Inflammation- and Metastasis-Related Proteins Expression Changes in Early Stages in Tumor and Non-Tumor Adjacent Tissues of Colorectal Cancer Samples
Chronic inflammation can induce malignant cell transformation, having an important role in all colorectal cancer (CRC) phases. Non-tumor adjacent tissue plays an important role in tumor progression, but its implication in CRC has not yet been fully elucidated. The aim was to analyze the expression o...
Gespeichert in:
| Veröffentlicht in: | Cancers 2022-09, Vol.14 (18), p.4487 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 18 |
| container_start_page | 4487 |
| container_title | Cancers |
| container_volume | 14 |
| creator | Alorda-Clara, Marina Torrens-Mas, Margalida Hernández-López, Reyniel Ibarra de la Rosa, Javier M Falcó, Esther Fernández, Teresa Company, Maria Margarita Sastre-Serra, Jorge Oliver, Jordi Pons, Daniel Gabriel Roca, Pilar |
| description | Chronic inflammation can induce malignant cell transformation, having an important role in all colorectal cancer (CRC) phases. Non-tumor adjacent tissue plays an important role in tumor progression, but its implication in CRC has not yet been fully elucidated. The aim was to analyze the expression of inflammatory, epithelial-mesenchymal transition (EMT), and metastasis-related proteins in both tumor and non-tumor adjacent tissues from CRC patients by western blot. Tumor tissue presented an increase in metastasis and EMT-related proteins compared to non-tumor adjacent tissue, especially in stage II. Tumor tissue stage II also presented an increase in inflammatory-related proteins compared to other stages, which was also seen in non-tumor adjacent tissue stage II. Additionally, the relapse-free survival study of Vimentin and VEGF-B expression levels in stage II patients showed that the higher the expression levels of each protein, the lower 10-year relapse-free survival. These could suggest that some metastasis-related signalling pathways may be activated in stage II in tumor tissue, accompanied by an increase in inflammation. Furthermore, non-tumor adjacent tissue presented an increase of the inflammatory status that could be the basis for future tumor progression. In conclusion, these proteins could be useful as biomarkers of diagnosis for CRC at early stages. |
| doi_str_mv | 10.3390/cancers14184487 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9497293</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A745271555</galeid><sourcerecordid>A745271555</sourcerecordid><originalsourceid>FETCH-LOGICAL-c465t-551364305e370fbe8c957d102c8cc7875c54ee31fc47e656d73ef7b327e1a553</originalsourceid><addsrcrecordid>eNptkstq3DAUhk1poSHJultBN904sSzJsjeFwUzbQHqhmb04Ix9PNMjSVJJD8yB932gulCZUEuj2nV_nF6co3tHqirGuutbgNIZIOW05b-Wr4qyuZF02Tcdf_7N-W1zGuK1yY4zKRp4Vf27caGGaIBnvSgJuIF8xQczDxPInWkg4kB_BJzQukuXvXcAYM0v6e3AbjMQ4soRgH8ldgtN-NU8-HLS-ZdHjbjFsQaNLZGVinDPnR9J76wPqBJb0BwPkDqadxXhRvBnBRrw8zefF6tNy1X8pb79_vukXt6XmjUilEJQ1nFUCmazGNba6E3KgVa1brWUrhRYckdFRc4mNaAbJcJRrVkukIAQ7Lz4eZXfzesJhn14Aq3bBTBAelQejnt84c682_kF1vJN1x7LAh5NA8L-yqaQmEzVaCw79HFUt8y93ktU0o-9foFs_B5fd7alGVJIfBE_UBiwq40af39V7UbWQXGRSHPK--g-V-4CT0d7haPL5s4DrY4AOPsaA41-PtFL7AlIvCog9AbiduyY</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2716507493</pqid></control><display><type>article</type><title>Inflammation- and Metastasis-Related Proteins Expression Changes in Early Stages in Tumor and Non-Tumor Adjacent Tissues of Colorectal Cancer Samples</title><source>PubMed Central Open Access</source><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Alorda-Clara, Marina ; Torrens-Mas, Margalida ; Hernández-López, Reyniel ; Ibarra de la Rosa, Javier M ; Falcó, Esther ; Fernández, Teresa ; Company, Maria Margarita ; Sastre-Serra, Jorge ; Oliver, Jordi ; Pons, Daniel Gabriel ; Roca, Pilar</creator><creatorcontrib>Alorda-Clara, Marina ; Torrens-Mas, Margalida ; Hernández-López, Reyniel ; Ibarra de la Rosa, Javier M ; Falcó, Esther ; Fernández, Teresa ; Company, Maria Margarita ; Sastre-Serra, Jorge ; Oliver, Jordi ; Pons, Daniel Gabriel ; Roca, Pilar</creatorcontrib><description>Chronic inflammation can induce malignant cell transformation, having an important role in all colorectal cancer (CRC) phases. Non-tumor adjacent tissue plays an important