Beneficial effects of autologous mesenchymal stem cell transplantation in active progressive multiple sclerosis
In this study (trial registration: NCT02166021), we aimed to evaluate the optimal way of administration, the safety and the clinical efficacy of mesenchymal stem cell (MSC) transplantation in patients with active and progressive multiple sclerosis. Forty-eight patients (28 males and 20 females) with...
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| Veröffentlicht in: | Brain (London, England : 1878) England : 1878), 2020-12, Vol.143 (12), p.3574-3588 |
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| creator | Petrou, Panayiota Kassis, Ibrahim Levin, Netta Paul, Friedemann Backner, Yael Benoliel, Tal Oertel, Frederike Cosima Scheel, Michael Hallimi, Michelle Yaghmour, Nour Hur, Tamir Ben Ginzberg, Ariel Levy, Yarden Abramsky, Oded Karussis, Dimitrios |
| description | In this study (trial registration: NCT02166021), we aimed to evaluate the optimal way of administration, the safety and the clinical efficacy of mesenchymal stem cell (MSC) transplantation in patients with active and progressive multiple sclerosis. Forty-eight patients (28 males and 20 females) with progressive multiple sclerosis (Expanded Disability Status Scale: 3.0-6.5, mean : 5.6 ± 0.8, mean age: 47.5 ± 12.3) and evidence of either clinical worsening or activity during the previous year, were enrolled (between 2015 and 2018). Patients were randomized into three groups and treated intrathecally (IT) or intravenously (IV) with autologous MSCs (1 × 106/kg) or sham injections. After 6 months, half of the patients from the MSC-IT and MSC-IV groups were retreated with MSCs, and the other half with sham injections. Patients initially assigned to sham treatment were divided into two subgroups and treated with either MSC-IT or MSC-IV. The study duration was 14 months. No serious treatment-related safety issues were detected. Significantly fewer patients experienced treatment failure in the MSC-IT and MSC-IV groups compared with those in the sham-treated group (6.7%, 9.7%, and 41.9%, respectively, P = 0.0003 and P = 0.0008). During the 1-year follow-up, 58.6% and 40.6% of patients treated with MSC-IT and MSC-IV, respectively, exhibited no evidence of disease activity compared with 9.7% in the sham-treated group (P |
| doi_str_mv | 10.1093/brain/awaa333 |
| format | Article |
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Forty-eight patients (28 males and 20 females) with progressive multiple sclerosis (Expanded Disability Status Scale: 3.0-6.5, mean : 5.6 ± 0.8, mean age: 47.5 ± 12.3) and evidence of either clinical worsening or activity during the previous year, were enrolled (between 2015 and 2018). Patients were randomized into three groups and treated intrathecally (IT) or intravenously (IV) with autologous MSCs (1 × 106/kg) or sham injections. After 6 months, half of the patients from the MSC-IT and MSC-IV groups were retreated with MSCs, and the other half with sham injections. Patients initially assigned to sham treatment were divided into two subgroups and treated with either MSC-IT or MSC-IV. The study duration was 14 months. No serious treatment-related safety issues were detected. Significantly fewer patients experienced treatment failure in the MSC-IT and MSC-IV groups compared with those in the sham-treated group (6.7%, 9.7%, and 41.9%, respectively, P = 0.0003 and P = 0.0008). During the 1-year follow-up, 58.6% and 40.6% of patients treated with MSC-IT and MSC-IV, respectively, exhibited no evidence of disease activity compared with 9.7% in the sham-treated group (P < 0.0001 and P < 0.0048, respectively). MSC-IT transplantation induced additional benefits on the relapse rate, on the monthly changes of the T2 lesion load on MRI, and on the timed 25-foot walking test, 9-hole peg test, optical coherence tomography, functional MRI and cognitive tests. Treatment with MSCs was well-tolerated in progressive multiple sclerosis and induced short-term beneficial effects regarding the primary end points, especially in the patients with active disease. The intrathecal administration was more efficacious than the intravenous in several parameters of the disease. A phase III trial is warranted to confirm these findings.