V617F‐independent upregulation of JAK2 gene expression in patients with inflammatory bowel disease
Background Inflammatory bowel disease (IBD) is one of the most important immune‐mediated disorders of the gastrointestinal tract. Besides, IBD is associated with numerous extraintestinal complications such as venous thromboembolism (VTE), an important risk factor for vascular complications, which re...
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| Veröffentlicht in: | Journal of cellular biochemistry 2019-09, Vol.120 (9), p.15746-15755 |
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| creator | Asadzadeh‐Aghdaei, Hamid Mashayekhi, Kazem Koushki, Khadijeh Azimzadeh, Pedram Rostami‐Nejad, Mohammad Amani, Davar Chaleshi, Vahid Haftcheshmeh, Saeed Mohammadian Sahebkar, Amirhossein Zali, Mohammad Reza |
| description | Background
Inflammatory bowel disease (IBD) is one of the most important immune‐mediated disorders of the gastrointestinal tract. Besides, IBD is associated with numerous extraintestinal complications such as venous thromboembolism (VTE), an important risk factor for vascular complications, which results in the increased morbidity and mortality. The JAK2 (Janus kinase 2) V617F mutation is a well‐known point mutation which is involved in the pathogenesis of IBD, and VTE. Therefore, the aims of this study were to evaluate expression of JAK2 and association of V617F mutation in JAK2 of Iranian patients with IBD.
Methods
Two hundred and forty‐six patients with IBD (209 UC and 37 CD) and 206 healthy controls were enrolled in this study. The genomic DNA and total RNA were extracted from peripheral blood mononuclear cells (PBMCs). Then, the JAK2 V617F mutation detection was performed using the restriction fragment length polymorphism (RFLP) method. In addition, the JAK2 mRNA expression was evaluated using a quantitative polymerase chain reaction (q‐PCR) using the SYBR Green assay.
Results
There was no association of V61F mutation in patients with IBD with or without thrombosis compared with healthy control. However, the relative mRNA expression of JAK2 was significantly upregulated in patients with IBD in comparison with healthy control (P |
| doi_str_mv | 10.1002/jcb.28844 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2231910680</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2231910680</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3534-e176625a099408861944c4957ce644bb4e3f8c04fe2d169c4f5a954e4e070e903</originalsourceid><addsrcrecordid>eNp1kEtOw0AMhkcIBKWw4AJoJDawCPXMOI9ZQsUbiQ2wjSaJA6nyIpOodMcROCMnYUqBBRIbW7I__bI_xvYEHAsAOZmlybGMIsQ1NhKgQw8DxHU2glCBJ5WQW2zb2hkAaK3kJttSAgIdIYxY9hiI8Pzj7b2oM2rJlbrnQ9vR01Cavmhq3uT8-uRG8ieqidOrW1m7nBc1bx3heMvnRf_sBnlpqsr0TbfgSTOnkmeFJWNph23kprS0-93H7OH87H566d3eXVxNT269VPkKPRJhEEjfuCsRoigQGjFF7YcpuX-SBEnlUQqYk8xEoFPMfaN9JCQIgTSoMTtc5bZd8zKQ7eOqsCmVpampGWwsnQvtXo-W6MEfdNYMXe2uc1TgHIboK0cdrai0a6ztKI_brqhMt4gFxEv1sVMff6l37P534pBUlP2SP64dMFkB86Kkxf9J8fX0dBX5CSXbjKI</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2260977453</pqid></control><display><type>article</type><title>V617F‐independent upregulation of JAK2 gene expression in patients with inflammatory bowel disease</title><source>Access via Wiley Online Library</source><creator>Asadzadeh‐Aghdaei, Hamid ; Mashayekhi, Kazem ; Koushki, Khadijeh ; Azimzadeh, Pedram ; Rostami‐Nejad, Mohammad ; Amani, Davar ; Chaleshi, Vahid ; Haftcheshmeh, Saeed Mohammadian ; Sahebkar, Amirhossein ; Zali, Mohammad Reza</creator><creatorcontrib>Asadzadeh‐Aghdaei, Hamid ; Mashayekhi, Kazem ; Koushki, Khadijeh ; Azimzadeh, Pedram ; Rostami‐Nejad, Mohammad ; Amani, Davar ; Chaleshi, Vahid ; Haftcheshmeh, Saeed Mohammadian ; Sahebkar, Amirhossein ; Zali, Mohammad Reza</creatorcontrib><description>Background
Inflammatory bowel disease (IBD) is one of the most important immune‐mediated disorders of the gastrointestinal tract. Besides, IBD is associated with numerous extraintestinal complications such as venous thromboembolism (VTE), an important risk factor for vascular complications, which results in the increased morbidity and mortality. The JAK2 (Janus kinase 2) V617F mutation is a well‐known point mutation which is involved in the pathogenesis of IBD, and VTE. Therefore, the aims of this study were to evaluate expression of JAK2 and association of V617F mutation in JAK2 of Iranian patients with IBD.
