HMGB1-Mediated Neuroinflammatory Responses in Brain Injuries: Potential Mechanisms and Therapeutic Opportunities
Brain injuries are devastating conditions, representing a global cause of mortality and morbidity, with no effective treatment to date. Increased evidence supports the role of neuroinflammation in driving several forms of brain injuries. High mobility group box 1 (HMGB1) protein is a pro-inflammator...
Gespeichert in:
Veröffentlicht in: | International journal of molecular sciences 2020-06, Vol.21 (13), p.4609 |
---|---|
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 | 13 |
container_start_page | 4609 |
container_title | International journal of molecular sciences |
container_volume | 21 |
creator | Paudel, Yam Nath Angelopoulou, Efthalia Piperi, Christina Othman, Iekhsan Shaikh, Mohd Farooq |
description | Brain injuries are devastating conditions, representing a global cause of mortality and morbidity, with no effective treatment to date. Increased evidence supports the role of neuroinflammation in driving several forms of brain injuries. High mobility group box 1 (HMGB1) protein is a pro-inflammatory-like cytokine with an initiator role in neuroinflammation that has been implicated in Traumatic brain injury (TBI) as well as in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Herein, we discuss the implication of HMGB1-induced neuroinflammatory responses in these brain injuries, mediated through binding to the receptor for advanced glycation end products (RAGE), toll-like receptor4 (TLR4) and other inflammatory mediators. Moreover, we provide evidence on the biomarker potential of HMGB1 and the significance of its nucleocytoplasmic translocation during brain injuries along with the promising neuroprotective effects observed upon HMGB1 inhibition/neutralization in TBI and EBI induced by SAH. Overall, this review addresses the current advances on neuroinflammation driven by HMGB1 in brain injuries indicating a future treatment opportunity that may overcome current therapeutic gaps. |
doi_str_mv | 10.3390/ijms21134609 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7370155</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2419899913</sourcerecordid><originalsourceid>FETCH-LOGICAL-c478t-266aaed49057e660f49fc26ac650d2df7be25d00a91b768544ac0a90903cc0123</originalsourceid><addsrcrecordid>eNpdkU1v1DAQhi0Eoh9w44wsceFAYGzHzpoDEq2grdSlCJWz5XUmrFeJHWwHqf--hpZq4TIfmmdezegl5AWDt0JoeOd3U-aMiVaBfkQOWct5A6C6x3v1ATnKeQfABZf6KTkQXDGQwA_JfL4-O2HNGntvC_b0Cy4p-jCMdppsiemGfsM8x5AxUx_oSbI1XoTdkjzm9_RrLBiKtyNdo9va4POUqQ09vd5isjMuxTt6Nc8xlSX4UneekSeDHTM-v8_H5PvnT9en583l1dnF6cfLxrXdqjRcKWuxbzXIDpWCodWD48o6JaHn_dBtkMsewGq26dRKtq11tQENwjlgXByTD3e687KZsHf1zGRHMyc_2XRjovXm30nwW_Mj_jKd6IBJWQVe3wuk-HPBXMzks8NxtAHjkg1vme4Yl4JV9NV_6C4uKdT3_lArrTUTlXpzR7kUc044PBzDwPy20uxbWfGX-w88wH-9E7e3A5u3</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2419899913</pqid></control><display><type>article</type><title>HMGB1-Mediated Neuroinflammatory Responses in Brain Injuries: Potential Mechanisms and Therapeutic Opportunities</title><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>MEDLINE</source><source>PubMed Central</source><source>EZB*</source><creator>Paudel, Yam Nath ; Angelopoulou, Efthalia ; Piperi, Christina ; Othman, Iekhsan ; Shaikh, Mohd Farooq</creator><creatorcontrib>Paudel, Yam Nath ; Angelopoulou, Efthalia ; Piperi, Christina ; Othman, Iekhsan ; Shaikh, Mohd Farooq</creatorcontrib><description>Brain injuries are devastating conditions, representing a global cause of mortality and morbidity, with no effective treatment to date. Increased evidence supports the role of neuroinflammation in driving several forms of brain injuries. High mobility group box 1 (HMGB1) protein is a pro-inflammatory-like cytokine with an initiator role in neuroinflammation that has been implicated in Traumatic brain injury (TBI) as well as in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Herein, we discuss the implication of HMGB1-induced neuroinflammatory responses in these brain injuries, mediated through binding to the receptor for advanced glycation end products (RAGE), toll-like receptor4 (TLR4) and other inflammatory mediators. Moreover, we provide evidence on the biomarker potential of HMGB1 and the significance of its nucleocytoplasmic translocation during brain injuries along with the promising neuroprotective effects observed upon HMGB1 inhibition/neutralization in TBI and EBI induced by SAH. Overall, this review addresses the current advances on neuroinflammation driven by HMGB1 in brain injuries indicating a future treatment opportunity that may overcome current therapeutic gaps.