Loading…

Daily life stress and the cortisol awakening response over a 13-months stress period – Findings from the LawSTRESS project

The LawSTRESS project is a controlled prospective-longitudinal study on psychological, endocrine, central nervous and genetic predictors of responses to long-lasting academic stress in a homogenous cohort. In this first project report, we focused on the association between daily life stress and the...

Full description

Saved in:
Bibliographic Details
Published in:Psychoneuroendocrinology 2022-07, Vol.141, p.105771-105771, Article 105771
Main Authors: Giglberger, Marina, Peter, Hannah L., Kraus, Elisabeth, Kreuzpointner, Ludwig, Zänkert, Sandra, Henze, Gina-Isabelle, Bärtl, Christoph, Konzok, Julian, Kirsch, Peter, Rietschel, Marcella, Kudielka, Brigitte M., Wüst, Stefan
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-c422t-9066b4b0e2da4d7ed72ba01127046cd68e21194caf88a58a588362621c4039c13
cites cdi_FETCH-LOGICAL-c422t-9066b4b0e2da4d7ed72ba01127046cd68e21194caf88a58a588362621c4039c13
container_end_page 105771
container_issue
container_start_page 105771
container_title Psychoneuroendocrinology
container_volume 141
creator Giglberger, Marina
Peter, Hannah L.
Kraus, Elisabeth
Kreuzpointner, Ludwig
Zänkert, Sandra
Henze, Gina-Isabelle
Bärtl, Christoph
Konzok, Julian
Kirsch, Peter
Rietschel, Marcella
Kudielka, Brigitte M.
Wüst, Stefan
description The LawSTRESS project is a controlled prospective-longitudinal study on psychological, endocrine, central nervous and genetic predictors of responses to long-lasting academic stress in a homogenous cohort. In this first project report, we focused on the association between daily life stress and the cortisol awakening response (CAR). The CAR, a distinct cortisol rise in the first 30–45 min after morning awakening, is a well-established marker of cortisol regulation in psychoneuroendocrinology. Law students from Bavarian universities (total n = 452) have been studied over a 13-months period at six sampling points starting 12 months prior exam. The stress group (SG) consisted of students experiencing a long-lasting and significant stress period, namely the preparation for the first state examination for law students. Law students assigned to the control group (CG) were studied over an equally long period without particular and sustained stress exposure. To investigate stress related alterations in the CAR, we examined a subsample of the LawSTRESS project consisting of 204 students with 97 participants from the SG (69.1% female, mean age = 22.84 ± 1.82) and 107 from the CG (78.5% female, mean age = 20.95 ± 1.93). At each sampling point, saliva samples for cortisol assessment were collected immediately upon awakening and 30 as well as 45 min later. Perceived stress in daily life was measured by repeated ambulatory assessments (about 100 queries over six sampling points). The time course of perceived stress levels in the two groups differed significantly, with the SG showing an increase in perceived stress until the exam and a decrease thereafter. Stress levels in the CG were relatively stable. The CAR was not significantly different between groups at baseline. However, a blunted CAR in the SG compared to the baseline measure and to the CG developed over the measurement timepoints and reached significance during the exam. Remarkably, this effect was neither associated with the increase in perceived stress nor with anxiety and depression symptoms, test anxiety and chronic stress at baseline. The present study successfully assessed multidimensional stress trajectories over 13 months and it documented the significant burden, law students preparing for the first state examination are exposed to. This period was related to a blunted CAR with presumed physiological consequences (e.g., on energy metabolism and immune function). Mean psychological stress levels as well
doi_str_mv 10.1016/j.psyneuen.2022.105771