Methods
Two hundred and forty‐six patients with IBD (209 UC and 37 CD) and 206 healthy controls were enrolled in this study. The genomic DNA and total RNA were extracted from peripheral blood mononuclear cells (PBMCs). Then, the JAK2 V617F mutation detection was performed using the restriction fragment length polymorphism (RFLP) method. In addition, the JAK2 mRNA expression was evaluated using a quantitative polymerase chain reaction (q‐PCR) using the SYBR Green assay.
Results
There was no association of V61F mutation in patients with IBD with or without thrombosis compared with healthy control. However, the relative mRNA expression of JAK2 was significantly upregulated in patients with IBD in comparison with healthy control (P < 0.0001). In addition, the JAK2 mRNA expression was significantly decreased in patients with IBD having thrombosis compared with those without thrombosis (
P < 0.0001).
Conclusions
Taken together our findings suggested that JAK2 V61F‐independent upregulation of JAK2 mRNA expression in patients with IBD. Moreover, despite the absence of JAK2 V617F mutation in patients with IBD, the increased gene expression of JAK2 can be explained by another molecular mechanism such as regulation of gene expression at the transcriptional level which may play crucial roles in the pathogenesis of IBD.
The aims of this study were to evaluate the JAK2 V617F mutation detection and JAK2 gene expression in Iranian patients with IBD.</description><identifier>ISSN: 0730-2312</identifier><identifier>EISSN: 1097-4644</identifier><identifier>DOI: 10.1002/jcb.28844</identifier><identifier>PMID: 31069840</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Complications ; Deoxyribonucleic acid ; DNA ; Gastrointestinal system ; Gastrointestinal tract ; Gene expression ; Inflammatory bowel disease ; Inflammatory bowel diseases ; inflammatory bowel diseases (IBD) ; Intestine ; Janus kinase ; Janus kinase 2 ; Janus kinase 2 (JAK2) ; Kinases ; Leukocytes (mononuclear) ; Morbidity ; Mutation ; Pathogenesis ; Peripheral blood mononuclear cells ; Point mutation ; Polymerase chain reaction ; Polymorphism ; Restriction fragment length polymorphism ; Risk analysis ; Risk factors ; Thromboembolism ; Thrombosis ; Transcription ; Up-regulation ; V617F</subject><ispartof>Journal of cellular biochemistry, 2019-09, Vol.120 (9), p.15746-15755</ispartof><rights>2019 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3534-e176625a099408861944c4957ce644bb4e3f8c04fe2d169c4f5a954e4e070e903</citedby><cites>FETCH-LOGICAL-c3534-e176625a099408861944c4957ce644bb4e3f8c04fe2d169c4f5a954e4e070e903</cites><orcidid>0000-0002-8656-1444 ; 0000-0003-2495-1831</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%2Fjcb.28844$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcb.28844$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27929,27930,45579,45580</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31069840$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Asadzadeh‐Aghdaei, Hamid</creatorcontrib><creatorcontrib>Mashayekhi, Kazem</creatorcontrib><creatorcontrib>Koushki, Khadijeh</creatorcontrib><creatorcontrib>Azimzadeh, Pedram</creatorcontrib><creatorcontrib>Rostami‐Nejad, Mohammad</creatorcontrib><creatorcontrib>Amani, Davar</creatorcontrib><creatorcontrib>Chaleshi, Vahid</creatorcontrib><creatorcontrib>Haftcheshmeh, Saeed Mohammadian</creatorcontrib><creatorcontrib>Sahebkar, Amirhossein</creatorcontrib><creatorcontrib>Zali, Mohammad Reza</creatorcontrib><title>V617F‐independent upregulation of JAK2 gene expression in patients with inflammatory bowel disease</title><title>Journal of cellular biochemistry</title><addtitle>J Cell Biochem</addtitle><description>Background