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms21134609</identifier><identifier>PMID: 32610502</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Advanced glycosylation end products ; Animals ; Apoptosis ; Brain Injuries - metabolism ; Brain Injuries - pathology ; Brain Injuries, Traumatic - metabolism ; Brain Injuries, Traumatic - pathology ; Brain research ; Cell adhesion & migration ; Cytokines ; Cytokines - metabolism ; Edema ; Glycosylation ; Hemorrhage ; High mobility group proteins ; HMGB1 protein ; HMGB1 Protein - metabolism ; Humans ; Inflammation ; Inflammation - metabolism ; Kinases ; Microglia - metabolism ; Morbidity ; Mortality ; Neuroimmunomodulation ; Neuroprotection ; Neuroprotective Agents - pharmacology ; Pediatrics ; Proteins ; Receptor for Advanced Glycation End Products - metabolism ; Review ; Signal Transduction ; Subarachnoid hemorrhage ; Subarachnoid Hemorrhage - metabolism ; Subarachnoid Hemorrhage - pathology ; TLR4 protein ; Toll-Like Receptor 4 - metabolism ; Toll-like receptors ; Traumatic brain injury</subject><ispartof>International journal of molecular sciences, 2020-06, Vol.21 (13), p.4609</ispartof><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). 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-c478t-266aaed49057e660f49fc26ac650d2df7be25d00a91b768544ac0a90903cc0123</citedby><cites>FETCH-LOGICAL-c478t-266aaed49057e660f49fc26ac650d2df7be25d00a91b768544ac0a90903cc0123</cites><orcidid>0000-0001-9225-3678 ; 0000-0001-9865-6224 ; 0000-0002-2701-0618 ; 0000-0002-8804-6331 ; 0000-0002-1426-3384</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/PMC7370155/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370155/$$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/32610502$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Paudel, Yam Nath</creatorcontrib><creatorcontrib>Angelopoulou, Efthalia</creatorcontrib><creatorcontrib>Piperi, Christina</creatorcontrib><creatorcontrib>Othman, Iekhsan</creatorcontrib><creatorcontrib>Shaikh, Mohd Farooq</creatorcontrib><title>HMGB1-Mediated Neuroinflammatory Responses in Brain Injuries: Potential Mechanisms and Therapeutic Opportunities</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Brain injuries are devastating conditions, representing a global cause of mortality and morbidity, with no effective treatment to date. Increased evidence supports the role of neuroinflammation in driving several forms of brain injuries. High mobility group box 1 (HMGB1) protein is a pro-inflammatory-like cytokine with an initiator role in neuroinflammation that has been implicated in Traumatic brain injury (TBI) as well as in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Herein, we discuss the implication of HMGB1-induced neuroinflammatory responses in these brain injuries, mediated through binding to the receptor for advanced glycation end products (RAGE), toll-like receptor4 (TLR4) and other inflammatory mediators. Moreover, we provide evidence on the biomarker potential of HMGB1 and the significance of its nucleocytoplasmic translocation during brain injuries along with the promising neuroprotective effects observed upon HMGB1 inhibition/neutralization in TBI and EBI induced by SAH. Overall, this review addresses the current advances on neuroinflammation driven by HMGB1 in brain injuries indicating a future treatment opportunity that may overcome current therapeutic gaps.