</description><identifier>ISSN: 0006-8950</identifier><identifier>EISSN: 1460-2156</identifier><identifier>DOI: 10.1093/brain/awaa333</identifier><identifier>PMID: 33253391</identifier><language>eng</language><publisher>England</publisher><subject>Adult ; Brain - diagnostic imaging ; Disease Progression ; Double-Blind Method ; Endpoint Determination ; Female ; Follow-Up Studies ; Humans ; Injections, Intravenous ; Injections, Spinal ; Magnetic Resonance Imaging ; Male ; Mesenchymal Stem Cell Transplantation - adverse effects ; Mesenchymal Stem Cell Transplantation - methods ; Middle Aged ; Multiple Sclerosis - diagnostic imaging ; Multiple Sclerosis - psychology ; Multiple Sclerosis - therapy ; Multiple Sclerosis, Chronic Progressive - therapy ; Neuropsychological Tests ; Recurrence ; Tomography, Optical Coherence ; Treatment Outcome ; Walking</subject><ispartof>Brain (London, England : 1878), 2020-12, Vol.143 (12), p.3574-3588</ispartof><rights>The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c398t-a5697f9f262284bb75a659f311d45d11d8ef9b2ebe118c2efb306b7496f61c2d3</citedby><cites>FETCH-LOGICAL-c398t-a5697f9f262284bb75a659f311d45d11d8ef9b2ebe118c2efb306b7496f61c2d3</cites><orcidid>0000-0001-5529-1237 ; 0000-0001-5488-3046 ; 0000-0002-3667-0116</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33253391$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Petrou, Panayiota</creatorcontrib><creatorcontrib>Kassis, Ibrahim</creatorcontrib><creatorcontrib>Levin, Netta</creatorcontrib><creatorcontrib>Paul, Friedemann</creatorcontrib><creatorcontrib>Backner, Yael</creatorcontrib><creatorcontrib>Benoliel, Tal</creatorcontrib><creatorcontrib>Oertel, Frederike Cosima</creatorcontrib><creatorcontrib>Scheel, Michael</creatorcontrib><creatorcontrib>Hallimi, Michelle</creatorcontrib><creatorcontrib>Yaghmour, Nour</creatorcontrib><creatorcontrib>Hur, Tamir Ben</creatorcontrib><creatorcontrib>Ginzberg, Ariel</creatorcontrib><creatorcontrib>Levy, Yarden</creatorcontrib><creatorcontrib>Abramsky, Oded</creatorcontrib><creatorcontrib>Karussis, Dimitrios</creatorcontrib><title>Beneficial effects of autologous mesenchymal stem cell transplantation in active progressive multiple sclerosis</title><title>Brain (London, England : 1878)</title><addtitle>Brain</addtitle><description>In this study (trial registration: NCT02166021), we aimed to evaluate the optimal way of administration, the safety and the clinical efficacy of mesenchymal stem cell (MSC) transplantation in patients with active and progressive multiple sclerosis. Forty-eight patients (28 males and 20 females) with progressive multiple sclerosis (Expanded Disability Status Scale: 3.0-6.5, mean : 5.6 ± 0.8, mean age: 47.5 ± 12.3) and evidence of either clinical worsening or activity during the previous year, were enrolled (between 2015 and 2018). Patients were randomized into three groups and treated intrathecally (IT) or intravenously (IV) with autologous MSCs (1 × 106/kg) or sham injections. After 6 months, half of the patients from the MSC-IT and MSC-IV groups were retreated with MSCs, and the other half with sham injections. Patients initially assigned to sham treatment were divided into two subgroups and treated with either MSC-IT or MSC-IV. The study duration was 14 months. No serious treatment-related safety issues were detected. Significantly fewer patients experienced treatment failure in the MSC-IT and MSC-IV groups compared with those in the sham-treated group (6.7%, 9.7%, and 41.9%, respectively, P = 0.0003 and P = 0.0008). During the 1-year follow-up, 58.6% and 40.6% of patients treated with MSC-IT and MSC-IV, respectively, exhibited no evidence of disease activity compared with 9.7% in the sham-treated group (P < 0.0001 and P < 0.0048, respectively). MSC-IT transplantation induced additional benefits on the relapse rate, on the monthly changes of the T2 lesion load on MRI, and on the timed 25-foot walking test, 9-hole peg test, optical coherence tomography, functional MRI and cognitive tests. Treatment with MSCs was well-tolerated in progressive multiple sclerosis and induced short-term beneficial effects regarding the primary end points, especially in the patients with active disease. The intrathecal administration was more efficacious than the intravenous in several parameters of the disease. A phase III trial is warranted to confirm these findings.