Epigenetic Variability of Ribosomal Cistrons of Acrocentric Chromatids of Chromosomes 14 in Fetuses and Newborns with Down Syndrome
Following the completion of the Human Genome Project, the strategic focus of modern genetics shifted towards functional genomics, encompassing non-coding regions of DNA, including total non-coding DNA and satellite stalks with ribosomal cistrons. These consist of repetitive sequences of nucleotides...
Gespeichert in:
| Veröffentlicht in: | Cytology and genetics 2024-10, Vol.58 (5), p.513-522 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 522 |
|---|---|
| container_issue | 5 |
| container_start_page | 513 |
| container_title | Cytology and genetics |
| container_volume | 58 |
| creator | Teimuraz Lezhava Buadze, Tamar Sigua, Nino Jokhadze, Tinatin Gaiozishvili, Maia Sigua, Tamar Kulijanashvili, Natia |
| description | Following the completion of the Human Genome Project, the strategic focus of modern genetics shifted towards functional genomics, encompassing non-coding regions of DNA, including total non-coding DNA and satellite stalks with ribosomal cistrons. These consist of repetitive sequences of nucleotides localized in heterochromatin, the functions of which still require clarification. The present study investigates the activity of ribosomal cistrons within chromatid satellite stalks (NOR heterochromatin) of acrocentric chromosomes in patients with Down Syndrome +21 (DS). The study comprised: 29 healthy fetuses (441 metaphases from cultivated amniotic fluid); 8 fetuses with DS (190 metaphases from cultivated amniotic fluid); 10 healthy newborns (290 metaphases from cultivated lymphocytes); 10 newborn patients with DS (273 metaphases from cultivated lymphocytes) including: 5 newborn patients with trisomy DS (81 metaphases) and 5 mosaic form of newborns with DS (46, XX or 46, XY/47, XX, +21 or 47, XY, +21) (192 metaphases). The activity of ribosomal cistrons of chromatid on the 14 chromosomes included in associations in the control group (healthy fetuses and healthy newborns) corresponding to the order: 21 > 14 = 22 = 13 > 15 and 21 > 14 > 22 > 13 > 15, respectively. In fetuses with DS (21 > 22 > 15 > 13 > 14), in newborns with DS (21 > 13 > 15 = 22 > 14), and with mosaicism of cells of newborns with DS (21 > 13 > 15 > 22 > 14), a statistically significant decrease in the activity of entering associations of chromatids 14 chromosomes was noted. It is noteworthy that, in fetuses, in newborns, and with mosaicism of cells of newborns with DS activity of entering in associations of 14 chromatids with homologous 14 chromatids were not determined (21:21 > 13:13 > 15:15 > 22:22 > 14:14; 21:21 > 22:22 > 13:13 > 15: 15 > 14:14 and 21:21 > 13:13 > 22:22 > 15:15 > 14:14). In fetuses and newborns (control group), the order was: 21:21 > 22:22 > 14:14 > 13:13 = 15:15 and 14 : 14 = 22:22 > 21:21 > 13:13 > 15 : 15, respectively. These results indicate that in DS, the ribosomal cistrons of chromatids on chromosomes 14 undergo epigenetic changes, leading to a reduction in the activity of ribosomal cistrons on these chromatids. This provides a crucial foundation for the prevention, diagnosis, and treatment of DS. The study of ribosomal gene activity at the level of different acrocentric chromosomes in pathologies represents a new direction for medicine, offering insights into both di |
| doi_str_mv | 10.3103/S0095452724050074 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_3107467536</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3153784396</sourcerecordid><originalsourceid>FETCH-LOGICAL-c231t-9e12d32e0d3908a0c299e256c6cba3dad62819791c18bdf7e041f429609e6ef43</originalsourceid><addsrcrecordid>eNp1kctKAzEUhoMoWC8P4C7gxs1objPTLEutFygKVt0OmcyZGpkmNUkpXfviZlpBUFyFk__7fsIJQmeUXHJK-NWMEJmLnJVMkJyQUuyhAZVcZFIIso8GfZz1-SE6CuGdkLxgnA_Q52Rp5mAhGo1flTeqNp2JG-xa_GRqF9xCdXhsQvTOhv52pL3TYKNPwvjNpzyaZptsp96AgKnAxuIbiKuQJmUb_ADr2vnUsTbxDV-7tcWzjW2SAifooFVdgNPv8xi93Eyex3fZ9PH2fjyaZppxGjMJlDWcAWm4JENFNJMSWF7oQteKN6op2JDKUlJNh3XTlkAEbQWTBZFQQCv4MbrY9S69-1hBiNXCBA1dpyy4Vag4zXk5FFwWCT3_hb67lbfpdYlK2y3KnPcU3VFpJyF4aKulNwvlNxUlPcerP9-SHLZzQmLtHPxP8__SF3LljzI</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3107467536</pqid></control><display><type>article</type><title>Epigenetic