First Report of CR1 Polymorphisms and Soluble CR1 Levels Associated with Late Onset Alzheimer’s Disease (LOAD) in Latin America
The CR1 gene has been widely studied in Alzheimer’s disease (AD), since its first association with the disease in 2009. Even after 11 years of this discovery, the role of this gene in AD has not yet been fully elucidated and the association of its variants was not validated in Latin American populat...
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| Veröffentlicht in: | Journal of molecular neuroscience 2020-09, Vol.70 (9), p.1338-1344 |
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| creator | Kretzschmar, Gabriela Canalli Antoniazzi, Angela Adriane Hanel Oliveira, Luana Caroline Nisihara, Renato Mitsunori Petzl-Erler, Maria Luiza de Souza, Ricardo Lehtonen R. Boldt, Angelica Beate Winter |
| description | The
CR1
gene has been widely studied in Alzheimer’s disease (AD), since its first association with the disease in 2009. Even after 11 years of this discovery, the role of this gene in AD has not yet been fully elucidated and the association of its variants was not validated in Latin American populations. We genotyped five
CR1
single nucleotide polymorphisms (SNPs rs6656401, rs3849266, rs2274567, rs4844610, and rs12034383) in up to 162 AD patients and 137 controls through PCR-SSP and iPLEX MassARRAY Platform (Sequenom), and measured soluble CR1 (sCR1) levels in plasma of 40 AD patients and 39 controls with an enzyme-linked immunosorbent assay (ELISA). Homozygosity for haplotype
rs3849266*C_rs2274567*A
(
CA/CA
genotype) was associated with susceptibility to AD (OR = 2.94,
p
= 0.018). Patients presented higher sCR1 levels in plasma than controls (
p
= 0.038). Furthermore, patients that carry the
rs2274567*G
allele (p.1208Arg) presented higher sCR1 levels than
A/A
(p.1208His/His) homozygotes (
p
= 0.036). This is the first study to validate the association of
CR1
polymorphisms with late-onset Alzheimer’s disease, as well as to evaluate sCR1 levels in a Latin American population. SNPs present in the regulatory and coding regions of this gene may be playing a key role in the observed association, probably by interfering in Aβ plaques clearance. Inhibition may be due to the increase in local sCR1 levels observed in patients, which may result from polymorphisms leading to larger isoforms of CR1 and/or structural alterations of the protein that makes it less functional, as well as increased vesiculation of the molecules. |
| doi_str_mv | 10.1007/s12031-020-01547-2 |
| format | Article |
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CR1
gene has been widely studied in Alzheimer’s disease (AD), since its first association with the disease in 2009. Even after 11 years of this discovery, the role of this gene in AD has not yet been fully elucidated and the association of its variants was not validated in Latin American populations. We genotyped five
CR1
single nucleotide polymorphisms (SNPs rs6656401, rs3849266, rs2274567, rs4844610, and rs12034383) in up to 162 AD patients and 137 controls through PCR-SSP and iPLEX MassARRAY Platform (Sequenom), and measured soluble CR1 (sCR1) levels in plasma of 40 AD patients and 39 controls with an enzyme-linked immunosorbent assay (ELISA). Homozygosity for haplotype
rs3849266*C_rs2274567*A
(
CA/CA
genotype) was associated with susceptibility to AD (OR = 2.94,
p
= 0.018). Patients presented higher sCR1 levels in plasma than controls (
p
= 0.038). Furthermore, patients that carry the
rs2274567*G
allele (p.1208Arg) presented higher sCR1 levels than
A/A
(p.1208His/His) homozygotes (
p
= 0.036). This is the first study to validate the association of
CR1
polymorphisms with late-onset Alzheimer’s disease, as well as to evaluate sCR1 levels in a Latin American population. SNPs present in the regulatory and coding regions of this gene may be playing a key role in the observed association, probably by interfering in Aβ plaques clearance. Inhibition may be due to the increase in local sCR1 levels observed in patients, which may result from polymorphisms leading to larger isoforms of CR1 and/or structural alterations of the protein that makes it less functional, as well as increased vesiculation of the molecules.