Reduction in TIMP‐2 serum levels predicts remission of inflammatory bowel diseases
Background Growing evidence indicates tissue inhibitors of matrix metalloproteinases (TIMPs) as potential players in inflammatory bowel disease (IBD), but, no prospective data are available in IBD remission/relapse. Material & methods In this prospective pilot study, a cohort of IBD patients (n ...
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| Veröffentlicht in: | European journal of clinical investigation 2018-10, Vol.48 (10), p.e13002-n/a |
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| creator | Carbone, Federico Bodini, Giorgia Brunacci, Matteo Bonaventura, Aldo Vecchiè, Alessandra Liberale, Luca Crespi, Mattia Baldissarro, Isabella Dallegri, Franco Savarino, Vincenzo Montecucco, Fabrizio Giannini, Edoardo G. |
| description | Background
Growing evidence indicates tissue inhibitors of matrix metalloproteinases (TIMPs) as potential players in inflammatory bowel disease (IBD), but, no prospective data are available in IBD remission/relapse.
Material & methods
In this prospective pilot study, a cohort of IBD patients (n = 32) was enrolled and treated with monoclonal anti‐TNF‐α antibodies. Patients were clinically followed up for a median period of 54 weeks. Serum circulating levels of C‐reactive protein (CRP), TIMP‐1 and ‐2, matrix metalloproteinase (MMP)‐9 and ‐8, myeloperoxidase (MPO) and neutrophil elastase (NE) were assessed by ELISA at enrolment and at the end of the treatment.
Results
The percentage (%) TIMP‐2 reduction from baseline to end of treatment was independently associated with IBD remission at the end of treatment and follow‐up as well. ROC curve analysis further confirmed the good prognostic accuracy of % TIMP‐2 reduction over the treatment period. Conversely, no other change in inflammatory molecule concentrations was able to predict short‐ or long‐term IBD remission.
Conclusions
This study indicates TIMP‐2 reduction during IBD treatment with monoclonal anti‐TNF‐α antibodies as a potential prognostic parameter of short and long term remission. To understand if TIMP‐2 is an innocent biomarker or an active pathophysiological factor in IBD remains to be clarified. |
| doi_str_mv | 10.1111/eci.13002 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2070800531</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2113713634</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3532-ac81dce2104ff8d0288fa37ebd0a2ed2da53b2f5f225d58ee71bfebbbb0ecc13</originalsourceid><addsrcrecordid>eNp10MFKw0AQBuBFFFurB19AAl70kHZ2tmniUUrVQkWR3pfN7iykJE3dbSy9-Qg-o0_i1lQPgnOZy8fPz8_YOYc-DzcgXfS5AMAD1uVilMQoRnjIugB8GONNih124v0CADIu8Jh1guUcRthl8xcyjV4X9TIqltF8-vj8-f6BkSfXVFFJb1T6aOXIFHrtI0dV4f3O1jZwW6qqUuvabaO83lAZmcKT8uRP2ZFVpaez_e-x-d1kPn6IZ0_30_HtLNYiERgrnXGjCTkMrc0MYJZZJVLKDSgkg0YlIkebWMTEJBlRynNLeTggrbnosas2duXq14b8WoZ6mspSLaluvERIIQNIxI5e_qGLunHLUE4i5yINq4lhUNet0q723pGVK1dUym0lB7lbWoal5ffSwV7sE5u8IvMrf6YNYNCCTVHS9v8kORlP28gv2jSIxQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2113713634</pqid></control><display><type>article</type><title>Reduction in TIMP‐2 serum levels predicts remission of inflammatory bowel diseases</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Carbone, Federico ; Bodini, Giorgia ; Brunacci, Matteo ; Bonaventura, Aldo ; Vecchiè, Alessandra ; Liberale, Luca ; Crespi, Mattia ; Baldissarro, Isabella ; Dallegri, Franco ; Savarino, Vincenzo ; Montecucco, Fabrizio ; Giannini, Edoardo G.</creator><creatorcontrib>Carbone, Federico ; Bodini, Giorgia ; Brunacci, Matteo ; Bonaventura, Aldo ; Vecchiè, Alessandra ; Liberale, Luca ; Crespi, Mattia ; Baldissarro, Isabella ; Dallegri, Franco ; Savarino, Vincenzo ; Montecucco, Fabrizio ; Giannini, Edoardo G.</creatorcontrib><description>Background
Growing evidence indicates tissue inhibitors of matrix metalloproteinases (TIMPs) as potential players in inflammatory bowel disease (IBD), but, no prospective data are available in IBD remission/relapse.