</description><subject>Advanced glycosylation end products</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Brain Injuries - metabolism</subject><subject>Brain Injuries - pathology</subject><subject>Brain Injuries, Traumatic - metabolism</subject><subject>Brain Injuries, Traumatic - pathology</subject><subject>Brain research</subject><subject>Cell adhesion & migration</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Edema</subject><subject>Glycosylation</subject><subject>Hemorrhage</subject><subject>High mobility group proteins</subject><subject>HMGB1 protein</subject><subject>HMGB1 Protein - metabolism</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Inflammation - metabolism</subject><subject>Kinases</subject><subject>Microglia - metabolism</subject><subject>Morbidity</subject><subject>Mortality</subject><subject>Neuroimmunomodulation</subject><subject>Neuroprotection</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Pediatrics</subject><subject>Proteins</subject><subject>Receptor for Advanced Glycation End Products - metabolism</subject><subject>Review</subject><subject>Signal Transduction</subject><subject>Subarachnoid hemorrhage</subject><subject>Subarachnoid Hemorrhage - metabolism</subject><subject>Subarachnoid Hemorrhage - pathology</subject><subject>TLR4 protein</subject><subject>Toll-Like Receptor 4 - metabolism</subject><subject>Toll-like receptors</subject><subject>Traumatic brain injury</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkU1v1DAQhi0Eoh9w44wsceFAYGzHzpoDEq2grdSlCJWz5XUmrFeJHWwHqf--hpZq4TIfmmdezegl5AWDt0JoeOd3U-aMiVaBfkQOWct5A6C6x3v1ATnKeQfABZf6KTkQXDGQwA_JfL4-O2HNGntvC_b0Cy4p-jCMdppsiemGfsM8x5AxUx_oSbI1XoTdkjzm9_RrLBiKtyNdo9va4POUqQ09vd5isjMuxTt6Nc8xlSX4UneekSeDHTM-v8_H5PvnT9en583l1dnF6cfLxrXdqjRcKWuxbzXIDpWCodWD48o6JaHn_dBtkMsewGq26dRKtq11tQENwjlgXByTD3e687KZsHf1zGRHMyc_2XRjovXm30nwW_Mj_jKd6IBJWQVe3wuk-HPBXMzks8NxtAHjkg1vme4Yl4JV9NV_6C4uKdT3_lArrTUTlXpzR7kUc044PBzDwPy20uxbWfGX-w88wH-9E7e3A5u3</recordid><startdate>20200629</startdate><enddate>20200629</enddate><creator>Paudel, Yam Nath</creator><creator>Angelopoulou, Efthalia</creator><creator>Piperi, Christina</creator><creator>Othman, Iekhsan</creator><creator>Shaikh, Mohd Farooq</creator><general>MDPI AG</general><general>MDPI</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>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</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/0000-0001-9225-3678</orcidid><orcidid>https://orcid.org/0000-0001-9865-6224</orcidid><orcidid>https://orcid.org/0000-0002-2701-0618</orcidid><orcidid>https://orcid.org/0000-0002-8804-6331</orcidid><orcidid>https://orcid.org/0000-0002-1426-3384</orcidid></search><sort><creationdate>20200629</creationdate><title>HMGB1-Mediated Neuroinflammatory Responses in Brain Injuries: Potential Mechanisms and Therapeutic Opportunities</title><author>Paudel, Yam Nath ; Angelopoulou, Efthalia ; Piperi, Christina ; Othman, Iekhsan ; Shaikh, Mohd Farooq</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-266aaed49057e660f49fc26ac650d2df7be25d00a91b768544ac0a90903cc0123</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Advanced glycosylation end products</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Brain Injuries - metabolism</topic><topic>Brain Injuries - pathology</topic><topic>Brain Injuries, Traumatic - metabolism</topic><topic>Brain Injuries, Traumatic - pathology</topic><topic>Brain research</topic><topic>Cell adhesion & migration</topic><topic>Cytokines</topic><topic>Cytokines - metabolism</topic><topic>Edema</topic><topic>Glycosylation</topic><topic>Hemorrhage</topic><topic>High mobility group proteins</topic><topic>HMGB1 protein</topic><topic>HMGB1 Protein - metabolism</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Inflammation - metabolism</topic><topic>Kinases</topic><topic>Microglia - metabolism</topic><topic>Morbidity</topic><topic>Mortality</topic><topic>Neuroimmunomodulation</topic><topic>Neuroprotection</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Pediatrics</topic><topic>Proteins</topic><topic>Receptor for Advanced Glycation End Products - metabolism</topic><topic>Review</topic><topic>Signal Transduction</topic><topic>Subarachnoid hemorrhage</topic><topic>Subarachnoid Hemorrhage - metabolism</topic><topic>Subarachnoid Hemorrhage - pathology</topic><topic>TLR4 protein</topic><topic>Toll-Like Receptor 4 - metabolism</topic><topic>Toll-like receptors</topic><topic>Traumatic brain injury</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Paudel, Yam Nath</creatorcontrib><creatorcontrib>Angelopoulou, Efthalia</creatorcontrib><creatorcontrib>Piperi, Christina</creatorcontrib><creatorcontrib>Othman, Iekhsan</creatorcontrib><creatorcontrib>Shaikh, Mohd