Self-assembled RNA-triple-helix hydrogel scaffold for microRNA modulation in the tumour microenvironment
The therapeutic potential of miRNA (miR) in cancer is limited by the lack of efficient delivery vehicles. Here, we show that a self-assembled dual-colour RNA-triple-helix structure comprising two miRNAs—a miR mimic (tumour suppressor miRNA) and an antagomiR (oncomiR inhibitor)—provides outstanding c...
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| Veröffentlicht in: | Nature materials 2016-03, Vol.15 (3), p.353-363 |
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| creator | Conde, João Oliva, Nuria Atilano, Mariana Song, Hyun Seok Artzi, Natalie |
| description | The therapeutic potential of miRNA (miR) in cancer is limited by the lack of efficient delivery vehicles. Here, we show that a self-assembled dual-colour RNA-triple-helix structure comprising two miRNAs—a miR mimic (tumour suppressor miRNA) and an antagomiR (oncomiR inhibitor)—provides outstanding capability to synergistically abrogate tumours. Conjugation of RNA triple helices to dendrimers allows the formation of stable triplex nanoparticles, which form an RNA-triple-helix adhesive scaffold upon interaction with dextran aldehyde, the latter able to chemically interact and adhere to natural tissue amines in the tumour. We also show that the self-assembled RNA-triple-helix conjugates remain functional
in vitro
and
in vivo
, and that they lead to nearly 90% levels of tumour shrinkage two weeks post-gel implantation in a triple-negative breast cancer mouse model. Our findings suggest that the RNA-triple-helix hydrogels can be used as an efficient anticancer platform to locally modulate the expression of endogenous miRs in cancer.
Tissue-adhesive scaffolds made by the conjugation of RNA triple helices to dendrimers lead to ∼90% shrinkage of tumours two weeks after implantation in a triple-negative breast cancer mouse model. |
| doi_str_mv | 10.1038/nmat4497 |
| format | Article |
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in vitro
and
in vivo
, and that they lead to nearly 90% levels of tumour shrinkage two weeks post-gel implantation in a triple-negative breast cancer mouse model. Our findings suggest that the RNA-triple-helix hydrogels can be used as an efficient anticancer platform to locally modulate the expression of endogenous miRs in cancer.
Tissue-adhesive scaffolds made by the conjugation of RNA triple helices to dendrimers lead to ∼90% shrinkage of tumours two weeks after implantation in a triple-negative breast cancer mouse model.</description><identifier>ISSN: 1476-1122</identifier><identifier>EISSN: 1476-4660</identifier><identifier>DOI: 10.1038/nmat4497</identifier><identifier>PMID: 26641016</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>121/135 ; 121/143 ; 140/125 ; 631/61/391/2307 ; 639/166/985 ; 639/301/54/990 ; 639/925/352/2733 ; 639/925/357/341 ; Aldehydes ; Amines ; Animals ; Biomaterials ; Biomedical materials ; Breast ; Cancer ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cell Survival ; Cellular Microenvironment ; Condensed Matter Physics ; Endocytosis - drug effects ; Gene Expression Regulation, Neoplastic ; Humans ; Hydrogels ; Hydrogels - chemistry ; Implantation ; Materials Science ; Mice ; MicroRNAs ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Microscopy, Electron, Scanning ; Nanoparticles ; Nanotechnology ; Neoplasms - metabolism ; Nucleic Acid Conformation ; Optical and Electronic Materials ; Ribonucleic acids ; Scaffolds ; Tumors ; Tumours</subject><ispartof>Nature materials, 2016-03, Vol.15 (3), p.353-363</ispartof><rights>Springer Nature Limited 2015</rights><rights>Copyright Nature Publishing Group Mar 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c607t-69955301b4d1ed4afc7e02986b57ede118c1a425267d87e1fb9e4eb8f03356f3</citedby><cites>FETCH-LOGICAL-c607t-69955301b4d1ed4afc7e02986b57ede118c1a425267d87e1fb9e4eb8f03356f3</cites><orcidid>0000-0001-8422-6792</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nmat4497$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nmat4497$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26641016$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Conde, João</creatorcontrib><creatorcontrib>Oliva, Nuria</creatorcontrib><creatorcontrib>Atilano, Mariana</creatorcontrib><creatorcontrib>Song, Hyun Seok</creatorcontrib><creatorcontrib>Artzi, Natalie</creatorcontrib><title>Self-assembled RNA-triple-helix hydrogel scaffold for microRNA modulation in the tumour microenvironment</title><title>Nature materials</title><addtitle>Nature Mater</addtitle><addtitle>Nat Mater</addtitle><description>The therapeutic potential of miRNA (miR) in cancer is limited by the lack of efficient delivery vehicles. Here, we show that a self-assembled dual-colour RNA-triple-helix structure comprising two miRNAs—a miR mimic (tumour suppressor miRNA) and an antagomiR (oncomiR inhibitor)—provides outstanding capability to synergistically abrogate tumours. Conjugation of RNA triple helices to dendrimers allows the formation of stable triplex nanoparticles, which form an RNA-triple-helix adhesive scaffold upon interaction with dextran aldehyde, the latter able to chemically interact and adhere to natural tissue amines in the tumour. We also show that the self-assembled RNA-triple-helix conjugates remain functional
in vitro
and
in vivo
, and that they lead to nearly 90% levels of tumour shrinkage two weeks post-gel implantation in a triple-negative breast cancer mouse model. Our findings suggest that the RNA-triple-helix hydrogels can be used as an efficient anticancer platform to locally modulate the expression of endogenous miRs in cancer.