</description><identifier>ISSN: 0895-8696</identifier><identifier>EISSN: 1559-1166</identifier><identifier>DOI: 10.1007/s12031-020-01547-2</identifier><identifier>PMID: 32388800</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Alzheimer's disease ; Biomedical and Life Sciences ; Biomedicine ; Cell Biology ; CR1 gene ; Enzyme-linked immunosorbent assay ; Haplotypes ; Homozygosity ; Homozygotes ; Isoforms ; Neurochemistry ; Neurodegenerative diseases ; Neurology ; Neurosciences ; Nucleotides ; Proteomics ; Senile plaques ; Single-nucleotide polymorphism</subject><ispartof>Journal of molecular neuroscience, 2020-09, Vol.70 (9), p.1338-1344</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2020</rights><rights>Springer Science+Business Media, LLC, part of Springer Nature 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-7c698f170f3cc91b855de7b04a11f1e7aca64268299c6292c8d6fc01fd59c37b3</citedby><cites>FETCH-LOGICAL-c375t-7c698f170f3cc91b855de7b04a11f1e7aca64268299c6292c8d6fc01fd59c37b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12031-020-01547-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12031-020-01547-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32388800$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kretzschmar, Gabriela Canalli</creatorcontrib><creatorcontrib>Antoniazzi, Angela Adriane Hanel</creatorcontrib><creatorcontrib>Oliveira, Luana Caroline</creatorcontrib><creatorcontrib>Nisihara, Renato Mitsunori</creatorcontrib><creatorcontrib>Petzl-Erler, Maria Luiza</creatorcontrib><creatorcontrib>de Souza, Ricardo Lehtonen R.</creatorcontrib><creatorcontrib>Boldt, Angelica Beate Winter</creatorcontrib><title>First Report of CR1 Polymorphisms and Soluble CR1 Levels Associated with Late Onset Alzheimer’s Disease (LOAD) in Latin America</title><title>Journal of molecular neuroscience</title><addtitle>J Mol Neurosci</addtitle><addtitle>J Mol Neurosci</addtitle><description>The
CR1
gene has been widely studied in Alzheimer’s disease (AD), since its first association with the disease in 2009. Even after 11 years of this discovery, the role of this gene in AD has not yet been fully elucidated and the association of its variants was not validated in Latin American populations. We genotyped five
CR1
single nucleotide polymorphisms (SNPs rs6656401, rs3849266, rs2274567, rs4844610, and rs12034383) in up to 162 AD patients and 137 controls through PCR-SSP and iPLEX MassARRAY Platform (Sequenom), and measured soluble CR1 (sCR1) levels in plasma of 40 AD patients and 39 controls with an enzyme-linked immunosorbent assay (ELISA). Homozygosity for haplotype
rs3849266*C_rs2274567*A
(
CA/CA
genotype) was associated with susceptibility to AD (OR = 2.94,
p
= 0.018). Patients presented higher sCR1 levels in plasma than controls (
p
= 0.038). Furthermore, patients that carry the
rs2274567*G
allele (p.1208Arg) presented higher sCR1 levels than
A/A
(p.1208His/His) homozygotes (
p
= 0.036). This is the first study to validate the association of
CR1
polymorphisms with late-onset Alzheimer’s disease, as well as to evaluate sCR1 levels in a Latin American population. SNPs present in the regulatory and coding regions of this gene may be playing a key role in the observed association, probably by interfering in Aβ plaques clearance. Inhibition may be due to the increase in local sCR1 levels observed in patients, which may result from polymorphisms leading to larger isoforms of CR1 and/or structural alterations of the protein that makes it less functional, as well as increased vesiculation of the molecules.</description><subject>Alzheimer's disease</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell Biology</subject><subject>CR1 gene</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Haplotypes</subject><subject>Homozygosity</subject><subject>Homozygotes</subject><subject>Isoforms</subject><subject>Neurochemistry</subject><subject>Neurodegenerative diseases</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Nucleotides</subject><subject>Proteomics</subject><subject>Senile plaques</subject><subject>Single-nucleotide polymorphism</subject><issn>0895-8696</issn><issn>1559-1166</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kcFu1DAQhi0EotvCC3BAlriUQ8DjxI5zXG0pIEVaVOAcOc6EdZXEiycBlRN9DF6PJ8HtFpA4cBmPNN_8Y-lj7AmIFyBE-ZJAihwyIUUmQBVlJu-xFShVZQBa32crYSqVGV3pI3ZMdCmEhALMQ3aUy9wYI8SKXZ_7SDO_wH2IMw8931wAfxeGqzHE_c7TSNxOHX8fhqUd8HZa4xcciK-JgvN2xo5_9fOO16nl24lw5uvh2w79iPHn9x_EzzyhJeSn9XZ99pz76QZNdZ0A7-wj9qC3A-Hju_eEfTx_9WHzJqu3r99u1nXm8lLNWel0ZXooRZ87V0FrlOqwbEVhAXrA0jqrC6mNrCqnZSWd6XTvBPSdqlJCm5-w00PuPobPC9LcjJ4cDoOdMCzUyEIACKmMSuizf9DLsMQp_S5R6YAEo02i5IFyMRBF7Jt99KONVw2I5kZQcxDUJEHNraBGpqWnd9FLO2L3Z-W3kQTkB4DSaPqE8e_t_8T-ApKkmnU</recordid><startdate>20200901</startdate><enddate>20200901</enddate><creator>Kretzschmar, Gabriela Canalli</creator><creator>Antoniazzi, Angela Adriane Hanel</creator><creator>Oliveira, Luana Caroline</creator><creator>Nisihara, Renato Mitsunori</creator><creator>Petzl-Erler, Maria Luiza</creator><creator>de Souza, Ricardo Lehtonen R.