role in tumor progression, but its implication in CRC has not yet been fully elucidated. The aim was to analyze the expression of inflammatory, epithelial-mesenchymal transition (EMT), and metastasis-related proteins in both tumor and non-tumor adjacent tissues from CRC patients by western blot. Tumor tissue presented an increase in metastasis and EMT-related proteins compared to non-tumor adjacent tissue, especially in stage II. Tumor tissue stage II also presented an increase in inflammatory-related proteins compared to other stages, which was also seen in non-tumor adjacent tissue stage II. Additionally, the relapse-free survival study of Vimentin and VEGF-B expression levels in stage II patients showed that the higher the expression levels of each protein, the lower 10-year relapse-free survival. These could suggest that some metastasis-related signalling pathways may be activated in stage II in tumor tissue, accompanied by an increase in inflammation. Furthermore, non-tumor adjacent tissue presented an increase of the inflammatory status that could be the basis for future tumor progression. In conclusion, these proteins could be useful as biomarkers of diagnosis for CRC at early stages.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers14184487</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Biotechnology ; Cancer ; Colorectal cancer ; Colorectal carcinoma ; Cytokines ; Development and progression ; Enzymes ; Gene expression ; Genetic aspects ; Health aspects ; Homogenization ; Inflammation ; Laboratories ; Males ; Membranes ; Mesenchyme ; Metastases ; Metastasis ; Patients ; Proteins ; Signal transduction ; Survival analysis ; Tumors ; Vascular endothelial growth factor ; Vimentin</subject><ispartof>Cancers, 2022-09, Vol.14 (18), p.4487</ispartof><rights>COPYRIGHT 2022 MDPI AG</rights><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 by the authors. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c465t-551364305e370fbe8c957d102c8cc7875c54ee31fc47e656d73ef7b327e1a553</citedby><cites>FETCH-LOGICAL-c465t-551364305e370fbe8c957d102c8cc7875c54ee31fc47e656d73ef7b327e1a553</cites><orcidid>0000-0002-2983-1620 ; 0000-0002-3610-7809 ; 0000-0002-5702-7306 ; 0000-0003-3405-0535 ; 0000-0002-2931-7939 ; 0000-0003-3878-5424</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9497293/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9497293/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27922,27923,53789,53791</link.rule.ids></links><search><creatorcontrib>Alorda-Clara, Marina</creatorcontrib><creatorcontrib>Torrens-Mas, Margalida</creatorcontrib><creatorcontrib>Hernández-López, Reyniel</creatorcontrib><creatorcontrib>Ibarra de la Rosa, Javier M</creatorcontrib><creatorcontrib>Falcó, Esther</creatorcontrib><creatorcontrib>Fernández, Teresa</creatorcontrib><creatorcontrib>Company, Maria Margarita</creatorcontrib><creatorcontrib>Sastre-Serra, Jorge</creatorcontrib><creatorcontrib>Oliver, Jordi</creatorcontrib><creatorcontrib>Pons, Daniel Gabriel</creatorcontrib><creatorcontrib>Roca, Pilar</creatorcontrib><title>Inflammation- and Metastasis-Related Proteins Expression Changes in Early Stages in Tumor and Non-Tumor Adjacent Tissues of Colorectal Cancer Samples</title><title>Cancers</title><description>Chronic inflammation can induce malignant cell transformation, having an important role in all colorectal cancer (CRC) phases. Non-tumor adjacent tissue plays an important role in tumor progression, but its implication in CRC has not yet been fully elucidated. The aim was to analyze the expression of inflammatory, epithelial-mesenchymal transition (EMT), and metastasis-related proteins in both tumor and non-tumor adjacent tissues from CRC patients by western blot. Tumor tissue presented an increase in metastasis and EMT-related proteins compared to non-tumor adjacent tissue, especially in stage II. Tumor tissue stage II also presented an increase in inflammatory-related proteins compared to other stages, which was also seen in non-tumor adjacent tissue stage II. Additionally, the relapse-free survival study of Vimentin and VEGF-B expression levels in stage II patients showed that the higher the expression levels of each protein, the lower 10-year relapse-free survival. These could suggest that some metastasis-related signalling pathways may be activated in stage II in tumor tissue, accompanied by an increase in inflammation. Furthermore, non-tumor adjacent tissue presented an increase of the inflammatory status that could be the basis for future tumor progression. In conclusion, these proteins could be useful as biomarkers of diagnosis for CRC at early stages.