format article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2658228538</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0306453022001123</els_id><sourcerecordid>2658228538</sourcerecordid><originalsourceid>FETCH-LOGICAL-c422t-9066b4b0e2da4d7ed72ba01127046cd68e21194caf88a58a588362621c4039c13</originalsourceid><addsrcrecordid>eNqFkM9uEzEQxi1ERUPhFSofuWzwn12vcwOVFpAiITXt2XLsWeqway-eTatIPfAOvCFPgkMarpVGGmnm--bT_Ag552zOGVfvN_MRdxG2EOeCCVGGTdvyF2TGdSsrKRV7SWZMMlXVjWSn5DXihjGmtBKvyKlsar2QXM7I4ycb-h3tQwcUpwyI1EZPpzugLuUpYOqpfbA_IIb4nZb9mCICTfeQqaVcVkOK0x0evSPkkDz98-s3vQrRFw_SLqfh38GlfVjdXF-uVnTMaQNuekNOOtsjvH3qZ-T26vLm4ku1_Pb568XHZeVqIaZqwZRa12sGwtvat-BbsbaMc9GyWjmvNAjOF7Wznda22ZeWSijBXc3kwnF5Rt4d7pbcn1vAyQwBHfS9jZC2aIRqtBC6kbpI1UHqckLM0Jkxh8HmneHM7MmbjTmSN3vy5kC-GM-fMrbrAfx_2xF1EXw4CKB8eh8gG3QBogMfcmFhfArPZfwFSaaZRA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2658228538</pqid></control><display><type>article</type><title>Daily life stress and the cortisol awakening response over a 13-months stress period – Findings from the LawSTRESS project</title><source>ScienceDirect Freedom Collection</source><creator>Giglberger, Marina ; Peter, Hannah L. ; Kraus, Elisabeth ; Kreuzpointner, Ludwig ; Zänkert, Sandra ; Henze, Gina-Isabelle ; Bärtl, Christoph ; Konzok, Julian ; Kirsch, Peter ; Rietschel, Marcella ; Kudielka, Brigitte M. ; Wüst, Stefan</creator><creatorcontrib>Giglberger, Marina ; Peter, Hannah L. ; Kraus, Elisabeth ; Kreuzpointner, Ludwig ; Zänkert, Sandra ; Henze, Gina-Isabelle ; Bärtl, Christoph ; Konzok, Julian ; Kirsch, Peter ; Rietschel, Marcella ; Kudielka, Brigitte M. ; Wüst, Stefan</creatorcontrib><description>The LawSTRESS project is a controlled prospective-longitudinal study on psychological, endocrine, central nervous and genetic predictors of responses to long-lasting academic stress in a homogenous cohort. In this first project report, we focused on the association between daily life stress and the cortisol awakening response (CAR). The CAR, a distinct cortisol rise in the first 30–45 min after morning awakening, is a well-established marker of cortisol regulation in psychoneuroendocrinology. Law students from Bavarian universities (total n = 452) have been studied over a 13-months period at six sampling points starting 12 months prior exam. The stress group (SG) consisted of students experiencing a long-lasting and significant stress period, namely the preparation for the first state examination for law students. Law students assigned to the control group (CG) were studied over an equally long period without particular and sustained stress exposure. To investigate stress related alterations in the CAR, we examined a subsample of the LawSTRESS project consisting of 204 students with 97 participants from the SG (69.1% female, mean age = 22.84 ± 1.82) and 107 from the CG (78.5% female, mean age = 20.95 ± 1.93). At each sampling point, saliva samples for cortisol assessment were collected immediately upon awakening and 30 as well as 45 min later. Perceived stress in daily life was measured by repeated ambulatory assessments (about 100 queries over six sampling points). The time course of perceived stress levels in the two groups differed significantly, with the SG showing an increase in perceived stress until the exam and a decrease thereafter. Stress levels in the CG were relatively stable. The CAR was not significantly different between groups at baseline. However, a blunted CAR in the SG compared to the baseline measure and to the CG developed over the measurement timepoints and reached significance during the exam. Remarkably, this effect was neither associated with the increase in perceived stress nor with anxiety and depression symptoms, test anxiety and chronic stress at baseline. The present study successfully assessed multidimensional stress trajectories over 13 months and it documented the significant burden, law students preparing for the first state examination are exposed to. This period was related to a blunted CAR with presumed physiological consequences (e.g., on energy metabolism and immune function). Mean psychological stress levels as well as the CAR returned to baseline levels after the exam, suggesting a fast recovery in the majority of the participants. •Prospective-longitudinal (quasi-) experimental project.•Examination of 452 participants over a 13-months period with six timepoints.•Increase in perceived stress levels, anxiety and depression symptoms.•Blunted cortisol awakening response (CAR) in examination stress group.•No association between changes in daily life stress and the CAR.