Loading…

Improvement Effects of Myelophil on Symptoms of Chronic Fatigue Syndrome in a Reserpine-Induced Mouse Model

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is associated with various symptoms, such as depression, pain, and fatigue. To date, the pathological mechanisms and therapeutics remain uncertain. The purpose of this study was to investigate the effect of myelophil (MYP), composed of Astr...

Full description

Saved in:
Bibliographic Details
Published in:International journal of molecular sciences 2021-10, Vol.22 (19), p.10199
Main Authors: Song, Ji-Hye, Won, Seul-Ki, Eom, Geun-Hyang, Lee, Da-Som, Park, Byung-Jin, Lee, Jin-Seok, Son, Chang-Gue, Park, Ji-Yeun
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c392t-9582b5c10994f76d4af17634b6857e60de5f489116b833aca1f9684ae1f550063
cites cdi_FETCH-LOGICAL-c392t-9582b5c10994f76d4af17634b6857e60de5f489116b833aca1f9684ae1f550063
container_end_page
container_issue 19
container_start_page 10199
container_title International journal of molecular sciences
container_volume 22
creator Song, Ji-Hye
Won, Seul-Ki
Eom, Geun-Hyang
Lee, Da-Som
Park, Byung-Jin
Lee, Jin-Seok
Son, Chang-Gue
Park, Ji-Yeun
description Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is associated with various symptoms, such as depression, pain, and fatigue. To date, the pathological mechanisms and therapeutics remain uncertain. The purpose of this study was to investigate the effect of myelophil (MYP), composed of Astragali Radix and Salviaemiltiorrhizae Radix, on depression, pain, and fatigue behaviors and its underlying mechanisms. Reserpine (2 mg/kg for 10 days, intraperitoneally) induced depression, pain, and fatigue behaviors in mice. MYP treatment (100 mg/kg for 10 days, intragastrically) significantly improved depression behaviors, mechanical and thermal hypersensitivity, and fatigue behavior. MYP treatment regulated the expression of c-Fos, 5-HT1A/B receptors, and transforming growth factor β (TGF-β) in the brain, especially in the motor cortex, hippocampus, and nucleus of the solitary tract. MYP treatment decreased ionized calcium binding adapter molecule 1 (Iba1) expression in the hippocampus and increased tyrosine hydroxylase (TH) expression and the levels of dopamine and serotonin in the striatum. MYP treatment altered inflammatory and anti-oxidative-related mRNA expression in the spleen and liver. In conclusion, MYP was effective in recovering major symptoms of ME/CFS and was associated with the regulation of dopaminergic and serotonergic pathways and TGF-β expression in the brain, as well as anti-inflammatory and anti-oxidant mechanisms in internal organs.
doi_str_mv 10.3390/ijms221910199
format article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8508381</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2581014897</sourcerecordid><originalsourceid>FETCH-LOGICAL-c392t-9582b5c10994f76d4af17634b6857e60de5f489116b833aca1f9684ae1f550063</originalsourceid><addsrcrecordid>eNpdkc1LHTEUxYNYqtUu3QfcuJk2H5OZZCOUh7YPFKGt65CXufHldZJMkxnh_fdNVUp1c--F8-NwDwehM0o-ca7IZ78LhTGqKKFKHaBj2jLWENL1h__dR-hDKTtCGGdCvUdHvO24FC05Rr_WYcrpEQLEGV85B3YuODl8u4cxTVs_4hTxj32Y5hSehNU2p-gtvjazf1iganHIKQD2ERv8HQrkyUdo1nFYLAz4Ni0F6hxgPEXvnBkLfHzZJ-j--urn6ltzc_d1vfpy01iu2NwoIdlGWEqUal3fDa1xtO94u-mk6KEjAwjXSkVpt5GcG2uoU51sDVAnRE3LT9Dls--0bAIMtkbLZtRT9sHkvU7G69dK9Fv9kB61FERySavBxYtBTr8XKLMOvlgYRxOhxtFMSCoJI5JU9PwNuktLjjXeE0Vo_bSvVPNM2ZxKyeD-PUOJ_lujflUj_wPX049C</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2581014897</pqid></control><display><type>article</type><title>Improvement Effects of Myelophil on Symptoms of Chronic Fatigue Syndrome in a Reserpine-Induced Mouse Model</title><source>Publicly Available Content (ProQuest)</source><source>PubMed Central</source><creator>Song, Ji-Hye ; Won, Seul-Ki ; Eom, Geun-Hyang ; Lee, Da-Som ; Park, Byung-Jin ; Lee, Jin-Seok ; Son, Chang-Gue ; Park, Ji-Yeun</creator><creatorcontrib>Song, Ji-Hye ; Won, Seul-Ki ; Eom, Geun-Hyang ; Lee, Da-Som ; Park, Byung-Jin ; Lee, Jin-Seok ; Son, Chang-Gue ; Park, Ji-Yeun</creatorcontrib><description>Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is associated with various symptoms, such as depression, pain, and fatigue. To date, the pathological mechanisms and therapeutics