Inflammatory bowel disease (IBD) is one of the most important immune‐mediated disorders of the gastrointestinal tract. Besides, IBD is associated with numerous extraintestinal complications such as venous thromboembolism (VTE), an important risk factor for vascular complications, which results in the increased morbidity and mortality. The JAK2 (Janus kinase 2) V617F mutation is a well‐known point mutation which is involved in the pathogenesis of IBD, and VTE. Therefore, the aims of this study were to evaluate expression of JAK2 and association of V617F mutation in JAK2 of Iranian patients with IBD.
Methods
Two hundred and forty‐six patients with IBD (209 UC and 37 CD) and 206 healthy controls were enrolled in this study. The genomic DNA and total RNA were extracted from peripheral blood mononuclear cells (PBMCs). Then, the JAK2 V617F mutation detection was performed using the restriction fragment length polymorphism (RFLP) method. In addition, the JAK2 mRNA expression was evaluated using a quantitative polymerase chain reaction (q‐PCR) using the SYBR Green assay.
Results
There was no association of V61F mutation in patients with IBD with or without thrombosis compared with healthy control. However, the relative mRNA expression of JAK2 was significantly upregulated in patients with IBD in comparison with healthy control (P < 0.0001). In addition, the JAK2 mRNA expression was significantly decreased in patients with IBD having thrombosis compared with those without thrombosis (
P < 0.0001).
Conclusions
Taken together our findings suggested that JAK2 V61F‐independent upregulation of JAK2 mRNA expression in patients with IBD. Moreover, despite the absence of JAK2 V617F mutation in patients with IBD, the increased gene expression of JAK2 can be explained by another molecular mechanism such as regulation of gene expression at the transcriptional level which may play crucial roles in the pathogenesis of IBD.
The aims of this study were to evaluate the JAK2 V617F mutation detection and JAK2 gene expression in Iranian patients with IBD.</description><subject>Complications</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Gastrointestinal system</subject><subject>Gastrointestinal tract</subject><subject>Gene expression</subject><subject>Inflammatory bowel disease</subject><subject>Inflammatory bowel diseases</subject><subject>inflammatory bowel diseases (IBD)</subject><subject>Intestine</subject><subject>Janus kinase</subject><subject>Janus kinase 2</subject><subject>Janus kinase 2 (JAK2)</subject><subject>Kinases</subject><subject>Leukocytes (mononuclear)</subject><subject>Morbidity</subject><subject>Mutation</subject><subject>Pathogenesis</subject><subject>Peripheral blood mononuclear cells</subject><subject>Point mutation</subject><subject>Polymerase chain reaction</subject><subject>Polymorphism</subject><subject>Restriction fragment length polymorphism</subject><subject>Risk analysis</subject><subject>Risk