</description><identifier>ISSN: 0306-4530</identifier><identifier>EISSN: 1873-3360</identifier><identifier>DOI: 10.1016/j.psyneuen.2022.105771</identifier><identifier>PMID: 35489313</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adult ; Ambulatory assessment ; Chronic stress ; Circadian Rhythm - physiology ; Cortisol awakening response ; Female ; Humans ; Hydrocortisone - metabolism ; Longitudinal and experimental design ; Longitudinal Studies ; Male ; Prospective Studies ; Saliva - metabolism ; Stress, Psychological - metabolism ; Wakefulness - physiology ; Young Adult</subject><ispartof>Psychoneuroendocrinology, 2022-07, Vol.141, p.105771-105771, Article 105771</ispartof><rights>2022 Elsevier Ltd</rights><rights>Copyright © 2022 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-9066b4b0e2da4d7ed72ba01127046cd68e21194caf88a58a588362621c4039c13</citedby><cites>FETCH-LOGICAL-c422t-9066b4b0e2da4d7ed72ba01127046cd68e21194caf88a58a588362621c4039c13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35489313$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Giglberger, Marina</creatorcontrib><creatorcontrib>Peter, Hannah L.</creatorcontrib><creatorcontrib>Kraus, Elisabeth</creatorcontrib><creatorcontrib>Kreuzpointner, Ludwig</creatorcontrib><creatorcontrib>Zänkert, Sandra</creatorcontrib><creatorcontrib>Henze, Gina-Isabelle</creatorcontrib><creatorcontrib>Bärtl, Christoph</creatorcontrib><creatorcontrib>Konzok, Julian</creatorcontrib><creatorcontrib>Kirsch, Peter</creatorcontrib><creatorcontrib>Rietschel, Marcella</creatorcontrib><creatorcontrib>Kudielka, Brigitte M.</creatorcontrib><creatorcontrib>Wüst, Stefan</creatorcontrib><title>Daily life stress and the cortisol awakening response over a 13-months stress period – Findings from the LawSTRESS project</title><title>Psychoneuroendocrinology</title><addtitle>Psychoneuroendocrinology</addtitle><description>The LawSTRESS project is a controlled prospective-longitudinal study on psychological, endocrine, central nervous and genetic predictors of responses to long-lasting academic stress in a homogenous cohort. In this first project report, we focused on the association between daily life stress and the cortisol awakening response (CAR). The CAR, a distinct cortisol rise in the first 30–45 min after morning awakening, is a well-established marker of cortisol regulation in psychoneuroendocrinology. Law students from Bavarian universities (total n = 452) have been studied over a 13-months period at six sampling points starting 12 months prior exam. The stress group (SG) consisted of students experiencing a long-lasting and significant stress period, namely the preparation for the first state examination for law students. Law students assigned to the control group (CG) were studied over an equally long period without particular and sustained stress exposure. To investigate stress related alterations in the CAR, we examined a subsample of the LawSTRESS project consisting of 204 students with 97 participants from the SG (69.1% female, mean age = 22.84 ± 1.82) and 107 from the CG (78.5% female, mean age = 20.95 ± 1.93). At each sampling point, saliva samples for cortisol assessment were collected immediately upon awakening and 30 as well as 45 min later. Perceived stress in daily life was measured by repeated ambulatory assessments (about 100 queries over six sampling points). The time course of perceived stress levels in the two groups differed significantly, with the SG showing an increase in perceived stress until the exam and a decrease thereafter. Stress levels in the CG were relatively stable. The CAR was not significantly different between groups at baseline. However, a blunted CAR in the SG compared to the baseline measure and to the CG developed over the measurement timepoints and reached significance during the exam. Remarkably, this effect was neither associated with the increase in perceived stress nor with anxiety and depression symptoms, test anxiety and chronic stress at baseline. The present study successfully assessed multidimensional stress trajectories over 13 months and it documented the significant burden, law students preparing for the first state examination are exposed to. This period was related to a blunted CAR with presumed physiological consequences (e.g., on energy metabolism and immune function). Mean psychological stress levels as well as the CAR returned to baseline levels after the exam, suggesting a fast recovery in the majority of the participants. •Prospective-longitudinal (quasi-) experimental project.•Examination of 452 participants over a 13-months period with six timepoints.•Increase in perceived stress levels, anxiety and depression symptoms.•Blunted cortisol awakening response (CAR) in examination stress group.•No association between changes in daily life stress and the CAR.