Material & methods
In this prospective pilot study, a cohort of IBD patients (n = 32) was enrolled and treated with monoclonal anti‐TNF‐α antibodies. Patients were clinically followed up for a median period of 54 weeks. Serum circulating levels of C‐reactive protein (CRP), TIMP‐1 and ‐2, matrix metalloproteinase (MMP)‐9 and ‐8, myeloperoxidase (MPO) and neutrophil elastase (NE) were assessed by ELISA at enrolment and at the end of the treatment.
Results
The percentage (%) TIMP‐2 reduction from baseline to end of treatment was independently associated with IBD remission at the end of treatment and follow‐up as well. ROC curve analysis further confirmed the good prognostic accuracy of % TIMP‐2 reduction over the treatment period. Conversely, no other change in inflammatory molecule concentrations was able to predict short‐ or long‐term IBD remission.
Conclusions
This study indicates TIMP‐2 reduction during IBD treatment with monoclonal anti‐TNF‐α antibodies as a potential prognostic parameter of short and long term remission. To understand if TIMP‐2 is an innocent biomarker or an active pathophysiological factor in IBD remains to be clarified.</description><identifier>ISSN: 0014-2972</identifier><identifier>EISSN: 1365-2362</identifier><identifier>DOI: 10.1111/eci.13002</identifier><identifier>PMID: 30011062</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Adult ; Antibodies ; Antibodies, Monoclonal - therapeutic use ; Area Under Curve ; Biomarkers ; Biomarkers - metabolism ; Elastase ; Enzyme-linked immunosorbent assay ; Female ; Humans ; Immunosuppressive Agents - therapeutic use ; inflammation ; Inflammatory bowel disease ; Inflammatory bowel diseases ; Inflammatory Bowel Diseases - blood ; Inflammatory Bowel Diseases - drug therapy ; Intestine ; Male ; Matrix metalloproteinase ; Matrix metalloproteinases ; Mesalamine - therapeutic use ; Metalloproteinase ; Middle Aged ; Monoclonal antibodies ; Patients ; Peroxidase ; Pilot Projects ; Prospective Studies ; Proteins ; Reduction ; Remission ; Remission Induction ; Serum levels ; tissue inhibitor of matrix metalloproteinase‐2 ; Tissue Inhibitor of Metalloproteinase-2 - metabolism ; Tissue inhibitor of metalloproteinases ; Tumor necrosis factor ; Young Adult</subject><ispartof>European journal of clinical investigation, 2018-10, Vol.48 (10), p.e13002-n/a</ispartof><rights>2018 Stichting European Society for Clinical Investigation Journal Foundation</rights><rights>2018 Stichting European Society for Clinical Investigation Journal Foundation.</rights><rights>Copyright © 2018 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3532-ac81dce2104ff8d0288fa37ebd0a2ed2da53b2f5f225d58ee71bfebbbb0ecc13</citedby><cites>FETCH-LOGICAL-c3532-ac81dce2104ff8d0288fa37ebd0a2ed2da53b2f5f225d58ee71bfebbbb0ecc13</cites><orcidid>0000-0003-0823-8729 ; 0000-0003-2957-4078</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Feci.13002$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Feci.13002$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30011062$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Carbone, Federico</creatorcontrib><creatorcontrib>Bodini, Giorgia</creatorcontrib><creatorcontrib>Brunacci, Matteo</creatorcontrib><creatorcontrib>Bonaventura, Aldo</creatorcontrib><creatorcontrib>Vecchiè, Alessandra</creatorcontrib><creatorcontrib>Liberale, Luca</creatorcontrib><creatorcontrib>Crespi, Mattia</creatorcontrib><creatorcontrib>Baldissarro, Isabella</creatorcontrib><creatorcontrib>Dallegri, Franco</creatorcontrib><creatorcontrib>Savarino, Vincenzo</creatorcontrib><creatorcontrib>Montecucco, Fabrizio</creatorcontrib><creatorcontrib>Giannini, Edoardo G.</creatorcontrib><title>Reduction in TIMP‐2 serum levels predicts remission of inflammatory bowel diseases</title><title>European journal of clinical investigation</title><addtitle>Eur J Clin Invest</addtitle><description>Background