remain uncertain. The purpose of this study was to investigate the effect of myelophil (MYP), composed of Astragali Radix and Salviaemiltiorrhizae Radix, on depression, pain, and fatigue behaviors and its underlying mechanisms. Reserpine (2 mg/kg for 10 days, intraperitoneally) induced depression, pain, and fatigue behaviors in mice. MYP treatment (100 mg/kg for 10 days, intragastrically) significantly improved depression behaviors, mechanical and thermal hypersensitivity, and fatigue behavior. MYP treatment regulated the expression of c-Fos, 5-HT1A/B receptors, and transforming growth factor β (TGF-β) in the brain, especially in the motor cortex, hippocampus, and nucleus of the solitary tract. MYP treatment decreased ionized calcium binding adapter molecule 1 (Iba1) expression in the hippocampus and increased tyrosine hydroxylase (TH) expression and the levels of dopamine and serotonin in the striatum. MYP treatment altered inflammatory and anti-oxidative-related mRNA expression in the spleen and liver. In conclusion, MYP was effective in recovering major symptoms of ME/CFS and was associated with the regulation of dopaminergic and serotonergic pathways and TGF-β expression in the brain, as well as anti-inflammatory and anti-oxidant mechanisms in internal organs.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms221910199</identifier><identifier>PMID: 34638540</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Analgesics ; Antioxidants ; Behavior ; Brain ; c-Fos protein ; Chronic fatigue syndrome ; Cytokines ; Dopamine ; Dopamine receptors ; Fatigue ; Fibromyalgia ; Gene expression ; Growth factors ; Hippocampus ; Hydroxylase ; Hypersensitivity ; Inflammation ; Mechanical properties ; Mental depression ; Neostriatum ; Organs ; Oxidants ; Oxidative stress ; Oxidizing agents ; Pain ; Reserpine ; Serotonin ; Serotonin S1 receptors ; Solitary tract nucleus ; Spleen ; Transforming growth factor-b ; Tyrosine ; Tyrosine 3-monooxygenase</subject><ispartof>International journal of molecular sciences, 2021-10, Vol.22 (19), p.10199</ispartof><rights>2021 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>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c392t-9582b5c10994f76d4af17634b6857e60de5f489116b833aca1f9684ae1f550063</citedby><cites>FETCH-LOGICAL-c392t-9582b5c10994f76d4af17634b6857e60de5f489116b833aca1f9684ae1f550063</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2581014897/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2581014897?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,25730,27900,27901,36988,36989,44565,53765,53767,75095</link.rule.ids></links><search><creatorcontrib>Song, Ji-Hye</creatorcontrib><creatorcontrib>Won, Seul-Ki</creatorcontrib><creatorcontrib>Eom, Geun-Hyang</creatorcontrib><creatorcontrib>Lee, Da-Som</creatorcontrib><creatorcontrib>Park, Byung-Jin</creatorcontrib><creatorcontrib>Lee, Jin-Seok</creatorcontrib><creatorcontrib>Son, Chang-Gue</creatorcontrib><creatorcontrib>Park, Ji-Yeun</creatorcontrib><title>Improvement Effects of Myelophil on Symptoms of Chronic Fatigue Syndrome in a Reserpine-Induced Mouse Model</title><title>International journal of molecular sciences</title><description>Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is associated with various symptoms, such as depression, pain, and fatigue. To date, the pathological mechanisms and therapeutics remain uncertain. The purpose of this study was to investigate the effect of myelophil (MYP), composed of Astragali Radix and Salviaemiltiorrhizae Radix, on depression, pain, and fatigue behaviors and its underlying mechanisms. Reserpine (2 mg/kg for 10 days, intraperitoneally) induced depression, pain, and fatigue behaviors in mice. MYP treatment (100 mg/kg for 10 days, intragastrically) significantly improved depression behaviors, mechanical and thermal hypersensitivity, and fatigue behavior. MYP treatment regulated the expression of c-Fos, 5-HT1A/B receptors, and transforming growth factor β (TGF-β) in the brain, especially in the motor cortex, hippocampus, and nucleus of the solitary tract. MYP treatment decreased ionized calcium binding adapter molecule 1 (Iba1) expression in the hippocampus and increased tyrosine hydroxylase (TH) expression and the levels of dopamine and serotonin in the striatum. MYP treatment altered inflammatory and anti-oxidative-related mRNA expression in the spleen and liver. In conclusion, MYP was effective in recovering major symptoms of ME/CFS and was associated with the regulation of dopaminergic and serotonergic pathways and TGF-β expression in the brain, as well as anti-inflammatory and anti-oxidant mechanisms in internal organs.