</description><subject>Biotechnology</subject><subject>Cancer</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Cytokines</subject><subject>Development and progression</subject><subject>Enzymes</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Homogenization</subject><subject>Inflammation</subject><subject>Laboratories</subject><subject>Males</subject><subject>Membranes</subject><subject>Mesenchyme</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Patients</subject><subject>Proteins</subject><subject>Signal transduction</subject><subject>Survival analysis</subject><subject>Tumors</subject><subject>Vascular endothelial growth factor</subject><subject>Vimentin</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptkstq3DAUhk1poSHJultBN904sSzJsjeFwUzbQHqhmb04Ix9PNMjSVJJD8yB932gulCZUEuj2nV_nF6co3tHqirGuutbgNIZIOW05b-Wr4qyuZF02Tcdf_7N-W1zGuK1yY4zKRp4Vf27caGGaIBnvSgJuIF8xQczDxPInWkg4kB_BJzQukuXvXcAYM0v6e3AbjMQ4soRgH8ldgtN-NU8-HLS-ZdHjbjFsQaNLZGVinDPnR9J76wPqBJb0BwPkDqadxXhRvBnBRrw8zefF6tNy1X8pb79_vukXt6XmjUilEJQ1nFUCmazGNba6E3KgVa1brWUrhRYckdFRc4mNaAbJcJRrVkukIAQ7Lz4eZXfzesJhn14Aq3bBTBAelQejnt84c682_kF1vJN1x7LAh5NA8L-yqaQmEzVaCw79HFUt8y93ktU0o-9foFs_B5fd7alGVJIfBE_UBiwq40af39V7UbWQXGRSHPK--g-V-4CT0d7haPL5s4DrY4AOPsaA41-PtFL7AlIvCog9AbiduyY</recordid><startdate>20220901</startdate><enddate>20220901</enddate><creator>Alorda-Clara, Marina</creator><creator>Torrens-Mas, Margalida</creator><creator>Hernández-López, Reyniel</creator><creator>Ibarra de la Rosa, Javier M</creator><creator>Falcó, Esther</creator><creator>Fernández, Teresa</creator><creator>Company, Maria Margarita</creator><creator>Sastre-Serra, Jorge</creator><creator>Oliver, Jordi</creator><creator>Pons, Daniel Gabriel</creator><creator>Roca, Pilar</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2983-1620</orcidid><orcidid>https://orcid.org/0000-0002-3610-7809</orcidid><orcidid>https://orcid.org/0000-0002-5702-7306</orcidid><orcidid>https://orcid.org/0000-0003-3405-0535</orcidid><orcidid>https://orcid.org/0000-0002-2931-7939</orcidid><orcidid>https://orcid.org/0000-0003-3878-5424</orcidid></search><sort><creationdate>20220901</creationdate><title>Inflammation- and Metastasis-Related Proteins Expression Changes in Early Stages in Tumor and Non-Tumor Adjacent Tissues of Colorectal Cancer Samples</title><author>Alorda-Clara, Marina ; Torrens-Mas, Margalida ; Hernández-López, Reyniel ; Ibarra de la Rosa, Javier M ; Falcó, Esther ; Fernández, Teresa ; Company, Maria Margarita ; Sastre-Serra, Jorge ; Oliver, Jordi ; Pons, Daniel Gabriel ; Roca, Pilar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c465t-551364305e370fbe8c957d102c8cc7875c54ee31fc47e656d73ef7b327e1a553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Biotechnology</topic><topic>Cancer</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Cytokines</topic><topic>Development and progression</topic><topic>Enzymes</topic><topic>Gene expression</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Homogenization</topic><topic>Inflammation</topic><topic>Laboratories</topic><topic>Males</topic><topic>Membranes</topic><topic>Mesenchyme</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Patients</topic><topic>Proteins</topic><topic>Signal transduction</topic><topic>Survival analysis</topic><topic>Tumors</topic><topic>Vascular endothelial growth factor</topic><topic>Vimentin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Alorda-Clara, Marina</creatorcontrib><creatorcontrib>Torrens-Mas, Margalida</creatorcontrib><creatorcontrib>Hernández-López, Reyniel</creatorcontrib><creatorcontrib>Ibarra de la Rosa, Javier M</creatorcontrib><creatorcontrib>Falcó, Esther</creatorcontrib><creatorcontrib>Fernández, Teresa</creatorcontrib><creatorcontrib>Company, Maria Margarita</creatorcontrib><creatorcontrib>Sastre-Serra, Jorge</creatorcontrib><creatorcontrib>Oliver, Jordi</creatorcontrib><creatorcontrib>Pons, Daniel