</creator><creator>Boldt, Angelica Beate Winter</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7QR</scope><scope>7T7</scope><scope>7TK</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7N</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20200901</creationdate><title>First Report of CR1 Polymorphisms and Soluble CR1 Levels Associated with Late Onset Alzheimer’s Disease (LOAD) in Latin America</title><author>Kretzschmar, Gabriela Canalli ; Antoniazzi, Angela Adriane Hanel ; Oliveira, Luana Caroline ; Nisihara, Renato Mitsunori ; Petzl-Erler, Maria Luiza ; de Souza, Ricardo Lehtonen R. ; Boldt, Angelica Beate Winter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-7c698f170f3cc91b855de7b04a11f1e7aca64268299c6292c8d6fc01fd59c37b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Alzheimer's disease</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cell Biology</topic><topic>CR1 gene</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Haplotypes</topic><topic>Homozygosity</topic><topic>Homozygotes</topic><topic>Isoforms</topic><topic>Neurochemistry</topic><topic>Neurodegenerative diseases</topic><topic>Neurology</topic><topic>Neurosciences</topic><topic>Nucleotides</topic><topic>Proteomics</topic><topic>Senile plaques</topic><topic>Single-nucleotide polymorphism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kretzschmar, Gabriela Canalli</creatorcontrib><creatorcontrib>Antoniazzi, Angela Adriane Hanel</creatorcontrib><creatorcontrib>Oliveira, Luana Caroline</creatorcontrib><creatorcontrib>Nisihara, Renato Mitsunori</creatorcontrib><creatorcontrib>Petzl-Erler, Maria Luiza</creatorcontrib><creatorcontrib>de Souza, Ricardo Lehtonen R.</creatorcontrib><creatorcontrib>Boldt, Angelica Beate Winter</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Chemoreception Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</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 One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of molecular neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kretzschmar, Gabriela Canalli</au><au>Antoniazzi, Angela Adriane Hanel</au><au>Oliveira, Luana Caroline</au><au>Nisihara, Renato Mitsunori</au><au>Petzl-Erler, Maria Luiza</au><au>de Souza, Ricardo Lehtonen R.</au><au>Boldt, Angelica Beate Winter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>First Report of CR1 Polymorphisms and Soluble CR1 Levels Associated with Late Onset Alzheimer’s Disease (LOAD) in Latin America</atitle><jtitle>Journal of molecular neuroscience</jtitle><stitle>J Mol Neurosci</stitle><addtitle>J Mol Neurosci</addtitle><date>2020-09-01</date><risdate>2020</risdate><volume>70</volume><issue>9</issue><spage>1338</spage><epage>1344</epage><pages>1338-1344</pages><issn>0895-8696</issn><eissn>1559-1166</eissn><abstract>The
CR1
gene has been widely studied in Alzheimer’s disease (AD), since its first association with the disease in 2009. Even after 11 years of this discovery, the role of this gene in AD has not yet been fully elucidated and the association of its variants was not validated in Latin American populations. We genotyped five
CR1
single nucleotide polymorphisms (SNPs rs6656401, rs3849266, rs2274567, rs4844610, and rs12034383) in up to 162 AD patients and 137 controls through PCR-SSP and iPLEX MassARRAY Platform (Sequenom), and measured soluble CR1 (sCR1) levels in plasma of 40 AD patients and 39 controls with an enzyme-linked immunosorbent assay (ELISA). Homozygosity for haplotype
rs3849266*C_rs2274567*A
(
CA/CA
genotype) was associated with susceptibility to AD (OR = 2.94,
p
= 0.018). Patients presented higher sCR1 levels in plasma than controls (
p
= 0.038). Furthermore, patients that carry the
rs2274567*G
allele (p.1208Arg) presented higher sCR1 levels than
A/A
(p.1208His/His) homozygotes (
p
= 0.036). This is the first study to validate the association of
CR1
polymorphisms with late-onset Alzheimer’s disease, as well as to evaluate sCR1 levels in a Latin American population. SNPs present in the regulatory and coding regions of this gene may be playing a key role in the observed association, probably by interfering in Aβ plaques clearance. Inhibition may be due to the increase in local sCR1 levels observed in patients, which may result from polymorphisms leading to larger isoforms of CR1 and/or structural alterations of the protein that makes it less functional, as well as increased vesiculation of the molecules.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>32388800</pmid><doi>10.1007/s12031-020-01547-2</doi><tpages>7</tpages></addata></record> |
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| subjects | Alzheimer's disease Biomedical and Life Sciences Biomedicine Cell Biology CR1 gene Enzyme-linked immunosorbent assay Haplotypes Homozygosity Homozygotes Isoforms Neurochemistry Neurodegenerative diseases Neurology Neurosciences Nucleotides Proteomics Senile plaques Single-nucleotide polymorphism |
| title | First Report of CR1 Polymorphisms and Soluble CR1 Levels Associated with Late Onset Alzheimer’s Disease (LOAD) in Latin America |
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