Variability of Ribosomal Cistrons of Acrocentric Chromatids of Chromosomes 14 in Fetuses and Newborns with Down Syndrome</title><source>SpringerLink Journals - AutoHoldings</source><creator>Teimuraz Lezhava ; Buadze, Tamar ; Sigua, Nino ; Jokhadze, Tinatin ; Gaiozishvili, Maia ; Sigua, Tamar ; Kulijanashvili, Natia</creator><creatorcontrib>Teimuraz Lezhava ; Buadze, Tamar ; Sigua, Nino ; Jokhadze, Tinatin ; Gaiozishvili, Maia ; Sigua, Tamar ; Kulijanashvili, Natia</creatorcontrib><description>Following the completion of the Human Genome Project, the strategic focus of modern genetics shifted towards functional genomics, encompassing non-coding regions of DNA, including total non-coding DNA and satellite stalks with ribosomal cistrons. These consist of repetitive sequences of nucleotides localized in heterochromatin, the functions of which still require clarification. The present study investigates the activity of ribosomal cistrons within chromatid satellite stalks (NOR heterochromatin) of acrocentric chromosomes in patients with Down Syndrome +21 (DS). The study comprised: 29 healthy fetuses (441 metaphases from cultivated amniotic fluid); 8 fetuses with DS (190 metaphases from cultivated amniotic fluid); 10 healthy newborns (290 metaphases from cultivated lymphocytes); 10 newborn patients with DS (273 metaphases from cultivated lymphocytes) including: 5 newborn patients with trisomy DS (81 metaphases) and 5 mosaic form of newborns with DS (46, XX or 46, XY/47, XX, +21 or 47, XY, +21) (192 metaphases). The activity of ribosomal cistrons of chromatid on the 14 chromosomes included in associations in the control group (healthy fetuses and healthy newborns) corresponding to the order: 21 > 14 = 22 = 13 > 15 and 21 > 14 > 22 > 13 > 15, respectively. In fetuses with DS (21 > 22 > 15 > 13 > 14), in newborns with DS (21 > 13 > 15 = 22 > 14), and with mosaicism of cells of newborns with DS (21 > 13 > 15 > 22 > 14), a statistically significant decrease in the activity of entering associations of chromatids 14 chromosomes was noted. It is noteworthy that, in fetuses, in newborns, and with mosaicism of cells of newborns with DS activity of entering in associations of 14 chromatids with homologous 14 chromatids were not determined (21:21 > 13:13 > 15:15 > 22:22 > 14:14; 21:21 > 22:22 > 13:13 > 15: 15 > 14:14 and 21:21 > 13:13 > 22:22 > 15:15 > 14:14). In fetuses and newborns (control group), the order was: 21:21 > 22:22 > 14:14 > 13:13 = 15:15 and 14 : 14 = 22:22 > 21:21 > 13:13 > 15 : 15, respectively. These results indicate that in DS, the ribosomal cistrons of chromatids on chromosomes 14 undergo epigenetic changes, leading to a reduction in the activity of ribosomal cistrons on these chromatids. This provides a crucial foundation for the prevention, diagnosis, and treatment of DS. The study of ribosomal gene activity at the level of different acrocentric chromosomes in pathologies represents a new direction for medicine, offering insights into both disease diagnosis and the development of novel treatment strategies in the future.</description><identifier>ISSN: 0095-4527</identifier><identifier>EISSN: 1934-9440</identifier><identifier>DOI: 10.3103/S0095452724050074</identifier><language>eng</language><publisher>Moscow: Pleiades Publishing</publisher><subject>Amniotic fluid ; Biomedical and Life Sciences ; Biomedicine ; Chromatids ; Chromosomes ; Cistrons ; Diagnosis ; disease diagnosis ; Down syndrome ; Down's syndrome ; Epigenetics ; Fetuses ; genes ; Genetic variability ; genomics ; Heterochromatin ; Human Genetics ; Human Genome Project ; humans ; intergenic DNA ; Lymphocytes ; medicine ; Mosaicism ; Neonates ; Nucleotide sequence ; nucleotides ; Satellite DNA ; satellites ; Statistical analysis ; trisomics ; Trisomy</subject><ispartof>Cytology and genetics, 2024-10, Vol.58 (5), p.513-522</ispartof><rights>Allerton Press, Inc. 2024. ISSN 0095-4527, Cytology and Genetics, 2024, Vol. 58, No. 5, pp. 513–522. © Allerton Press, Inc., 2024. Ukrainian Text © The Author(s), 2024, published in Tsitologiya i Genetika, 2024, Vol. 58, No. 5, pp. 101–102.