Combined hydrothermal pre-treatment and enzymatic hydrolysis of corn fibre: Production of ferulic acid extracts and assessment of their antioxidant and antiproliferative properties

[Display omitted] •Ultraflo®XL enzyme preparation led to the highest ferulic acid recovery yield.•The best pre-treatment increased the ferulic acid recovery yield by 3.7 times.•The best pre-treatment had the lowest concentration of sugars degradation products.•All pre-treatments led to an improved q...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Industrial crops and products 2021-10, Vol.170, p.113731, Article 113731
Hauptverfasser: Valério, Rita, Serra, Ana Teresa, Baixinho, João, Cardeira, Martim, Fernández, Naiara, Bronze, Maria Rosário, Duarte, Luís C., Tavares, Maria L., Crespo, João G., Brazinha, Carla
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page
container_issue
container_start_page 113731
container_title Industrial crops and products
container_volume 170
creator Valério, Rita
Serra, Ana Teresa
Baixinho, João
Cardeira, Martim
Fernández, Naiara
Bronze, Maria Rosário
Duarte, Luís C.
Tavares, Maria L.
Crespo, João G.
Brazinha, Carla
description [Display omitted] •Ultraflo®XL enzyme preparation led to the highest ferulic acid recovery yield.•The best pre-treatment increased the ferulic acid recovery yield by 3.7 times.•The best pre-treatment had the lowest concentration of sugars degradation products.•All pre-treatments led to an improved quality of the bioactivity of the extracts. Ferulic acid may be used as a nutraceutical ingredient or as a substrate to produce bio-vanillin. There is an increasing market demand for ferulic acid obtained from natural sources such as low-cost agro-industrial by-products, due to its potential applications as nutraceutical ingredient and as a substrate to produce bio-vanillin. This work aims to study ferulic acid recovery from corn fibre (one of the most abundant natural sources of ferulic acid), involving an integrated process of hydrothermal pre-treatment followed by enzymatic hydrolysis. The objective is primarily to produce natural extracts with a maximum ferulic acid recovery yield, but it is also to assess their antioxidant and antiproliferative properties and their cytotoxicity. Different commercial enzyme preparations were tested for release of ferulic acid from corn fibre. The best results were obtained for Ultraflo ®XL in a concentration of 2 % (wenzyme preparation/w dry corn fibre) at a pH of 5 and at 55 °C, presenting a recovery yield of esterified ferulic acid of 7.83 ± 1.35 % (wrecovered ferulic acid/wtotal esterified ferulic acid), which corresponds to 0.13 ± 0.02 % (wferulic acid/w dry corn fibre). When using a hydrothermal pre-treatment at a temperature of 140 °C for 40 min, prior to the use of the same enzymatic hydrolysis procedure, the recovery yield of esterified ferulic acid increased to 28.94 ± 2.40 % (w recovered ferulic acid/ wtotal esterified ferulic acid), which corresponds to 4.9 ± 0.3 % (wferulic acid/wdry corn fibre). The use of this pre-treatment leads not only to the highest yield of ferulic acid, but also to the lowest concentration of furfural and hydroxymethylfurfural, without the formation of formic and levulinic acid (not detected). All pre-treatments tested led to an improved quality of the extract in terms of bioactivity.