Farooq</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>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest research library</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>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Paudel, Yam Nath</au><au>Angelopoulou, Efthalia</au><au>Piperi, Christina</au><au>Othman, Iekhsan</au><au>Shaikh, Mohd Farooq</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HMGB1-Mediated Neuroinflammatory Responses in Brain Injuries: Potential Mechanisms and Therapeutic Opportunities</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2020-06-29</date><risdate>2020</risdate><volume>21</volume><issue>13</issue><spage>4609</spage><pages>4609-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Brain injuries are devastating conditions, representing a global cause of mortality and morbidity, with no effective treatment to date. Increased evidence supports the role of neuroinflammation in driving several forms of brain injuries. High mobility group box 1 (HMGB1) protein is a pro-inflammatory-like cytokine with an initiator role in neuroinflammation that has been implicated in Traumatic brain injury (TBI) as well as in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Herein, we discuss the implication of HMGB1-induced neuroinflammatory responses in these brain injuries, mediated through binding to the receptor for advanced glycation end products (RAGE), toll-like receptor4 (TLR4) and other inflammatory mediators. Moreover, we provide evidence on the biomarker potential of HMGB1 and the significance of its nucleocytoplasmic translocation during brain injuries along with the promising neuroprotective effects observed upon HMGB1 inhibition/neutralization in TBI and EBI induced by SAH. Overall, this review addresses the current advances on neuroinflammation driven by HMGB1 in brain injuries indicating a future treatment opportunity that may overcome current therapeutic gaps.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>32610502</pmid><doi>10.3390/ijms21134609</doi><orcidid>https://orcid.org/0000-0001-9225-3678</orcidid><orcidid>https://orcid.org/0000-0001-9865-6224</orcidid><orcidid>https://orcid.org/0000-0002-2701-0618</orcidid><orcidid>https://orcid.org/0000-0002-8804-6331</orcidid><orcidid>https://orcid.org/0000-0002-1426-3384</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1422-0067 |
ispartof | International journal of molecular sciences, 2020-06, Vol.21 (13), p.4609 |
issn | 1422-0067 1661-6596 1422-0067 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7370155 |
source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; PubMed Central; EZB* |
subjects | Advanced glycosylation end products Animals Apoptosis Brain Injuries - metabolism Brain Injuries - pathology Brain Injuries, Traumatic - metabolism Brain Injuries, Traumatic - pathology Brain research Cell adhesion & migration Cytokines Cytokines - metabolism Edema Glycosylation Hemorrhage High mobility group proteins HMGB1 protein HMGB1 Protein - metabolism Humans Inflammation Inflammation - metabolism Kinases Microglia - metabolism Morbidity Mortality Neuroimmunomodulation Neuroprotection Neuroprotective Agents - pharmacology Pediatrics Proteins Receptor for Advanced Glycation End Products - metabolism Review Signal Transduction Subarachnoid hemorrhage Subarachnoid Hemorrhage - metabolism Subarachnoid Hemorrhage - pathology TLR4 protein Toll-Like Receptor 4 - metabolism Toll-like receptors Traumatic brain injury |
title | HMGB1-Mediated Neuroinflammatory Responses in Brain Injuries: Potential Mechanisms and Therapeutic Opportunities |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-11T19%3A34%3A05IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=HMGB1-Mediated%20Neuroinflammatory%20Responses%20in%20Brain%20Injuries:%20Potential%20Mechanisms%20and%20Therapeutic%20Opportunities&rft.jtitle=International%20journal%20of%20molecular%20sciences&rft.au=Paudel,%20Yam%20Nath&rft.date=2020-06-29&rft.volume=21&rft.issue=13&rft.spage=4609&rft.pages=4609-&rft.issn=1422-0067&rft.eissn=1422-0067&rft_id=info:doi/10.3390/ijms21134609&rft_dat=%3Cproquest_pubme%3E2419899913%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2419899913&rft_id=info:pmid/32610502&rfr_iscdi=true |