Analysis of CXCL9, PD1 and PD-L1 mRNA in Stage T1 Non-Muscle Invasive Bladder Cancer and Their Association with Prognosis
Non-muscle invasive bladder cancer (NMIBC), which is characterized by a recurrence rate of approximately 30% and very long treatment times, remains a major unresolved problem for patients and the health care system. The immunological interplay between tumor cells and the immune environment is import...
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| Veröffentlicht in: | Cancers 2020-09, Vol.12 (10), p.2794 |
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| creator | Kubon, Jennifer Sikic, Danijel Eckstein, Markus Weyerer, Veronika Stöhr, Robert Neumann, Angela Keck, Bastian Wullich, Bernd Hartmann, Arndt Wirtz, Ralph M Taubert, Helge Wach, Sven |
| description | Non-muscle invasive bladder cancer (NMIBC), which is characterized by a recurrence rate of approximately 30% and very long treatment times, remains a major unresolved problem for patients and the health care system. The immunological interplay between tumor cells and the immune environment is important for tumor development. Therefore, we analyzed the mRNA of three immune markers,
,
and
, in NMIBC by qRT-PCR. The results were subsequently correlated with clinicopathological parameters and prognostic data. Altogether, as expected, higher age was an independent prognostic factor for overall survival (OS) and disease-specific survival (DSS), but not for recurrence-free survival (RFS). Lower
mRNA was observed in multivariate Cox's regression analysis to be an independent prognostic parameter for reduced OS (relative risk; RR = 2.08;
= 0.049), DSS (RR = 4.49;
= 0.006) and RFS (RR = 2.69;
= 0.005). In addition,
mRNA was an independent prognostic factor for DSS (RR = 5.02;
= 0.042) and RFS (RR = 2.07;
= 0.044). Moreover, in univariate Cox's regression analysis, the stratification of patients revealed that low
or low PD1 mRNA was associated with reduced RFS in the younger patient group (≤71 years), but not in the older patient group (>71 years). In addition, low
or low
was associated with shorter RFS in patients with higher tumor cell proliferation and in patients without instillation therapy. In conclusion, the characterization of mRNA levels of immune markers differentiates NIMBC patients with respect to prognosis. |
| doi_str_mv | 10.3390/cancers12102794 |
| format | Article |
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,
and
, in NMIBC by qRT-PCR. The results were subsequently correlated with clinicopathological parameters and prognostic data. Altogether, as expected, higher age was an independent prognostic factor for overall survival (OS) and disease-specific survival (DSS), but not for recurrence-free survival (RFS). Lower
mRNA was observed in multivariate Cox's regression analysis to be an independent prognostic parameter for reduced OS (relative risk; RR = 2.08;
= 0.049), DSS (RR = 4.49;
= 0.006) and RFS (RR = 2.69;
= 0.005). In addition,
mRNA was an independent prognostic factor for DSS (RR = 5.02;
= 0.042) and RFS (RR = 2.07;
= 0.044). Moreover, in univariate Cox's regression analysis, the stratification of patients revealed that low
or low PD1 mRNA was associated with reduced RFS in the younger patient group (≤71 years), but not in the older patient group (>71 years). In addition, low
or low
was associated with shorter RFS in patients with higher tumor cell proliferation and in patients without instillation therapy. In conclusion, the characterization of mRNA levels of immune markers differentiates NIMBC patients with respect to prognosis.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers12102794</identifier><identifier>PMID: 33003392</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Age groups ; Apoptosis ; Bladder cancer ; Cancer ; Cancer therapies ; Cell proliferation ; Chromosomes ; Gene expression ; Genetic aspects ; Health aspects ; Health care ; Invasiveness ; Keratin ; Ligands ; Medical prognosis ; Messenger RNA ; Methods ; mRNA ; Patients ; PD-1 protein ; PD-L1 protein ; Prognosis ; Regression analysis ; RNA sequencing ; Tumor cells</subject><ispartof>Cancers, 2020-09, Vol.12 (10), p.2794</ispartof><rights>COPYRIGHT 2020 MDPI AG</rights><rights>2020 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 (http://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>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c449t-df0bc60c6a22063daef9c3340fc7eeefbafa9e48d29931e1333ca7ba1dd559083</citedby><cites>FETCH-LOGICAL-c449t-df0bc60c6a22063daef9c3340fc7eeefbafa9e48d29931e1333ca7ba1dd559083</cites><orcidid>0000-0002-9077-1727</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/PMC7601021/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601021/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33003392$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kubon, Jennifer</creatorcontrib><creatorcontrib>Sikic, Danijel</creatorcontrib><creatorcontrib>Eckstein, Markus</creatorcontrib><creatorcontrib>Weyerer, Veronika</creatorcontrib><creatorcontrib>Stöhr, Robert</creatorcontrib><creatorcontrib>Neumann, Angela</creatorcontrib><creatorcontrib>Keck, Bastian</creatorcontrib><creatorcontrib>Wullich, Bernd</creatorcontrib><creatorcontrib>Hartmann, Arndt</creatorcontrib><creatorcontrib>Wirtz, Ralph M</creatorcontrib><creatorcontrib>Taubert, Helge</creatorcontrib><creatorcontrib>Wach, Sven</creatorcontrib><title>Analysis of CXCL9, PD1 and PD-L1 mRNA in Stage T1 Non-Muscle Invasive Bladder Cancer and Their Association with Prognosis</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>Non-muscle invasive bladder cancer (NMIBC), which is characterized by a recurrence rate of approximately 30% and very long treatment times, remains a major unresolved problem for patients and the health care system. The immunological interplay between tumor cells and the immune environment is important for tumor development. Therefore, we analyzed the mRNA of three immune markers,
,
and
, in NMIBC by qRT-PCR. The results were subsequently correlated with clinicopathological parameters and prognostic data. Altogether, as expected, higher age was an independent prognostic factor for overall survival (OS) and disease-specific survival (DSS), but not for recurrence-free survival (RFS). Lower
mRNA was observed in multivariate Cox's regression analysis to be an independent prognostic parameter for reduced OS (relative risk; RR = 2.08;
= 0.049), DSS (RR = 4.49;
= 0.006) and RFS (RR = 2.69;
= 0.005). In addition,
mRNA was an independent prognostic factor for DSS (RR = 5.02;
= 0.042) and RFS (RR = 2.07;
= 0.044). Moreover, in univariate Cox's regression analysis, the stratification of patients revealed that low
or low PD1 mRNA was associated with reduced RFS in the younger patient group (≤71 years), but not in the older patient group (>71 years). In addition, low
or low
was associated with shorter RFS in patients with higher tumor cell proliferation and in patients without instillation therapy. In conclusion, the characterization of mRNA levels of immune markers differentiates NIMBC patients with respect to prognosis.</description><subject>Age groups</subject><subject>Apoptosis</subject><subject>Bladder cancer</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Cell proliferation</subject><subject>Chromosomes</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Health care</subject><subject>Invasiveness</subject><subject>Keratin</subject><subject>Ligands</subject><subject>Medical prognosis</subject><subject>Messenger RNA</subject><subject>Methods</subject><subject>mRNA</subject><subject>Patients</subject><subject>PD-1 protein</subject><subject>PD-L1 protein</subject><subject>Prognosis</subject><subject>Regression analysis</subject><subject>RNA sequencing</subject><subject>Tumor cells</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkU1v1DAQhiMEolXpmRuyxIUDof6KE1-QllCg0lIqWCRu1qwz2XWVtYudbLX_Hm9bSqkv45GfeWc8b1G8ZPSdEJqeWPAWY2KcUV5r-aQ45LTmpVJaPn1wPyiOU7qk-QjBalU_Lw6E2CeaHxa7mYdhl1wioSftr3au35KLj4yA73Is54xsvp_PiPPkxwgrJAtGzoMvv07JDkjO_BaS2yL5MEDXYSTtzUg31Ys1ukhmKQXrYHTBk2s3rslFDCsfcsMXxbMehoTHd_Go-PnpdNF-KeffPp-1s3lppdRj2fV0aRW1CjinSnSAvbZCSNrbGhH7JfSgUTYd11owZEIIC_USWNdVlaaNOCre3-peTcsNdhb9GGEwV9FtIO5MAGf-f_FubVZha2pF82JZFnhzJxDD7wnTaDYuWRwG8BimZLiUjaQVp1VGXz9CL8MU84YzVcm6ElyK5h-1ggGN833Ife1e1MyU5LVqlKKZOrmlbAwpRezvR2bU7P03j_zPFa8e_vSe_-u2-AOxjKqE</recordid><startdate>20200929</startdate><enddate>20200929</enddate><creator>Kubon, Jennifer</creator><creator>Sikic, Danijel</creator><creator>Eckstein, Markus</creator><creator>Weyerer, Veronika</creator><creator>Stöhr, Robert</creator><creator>Neumann, Angela</creator><creator>Keck, Bastian</creator><creator>Wullich, Bernd</creator><creator>Hartmann, Arndt</creator><creator>Wirtz, Ralph M</creator><creator>Taubert, Helge</creator><creator>Wach, Sven</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><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>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-9077-1727</orcidid></search><sort><creationdate>20200929</creationdate><title>Analysis of CXCL9, PD1 and PD-L1 mRNA in Stage T1 Non-Muscle Invasive Bladder Cancer and Their Association with Prognosis</title><author>Kubon, Jennifer ; Sikic, Danijel ; Eckstein, Markus ; Weyerer, Veronika ; Stöhr, Robert ; Neumann, Angela ; Keck, Bastian ; Wullich, Bernd ; Hartmann, Arndt ; Wirtz, Ralph M ; Taubert, Helge ; Wach, Sven</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c449t-df0bc60c6a22063daef9c3340fc7eeefbafa9e48d29931e1333ca7ba1dd559083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Age groups</topic><topic>Apoptosis</topic><topic>Bladder cancer</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Cell proliferation</topic><topic>Chromosomes</topic><topic>Gene expression</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Health care</topic><topic>Invasiveness</topic><topic>Keratin</topic><topic>Ligands</topic><topic>Medical prognosis</topic><topic>Messenger RNA</topic><topic>Methods</topic><topic>mRNA</topic><topic>Patients</topic><topic>PD-1 protein</topic><topic>PD-L1 protein</topic><topic>Prognosis</topic><topic>Regression analysis</topic><topic>RNA sequencing</topic><topic>Tumor cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kubon, Jennifer</creatorcontrib><creatorcontrib>Sikic, Danijel</creatorcontrib><creatorcontrib>Eckstein, Markus</creatorcontrib><creatorcontrib>Weyerer, Veronika</creatorcontrib><creatorcontrib>Stöhr, Robert</creatorcontrib><creatorcontrib>Neumann, Angela</creatorcontrib><creatorcontrib>Keck, Bastian</creatorcontrib><creatorcontrib>Wullich, Bernd</creatorcontrib><creatorcontrib>Hartmann, Arndt</creatorcontrib><creatorcontrib>Wirtz, Ralph M</creatorcontrib><creatorcontrib>Taubert, Helge</creatorcontrib><creatorcontrib>Wach, Sven</creatorcontrib><collection>PubMed</collection><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 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>Kubon, Jennifer</au><au>Sikic, Danijel</au><au>Eckstein, Markus</au><au>Weyerer, Veronika</au><au>Stöhr, Robert</au><au>Neumann, Angela</au><au>Keck, Bastian</au><au>Wullich, Bernd</au><au>Hartmann, Arndt</au><au>Wirtz, Ralph M</au><au>Taubert, Helge</au><au>Wach, Sven</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Analysis of CXCL9, PD1 and PD-L1 mRNA in Stage T1 Non-Muscle Invasive Bladder Cancer and Their Association with Prognosis</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2020-09-29</date><risdate>2020</risdate><volume>12</volume><issue>10</issue><spage>2794</spage><pages>2794-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>Non-muscle invasive bladder cancer (NMIBC), which is characterized by a recurrence rate of approximately 30% and very long treatment times, remains a major unresolved problem for patients and the health care system. The immunological interplay between tumor cells and the immune environment is important for tumor development. Therefore, we analyzed the mRNA of three immune markers,
,
and
, in NMIBC by qRT-PCR. The results were subsequently correlated with clinicopathological parameters and prognostic data. Altogether, as expected, higher age was an independent prognostic factor for overall survival (OS) and disease-specific survival (DSS), but not for recurrence-free survival (RFS). Lower
mRNA was observed in multivariate Cox's regression analysis to be an independent prognostic parameter for reduced OS (relative risk; RR = 2.08;
= 0.049), DSS (RR = 4.49;
= 0.006) and RFS (RR = 2.69;
= 0.005). In addition,
mRNA was an independent prognostic factor for DSS (RR = 5.02;
= 0.042) and RFS (RR = 2.07;
= 0.044). Moreover, in univariate Cox's regression analysis, the stratification of patients revealed that low
or low PD1 mRNA was associated with reduced RFS in the younger patient group (≤71 years), but not in the older patient group (>71 years). In addition, low
or low
was associated with shorter RFS in patients with higher tumor cell proliferation and in patients without instillation therapy. In conclusion, the characterization of mRNA levels of immune markers differentiates NIMBC patients with respect to prognosis.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>33003392</pmid><doi>10.3390/cancers12102794</doi><orcidid>https://orcid.org/0000-0002-9077-1727</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access |
| subjects | Age groups Apoptosis Bladder cancer Cancer Cancer therapies Cell proliferation Chromosomes Gene expression Genetic aspects Health aspects Health care Invasiveness Keratin Ligands Medical prognosis Messenger RNA Methods mRNA Patients PD-1 protein PD-L1 protein Prognosis Regression analysis RNA sequencing Tumor cells |
| title | Analysis of CXCL9, PD1 and PD-L1 mRNA in Stage T1 Non-Muscle Invasive Bladder Cancer and Their Association with Prognosis |
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