Tissue-adhesive scaffolds made by the conjugation of RNA triple helices to dendrimers lead to ∼90% shrinkage of tumours two weeks after implantation in a triple-negative breast cancer mouse model.</description><subject>121/135</subject><subject>121/143</subject><subject>140/125</subject><subject>631/61/391/2307</subject><subject>639/166/985</subject><subject>639/301/54/990</subject><subject>639/925/352/2733</subject><subject>639/925/357/341</subject><subject>Aldehydes</subject><subject>Amines</subject><subject>Animals</subject><subject>Biomaterials</subject><subject>Biomedical materials</subject><subject>Breast</subject><subject>Cancer</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Cell Survival</subject><subject>Cellular Microenvironment</subject><subject>Condensed Matter Physics</subject><subject>Endocytosis - drug effects</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Hydrogels</subject><subject>Hydrogels - chemistry</subject><subject>Implantation</subject><subject>Materials Science</subject><subject>Mice</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Microscopy, Electron, Scanning</subject><subject>Nanoparticles</subject><subject>Nanotechnology</subject><subject>Neoplasms - metabolism</subject><subject>Nucleic Acid Conformation</subject><subject>Optical and Electronic Materials</subject><subject>Ribonucleic acids</subject><subject>Scaffolds</subject><subject>Tumors</subject><subject>Tumours</subject><issn>1476-1122</issn><issn>1476-4660</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkttqFTEUhgdRbK2CTyAD3ujFaJLJYXIjlOIJioL2PmQmK3tnk8M2mSnt2_RZ-mSmdrdse6NXWbA-vkV-_qZ5idE7jPrhfQx6plSKR80hpoJ3lHP0eDdjTMhB86yUDUIEM8afNgeEc4oR5ofN5id42-lSIIweTPvj23E3Z7f10K3Bu4t2fWlyWoFvy6StTd5cX9mU2-CmnCrchmQWr2eXYutiO6-hnZeQlnx99QeBeO5yigHi_Lx5YrUv8GL3HjVnnz6enXzpTr9__npyfNpNHIm541Iy1iM8UoPBUG0nAYjIgY9MgAGMhwlrShjhwgwCsB0lUBgHi_qecdsfNR9utdtlDGCmejlrr7bZBZ0vVdJO_b2Jbq1W6VxxJilmtAre7AQ5_VqgzCq4MoH3OkJaisJC9kQMQ03-36jgnFFE-v9A-YC5IAOr6OsH6KYGGmtmN0LUS0nEnrCmXEoGe_9FjNRNK9RdKyr6aj-Se_CuBhV4ewuUuooryHsXH8p-A6MRw4M</recordid><startdate>20160301</startdate><enddate>20160301</enddate><creator>Conde, João</creator><creator>Oliva, Nuria</creator><creator>Atilano, Mariana</creator><creator>Song, Hyun Seok</creator><creator>Artzi, Natalie</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>3V.</scope><scope>7SR</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8BQ</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>JG9</scope><scope>K9.</scope><scope>KB.</scope><scope>L6V</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7S</scope><scope>PDBOC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>Q9U</scope><scope>7X8</scope><scope>7TM</scope><scope>7U5</scope><scope>L7M</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8422-6792</orcidid></search><sort><creationdate>20160301</creationdate><title>Self-assembled RNA-triple-helix hydrogel scaffold for microRNA modulation in the tumour microenvironment</title><author>Conde, João ; Oliva, Nuria ; Atilano, Mariana ; Song, Hyun Seok ; Artzi, Natalie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c607t-69955301b4d1ed4afc7e02986b57ede118c1a425267d87e1fb9e4eb8f03356f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>121/135</topic><topic>121/143</topic><topic>140/125</topic><topic>631/61/391/2307</topic><topic>639/166/985</topic><topic>639/301/54/990</topic><topic>639/925/352/2733</topic><topic>639/925/357/341</topic><topic>Aldehydes</topic><topic>Amines</topic><topic>Animals</topic><topic>Biomaterials</topic><topic>Biomedical materials</topic><topic>Breast</topic><topic>Cancer</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Cell Survival</topic><topic>Cellular Microenvironment</topic><topic>Condensed Matter Physics</topic><topic>Endocytosis - drug effects</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Hydrogels</topic><topic>Hydrogels - chemistry</topic><topic>Implantation</topic><topic>Materials