doi_str_mv 10.1016/j.indcrop.2021.113731
format Article
fullrecord <record><control><sourceid>elsevier_rcaap</sourceid><recordid>TN_cdi_rcaap_revistas_10400_9_3616</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0926669021004957</els_id><sourcerecordid>S0926669021004957</sourcerecordid><originalsourceid>FETCH-LOGICAL-c383t-2f6cf4f50bd29bd5415cc9f04807e107d1790e55915eb0c69cf1bc448d7e834e3</originalsourceid><addsrcrecordid>eNqNkM1u1DAUhS0EEkPhEZAitijT6_w4CRuEogKVKpVFK7GzHPta9WgSR9eeodPn4gFxmhFbWPnvfOdcH8bec9hy4OJyt3WT0eTnbQEF33JeNiV_wTa8bYpclOXPl2wDXSFyITp4zd6EsAPgDRTNhv3u_Ti4CU32cDLk4wPSqPbZTJhHQhVHnGKmJpPh9HQaVXR6Fe5PwYXM20x7mjLrBsJP2Q_y5qCj89PyYpEO-6RX2iX8MZLSMTx7qRAwhGfrpEuZjtJ94h6dUee85TynHJdsUuwR00x-RooOw1v2yqp9wHfn9YLdf72667_nN7ffrvsvN7ku2zLmhRXaVraGwRTdYOqK11p3FqoWGuTQGN50gHXd8RoH0KLTlg-6qlrTYFtWWF6wevVN5YZAaOVMblR0khzkUr3cyXP1cqlertUn7uPK_cLB26AdThr_sgAg2q4SRdoAh6Ru_1_du6iWgnt_mGJCP6woaaVmSXh0IaqQZqsAZCdLwUUSfV5FmKo6OiR5zjCOUEdpvPvHf_4A3cfB7w</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Combined hydrothermal pre-treatment and enzymatic hydrolysis of corn fibre: Production of ferulic acid extracts and assessment of their antioxidant and antiproliferative properties</title><source>Web of Science - Science Citation Index Expanded - 2021&lt;img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /&gt;</source><source>Access via ScienceDirect (Elsevier)</source><creator>Valério, Rita ; Serra, Ana Teresa ; Baixinho, João ; Cardeira, Martim ; Fernández, Naiara ; Bronze, Maria Rosário ; Duarte, Luís C. ; Tavares, Maria L. ; Crespo, João G. ; Brazinha, Carla</creator><creatorcontrib>Valério, Rita ; Serra, Ana Teresa ; Baixinho, João ; Cardeira, Martim ; Fernández, Naiara ; Bronze, Maria Rosário ; Duarte, Luís C. ; Tavares, Maria L. ; Crespo, João G. ; Brazinha, Carla</creatorcontrib><description>[Display omitted] •Ultraflo®XL enzyme preparation led to the highest ferulic acid recovery yield.•The best pre-treatment increased the ferulic acid recovery yield by 3.7 times.•The best pre-treatment had the lowest concentration of sugars degradation products.•All pre-treatments led to an improved quality of the bioactivity of the extracts. Ferulic acid may be used as a nutraceutical ingredient or as a substrate to produce bio-vanillin. There is an increasing market demand for ferulic acid obtained from natural sources such as low-cost agro-industrial by-products, due to its potential applications as nutraceutical ingredient and as a substrate to produce bio-vanillin. This work aims to study ferulic acid recovery from corn fibre (one of the most abundant natural sources of ferulic acid), involving an integrated process of hydrothermal pre-treatment followed by enzymatic hydrolysis. The objective is primarily to produce natural extracts with a maximum ferulic acid recovery yield, but it is also to assess their antioxidant and antiproliferative properties and their cytotoxicity. Different commercial enzyme preparations were tested for release of ferulic acid from corn fibre. The best results were obtained for Ultraflo ®XL in a concentration of 2 % (wenzyme preparation/w dry corn fibre) at a pH of 5 and at 55 °C, presenting a recovery yield of esterified ferulic acid of 7.83 ± 1.35 % (wrecovered ferulic acid/wtotal esterified ferulic acid), which corresponds to 0.13 ± 0.02 % (wferulic acid/w dry corn fibre). When using a hydrothermal pre-treatment at a temperature of 140 °C for 40 min, prior to the use of the same enzymatic hydrolysis procedure, the recovery yield of esterified ferulic acid increased to 28.94 ± 2.40 % (w recovered ferulic acid/ wtotal esterified ferulic acid), which corresponds to 4.9 ± 0.3 % (wferulic acid/wdry corn fibre). The use of this pre-treatment leads not only to the highest yield of ferulic acid, but also to the lowest concentration of furfural and hydroxymethylfurfural, without the formation of formic and levulinic acid (not detected). All pre-treatments tested led to an improved quality of the extract in terms of bioactivity.</description><identifier>ISSN: 0926-6690</identifier><identifier>EISSN: 1872-633X</identifier><identifier>DOI: 10.1016/j.indcrop.2021.113731</identifier><language>eng</language><publisher>AMSTERDAM: Elsevier B.V</publisher><subject>Agricultural Engineering ; Agriculture ; Agronomy ; Corn fibre ; Enzymatic hydrolysis ; Ferulic acid ; Hemicellulose ; Hydrothermal pre-treatment ; Life Sciences &amp; Biomedicine ; Oligosaccharides ; Science &amp; Technology</subject><ispartof>Industrial crops and products, 2021-10, Vol.170, p.113731, Article 113731</ispartof><rights>2021 Elsevier B.V.