:
| Veröffentlicht in: | Angewandte Chemie 2022-07, Vol.134 (28), p.e202203662-n/a |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | n/a |
|---|---|
| container_issue | 28 |
| container_start_page | e202203662 |
| container_title | Angewandte Chemie |
| container_volume | 134 |
| creator | Torrente‐Rodríguez, Rebeca M. Montero‐Calle, Ana San Bartolomé, Clara Cano, Olga Vázquez, Mónica Iglesias‐Caballero, María Corral‐Lugo, Andrés McConnell, Michael J. Pascal, Mariona Mas, Vicente Pingarrón, José M. Barderas, Rodrigo Campuzano, Susana |
| description | The development of versatile and sensitive biotools to quantify specific SARS‐CoV‐2 immunoglobulins in SARS‐CoV‐2 infected and non‐infected individuals, built on the surface of magnetic microbeads functionalized with nucleocapsid (N) and in‐house expressed recombinant spike (S) proteins is reported. Amperometric interrogation of captured N‐ and S‐specific circulating total or individual immunoglobulin (Ig) isotypes (IgG, IgM, and IgA), subsequently labelled with HRP‐conjugated secondary antibodies, was performed at disposable single or multiplexed (8×) screen‐printed electrodes using the HQ/HRP/H2O2 system. The obtained results using N and in‐house expressed S ectodomains of five SARS‐CoV‐2 variants of concern (including the latest Delta and Omicron) allow identification of vulnerable populations from those with natural or acquired immunity, monitoring of infection, evaluation of vaccine efficiency, and even identification of the variant responsible for the infection.
A multiplexed amperometric bioplatform can detect and quantify total and isotype N‐ and S‐specific anti‐SARS‐CoV‐2 serum immunoglobulins within 75 minutes. The platform was used to analyze the global and isotype‐specific immune response of COVID‐19 convalescent and vaccinated individuals, and to detect variant‐specific S antibodies from variants of concern. |
| doi_str_mv | 10.1002/ange.202203662 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9348322</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2700313103</sourcerecordid><originalsourceid>FETCH-LOGICAL-c2902-ef3b8ab93fa7ebc0ab0e2bb2f6eb31a0269a3362d8a7851578f41006c0b4974e3</originalsourceid><addsrcrecordid>eNqFkc1u1DAUhSNERYfClrUlNmwy-CeJ4w3SMAylUktFW9haTnKTceXYg-1MmR2PwIoH5ElwO1URbNj4Lvydc6_OybIXBM8JxvS1sgPMKaYUs6qij7IZKSnJGS_542yGcVHkNS3EYfY0hGuMcUW5eJIdslIURFA6y35euRvlu4CWzkbvDFK2Q-db8EEP64hcjy4XF5e_vv9Yui_ppeidVoN1QYc78sxZHZ3XdkBx7d00rNHZZKLeGPgGHfo0KRt1VFFvAa0MtGmFssrsom6VQSfjOFlAFxA2zgZAb7ULYIPz4Vl20CsT4Pn9PMo-v19dLT_kp-fHJ8vFad5SgWkOPWtq1QjWKw5Ni1WDgTYN7StoGFGYVkIxVtGuVrwuScnrvkixVS1uCsELYEfZm73vZmpG6FpIISgjN16Pyu-kU1r-_WP1Wg5uKwUrakZpMnh1b-Dd1wlClKMOLRijLLgpSMoxZoQRzBL68h_02k0-pZGoqmaCc1aViZrvqda7EDz0D8cQLG8rl7eVy4fKk0DsBTfawO4_tFx8PF790f4GApW0JA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2683977365</pqid></control><display><type>article</type><title>Towards Control and Oversight of SARS‐CoV‐2 Diagnosis and Monitoring through Multiplexed Quantitative Electroanalytical Immune Response Biosensors</title><source>Wiley Online Library Journals Frontfile Complete</source><creator>Torrente‐Rodríguez, Rebeca M. ; Montero‐Calle, Ana ; San Bartolomé, Clara ; Cano, Olga ; Vázquez, Mónica ; Iglesias‐Caballero, María ; Corral‐Lugo, Andrés ; McConnell, Michael J. ; Pascal, Mariona ; Mas, Vicente ; Pingarrón, José M. ; Barderas, Rodrigo ; Campuzano, Susana</creator><creatorcontrib>Torrente‐Rodríguez, Rebeca M. ; Montero‐Calle, Ana ; San Bartolomé, Clara ; Cano, Olga ; Vázquez, Mónica ; Iglesias‐Caballero, María ; Corral‐Lugo, Andrés ; McConnell, Michael J. ; Pascal, Mariona ; Mas, Vicente ; Pingarrón, José M. ; Barderas, Rodrigo ; Campuzano, Susana</creatorcontrib><description>The development of versatile and sensitive biotools to quantify specific SARS‐CoV‐2 immunoglobulins in SARS‐CoV‐2 infected and non‐infected individuals, built on the surface of magnetic microbeads functionalized with nucleocapsid (N) and in‐house expressed recombinant spike (S) proteins is reported. Amperometric interrogation of captured N‐ and S‐specific circulating total or individual immunoglobulin (Ig) isotypes (IgG, IgM, and IgA), subsequently labelled with HRP‐conjugated secondary antibodies, was performed at disposable single or multiplexed (8×) screen‐printed electrodes using the HQ/HRP/H2O2 system. The obtained results using N and in‐house expressed S ectodomains of five SARS‐CoV‐2 variants of concern (including the latest Delta and Omicron) allow identification of vulnerable populations from those with natural or acquired immunity, monitoring of infection, evaluation of vaccine efficiency, and even identification of the variant responsible for the infection.
A multiplexed amperometric bioplatform can detect and quantify total and isotype N‐ and S‐specific anti‐SARS‐CoV‐2 serum immunoglobulins within 75 minutes. The platform was used to analyze the global and isotype‐specific immune response of COVID‐19 convalescent and vaccinated individuals, and to detect variant‐specific S antibodies from variants of concern.</description><identifier>ISSN: 0044-8249</identifier><identifier>EISSN: 1521-3757</identifier><identifier>DOI: 10.1002/ange.202203662</identifier><identifier>PMID: 35941922</identifier><language>eng</language><publisher>Weinheim: Wiley Subscription Services, Inc</publisher><subject>Antibodies ; Biosensors ; Chemistry ; Electrical measurement ; Electroanalytical Bioplatforms ; Forschungsartikel ; Hydrogen peroxide ; Immune Response ; Immune system ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin M ; Immunoglobulins ; Infections ; Interrogation ; Isotypes ; Microspheres ; Monitoring ; Multiplexing ; Nanoparticles ; Nucleocapsids ; Omicron ; SARS-Cov-2 ; Severe acute respiratory syndrome ; Severe acute respiratory syndrome coronavirus 2 ; Vaccines ; Viral Antigens</subject><ispartof>Angewandte Chemie, 2022-07, Vol.134 (28), p.e202203662-n/a</ispartof><rights>2022 The Authors. Angewandte Chemie published by Wiley-VCH GmbH</rights><rights>2022. This article is published under http://creativecommons.org/licenses/by-nc/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-c2902-ef3b8ab93fa7ebc0ab0e2bb2f6eb31a0269a3362d8a7851578f41006c0b4974e3</citedby><cites>FETCH-LOGICAL-c2902-ef3b8ab93fa7ebc0ab0e2bb2f6eb31a0269a3362d8a7851578f41006c0b4974e3</cites><orcidid>0000-0003-2271-1383 ; 0000-0002-2153-172X ; 0000-0003-3539-7469 ; 0000-0002-9928-6613 ; 0000-0001-5141-0454</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fange.202203662$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fange.202203662$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids></links><search><creatorcontrib>Torrente‐Rodríguez, Rebeca M.</creatorcontrib><creatorcontrib>Montero‐Calle, Ana</creatorcontrib><creatorcontrib>San Bartolomé, Clara</creatorcontrib><creatorcontrib>Cano, Olga</creatorcontrib><creatorcontrib>Vázquez, Mónica</creatorcontrib><creatorcontrib>Iglesias‐Caballero, María</creatorcontrib><creatorcontrib>Corral‐Lugo, Andrés</creatorcontrib><creatorcontrib>McConnell, Michael J.</creatorcontrib><creatorcontrib>Pascal, Mariona</creatorcontrib><creatorcontrib>Mas, Vicente</creatorcontrib><creatorcontrib>Pingarrón, José M.