Science</topic><topic>Mice</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Microscopy, Electron, Scanning</topic><topic>Nanoparticles</topic><topic>Nanotechnology</topic><topic>Neoplasms - metabolism</topic><topic>Nucleic Acid Conformation</topic><topic>Optical and Electronic Materials</topic><topic>Ribonucleic acids</topic><topic>Scaffolds</topic><topic>Tumors</topic><topic>Tumours</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Conde, João</creatorcontrib><creatorcontrib>Oliva, Nuria</creatorcontrib><creatorcontrib>Atilano, Mariana</creatorcontrib><creatorcontrib>Song, Hyun Seok</creatorcontrib><creatorcontrib>Artzi, Natalie</creatorcontrib><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>Engineered Materials Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</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>Materials Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>ProQuest Engineering Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Engineering Database</collection><collection>Materials Science Collection</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature materials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Conde, João</au><au>Oliva, Nuria</au><au>Atilano, Mariana</au><au>Song, Hyun Seok</au><au>Artzi, Natalie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Self-assembled RNA-triple-helix hydrogel scaffold for microRNA modulation in the tumour microenvironment</atitle><jtitle>Nature materials</jtitle><stitle>Nature Mater</stitle><addtitle>Nat Mater</addtitle><date>2016-03-01</date><risdate>2016</risdate><volume>15</volume><issue>3</issue><spage>353</spage><epage>363</epage><pages>353-363</pages><issn>1476-1122</issn><eissn>1476-4660</eissn><abstract>The therapeutic potential of miRNA (miR) in cancer is limited by the lack of efficient delivery vehicles. Here, we show that a self-assembled dual-colour RNA-triple-helix structure comprising two miRNAs—a miR mimic (tumour suppressor miRNA) and an antagomiR (oncomiR inhibitor)—provides outstanding capability to synergistically abrogate tumours. Conjugation of RNA triple helices to dendrimers allows the formation of stable triplex nanoparticles, which form an RNA-triple-helix adhesive scaffold upon interaction with dextran aldehyde, the latter able to chemically interact and adhere to natural tissue amines in the tumour. We also show that the self-assembled RNA-triple-helix conjugates remain functional
in vitro
and
in vivo
, and that they lead to nearly 90% levels of tumour shrinkage two weeks post-gel implantation in a triple-negative breast cancer mouse model. Our findings suggest that the RNA-triple-helix hydrogels can be used as an efficient anticancer platform to locally modulate the expression of endogenous miRs in cancer.
Tissue-adhesive scaffolds made by the conjugation of RNA triple helices to dendrimers lead to ∼90% shrinkage of tumours two weeks after implantation in a triple-negative breast cancer mouse model.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26641016</pmid><doi>10.1038/nmat4497</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-8422-6792</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 121/135 121/143 140/125 631/61/391/2307 639/166/985 639/301/54/990 639/925/352/2733 639/925/357/341 Aldehydes Amines Animals Biomaterials Biomedical materials Breast Cancer Cell Line, Tumor Cell Movement Cell Proliferation Cell Survival Cellular Microenvironment Condensed Matter Physics Endocytosis - drug effects Gene Expression Regulation, Neoplastic Humans Hydrogels Hydrogels - chemistry Implantation Materials Science Mice MicroRNAs MicroRNAs - genetics MicroRNAs - metabolism Microscopy, Electron, Scanning Nanoparticles Nanotechnology Neoplasms - metabolism Nucleic Acid Conformation Optical and Electronic Materials Ribonucleic acids Scaffolds Tumors Tumours |
| title | Self-assembled RNA-triple-helix hydrogel scaffold for microRNA modulation in the tumour microenvironment |
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