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>24</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000689462000010</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c383t-2f6cf4f50bd29bd5415cc9f04807e107d1790e55915eb0c69cf1bc448d7e834e3</citedby><cites>FETCH-LOGICAL-c383t-2f6cf4f50bd29bd5415cc9f04807e107d1790e55915eb0c69cf1bc448d7e834e3</cites><orcidid>0000-0001-5820-3669 ; 0000-0002-2450-1761 ; 0000-0002-3902-2966 ; 0000-0002-0610-7664 ; 0000-0002-7784-0265 ; 0000-0002-8113-6094 ; 0000-0001-5016-4634 ; 0000-0001-8714-3781 ; 0000-0002-8618-8299</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.indcrop.2021.113731$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,782,786,3554,27933,27934,39267,46004</link.rule.ids></links><search><creatorcontrib>Valério, Rita</creatorcontrib><creatorcontrib>Serra, Ana Teresa</creatorcontrib><creatorcontrib>Baixinho, João</creatorcontrib><creatorcontrib>Cardeira, Martim</creatorcontrib><creatorcontrib>Fernández, Naiara</creatorcontrib><creatorcontrib>Bronze, Maria Rosário</creatorcontrib><creatorcontrib>Duarte, Luís C.</creatorcontrib><creatorcontrib>Tavares, Maria L.</creatorcontrib><creatorcontrib>Crespo, João G.</creatorcontrib><creatorcontrib>Brazinha, Carla</creatorcontrib><title>Combined hydrothermal pre-treatment and enzymatic hydrolysis of corn fibre: Production of ferulic acid extracts and assessment of their antioxidant and antiproliferative properties</title><title>Industrial crops and products</title><addtitle>IND CROP PROD</addtitle><description>[Display omitted] •Ultraflo®XL enzyme preparation led to the highest ferulic acid recovery yield.•The best pre-treatment increased the ferulic acid recovery yield by 3.7 times.•The best pre-treatment had the lowest concentration of sugars degradation products.•All pre-treatments led to an improved quality of the bioactivity of the extracts. Ferulic acid may be used as a nutraceutical ingredient or as a substrate to produce bio-vanillin. There is an increasing market demand for ferulic acid obtained from natural sources such as low-cost agro-industrial by-products, due to its potential applications as nutraceutical ingredient and as a substrate to produce bio-vanillin. This work aims to study ferulic acid recovery from corn fibre (one of the most abundant natural sources of ferulic acid), involving an integrated process of hydrothermal pre-treatment followed by enzymatic hydrolysis. The objective is primarily to produce natural extracts with a maximum ferulic acid recovery yield, but it is also to assess their antioxidant and antiproliferative properties and their cytotoxicity. Different commercial enzyme preparations were tested for release of ferulic acid from corn fibre. The best results were obtained for Ultraflo ®XL in a concentration of 2 % (wenzyme preparation/w dry corn fibre) at a pH of 5 and at 55 °C, presenting a recovery yield of esterified ferulic acid of 7.83 ± 1.35 % (wrecovered ferulic acid/wtotal esterified ferulic acid), which corresponds to 0.13 ± 0.02 % (wferulic acid/w dry corn fibre). When using a hydrothermal pre-treatment at a temperature of 140 °C for 40 min, prior to the use of the same enzymatic hydrolysis procedure, the recovery yield of esterified ferulic acid increased to 28.94 ± 2.40 % (w recovered ferulic acid/ wtotal esterified ferulic acid), which corresponds to 4.9 ± 0.3 % (wferulic acid/wdry corn fibre). The use of this pre-treatment leads not only to the highest yield of ferulic acid, but also to the lowest concentration of furfural and hydroxymethylfurfural, without the formation of formic and levulinic acid (not detected). All pre-treatments tested led to an improved quality of the extract in terms of bioactivity.