Growing evidence indicates tissue inhibitors of matrix metalloproteinases (TIMPs) as potential players in inflammatory bowel disease (IBD), but, no prospective data are available in IBD remission/relapse.
Material & methods
In this prospective pilot study, a cohort of IBD patients (n = 32) was enrolled and treated with monoclonal anti‐TNF‐α antibodies. Patients were clinically followed up for a median period of 54 weeks. Serum circulating levels of C‐reactive protein (CRP), TIMP‐1 and ‐2, matrix metalloproteinase (MMP)‐9 and ‐8, myeloperoxidase (MPO) and neutrophil elastase (NE) were assessed by ELISA at enrolment and at the end of the treatment.
Results
The percentage (%) TIMP‐2 reduction from baseline to end of treatment was independently associated with IBD remission at the end of treatment and follow‐up as well. ROC curve analysis further confirmed the good prognostic accuracy of % TIMP‐2 reduction over the treatment period. Conversely, no other change in inflammatory molecule concentrations was able to predict short‐ or long‐term IBD remission.
Conclusions
This study indicates TIMP‐2 reduction during IBD treatment with monoclonal anti‐TNF‐α antibodies as a potential prognostic parameter of short and long term remission. To understand if TIMP‐2 is an innocent biomarker or an active pathophysiological factor in IBD remains to be clarified.</description><subject>Adult</subject><subject>Antibodies</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Area Under Curve</subject><subject>Biomarkers</subject><subject>Biomarkers - metabolism</subject><subject>Elastase</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Female</subject><subject>Humans</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>inflammation</subject><subject>Inflammatory bowel disease</subject><subject>Inflammatory bowel diseases</subject><subject>Inflammatory Bowel Diseases - blood</subject><subject>Inflammatory Bowel Diseases - drug therapy</subject><subject>Intestine</subject><subject>Male</subject><subject>Matrix metalloproteinase</subject><subject>Matrix metalloproteinases</subject><subject>Mesalamine - therapeutic use</subject><subject>Metalloproteinase</subject><subject>Middle Aged</subject><subject>Monoclonal antibodies</subject><subject>Patients</subject><subject>Peroxidase</subject><subject>Pilot Projects</subject><subject>Prospective Studies</subject><subject>Proteins</subject><subject>Reduction</subject><subject>Remission</subject><subject>Remission Induction</subject><subject>Serum levels</subject><subject>tissue inhibitor of matrix metalloproteinase‐2</subject><subject>Tissue Inhibitor of Metalloproteinase-2 - metabolism</subject><subject>Tissue inhibitor of metalloproteinases</subject><subject>Tumor necrosis factor</subject><subject>Young