</creatorcontrib><creatorcontrib>Barderas, Rodrigo</creatorcontrib><creatorcontrib>Campuzano, Susana</creatorcontrib><title>Towards Control and Oversight of SARS‐CoV‐2 Diagnosis and Monitoring through Multiplexed Quantitative Electroanalytical Immune Response Biosensors</title><title>Angewandte Chemie</title><description>The development of versatile and sensitive biotools to quantify specific SARS‐CoV‐2 immunoglobulins in SARS‐CoV‐2 infected and non‐infected individuals, built on the surface of magnetic microbeads functionalized with nucleocapsid (N) and in‐house expressed recombinant spike (S) proteins is reported. Amperometric interrogation of captured N‐ and S‐specific circulating total or individual immunoglobulin (Ig) isotypes (IgG, IgM, and IgA), subsequently labelled with HRP‐conjugated secondary antibodies, was performed at disposable single or multiplexed (8×) screen‐printed electrodes using the HQ/HRP/H2O2 system. The obtained results using N and in‐house expressed S ectodomains of five SARS‐CoV‐2 variants of concern (including the latest Delta and Omicron) allow identification of vulnerable populations from those with natural or acquired immunity, monitoring of infection, evaluation of vaccine efficiency, and even identification of the variant responsible for the infection.
A multiplexed amperometric bioplatform can detect and quantify total and isotype N‐ and S‐specific anti‐SARS‐CoV‐2 serum immunoglobulins within 75 minutes. The platform was used to analyze the global and isotype‐specific immune response of COVID‐19 convalescent and vaccinated individuals, and to detect variant‐specific S antibodies from variants of concern.</description><subject>Antibodies</subject><subject>Biosensors</subject><subject>Chemistry</subject><subject>Electrical measurement</subject><subject>Electroanalytical Bioplatforms</subject><subject>Forschungsartikel</subject><subject>Hydrogen peroxide</subject><subject>Immune Response</subject><subject>Immune system</subject><subject>Immunoglobulin A</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulin M</subject><subject>Immunoglobulins</subject><subject>Infections</subject><subject>Interrogation</subject><subject>Isotypes</subject><subject>Microspheres</subject><subject>Monitoring</subject><subject>Multiplexing</subject><subject>Nanoparticles</subject><subject>Nucleocapsids</subject><subject>Omicron</subject><subject>SARS-Cov-2</subject><subject>Severe acute respiratory syndrome</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Vaccines</subject><subject>Viral Antigens</subject><issn>0044-8249</issn><issn>1521-3757</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><recordid>eNqFkc1u1DAUhSNERYfClrUlNmwy-CeJ4w3SMAylUktFW9haTnKTceXYg-1MmR2PwIoH5ElwO1URbNj4Lvydc6_OybIXBM8JxvS1sgPMKaYUs6qij7IZKSnJGS_542yGcVHkNS3EYfY0hGuMcUW5eJIdslIURFA6y35euRvlu4CWzkbvDFK2Q-db8EEP64hcjy4XF5e_vv9Yui_ppeidVoN1QYc78sxZHZ3XdkBx7d00rNHZZKLeGPgGHfo0KRt1VFFvAa0MtGmFssrsom6VQSfjOFlAFxA2zgZAb7ULYIPz4Vl20CsT4Pn9PMo-v19dLT_kp-fHJ8vFad5SgWkOPWtq1QjWKw5Ni1WDgTYN7StoGFGYVkIxVtGuVrwuScnrvkixVS1uCsELYEfZm73vZmpG6FpIISgjN16Pyu-kU1r-_WP1Wg5uKwUrakZpMnh1b-Dd1wlClKMOLRijLLgpSMoxZoQRzBL68h_02k0-pZGoqmaCc1aViZrvqda7EDz0D8cQLG8rl7eVy4fKk0DsBTfawO4_tFx8PF790f4GApW0JA</recordid><startdate>20220711</startdate><enddate>20220711</enddate><creator>Torrente‐Rodríguez, Rebeca M.</creator><creator>Montero‐Calle, Ana</creator><creator>San Bartolomé, Clara</creator><creator>Cano, Olga</creator><creator>Vázquez, Mónica</creator><creator>Iglesias‐Caballero, María</creator><creator>Corral‐Lugo, Andrés</creator><creator>McConnell, Michael J.