</description><subject>Agricultural Engineering</subject><subject>Agriculture</subject><subject>Agronomy</subject><subject>Corn fibre</subject><subject>Enzymatic hydrolysis</subject><subject>Ferulic acid</subject><subject>Hemicellulose</subject><subject>Hydrothermal pre-treatment</subject><subject>Life Sciences &amp; Biomedicine</subject><subject>Oligosaccharides</subject><subject>Science &amp; Technology</subject><issn>0926-6690</issn><issn>1872-633X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>HGBXW</sourceid><recordid>eNqNkM1u1DAUhS0EEkPhEZAitijT6_w4CRuEogKVKpVFK7GzHPta9WgSR9eeodPn4gFxmhFbWPnvfOdcH8bec9hy4OJyt3WT0eTnbQEF33JeNiV_wTa8bYpclOXPl2wDXSFyITp4zd6EsAPgDRTNhv3u_Ti4CU32cDLk4wPSqPbZTJhHQhVHnGKmJpPh9HQaVXR6Fe5PwYXM20x7mjLrBsJP2Q_y5qCj89PyYpEO-6RX2iX8MZLSMTx7qRAwhGfrpEuZjtJ94h6dUee85TynHJdsUuwR00x-RooOw1v2yqp9wHfn9YLdf72667_nN7ffrvsvN7ku2zLmhRXaVraGwRTdYOqK11p3FqoWGuTQGN50gHXd8RoH0KLTlg-6qlrTYFtWWF6wevVN5YZAaOVMblR0khzkUr3cyXP1cqlertUn7uPK_cLB26AdThr_sgAg2q4SRdoAh6Ru_1_du6iWgnt_mGJCP6woaaVmSXh0IaqQZqsAZCdLwUUSfV5FmKo6OiR5zjCOUEdpvPvHf_4A3cfB7w</recordid><startdate>20211015</startdate><enddate>20211015</enddate><creator>Valério, Rita</creator><creator>Serra, Ana Teresa</creator><creator>Baixinho, João</creator><creator>Cardeira, Martim</creator><creator>Fernández, Naiara</creator><creator>Bronze, Maria Rosário</creator><creator>Duarte, Luís C.</creator><creator>Tavares, Maria L.</creator><creator>Crespo, João G.</creator><creator>Brazinha, Carla</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>RCLKO</scope><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0001-5820-3669</orcidid><orcidid>https://orcid.org/0000-0002-2450-1761</orcidid><orcidid>https://orcid.org/0000-0002-3902-2966</orcidid><orcidid>https://orcid.org/0000-0002-0610-7664</orcidid><orcidid>https://orcid.org/0000-0002-7784-0265</orcidid><orcidid>https://orcid.org/0000-0002-8113-6094</orcidid><orcidid>https://orcid.org/0000-0001-5016-4634</orcidid><orcidid>https://orcid.org/0000-0001-8714-3781</orcidid><orcidid>https://orcid.org/0000-0002-8618-8299</orcidid></search><sort><creationdate>20211015</creationdate><title>Combined hydrothermal pre-treatment and enzymatic hydrolysis of corn fibre: Production of ferulic acid extracts and assessment of their antioxidant and antiproliferative properties</title><author>Valério, Rita ; Serra, Ana Teresa ; Baixinho, João ; Cardeira, Martim ; Fernández, Naiara ; Bronze, Maria Rosário ; Duarte, Luís C. ; Tavares, Maria L. ; Crespo, João G. ; Brazinha, Carla</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c383t-2f6cf4f50bd29bd5415cc9f04807e107d1790e55915eb0c69cf1bc448d7e834e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Agricultural Engineering</topic><topic>Agriculture</topic><topic>Agronomy</topic><topic>Corn fibre</topic><topic>Enzymatic hydrolysis</topic><topic>Ferulic acid</topic><topic>Hemicellulose</topic><topic>Hydrothermal pre-treatment</topic><topic>Life Sciences &amp; Biomedicine</topic><topic>Oligosaccharides</topic><topic>Science &amp; Technology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Valério, Rita</creatorcontrib><creatorcontrib>Serra, Ana Teresa</creatorcontrib><creatorcontrib>Baixinho, João</creatorcontrib><creatorcontrib>Cardeira, Martim</creatorcontrib><creatorcontrib>Fernández, Naiara</creatorcontrib><creatorcontrib>Bronze, Maria Rosário</creatorcontrib><creatorcontrib>Duarte, Luís C.</creatorcontrib><creatorcontrib>Tavares, Maria L.</creatorcontrib><creatorcontrib>Crespo, João G.</creatorcontrib><creatorcontrib>Brazinha, Carla</creatorcontrib><collection>RCAAP open access repository</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Web of Science - Science Citation Index Expanded - 2021</collection><collection>CrossRef</collection><jtitle>Industrial crops and products</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Valério, Rita</au><au>Serra, Ana Teresa</au><au>Baixinho, João</au><au>Cardeira, Martim</au><au>Fernández, Naiara</au><au>Bronze, Maria Rosário</au><au>Duarte, Luís C.</au><au>Tavares, Maria L.</au><au>Crespo, João G.</au><au>Brazinha, Carla</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Combined hydrothermal pre-treatment and enzymatic hydrolysis of corn fibre: Production of ferulic acid extracts and assessment of their antioxidant and antiproliferative properties</atitle><jtitle>Industrial crops and products</jtitle><stitle>IND CROP PROD</stitle><date>2021-10-15</date><risdate>2021</risdate><volume>170</volume><spage>113731</spage><pages>113731-</pages><artnum>113731</artnum><issn>0926-6690</issn><eissn>1872-633X</eissn><abstract>[Display omitted] •Ultraflo®XL enzyme preparation led to the highest ferulic acid recovery yield.