</description><subject>Analgesics</subject><subject>Antioxidants</subject><subject>Behavior</subject><subject>Brain</subject><subject>c-Fos protein</subject><subject>Chronic fatigue syndrome</subject><subject>Cytokines</subject><subject>Dopamine</subject><subject>Dopamine receptors</subject><subject>Fatigue</subject><subject>Fibromyalgia</subject><subject>Gene expression</subject><subject>Growth factors</subject><subject>Hippocampus</subject><subject>Hydroxylase</subject><subject>Hypersensitivity</subject><subject>Inflammation</subject><subject>Mechanical properties</subject><subject>Mental depression</subject><subject>Neostriatum</subject><subject>Organs</subject><subject>Oxidants</subject><subject>Oxidative stress</subject><subject>Oxidizing agents</subject><subject>Pain</subject><subject>Reserpine</subject><subject>Serotonin</subject><subject>Serotonin S1 receptors</subject><subject>Solitary tract nucleus</subject><subject>Spleen</subject><subject>Transforming growth factor-b</subject><subject>Tyrosine</subject><subject>Tyrosine 3-monooxygenase</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNpdkc1LHTEUxYNYqtUu3QfcuJk2H5OZZCOUh7YPFKGt65CXufHldZJMkxnh_fdNVUp1c--F8-NwDwehM0o-ca7IZ78LhTGqKKFKHaBj2jLWENL1h__dR-hDKTtCGGdCvUdHvO24FC05Rr_WYcrpEQLEGV85B3YuODl8u4cxTVs_4hTxj32Y5hSehNU2p-gtvjazf1iganHIKQD2ERv8HQrkyUdo1nFYLAz4Ni0F6hxgPEXvnBkLfHzZJ-j--urn6ltzc_d1vfpy01iu2NwoIdlGWEqUal3fDa1xtO94u-mk6KEjAwjXSkVpt5GcG2uoU51sDVAnRE3LT9Dls--0bAIMtkbLZtRT9sHkvU7G69dK9Fv9kB61FERySavBxYtBTr8XKLMOvlgYRxOhxtFMSCoJI5JU9PwNuktLjjXeE0Vo_bSvVPNM2ZxKyeD-PUOJ_lujflUj_wPX049C</recordid><startdate>20211001</startdate><enddate>20211001</enddate><creator>Song, Ji-Hye</creator><creator>Won, Seul-Ki</creator><creator>Eom, Geun-Hyang</creator><creator>Lee, Da-Som</creator><creator>Park, Byung-Jin</creator><creator>Lee, Jin-Seok</creator><creator>Son, Chang-Gue</creator><creator>Park, Ji-Yeun</creator><general>MDPI AG</general><general>MDPI</general><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>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20211001</creationdate><title>Improvement Effects of Myelophil on Symptoms of Chronic Fatigue Syndrome in a Reserpine-Induced Mouse Model</title><author>Song, Ji-Hye ; Won, Seul-Ki ; Eom, Geun-Hyang ; Lee, Da-Som ; Park, Byung-Jin ; Lee, Jin-Seok ; Son, Chang-Gue ; Park, Ji-Yeun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c392t-9582b5c10994f76d4af17634b6857e60de5f489116b833aca1f9684ae1f550063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Analgesics</topic><topic>Antioxidants</topic><topic>Behavior</topic><topic>Brain</topic><topic>c-Fos protein</topic><topic>Chronic fatigue syndrome</topic><topic>Cytokines</topic><topic>Dopamine</topic><topic>Dopamine receptors</topic><topic>Fatigue</topic><topic>Fibromyalgia</topic><topic>Gene expression</topic><topic>Growth factors</topic><topic>Hippocampus</topic><topic>Hydroxylase</topic><topic>Hypersensitivity</topic><topic>Inflammation</topic><topic>Mechanical properties</topic><topic>Mental depression</topic><topic>Neostriatum</topic><topic>Organs</topic><topic>Oxidants</topic><topic>Oxidative stress</topic><topic>Oxidizing agents</topic><topic>Pain</topic><topic>Reserpine</topic><topic>Serotonin</topic><topic>Serotonin S1 receptors</topic><topic>Solitary tract nucleus</topic><topic>Spleen</topic><topic>Transforming growth factor-b</topic><topic>Tyrosine</topic><topic>Tyrosine 3-monooxygenase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Song, Ji-Hye</creatorcontrib><creatorcontrib>Won, Seul-Ki</creatorcontrib><creatorcontrib>Eom, Geun-Hyang</creatorcontrib><creatorcontrib>Lee, Da-Som</creatorcontrib><creatorcontrib>Park, Byung-Jin</creatorcontrib><creatorcontrib>Lee, Jin-Seok</creatorcontrib><creatorcontrib>Son, Chang-Gue</creatorcontrib><creatorcontrib>Park, Ji-Yeun</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Health &amp; 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 &amp; Medical Complete (Alumni)</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest Research Library</collection><collection>Research Library (Corporate)</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>Publicly Available Content (ProQuest)</collection><collection>ProQuest Health &amp; Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health &amp; Nursing</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>Song, Ji-Hye</au><au>Won, Seul-Ki</au><au>Eom, Geun-Hyang</au><au>Lee, Da-Som</au><au>Park, Byung-Jin</au><au>Lee, Jin-Seok</au><au>Son, Chang-Gue</au><au>Park, Ji-Yeun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Improvement Effects of Myelophil on Symptoms of Chronic Fatigue Syndrome in a Reserpine-Induced Mouse Model</atitle><jtitle>International journal of molecular sciences</jtitle><date>2021-10-01</date><risdate>2021</risdate><volume>22</volume><issue>19</issue><spage>10199</spage><pages>10199-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is associated with various symptoms, such as depression, pain, and fatigue. To date, the pathological mechanisms and therapeutics remain uncertain. The purpose of this study was to investigate the effect of myelophil (MYP), composed of Astragali Radix and Salviaemiltiorrhizae Radix, on depression, pain, and fatigue behaviors and its underlying mechanisms. Reserpine (2 mg/kg for 10 days, intraperitoneally) induced depression, pain, and fatigue behaviors in mice. MYP treatment (100 mg/kg for 10 days, intragastrically) significantly improved depression behaviors, mechanical and thermal hypersensitivity, and fatigue behavior. MYP treatment regulated the expression of c-Fos, 5-HT1A/B receptors, and transforming growth factor β (TGF-β) in the brain, especially in the motor cortex, hippocampus, and nucleus of the solitary tract. MYP treatment decreased ionized calcium binding adapter molecule 1 (Iba1) expression in the hippocampus and increased tyrosine hydroxylase (TH) expression and the levels of dopamine and serotonin in the striatum. MYP treatment altered inflammatory and anti-oxidative-related mRNA expression in the spleen and liver. In conclusion, MYP was effective in recovering major symptoms of ME/CFS and was associated with the regulation of dopaminergic and serotonergic pathways and TGF-β expression in the brain, as well as anti-inflammatory and anti-oxidant mechanisms in internal organs.</abstract><cop>Basel</cop><pub>MDPI AG</pub><pmid>34638540</pmid><doi>10.3390/ijms221910199</doi><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1422-0067
ispartof International journal of molecular sciences, 2021-10, Vol.22 (19), p.10199
issn 1422-0067
1661-6596
1422-0067
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8508381
source Publicly Available Content (ProQuest); PubMed Central
subjects Analgesics
Antioxidants
Behavior
Brain
c-Fos protein
Chronic fatigue syndrome
Cytokines
Dopamine
Dopamine receptors
Fatigue
Fibromyalgia
Gene expression
Growth factors
Hippocampus
Hydroxylase
Hypersensitivity
Inflammation
Mechanical properties
Mental depression
Neostriatum
Organs
Oxidants
Oxidative stress
Oxidizing agents
Pain
Reserpine
Serotonin
Serotonin S1 receptors
Solitary tract nucleus
Spleen
Transforming growth factor-b
Tyrosine
Tyrosine 3-monooxygenase
title Improvement Effects of Myelophil on Symptoms of Chronic Fatigue Syndrome in a Reserpine-Induced Mouse Model
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-24T16%3A34%3A39IST&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=Improvement%20Effects%20of%20Myelophil%20on%20Symptoms%20of%20Chronic%20Fatigue%20Syndrome%20in%20a%20Reserpine-Induced%20Mouse%20Model&rft.jtitle=International%20journal%20of%20molecular%20sciences&rft.au=Song,%20Ji-Hye&rft.date=2021-10-01&rft.volume=22&rft.issue=19&rft.spage=10199&rft.pages=10199-&rft.issn=1422-0067&rft.eissn=1422-0067&rft_id=info:doi/10.3390/ijms221910199&rft_dat=%3Cproquest_pubme%3E2581014897%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c392t-9582b5c10994f76d4af17634b6857e60de5f489116b833aca1f9684ae1f550063%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2581014897&rft_id=info:pmid/34638540&rfr_iscdi=true