factors</subject><subject>Thromboembolism</subject><subject>Thrombosis</subject><subject>Transcription</subject><subject>Up-regulation</subject><subject>V617F</subject><issn>0730-2312</issn><issn>1097-4644</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp1kEtOw0AMhkcIBKWw4AJoJDawCPXMOI9ZQsUbiQ2wjSaJA6nyIpOodMcROCMnYUqBBRIbW7I__bI_xvYEHAsAOZmlybGMIsQ1NhKgQw8DxHU2glCBJ5WQW2zb2hkAaK3kJttSAgIdIYxY9hiI8Pzj7b2oM2rJlbrnQ9vR01Cavmhq3uT8-uRG8ieqidOrW1m7nBc1bx3heMvnRf_sBnlpqsr0TbfgSTOnkmeFJWNph23kprS0-93H7OH87H566d3eXVxNT269VPkKPRJhEEjfuCsRoigQGjFF7YcpuX-SBEnlUQqYk8xEoFPMfaN9JCQIgTSoMTtc5bZd8zKQ7eOqsCmVpampGWwsnQvtXo-W6MEfdNYMXe2uc1TgHIboK0cdrai0a6ztKI_brqhMt4gFxEv1sVMff6l37P534pBUlP2SP64dMFkB86Kkxf9J8fX0dBX5CSXbjKI</recordid><startdate>201909</startdate><enddate>201909</enddate><creator>Asadzadeh‐Aghdaei, Hamid</creator><creator>Mashayekhi, Kazem</creator><creator>Koushki, Khadijeh</creator><creator>Azimzadeh, Pedram</creator><creator>Rostami‐Nejad, Mohammad</creator><creator>Amani, Davar</creator><creator>Chaleshi, Vahid</creator><creator>Haftcheshmeh, Saeed Mohammadian</creator><creator>Sahebkar, Amirhossein</creator><creator>Zali, Mohammad Reza</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T7</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-8656-1444</orcidid><orcidid>https://orcid.org/0000-0003-2495-1831</orcidid></search><sort><creationdate>201909</creationdate><title>V617F‐independent upregulation of JAK2 gene expression in patients with inflammatory bowel disease</title><author>Asadzadeh‐Aghdaei, Hamid ; Mashayekhi, Kazem ; Koushki, Khadijeh ; Azimzadeh, Pedram ; Rostami‐Nejad, Mohammad ; Amani, Davar ; Chaleshi, Vahid ; Haftcheshmeh, Saeed Mohammadian ; Sahebkar, Amirhossein ; Zali, Mohammad Reza</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3534-e176625a099408861944c4957ce644bb4e3f8c04fe2d169c4f5a954e4e070e903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Complications</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Gastrointestinal system</topic><topic>Gastrointestinal tract</topic><topic>Gene expression</topic><topic>Inflammatory bowel disease</topic><topic>Inflammatory bowel diseases</topic><topic>inflammatory bowel diseases (IBD)</topic><topic>Intestine</topic><topic>Janus kinase</topic><topic>Janus kinase 2</topic><topic>Janus kinase 2 (JAK2)</topic><topic>Kinases</topic><topic>Leukocytes (mononuclear)</topic><topic>Morbidity</topic><topic>Mutation</topic><topic>Pathogenesis</topic><topic>Peripheral blood mononuclear cells</topic><topic>Point mutation</topic><topic>Polymerase chain reaction</topic><topic>Polymorphism</topic><topic>Restriction fragment length polymorphism</topic><topic>Risk analysis</topic><topic>Risk factors</topic><topic>Thromboembolism</topic><topic>Thrombosis</topic><topic>Transcription</topic><topic>Up-regulation</topic><topic>V617F</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Asadzadeh‐Aghdaei, Hamid</creatorcontrib><creatorcontrib>Mashayekhi, Kazem</creatorcontrib><creatorcontrib>Koushki, Khadijeh</creatorcontrib><creatorcontrib>Azimzadeh, Pedram</creatorcontrib><creatorcontrib>Rostami‐Nejad, Mohammad</creatorcontrib><creatorcontrib>Amani, Davar</creatorcontrib><creatorcontrib>Chaleshi, Vahid</creatorcontrib><creatorcontrib>Haftcheshmeh, Saeed Mohammadian</creatorcontrib><creatorcontrib>Sahebkar, Amirhossein</creatorcontrib><creatorcontrib>Zali, Mohammad Reza</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences 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>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cellular biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Asadzadeh‐Aghdaei, Hamid</au><au>Mashayekhi, Kazem</au><au>Koushki, Khadijeh</au><au>Azimzadeh, Pedram</au><au>Rostami‐Nejad, Mohammad</au><au>Amani, Davar</au><au>Chaleshi, Vahid</au><au>Haftcheshmeh, Saeed Mohammadian</au><au>Sahebkar, Amirhossein</au><au>Zali, Mohammad Reza</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>V617F‐independent upregulation of JAK2 gene expression in patients with inflammatory bowel disease</atitle><jtitle>Journal of cellular biochemistry</jtitle><addtitle>J Cell Biochem</addtitle><date>2019-09</date><risdate>2019</risdate><volume>120</volume><issue>9</issue><spage>15746</spage><epage>15755</epage><pages>15746-15755</pages><issn>0730-2312</issn><eissn>1097-4644</eissn><abstract>Background