Adult</subject><issn>0014-2972</issn><issn>1365-2362</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10MFKw0AQBuBFFFurB19AAl70kHZ2tmniUUrVQkWR3pfN7iykJE3dbSy9-Qg-o0_i1lQPgnOZy8fPz8_YOYc-DzcgXfS5AMAD1uVilMQoRnjIugB8GONNih124v0CADIu8Jh1guUcRthl8xcyjV4X9TIqltF8-vj8-f6BkSfXVFFJb1T6aOXIFHrtI0dV4f3O1jZwW6qqUuvabaO83lAZmcKT8uRP2ZFVpaez_e-x-d1kPn6IZ0_30_HtLNYiERgrnXGjCTkMrc0MYJZZJVLKDSgkg0YlIkebWMTEJBlRynNLeTggrbnosas2duXq14b8WoZ6mspSLaluvERIIQNIxI5e_qGLunHLUE4i5yINq4lhUNet0q723pGVK1dUym0lB7lbWoal5ffSwV7sE5u8IvMrf6YNYNCCTVHS9v8kORlP28gv2jSIxQ</recordid><startdate>201810</startdate><enddate>201810</enddate><creator>Carbone, Federico</creator><creator>Bodini, Giorgia</creator><creator>Brunacci, Matteo</creator><creator>Bonaventura, Aldo</creator><creator>Vecchiè, Alessandra</creator><creator>Liberale, Luca</creator><creator>Crespi, Mattia</creator><creator>Baldissarro, Isabella</creator><creator>Dallegri, Franco</creator><creator>Savarino, Vincenzo</creator><creator>Montecucco, Fabrizio</creator><creator>Giannini, Edoardo G.</creator><general>Blackwell Publishing Ltd</general><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>7QO</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-0823-8729</orcidid><orcidid>https://orcid.org/0000-0003-2957-4078</orcidid></search><sort><creationdate>201810</creationdate><title>Reduction in TIMP‐2 serum levels predicts remission of inflammatory bowel diseases</title><author>Carbone, Federico ; Bodini, Giorgia ; Brunacci, Matteo ; Bonaventura, Aldo ; Vecchiè, Alessandra ; Liberale, Luca ; Crespi, Mattia ; Baldissarro, Isabella ; Dallegri, Franco ; Savarino, Vincenzo ; Montecucco, Fabrizio ; Giannini, Edoardo G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3532-ac81dce2104ff8d0288fa37ebd0a2ed2da53b2f5f225d58ee71bfebbbb0ecc13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Antibodies</topic><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>Area Under Curve</topic><topic>Biomarkers</topic><topic>Biomarkers - metabolism</topic><topic>Elastase</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Female</topic><topic>Humans</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>inflammation</topic><topic>Inflammatory bowel disease</topic><topic>Inflammatory bowel diseases</topic><topic>Inflammatory Bowel Diseases - blood</topic><topic>Inflammatory Bowel Diseases - drug therapy</topic><topic>Intestine</topic><topic>Male</topic><topic>Matrix metalloproteinase</topic><topic>Matrix metalloproteinases</topic><topic>Mesalamine - therapeutic use</topic><topic>Metalloproteinase</topic><topic>Middle Aged</topic><topic>Monoclonal antibodies</topic><topic>Patients</topic><topic>Peroxidase</topic><topic>Pilot Projects</topic><topic>Prospective Studies</topic><topic>Proteins</topic><topic>Reduction</topic><topic>Remission</topic><topic>Remission Induction</topic><topic>Serum levels</topic><topic>tissue inhibitor of matrix metalloproteinase‐2</topic><topic>Tissue Inhibitor of Metalloproteinase-2 - metabolism</topic><topic>Tissue inhibitor of metalloproteinases</topic><topic>Tumor necrosis factor</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Carbone, Federico</creatorcontrib><creatorcontrib>Bodini, Giorgia</creatorcontrib><creatorcontrib>Brunacci, Matteo</creatorcontrib><creatorcontrib>Bonaventura, Aldo</creatorcontrib><creatorcontrib>Vecchiè, Alessandra</creatorcontrib><creatorcontrib>Liberale, Luca</creatorcontrib><creatorcontrib>Crespi, Mattia</creatorcontrib><creatorcontrib>Baldissarro, Isabella</creatorcontrib><creatorcontrib>Dallegri, Franco</creatorcontrib><creatorcontrib>Savarino, Vincenzo</creatorcontrib><creatorcontrib>Montecucco, Fabrizio</creatorcontrib><creatorcontrib>Giannini, Edoardo G.