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c231t-9e12d32e0d3908a0c299e256c6cba3dad62819791c18bdf7e041f429609e6ef43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.3103/S0095452724050074$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.3103/S0095452724050074$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,778,782,27907,27908,41471,42540,51302</link.rule.ids></links><search><creatorcontrib>Teimuraz Lezhava</creatorcontrib><creatorcontrib>Buadze, Tamar</creatorcontrib><creatorcontrib>Sigua, Nino</creatorcontrib><creatorcontrib>Jokhadze, Tinatin</creatorcontrib><creatorcontrib>Gaiozishvili, Maia</creatorcontrib><creatorcontrib>Sigua, Tamar</creatorcontrib><creatorcontrib>Kulijanashvili, Natia</creatorcontrib><title>Epigenetic Variability of Ribosomal Cistrons of Acrocentric Chromatids of Chromosomes 14 in Fetuses and Newborns with Down Syndrome</title><title>Cytology and genetics</title><addtitle>Cytol. Genet</addtitle><description>Following the completion of the Human Genome Project, the strategic focus of modern genetics shifted towards functional genomics, encompassing non-coding regions of DNA, including total non-coding DNA and satellite stalks with ribosomal cistrons. These consist of repetitive sequences of nucleotides localized in heterochromatin, the functions of which still require clarification. The present study investigates the activity of ribosomal cistrons within chromatid satellite stalks (NOR heterochromatin) of acrocentric chromosomes in patients with Down Syndrome +21 (DS). The study comprised: 29 healthy fetuses (441 metaphases from cultivated amniotic fluid); 8 fetuses with DS (190 metaphases from cultivated amniotic fluid); 10 healthy newborns (290 metaphases from cultivated lymphocytes); 10 newborn patients with DS (273 metaphases from cultivated lymphocytes) including: 5 newborn patients with trisomy DS (81 metaphases) and 5 mosaic form of newborns with DS (46, XX or 46, XY/47, XX, +21 or 47, XY, +21) (192 metaphases). The activity of ribosomal cistrons of chromatid on the 14 chromosomes included in associations in the control group (healthy fetuses and healthy newborns) corresponding to the order: 21 > 14 = 22 = 13 > 15 and 21 > 14 > 22 > 13 > 15, respectively. In fetuses with DS (21 > 22 > 15 > 13 > 14), in newborns with DS (21 > 13 > 15 = 22 > 14), and with mosaicism of cells of newborns with DS (21 > 13 > 15 > 22 > 14), a statistically significant decrease in the activity of entering associations of chromatids 14 chromosomes was noted. It is noteworthy that, in fetuses, in newborns, and with mosaicism of cells of newborns with DS activity of entering in associations of 14 chromatids with homologous 14 chromatids were not determined (21:21 > 13:13 > 15:15 > 22:22 > 14:14; 21:21 > 22:22 > 13:13 > 15: 15 > 14:14 and 21:21 > 13:13 > 22:22 > 15:15 > 14:14). In fetuses and newborns (control group), the order was: 21:21 > 22:22 > 14:14 > 13:13 = 15:15 and 14 : 14 = 22:22 > 21:21 > 13:13 > 15 : 15, respectively. These results indicate that in DS, the ribosomal cistrons of chromatids on chromosomes 14 undergo epigenetic changes, leading to a reduction in the activity of ribosomal cistrons on these chromatids. This provides a crucial foundation for the prevention, diagnosis, and treatment of DS. The study of ribosomal gene activity at the level of different acrocentric chromosomes in pathologies represents a new direction for medicine, offering insights into both disease diagnosis and the development of novel treatment strategies in the future.