</description><subject>Adult</subject><subject>Brain - diagnostic imaging</subject><subject>Disease Progression</subject><subject>Double-Blind Method</subject><subject>Endpoint Determination</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Humans</subject><subject>Injections, Intravenous</subject><subject>Injections, Spinal</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Mesenchymal Stem Cell Transplantation - adverse effects</subject><subject>Mesenchymal Stem Cell Transplantation - methods</subject><subject>Middle Aged</subject><subject>Multiple Sclerosis - diagnostic imaging</subject><subject>Multiple Sclerosis - psychology</subject><subject>Multiple Sclerosis - therapy</subject><subject>Multiple Sclerosis, Chronic Progressive - therapy</subject><subject>Neuropsychological Tests</subject><subject>Recurrence</subject><subject>Tomography, Optical Coherence</subject><subject>Treatment Outcome</subject><subject>Walking</subject><issn>0006-8950</issn><issn>1460-2156</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kD1PwzAQhi0EoqUwsiKPLKH-SNx4hIovqRILzJHtnIuRExfbAfXfk9LCcnfDo1fvPQhdUnJDieRzHZXr5-pbKc75EZrSUpCC0UocoykhRBS1rMgEnaX0QQgtOROnaMI5qziXdIrCHfRgnXHKY7AWTE44WKyGHHxYhyHhDhL05n3bjUTK0GED3uMcVZ82XvVZZRd67HqsTHZfgDcxrCOktLu7wWe38YCT8RBDcukcnVjlE1wc9gy9Pdy_Lp-K1cvj8_J2VRgu61yoSsiFlZYJxupS60WlRCUtp7Qtq3acNVipGWigtDYMrOZE6EUphRXUsJbP0PU-d6zzOUDKTefSrrnqYfyqYaUQpKRyVDhDxR41Y8MUwTab6DoVtw0lzc5x8-u4OTge-atD9KA7aP_pP6n8B_BUfKo</recordid><startdate>20201201</startdate><enddate>20201201</enddate><creator>Petrou, Panayiota</creator><creator>Kassis, Ibrahim</creator><creator>Levin, Netta</creator><creator>Paul, Friedemann</creator><creator>Backner, Yael</creator><creator>Benoliel, Tal</creator><creator>Oertel, Frederike Cosima</creator><creator>Scheel, Michael</creator><creator>Hallimi, Michelle</creator><creator>Yaghmour, Nour</creator><creator>Hur, Tamir Ben</creator><creator>Ginzberg, Ariel</creator><creator>Levy, Yarden</creator><creator>Abramsky, Oded</creator><creator>Karussis, Dimitrios</creator><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>7X8</scope><orcidid>https://orcid.org/0000-0001-5529-1237</orcidid><orcidid>https://orcid.org/0000-0001-5488-3046</orcidid><orcidid>https://orcid.org/0000-0002-3667-0116</orcidid></search><sort><creationdate>20201201</creationdate><title>Beneficial effects of autologous mesenchymal stem cell transplantation in active progressive multiple sclerosis</title><author>Petrou, Panayiota ; Kassis, Ibrahim ; Levin, Netta ; Paul, Friedemann ; Backner, Yael ; Benoliel, Tal ; Oertel, Frederike Cosima ; Scheel, Michael ; Hallimi, Michelle ; Yaghmour, Nour ; Hur, Tamir Ben ; Ginzberg, Ariel ; Levy, Yarden ; Abramsky, Oded ; Karussis, Dimitrios</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c398t-a5697f9f262284bb75a659f311d45d11d8ef9b2ebe118c2efb306b7496f61c2d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adult</topic><topic>Brain - diagnostic imaging</topic><topic>Disease Progression</topic><topic>Double-Blind Method</topic><topic>Endpoint Determination</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Humans</topic><topic>Injections, Intravenous</topic><topic>Injections, Spinal</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Mesenchymal Stem Cell Transplantation - adverse effects</topic><topic>Mesenchymal Stem Cell Transplantation - methods</topic><topic>Middle Aged</topic><topic>Multiple Sclerosis - diagnostic imaging</topic><topic>Multiple Sclerosis - psychology</topic><topic>Multiple Sclerosis - therapy</topic><topic>Multiple Sclerosis, Chronic Progressive - therapy</topic><topic>Neuropsychological Tests</topic><topic>Recurrence</topic><topic>Tomography, Optical Coherence</topic><topic>Treatment Outcome</topic><topic>Walking</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Petrou, Panayiota</creatorcontrib><creatorcontrib>Kassis, Ibrahim</creatorcontrib><creatorcontrib>Levin, Netta</creatorcontrib><creatorcontrib>Paul, Friedemann</creatorcontrib><creatorcontrib>Backner, Yael</creatorcontrib><creatorcontrib>Benoliel, Tal</creatorcontrib><creatorcontrib>Oertel, Frederike Cosima</creatorcontrib><creatorcontrib>Scheel, Michael</creatorcontrib><creatorcontrib>Hallimi, Michelle</creatorcontrib><creatorcontrib>Yaghmour, Nour</creatorcontrib><creatorcontrib>Hur, Tamir