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Carbone, Federico</au><au>Bodini, Giorgia</au><au>Brunacci, Matteo</au><au>Bonaventura, Aldo</au><au>Vecchiè, Alessandra</au><au>Liberale, Luca</au><au>Crespi, Mattia</au><au>Baldissarro, Isabella</au><au>Dallegri, Franco</au><au>Savarino, Vincenzo</au><au>Montecucco, Fabrizio</au><au>Giannini, Edoardo G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reduction in TIMP‐2 serum levels predicts remission of inflammatory bowel diseases</atitle><jtitle>European journal of clinical investigation</jtitle><addtitle>Eur J Clin Invest</addtitle><date>2018-10</date><risdate>2018</risdate><volume>48</volume><issue>10</issue><spage>e13002</spage><epage>n/a</epage><pages>e13002-n/a</pages><issn>0014-2972</issn><eissn>1365-2362</eissn><abstract>Background
Growing evidence indicates tissue inhibitors of matrix metalloproteinases (TIMPs) as potential players in inflammatory bowel disease (IBD), but, no prospective data are available in IBD remission/relapse.
Material & methods
In this prospective pilot study, a cohort of IBD patients (n = 32) was enrolled and treated with monoclonal anti‐TNF‐α antibodies. Patients were clinically followed up for a median period of 54 weeks. Serum circulating levels of C‐reactive protein (CRP), TIMP‐1 and ‐2, matrix metalloproteinase (MMP)‐9 and ‐8, myeloperoxidase (MPO) and neutrophil elastase (NE) were assessed by ELISA at enrolment and at the end of the treatment.
Results
The percentage (%) TIMP‐2 reduction from baseline to end of treatment was independently associated with IBD remission at the end of treatment and follow‐up as well. ROC curve analysis further confirmed the good prognostic accuracy of % TIMP‐2 reduction over the treatment period. Conversely, no other change in inflammatory molecule concentrations was able to predict short‐ or long‐term IBD remission.
Conclusions
This study indicates TIMP‐2 reduction during IBD treatment with monoclonal anti‐TNF‐α antibodies as a potential prognostic parameter of short and long term remission. To understand if TIMP‐2 is an innocent biomarker or an active pathophysiological factor in IBD remains to be clarified.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>30011062</pmid><doi>10.1111/eci.13002</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-0823-8729</orcidid><orcidid>https://orcid.org/0000-0003-2957-4078</orcidid></addata></record> |
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| subjects | Adult Antibodies Antibodies, Monoclonal - therapeutic use Area Under Curve Biomarkers Biomarkers - metabolism Elastase Enzyme-linked immunosorbent assay Female Humans Immunosuppressive Agents - therapeutic use inflammation Inflammatory bowel disease Inflammatory bowel diseases Inflammatory Bowel Diseases - blood Inflammatory Bowel Diseases - drug therapy Intestine Male Matrix metalloproteinase Matrix metalloproteinases Mesalamine - therapeutic use Metalloproteinase Middle Aged Monoclonal antibodies Patients Peroxidase Pilot Projects Prospective Studies Proteins Reduction Remission Remission Induction Serum levels tissue inhibitor of matrix metalloproteinase‐2 Tissue Inhibitor of Metalloproteinase-2 - metabolism Tissue inhibitor of metalloproteinases Tumor necrosis factor Young Adult |
| title | Reduction in TIMP‐2 serum levels predicts remission of inflammatory bowel diseases |
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