</description><subject>Amniotic fluid</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Chromatids</subject><subject>Chromosomes</subject><subject>Cistrons</subject><subject>Diagnosis</subject><subject>disease diagnosis</subject><subject>Down syndrome</subject><subject>Down's syndrome</subject><subject>Epigenetics</subject><subject>Fetuses</subject><subject>genes</subject><subject>Genetic variability</subject><subject>genomics</subject><subject>Heterochromatin</subject><subject>Human Genetics</subject><subject>Human Genome Project</subject><subject>humans</subject><subject>intergenic DNA</subject><subject>Lymphocytes</subject><subject>medicine</subject><subject>Mosaicism</subject><subject>Neonates</subject><subject>Nucleotide sequence</subject><subject>nucleotides</subject><subject>Satellite DNA</subject><subject>satellites</subject><subject>Statistical analysis</subject><subject>trisomics</subject><subject>Trisomy</subject><issn>0095-4527</issn><issn>1934-9440</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp1kctKAzEUhoMoWC8P4C7gxs1objPTLEutFygKVt0OmcyZGpkmNUkpXfviZlpBUFyFk__7fsIJQmeUXHJK-NWMEJmLnJVMkJyQUuyhAZVcZFIIso8GfZz1-SE6CuGdkLxgnA_Q52Rp5mAhGo1flTeqNp2JG-xa_GRqF9xCdXhsQvTOhv52pL3TYKNPwvjNpzyaZptsp96AgKnAxuIbiKuQJmUb_ADr2vnUsTbxDV-7tcWzjW2SAifooFVdgNPv8xi93Eyex3fZ9PH2fjyaZppxGjMJlDWcAWm4JENFNJMSWF7oQteKN6op2JDKUlJNh3XTlkAEbQWTBZFQQCv4MbrY9S69-1hBiNXCBA1dpyy4Vag4zXk5FFwWCT3_hb67lbfpdYlK2y3KnPcU3VFpJyF4aKulNwvlNxUlPcerP9-SHLZzQmLtHPxP8__SF3LljzI</recordid><startdate>20241001</startdate><enddate>20241001</enddate><creator>Teimuraz Lezhava</creator><creator>Buadze, Tamar</creator><creator>Sigua, Nino</creator><creator>Jokhadze, Tinatin</creator><creator>Gaiozishvili, Maia</creator><creator>Sigua, Tamar</creator><creator>Kulijanashvili, Natia</creator><general>Pleiades Publishing</general><general>Springer Nature B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7S9</scope><scope>L.6</scope></search><sort><creationdate>20241001</creationdate><title>Epigenetic Variability of Ribosomal Cistrons of Acrocentric Chromatids of Chromosomes 14 in Fetuses and Newborns with Down Syndrome</title><author>Teimuraz Lezhava ; Buadze, Tamar ; Sigua, Nino ; Jokhadze, Tinatin ; Gaiozishvili, Maia ; Sigua, Tamar ; Kulijanashvili, Natia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c231t-9e12d32e0d3908a0c299e256c6cba3dad62819791c18bdf7e041f429609e6ef43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Amniotic fluid</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Chromatids</topic><topic>Chromosomes</topic><topic>Cistrons</topic><topic>Diagnosis</topic><topic>disease diagnosis</topic><topic>Down syndrome</topic><topic>Down's syndrome</topic><topic>Epigenetics</topic><topic>Fetuses</topic><topic>genes</topic><topic>Genetic variability</topic><topic>genomics</topic><topic>Heterochromatin</topic><topic>Human Genetics</topic><topic>Human Genome Project</topic><topic>humans</topic><topic>intergenic DNA</topic><topic>Lymphocytes</topic><topic>medicine</topic><topic>Mosaicism</topic><topic>Neonates</topic><topic>Nucleotide sequence</topic><topic>nucleotides</topic><topic>Satellite DNA</topic><topic>satellites</topic><topic>Statistical analysis</topic><topic>trisomics</topic><topic>Trisomy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Teimuraz Lezhava</creatorcontrib><creatorcontrib>Buadze, Tamar</creatorcontrib><creatorcontrib>Sigua, Nino</creatorcontrib><creatorcontrib>Jokhadze, Tinatin</creatorcontrib><creatorcontrib>Gaiozishvili, Maia</creatorcontrib><creatorcontrib>Sigua, Tamar</creatorcontrib><creatorcontrib>Kulijanashvili, Natia</creatorcontrib><collection>CrossRef</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Cytology and genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Teimuraz Lezhava</au><au>Buadze, Tamar</au><au>Sigua, Nino</au><au>Jokhadze, Tinatin</au><au>Gaiozishvili, Maia</au><au>Sigua, Tamar</au><au>Kulijanashvili, Natia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epigenetic Variability of Ribosomal Cistrons of Acrocentric Chromatids of Chromosomes 14 in Fetuses and Newborns with Down Syndrome</atitle><jtitle>Cytology and genetics</jtitle><stitle>Cytol. Genet</stitle><date>2024-10-01</date><risdate>2024</risdate><volume>58</volume><issue>5</issue><spage>513</spage><epage>522</epage><pages>513-522</pages><issn>0095-4527</issn><eissn>1934-9440</eissn><abstract>Following the completion of the Human Genome Project, the strategic focus of modern