Inflammatory bowel disease (IBD) is one of the most important immune‐mediated disorders of the gastrointestinal tract. Besides, IBD is associated with numerous extraintestinal complications such as venous thromboembolism (VTE), an important risk factor for vascular complications, which results in the increased morbidity and mortality. The JAK2 (Janus kinase 2) V617F mutation is a well‐known point mutation which is involved in the pathogenesis of IBD, and VTE. Therefore, the aims of this study were to evaluate expression of JAK2 and association of V617F mutation in JAK2 of Iranian patients with IBD.
Methods
Two hundred and forty‐six patients with IBD (209 UC and 37 CD) and 206 healthy controls were enrolled in this study. The genomic DNA and total RNA were extracted from peripheral blood mononuclear cells (PBMCs). Then, the JAK2 V617F mutation detection was performed using the restriction fragment length polymorphism (RFLP) method. In addition, the JAK2 mRNA expression was evaluated using a quantitative polymerase chain reaction (q‐PCR) using the SYBR Green assay.
Results
There was no association of V61F mutation in patients with IBD with or without thrombosis compared with healthy control. However, the relative mRNA expression of JAK2 was significantly upregulated in patients with IBD in comparison with healthy control (P < 0.0001). In addition, the JAK2 mRNA expression was significantly decreased in patients with IBD having thrombosis compared with those without thrombosis (
P < 0.0001).
Conclusions
Taken together our findings suggested that JAK2 V61F‐independent upregulation of JAK2 mRNA expression in patients with IBD. Moreover, despite the absence of JAK2 V617F mutation in patients with IBD, the increased gene expression of JAK2 can be explained by another molecular mechanism such as regulation of gene expression at the transcriptional level which may play crucial roles in the pathogenesis of IBD.
The aims of this study were to evaluate the JAK2 V617F mutation detection and JAK2 gene expression in Iranian patients with IBD.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>31069840</pmid><doi>10.1002/jcb.28844</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-8656-1444</orcidid><orcidid>https://orcid.org/0000-0003-2495-1831</orcidid></addata></record> |
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| subjects | Complications Deoxyribonucleic acid DNA Gastrointestinal system Gastrointestinal tract Gene expression Inflammatory bowel disease Inflammatory bowel diseases inflammatory bowel diseases (IBD) Intestine Janus kinase Janus kinase 2 Janus kinase 2 (JAK2) Kinases Leukocytes (mononuclear) Morbidity Mutation Pathogenesis Peripheral blood mononuclear cells Point mutation Polymerase chain reaction Polymorphism Restriction fragment length polymorphism Risk analysis Risk factors Thromboembolism Thrombosis Transcription Up-regulation V617F |
| title | V617F‐independent upregulation of JAK2 gene expression in patients with inflammatory bowel disease |
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