Ben</creatorcontrib><creatorcontrib>Ginzberg, Ariel</creatorcontrib><creatorcontrib>Levy, Yarden</creatorcontrib><creatorcontrib>Abramsky, Oded</creatorcontrib><creatorcontrib>Karussis, Dimitrios</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Brain (London, England : 1878)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Petrou, Panayiota</au><au>Kassis, Ibrahim</au><au>Levin, Netta</au><au>Paul, Friedemann</au><au>Backner, Yael</au><au>Benoliel, Tal</au><au>Oertel, Frederike Cosima</au><au>Scheel, Michael</au><au>Hallimi, Michelle</au><au>Yaghmour, Nour</au><au>Hur, Tamir Ben</au><au>Ginzberg, Ariel</au><au>Levy, Yarden</au><au>Abramsky, Oded</au><au>Karussis, Dimitrios</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Beneficial effects of autologous mesenchymal stem cell transplantation in active progressive multiple sclerosis</atitle><jtitle>Brain (London, England : 1878)</jtitle><addtitle>Brain</addtitle><date>2020-12-01</date><risdate>2020</risdate><volume>143</volume><issue>12</issue><spage>3574</spage><epage>3588</epage><pages>3574-3588</pages><issn>0006-8950</issn><eissn>1460-2156</eissn><abstract>In this study (trial registration: NCT02166021), we aimed to evaluate the optimal way of administration, the safety and the clinical efficacy of mesenchymal stem cell (MSC) transplantation in patients with active and progressive multiple sclerosis. Forty-eight patients (28 males and 20 females) with progressive multiple sclerosis (Expanded Disability Status Scale: 3.0-6.5, mean : 5.6 ± 0.8, mean age: 47.5 ± 12.3) and evidence of either clinical worsening or activity during the previous year, were enrolled (between 2015 and 2018). Patients were randomized into three groups and treated intrathecally (IT) or intravenously (IV) with autologous MSCs (1 × 106/kg) or sham injections. After 6 months, half of the patients from the MSC-IT and MSC-IV groups were retreated with MSCs, and the other half with sham injections. Patients initially assigned to sham treatment were divided into two subgroups and treated with either MSC-IT or MSC-IV. The study duration was 14 months. No serious treatment-related safety issues were detected. Significantly fewer patients experienced treatment failure in the MSC-IT and MSC-IV groups compared with those in the sham-treated group (6.7%, 9.7%, and 41.9%, respectively, P = 0.0003 and P = 0.0008). During the 1-year follow-up, 58.6% and 40.6% of patients treated with MSC-IT and MSC-IV, respectively, exhibited no evidence of disease activity compared with 9.7% in the sham-treated group (P < 0.0001 and P < 0.0048, respectively). MSC-IT transplantation induced additional benefits on the relapse rate, on the monthly changes of the T2 lesion load on MRI, and on the timed 25-foot walking test, 9-hole peg test, optical coherence tomography, functional MRI and cognitive tests. Treatment with MSCs was well-tolerated in progressive multiple sclerosis and induced short-term beneficial effects regarding the primary end points, especially in the patients with active disease. The intrathecal administration was more efficacious than the intravenous in several parameters of the disease. A phase III trial is warranted to confirm these findings.</abstract><cop>England</cop><pmid>33253391</pmid><doi>10.1093/brain/awaa333</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0001-5529-1237</orcidid><orcidid>https://orcid.org/0000-0001-5488-3046</orcidid><orcidid>https://orcid.org/0000-0002-3667-0116</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Brain - diagnostic imaging Disease Progression Double-Blind Method Endpoint Determination Female Follow-Up Studies Humans Injections, Intravenous Injections, Spinal Magnetic Resonance Imaging Male Mesenchymal Stem Cell Transplantation - adverse effects Mesenchymal Stem Cell Transplantation - methods Middle Aged Multiple Sclerosis - diagnostic imaging Multiple Sclerosis - psychology Multiple Sclerosis - therapy Multiple Sclerosis, Chronic Progressive - therapy Neuropsychological Tests Recurrence Tomography, Optical Coherence Treatment Outcome Walking |
| title | Beneficial effects of autologous mesenchymal stem cell transplantation in active progressive multiple sclerosis |
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