</creator><creator>Pascal, Mariona</creator><creator>Mas, Vicente</creator><creator>Pingarrón, José M.</creator><creator>Barderas, Rodrigo</creator><creator>Campuzano, Susana</creator><general>Wiley Subscription Services, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>L7M</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2271-1383</orcidid><orcidid>https://orcid.org/0000-0002-2153-172X</orcidid><orcidid>https://orcid.org/0000-0003-3539-7469</orcidid><orcidid>https://orcid.org/0000-0002-9928-6613</orcidid><orcidid>https://orcid.org/0000-0001-5141-0454</orcidid></search><sort><creationdate>20220711</creationdate><title>Towards Control and Oversight of SARS‐CoV‐2 Diagnosis and Monitoring through Multiplexed Quantitative Electroanalytical Immune Response Biosensors</title><author>Torrente‐Rodríguez, Rebeca M. ; Montero‐Calle, Ana ; San Bartolomé, Clara ; Cano, Olga ; Vázquez, Mónica ; Iglesias‐Caballero, María ; Corral‐Lugo, Andrés ; McConnell, Michael J. ; Pascal, Mariona ; Mas, Vicente ; Pingarrón, José M. ; Barderas, Rodrigo ; Campuzano, Susana</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2902-ef3b8ab93fa7ebc0ab0e2bb2f6eb31a0269a3362d8a7851578f41006c0b4974e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Antibodies</topic><topic>Biosensors</topic><topic>Chemistry</topic><topic>Electrical measurement</topic><topic>Electroanalytical Bioplatforms</topic><topic>Forschungsartikel</topic><topic>Hydrogen peroxide</topic><topic>Immune Response</topic><topic>Immune system</topic><topic>Immunoglobulin A</topic><topic>Immunoglobulin G</topic><topic>Immunoglobulin M</topic><topic>Immunoglobulins</topic><topic>Infections</topic><topic>Interrogation</topic><topic>Isotypes</topic><topic>Microspheres</topic><topic>Monitoring</topic><topic>Multiplexing</topic><topic>Nanoparticles</topic><topic>Nucleocapsids</topic><topic>Omicron</topic><topic>SARS-Cov-2</topic><topic>Severe acute respiratory syndrome</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>Vaccines</topic><topic>Viral Antigens</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Torrente‐Rodríguez, Rebeca M.</creatorcontrib><creatorcontrib>Montero‐Calle, Ana</creatorcontrib><creatorcontrib>San Bartolomé, Clara</creatorcontrib><creatorcontrib>Cano, Olga</creatorcontrib><creatorcontrib>Vázquez, Mónica</creatorcontrib><creatorcontrib>Iglesias‐Caballero, María</creatorcontrib><creatorcontrib>Corral‐Lugo, Andrés</creatorcontrib><creatorcontrib>McConnell, Michael J.</creatorcontrib><creatorcontrib>Pascal, Mariona</creatorcontrib><creatorcontrib>Mas, Vicente</creatorcontrib><creatorcontrib>Pingarrón, José M.</creatorcontrib><creatorcontrib>Barderas, Rodrigo</creatorcontrib><creatorcontrib>Campuzano, Susana</creatorcontrib><collection>Wiley-Blackwell Open Access Titles</collection><collection>Wiley Free Content</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Angewandte Chemie</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Torrente‐Rodríguez, Rebeca M.</au><au>Montero‐Calle, Ana</au><au>San Bartolomé, Clara</au><au>Cano, Olga</au><au>Vázquez, Mónica</au><au>Iglesias‐Caballero, María</au><au>Corral‐Lugo, Andrés</au><au>McConnell, Michael J.</au><au>Pascal, Mariona</au><au>Mas, Vicente</au><au>Pingarrón, José M.