Gabriel</creatorcontrib><creatorcontrib>Roca, Pilar</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</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>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</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 China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Alorda-Clara, Marina</au><au>Torrens-Mas, Margalida</au><au>Hernández-López, Reyniel</au><au>Ibarra de la Rosa, Javier M</au><au>Falcó, Esther</au><au>Fernández, Teresa</au><au>Company, Maria Margarita</au><au>Sastre-Serra, Jorge</au><au>Oliver, Jordi</au><au>Pons, Daniel Gabriel</au><au>Roca, Pilar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inflammation- and Metastasis-Related Proteins Expression Changes in Early Stages in Tumor and Non-Tumor Adjacent Tissues of Colorectal Cancer Samples</atitle><jtitle>Cancers</jtitle><date>2022-09-01</date><risdate>2022</risdate><volume>14</volume><issue>18</issue><spage>4487</spage><pages>4487-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>Chronic inflammation can induce malignant cell transformation, having an important role in all colorectal cancer (CRC) phases. Non-tumor adjacent tissue plays an important role in tumor progression, but its implication in CRC has not yet been fully elucidated. The aim was to analyze the expression of inflammatory, epithelial-mesenchymal transition (EMT), and metastasis-related proteins in both tumor and non-tumor adjacent tissues from CRC patients by western blot. Tumor tissue presented an increase in metastasis and EMT-related proteins compared to non-tumor adjacent tissue, especially in stage II. Tumor tissue stage II also presented an increase in inflammatory-related proteins compared to other stages, which was also seen in non-tumor adjacent tissue stage II. Additionally, the relapse-free survival study of Vimentin and VEGF-B expression levels in stage II patients showed that the higher the expression levels of each protein, the lower 10-year relapse-free survival. These could suggest that some metastasis-related signalling pathways may be activated in stage II in tumor tissue, accompanied by an increase in inflammation. Furthermore, non-tumor adjacent tissue presented an increase of the inflammatory status that could be the basis for future tumor progression. In conclusion, these proteins could be useful as biomarkers of diagnosis for CRC at early stages.</abstract><cop>Basel</cop><pub>MDPI AG</pub><doi>10.3390/cancers14184487</doi><orcidid>https://orcid.org/0000-0002-2983-1620</orcidid><orcidid>https://orcid.org/0000-0002-3610-7809</orcidid><orcidid>https://orcid.org/0000-0002-5702-7306</orcidid><orcidid>https://orcid.org/0000-0003-3405-0535</orcidid><orcidid>https://orcid.org/0000-0002-2931-7939</orcidid><orcidid>https://orcid.org/0000-0003-3878-5424</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2072-6694 |
| ispartof | Cancers, 2022-09, Vol.14 (18), p.4487 |
| issn | 2072-6694 2072-6694 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9497293 |
| source | PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Biotechnology Cancer Colorectal cancer Colorectal carcinoma Cytokines Development and progression Enzymes Gene expression Genetic aspects Health aspects Homogenization Inflammation Laboratories Males Membranes Mesenchyme Metastases Metastasis Patients Proteins Signal transduction Survival analysis Tumors Vascular endothelial growth factor Vimentin |
| title | Inflammation- and Metastasis-Related Proteins Expression Changes in Early Stages in Tumor and Non-Tumor Adjacent Tissues of Colorectal Cancer Samples |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-14T06%3A19%3A44IST&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=Inflammation-%20and%20Metastasis-Related%20Proteins%20Expression%20Changes%20in%20Early%20Stages%20in%20Tumor%20and%20Non-Tumor%20Adjacent%20Tissues%20of%20Colorectal%20Cancer%20Samples&rft.jtitle=Cancers&rft.au=Alorda-Clara,%20Marina&rft.date=2022-09-01&rft.volume=14&rft.issue=18&rft.spage=4487&rft.pages=4487-&rft.issn=2072-6694&rft.eissn=2072-6694&rft_id=info:doi/10.3390/cancers14184487&rft_dat=%3Cgale_pubme%3EA745271555%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=2716507493&rft_id=info:pmid/&rft_galeid=A745271555&rfr_iscdi=true |