genetics shifted towards functional genomics, encompassing non-coding regions of DNA, including total non-coding DNA and satellite stalks with ribosomal cistrons. These consist of repetitive sequences of nucleotides localized in heterochromatin, the functions of which still require clarification. The present study investigates the activity of ribosomal cistrons within chromatid satellite stalks (NOR heterochromatin) of acrocentric chromosomes in patients with Down Syndrome +21 (DS). The study comprised: 29 healthy fetuses (441 metaphases from cultivated amniotic fluid); 8 fetuses with DS (190 metaphases from cultivated amniotic fluid); 10 healthy newborns (290 metaphases from cultivated lymphocytes); 10 newborn patients with DS (273 metaphases from cultivated lymphocytes) including: 5 newborn patients with trisomy DS (81 metaphases) and 5 mosaic form of newborns with DS (46, XX or 46, XY/47, XX, +21 or 47, XY, +21) (192 metaphases). The activity of ribosomal cistrons of chromatid on the 14 chromosomes included in associations in the control group (healthy fetuses and healthy newborns) corresponding to the order: 21 > 14 = 22 = 13 > 15 and 21 > 14 > 22 > 13 > 15, respectively. In fetuses with DS (21 > 22 > 15 > 13 > 14), in newborns with DS (21 > 13 > 15 = 22 > 14), and with mosaicism of cells of newborns with DS (21 > 13 > 15 > 22 > 14), a statistically significant decrease in the activity of entering associations of chromatids 14 chromosomes was noted. It is noteworthy that, in fetuses, in newborns, and with mosaicism of cells of newborns with DS activity of entering in associations of 14 chromatids with homologous 14 chromatids were not determined (21:21 > 13:13 > 15:15 > 22:22 > 14:14; 21:21 > 22:22 > 13:13 > 15: 15 > 14:14 and 21:21 > 13:13 > 22:22 > 15:15 > 14:14). In fetuses and newborns (control group), the order was: 21:21 > 22:22 > 14:14 > 13:13 = 15:15 and 14 : 14 = 22:22 > 21:21 > 13:13 > 15 : 15, respectively. These results indicate that in DS, the ribosomal cistrons of chromatids on chromosomes 14 undergo epigenetic changes, leading to a reduction in the activity of ribosomal cistrons on these chromatids. This provides a crucial foundation for the prevention, diagnosis, and treatment of DS. The study of ribosomal gene activity at the level of different acrocentric chromosomes in pathologies represents a new direction for medicine, offering insights into both disease diagnosis and the development of novel treatment strategies in the future.</abstract><cop>Moscow</cop><pub>Pleiades Publishing</pub><doi>10.3103/S0095452724050074</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0095-4527 |
| ispartof | Cytology and genetics, 2024-10, Vol.58 (5), p.513-522 |
| issn | 0095-4527 1934-9440 |
| language | eng |
| recordid | cdi_proquest_journals_3107467536 |
| source | SpringerLink Journals - AutoHoldings |
| subjects | Amniotic fluid Biomedical and Life Sciences Biomedicine Chromatids Chromosomes Cistrons Diagnosis disease diagnosis Down syndrome Down's syndrome Epigenetics Fetuses genes Genetic variability genomics Heterochromatin Human Genetics Human Genome Project humans intergenic DNA Lymphocytes medicine Mosaicism Neonates Nucleotide sequence nucleotides Satellite DNA satellites Statistical analysis trisomics Trisomy |
| title | Epigenetic Variability of Ribosomal Cistrons of Acrocentric Chromatids of Chromosomes 14 in Fetuses and Newborns with Down Syndrome |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-16T22%3A55%3A56IST&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=Epigenetic%20Variability%20of%20Ribosomal%20Cistrons%20of%20Acrocentric%20Chromatids%20of%20Chromosomes%2014%20in%20Fetuses%20and%20Newborns%20with%20Down%20Syndrome&rft.jtitle=Cytology%20and%20genetics&rft.au=Teimuraz%20Lezhava&rft.date=2024-10-01&rft.volume=58&rft.issue=5&rft.spage=513&rft.epage=522&rft.pages=513-522&rft.issn=0095-4527&rft.eissn=1934-9440&rft_id=info:doi/10.3103/S0095452724050074&rft_dat=%3Cproquest_cross%3E3153784396%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3107467536&rft_id=info:pmid/&rfr_iscdi=true |