•The best pre-treatment increased the ferulic acid recovery yield by 3.7 times.•The best pre-treatment had the lowest concentration of sugars degradation products.•All pre-treatments led to an improved quality of the bioactivity of the extracts. Ferulic acid may be used as a nutraceutical ingredient or as a substrate to produce bio-vanillin. There is an increasing market demand for ferulic acid obtained from natural sources such as low-cost agro-industrial by-products, due to its potential applications as nutraceutical ingredient and as a substrate to produce bio-vanillin. This work aims to study ferulic acid recovery from corn fibre (one of the most abundant natural sources of ferulic acid), involving an integrated process of hydrothermal pre-treatment followed by enzymatic hydrolysis. The objective is primarily to produce natural extracts with a maximum ferulic acid recovery yield, but it is also to assess their antioxidant and antiproliferative properties and their cytotoxicity. Different commercial enzyme preparations were tested for release of ferulic acid from corn fibre. The best results were obtained for Ultraflo ®XL in a concentration of 2 % (wenzyme preparation/w dry corn fibre) at a pH of 5 and at 55 °C, presenting a recovery yield of esterified ferulic acid of 7.83 ± 1.35 % (wrecovered ferulic acid/wtotal esterified ferulic acid), which corresponds to 0.13 ± 0.02 % (wferulic acid/w dry corn fibre). When using a hydrothermal pre-treatment at a temperature of 140 °C for 40 min, prior to the use of the same enzymatic hydrolysis procedure, the recovery yield of esterified ferulic acid increased to 28.94 ± 2.40 % (w recovered ferulic acid/ wtotal esterified ferulic acid), which corresponds to 4.9 ± 0.3 % (wferulic acid/wdry corn fibre). The use of this pre-treatment leads not only to the highest yield of ferulic acid, but also to the lowest concentration of furfural and hydroxymethylfurfural, without the formation of formic and levulinic acid (not detected). All pre-treatments tested led to an improved quality of the extract in terms of bioactivity.</abstract><cop>AMSTERDAM</cop><pub>Elsevier B.V</pub><doi>10.1016/j.indcrop.2021.113731</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-5820-3669</orcidid><orcidid>https://orcid.org/0000-0002-2450-1761</orcidid><orcidid>https://orcid.org/0000-0002-3902-2966</orcidid><orcidid>https://orcid.org/0000-0002-0610-7664</orcidid><orcidid>https://orcid.org/0000-0002-7784-0265</orcidid><orcidid>https://orcid.org/0000-0002-8113-6094</orcidid><orcidid>https://orcid.org/0000-0001-5016-4634</orcidid><orcidid>https://orcid.org/0000-0001-8714-3781</orcidid><orcidid>https://orcid.org/0000-0002-8618-8299</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0926-6690
ispartof Industrial crops and products, 2021-10, Vol.170, p.113731, Article 113731
issn 0926-6690
1872-633X
language eng
recordid cdi_rcaap_revistas_10400_9_3616
source Web of Science - Science Citation Index Expanded - 2021<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" />; Access via ScienceDirect (Elsevier)
subjects Agricultural Engineering
Agriculture
Agronomy
Corn fibre
Enzymatic hydrolysis
Ferulic acid
Hemicellulose
Hydrothermal pre-treatment
Life Sciences & Biomedicine
Oligosaccharides
Science & Technology
title Combined hydrothermal pre-treatment and enzymatic hydrolysis of corn fibre: Production of ferulic acid extracts and assessment of their antioxidant and antiproliferative properties
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-01T05%3A38%3A40IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-elsevier_rcaap&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Combined%20hydrothermal%20pre-treatment%20and%20enzymatic%20hydrolysis%20of%20corn%20fibre:%20Production%20of%20ferulic%20acid%20extracts%20and%20assessment%20of%20their%20antioxidant%20and%20antiproliferative%20properties&rft.jtitle=Industrial%20crops%20and%20products&rft.au=Val%C3%A9rio,%20Rita&rft.date=2021-10-15&rft.volume=170&rft.spage=113731&rft.pages=113731-&rft.artnum=113731&rft.issn=0926-6690&rft.eissn=1872-633X&rft_id=info:doi/10.1016/j.indcrop.2021.113731&rft_dat=%3Celsevier_rcaap%3ES0926669021004957%3C/elsevier_rcaap%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rft_els_id=S0926669021004957&rfr_iscdi=true