</description><subject>Adult</subject><subject>Ambulatory assessment</subject><subject>Chronic stress</subject><subject>Circadian Rhythm - physiology</subject><subject>Cortisol awakening response</subject><subject>Female</subject><subject>Humans</subject><subject>Hydrocortisone - metabolism</subject><subject>Longitudinal and experimental design</subject><subject>Longitudinal Studies</subject><subject>Male</subject><subject>Prospective Studies</subject><subject>Saliva - metabolism</subject><subject>Stress, Psychological - metabolism</subject><subject>Wakefulness - physiology</subject><subject>Young Adult</subject><issn>0306-4530</issn><issn>1873-3360</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNqFkM9uEzEQxi1ERUPhFSofuWzwn12vcwOVFpAiITXt2XLsWeqway-eTatIPfAOvCFPgkMarpVGGmnm--bT_Ag552zOGVfvN_MRdxG2EOeCCVGGTdvyF2TGdSsrKRV7SWZMMlXVjWSn5DXihjGmtBKvyKlsar2QXM7I4ycb-h3tQwcUpwyI1EZPpzugLuUpYOqpfbA_IIb4nZb9mCICTfeQqaVcVkOK0x0evSPkkDz98-s3vQrRFw_SLqfh38GlfVjdXF-uVnTMaQNuekNOOtsjvH3qZ-T26vLm4ku1_Pb568XHZeVqIaZqwZRa12sGwtvat-BbsbaMc9GyWjmvNAjOF7Wznda22ZeWSijBXc3kwnF5Rt4d7pbcn1vAyQwBHfS9jZC2aIRqtBC6kbpI1UHqckLM0Jkxh8HmneHM7MmbjTmSN3vy5kC-GM-fMrbrAfx_2xF1EXw4CKB8eh8gG3QBogMfcmFhfArPZfwFSaaZRA</recordid><startdate>20220701</startdate><enddate>20220701</enddate><creator>Giglberger, Marina</creator><creator>Peter, Hannah L.</creator><creator>Kraus, Elisabeth</creator><creator>Kreuzpointner, Ludwig</creator><creator>Zänkert, Sandra</creator><creator>Henze, Gina-Isabelle</creator><creator>Bärtl, Christoph</creator><creator>Konzok, Julian</creator><creator>Kirsch, Peter</creator><creator>Rietschel, Marcella</creator><creator>Kudielka, Brigitte M.</creator><creator>Wüst, Stefan</creator><general>Elsevier Ltd</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>7X8</scope></search><sort><creationdate>20220701</creationdate><title>Daily life stress and the cortisol awakening response over a 13-months stress period – Findings from the LawSTRESS project</title><author>Giglberger, Marina ; Peter, Hannah L. ; Kraus, Elisabeth ; Kreuzpointner, Ludwig ; Zänkert, Sandra ; Henze, Gina-Isabelle ; Bärtl, Christoph ; Konzok, Julian ; Kirsch, Peter ; Rietschel, Marcella ; Kudielka, Brigitte M. ; Wüst, Stefan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-9066b4b0e2da4d7ed72ba01127046cd68e21194caf88a58a588362621c4039c13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adult</topic><topic>Ambulatory assessment</topic><topic>Chronic stress</topic><topic>Circadian Rhythm - physiology</topic><topic>Cortisol awakening response</topic><topic>Female</topic><topic>Humans</topic><topic>Hydrocortisone - metabolism</topic><topic>Longitudinal and experimental design</topic><topic>Longitudinal Studies</topic><topic>Male</topic><topic>Prospective Studies</topic><topic>Saliva - metabolism</topic><topic>Stress, Psychological - metabolism</topic><topic>Wakefulness - physiology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Giglberger, Marina</creatorcontrib><creatorcontrib>Peter, Hannah L.</creatorcontrib><creatorcontrib>Kraus, Elisabeth</creatorcontrib><creatorcontrib>Kreuzpointner, Ludwig</creatorcontrib><creatorcontrib>Zänkert, Sandra</creatorcontrib><creatorcontrib>Henze, Gina-Isabelle</creatorcontrib><creatorcontrib>Bärtl, Christoph</creatorcontrib><creatorcontrib>Konzok, Julian</creatorcontrib><creatorcontrib>Kirsch, Peter</creatorcontrib><creatorcontrib>Rietschel, Marcella</creatorcontrib><creatorcontrib>Kudielka, Brigitte M.</creatorcontrib><creatorcontrib>Wüst, Stefan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Psychoneuroendocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Giglberger, Marina</au><au>Peter, Hannah L.</au><au>Kraus, Elisabeth</au><au>Kreuzpointner, Ludwig</au><au>Zänkert, Sandra</au><au>Henze, Gina-Isabelle</au><au>Bärtl, Christoph</au><au>Konzok, Julian</au><au>Kirsch, Peter</au><au>Rietschel, Marcella</au><au>Kudielka, Brigitte M.