</au><au>Barderas, Rodrigo</au><au>Campuzano, Susana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Towards Control and Oversight of SARS‐CoV‐2 Diagnosis and Monitoring through Multiplexed Quantitative Electroanalytical Immune Response Biosensors</atitle><jtitle>Angewandte Chemie</jtitle><date>2022-07-11</date><risdate>2022</risdate><volume>134</volume><issue>28</issue><spage>e202203662</spage><epage>n/a</epage><pages>e202203662-n/a</pages><issn>0044-8249</issn><eissn>1521-3757</eissn><abstract>The development of versatile and sensitive biotools to quantify specific SARS‐CoV‐2 immunoglobulins in SARS‐CoV‐2 infected and non‐infected individuals, built on the surface of magnetic microbeads functionalized with nucleocapsid (N) and in‐house expressed recombinant spike (S) proteins is reported. Amperometric interrogation of captured N‐ and S‐specific circulating total or individual immunoglobulin (Ig) isotypes (IgG, IgM, and IgA), subsequently labelled with HRP‐conjugated secondary antibodies, was performed at disposable single or multiplexed (8×) screen‐printed electrodes using the HQ/HRP/H2O2 system. The obtained results using N and in‐house expressed S ectodomains of five SARS‐CoV‐2 variants of concern (including the latest Delta and Omicron) allow identification of vulnerable populations from those with natural or acquired immunity, monitoring of infection, evaluation of vaccine efficiency, and even identification of the variant responsible for the infection.
A multiplexed amperometric bioplatform can detect and quantify total and isotype N‐ and S‐specific anti‐SARS‐CoV‐2 serum immunoglobulins within 75 minutes. The platform was used to analyze the global and isotype‐specific immune response of COVID‐19 convalescent and vaccinated individuals, and to detect variant‐specific S antibodies from variants of concern.</abstract><cop>Weinheim</cop><pub>Wiley Subscription Services, Inc</pub><pmid>35941922</pmid><doi>10.1002/ange.202203662</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-2271-1383</orcidid><orcidid>https://orcid.org/0000-0002-2153-172X</orcidid><orcidid>https://orcid.org/0000-0003-3539-7469</orcidid><orcidid>https://orcid.org/0000-0002-9928-6613</orcidid><orcidid>https://orcid.org/0000-0001-5141-0454</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0044-8249 |
| ispartof | Angewandte Chemie, 2022-07, Vol.134 (28), p.e202203662-n/a |
| issn | 0044-8249 1521-3757 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9348322 |
| source | Wiley Online Library Journals Frontfile Complete |
| subjects | Antibodies Biosensors Chemistry Electrical measurement Electroanalytical Bioplatforms Forschungsartikel Hydrogen peroxide Immune Response Immune system Immunoglobulin A Immunoglobulin G Immunoglobulin M Immunoglobulins Infections Interrogation Isotypes Microspheres Monitoring Multiplexing Nanoparticles Nucleocapsids Omicron SARS-Cov-2 Severe acute respiratory syndrome Severe acute respiratory syndrome coronavirus 2 Vaccines Viral Antigens |
| title | Towards Control and Oversight of SARS‐CoV‐2 Diagnosis and Monitoring through Multiplexed Quantitative Electroanalytical Immune Response Biosensors |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T19%3A23%3A28IST&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=Towards%20Control%20and%20Oversight%20of%20SARS%E2%80%90CoV%E2%80%902%20Diagnosis%20and%20Monitoring%20through%20Multiplexed%20Quantitative%20Electroanalytical%20Immune%20Response%20Biosensors&rft.jtitle=Angewandte%20Chemie&rft.au=Torrente%E2%80%90Rodr%C3%ADguez,%20Rebeca%20M.&rft.date=2022-07-11&rft.volume=134&rft.issue=28&rft.spage=e202203662&rft.epage=n/a&rft.pages=e202203662-n/a&rft.issn=0044-8249&rft.eissn=1521-3757&rft_id=info:doi/10.1002/ange.202203662&rft_dat=%3Cproquest_pubme%3E2700313103%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=2683977365&rft_id=info:pmid/35941922&rfr_iscdi=true |