</au><au>Wüst, Stefan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Daily life stress and the cortisol awakening response over a 13-months stress period – Findings from the LawSTRESS project</atitle><jtitle>Psychoneuroendocrinology</jtitle><addtitle>Psychoneuroendocrinology</addtitle><date>2022-07-01</date><risdate>2022</risdate><volume>141</volume><spage>105771</spage><epage>105771</epage><pages>105771-105771</pages><artnum>105771</artnum><issn>0306-4530</issn><eissn>1873-3360</eissn><abstract>The LawSTRESS project is a controlled prospective-longitudinal study on psychological, endocrine, central nervous and genetic predictors of responses to long-lasting academic stress in a homogenous cohort. In this first project report, we focused on the association between daily life stress and the cortisol awakening response (CAR). The CAR, a distinct cortisol rise in the first 30–45 min after morning awakening, is a well-established marker of cortisol regulation in psychoneuroendocrinology. Law students from Bavarian universities (total n = 452) have been studied over a 13-months period at six sampling points starting 12 months prior exam. The stress group (SG) consisted of students experiencing a long-lasting and significant stress period, namely the preparation for the first state examination for law students. Law students assigned to the control group (CG) were studied over an equally long period without particular and sustained stress exposure. To investigate stress related alterations in the CAR, we examined a subsample of the LawSTRESS project consisting of 204 students with 97 participants from the SG (69.1% female, mean age = 22.84 ± 1.82) and 107 from the CG (78.5% female, mean age = 20.95 ± 1.93). At each sampling point, saliva samples for cortisol assessment were collected immediately upon awakening and 30 as well as 45 min later. Perceived stress in daily life was measured by repeated ambulatory assessments (about 100 queries over six sampling points). The time course of perceived stress levels in the two groups differed significantly, with the SG showing an increase in perceived stress until the exam and a decrease thereafter. Stress levels in the CG were relatively stable. The CAR was not significantly different between groups at baseline. However, a blunted CAR in the SG compared to the baseline measure and to the CG developed over the measurement timepoints and reached significance during the exam. Remarkably, this effect was neither associated with the increase in perceived stress nor with anxiety and depression symptoms, test anxiety and chronic stress at baseline. The present study successfully assessed multidimensional stress trajectories over 13 months and it documented the significant burden, law students preparing for the first state examination are exposed to. This period was related to a blunted CAR with presumed physiological consequences (e.g., on energy metabolism and immune function). Mean psychological stress levels as well as the CAR returned to baseline levels after the exam, suggesting a fast recovery in the majority of the participants. •Prospective-longitudinal (quasi-) experimental project.•Examination of 452 participants over a 13-months period with six timepoints.•Increase in perceived stress levels, anxiety and depression symptoms.•Blunted cortisol awakening response (CAR) in examination stress group.•No association between changes in daily life stress and the CAR.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>35489313</pmid><doi>10.1016/j.psyneuen.2022.105771</doi><tpages>1</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0306-4530
ispartof Psychoneuroendocrinology, 2022-07, Vol.141, p.105771-105771, Article 105771
issn 0306-4530
1873-3360
language eng
recordid cdi_proquest_miscellaneous_2658228538
source ScienceDirect Freedom Collection
subjects Adult
Ambulatory assessment
Chronic stress
Circadian Rhythm - physiology
Cortisol awakening response
Female
Humans
Hydrocortisone - metabolism
Longitudinal and experimental design
Longitudinal Studies
Male
Prospective Studies
Saliva - metabolism
Stress, Psychological - metabolism
Wakefulness - physiology
Young Adult
title Daily life stress and the cortisol awakening response over a 13-months stress period – Findings from the LawSTRESS project
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-30T07%3A09%3A43IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Daily%20life%20stress%20and%20the%20cortisol%20awakening%20response%20over%20a%2013-months%20stress%20period%20%E2%80%93%20Findings%20from%20the%20LawSTRESS%20project&rft.jtitle=Psychoneuroendocrinology&rft.au=Giglberger,%20Marina&rft.date=2022-07-01&rft.volume=141&rft.spage=105771&rft.epage=105771&rft.pages=105771-105771&rft.artnum=105771&rft.issn=0306-4530&rft.eissn=1873-3360&rft_id=info:doi/10.1016/j.psyneuen.2022.105771&rft_dat=%3Cproquest_cross%3E2658228538%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c422t-9066b4b0e2da4d7ed72ba01127046cd68e21194caf88a58a588362621c4039c13%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2658228538&rft_id=info:pmid/35489313&rfr_iscdi=true