Loading…
Quantitation of nasal development in the early prenatal period using geometric morphometrics and MRI: a new insight into the critical period of Binder phenotype
Objectives Disturbance of the development of the nasal septum in the early prenatal period causes congenital facial anomalies characterized by a flat nose and defects of the anterior nasal spine (ANS), such as Binder phenotype. The present research aimed to assess the development of the nasal septum...
Saved in:
Published in: | Prenatal diagnosis 2017-09, Vol.37 (9), p.907-915 |
---|---|
Main Authors: | , , , , , , , , , , , |
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-c3456-7f2c9019818fd5ef5d8319a0f2693499a808008278e7baf8bb6f6ecffca98d2e3 |
---|---|
cites | cdi_FETCH-LOGICAL-c3456-7f2c9019818fd5ef5d8319a0f2693499a808008278e7baf8bb6f6ecffca98d2e3 |
container_end_page | 915 |
container_issue | 9 |
container_start_page | 907 |
container_title | Prenatal diagnosis |
container_volume | 37 |
creator | Katsube, Motoki Yamada, Shigehito Miyazaki, Reina Yamaguchi, Yutaka Makishima, Haruyuki Takakuwa, Tetsuya Yamamoto, Akira Fujii, Yosuke Morimoto, Naoki Ito, Tsuyoshi Imai, Hirohiko Suzuki, Shigehiko |
description | Objectives
Disturbance of the development of the nasal septum in the early prenatal period causes congenital facial anomalies characterized by a flat nose and defects of the anterior nasal spine (ANS), such as Binder phenotype. The present research aimed to assess the development of the nasal septum and the ANS with growth in the early prenatal period.
Methods
Magnetic resonance images were obtained from 56 specimens. Mid‐sagittal images were analyzed by using geometric morphometrics for the development of the nasal septum, and angle analysis was performed for the development of the ANS. Additionally, we calculated and visualized the ontogenetic allometry of the nasal septum.
Results
Our results showed that the nasal septum changed shape in the anteroposterior direction in smaller specimens, while it maintained an almost isometric shape in larger specimens. Furthermore, mathematical evidence revealed that the maturation periods of the shapes of the ANS and the nasal septum were around 12 and 14 weeks of gestation, respectively.
Conclusion
The anteroposterior development of the nasal septum is specific until 14 weeks of gestation, and it is important for nasal protrusion and the development of the ANS. Therefore, the disturbance of such development could induce low nasal deformity, including Binder phenotype. © 2017 John Wiley & Sons, Ltd.
What's already known about this topic?
When and how the anterior nasal spine (ANS) grows is unclear.
The disturbance of the development of the nasal septum during early prenatal period causes Binder phenotype. The critical period for this anomaly has been reported as 6 to 9 weeks of gestation by etiological research; however, embryological evidence regarding the same has not been presented.
What does this study add?
The nasal septum develops in the anteroposterior direction in the early prenatal period, which is important for nasal protrusion and the development of the ANS.
The shapes of the nasal septum and the ANS are matured at around the end of the first trimester of pregnancy.
The critical period for Binder phenotype could be extended to 14 weeks of gestation. |
doi_str_mv | 10.1002/pd.5106 |
format | article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1915881254</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1915881254</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3456-7f2c9019818fd5ef5d8319a0f2693499a808008278e7baf8bb6f6ecffca98d2e3</originalsourceid><addsrcrecordid>eNp10d1qFDEYgOFQLHatxTuQgAcKZWuS-Us80_5DRS31eMgmX3ZTZpKYZCx7N71Us91VQfBkMoGHNwkfQq8oOaGEsPdBnzSUtHtoRono5oSx6hmaEVr-K97QA_QipfsCORPdc3TAeNs1tahm6PHbJF22WWbrHfYGO5nkgDX8hMGHEVzG1uG8AgwyDmscIjiZiwgQrdd4StYt8RL8CDlahUcfw2q3SVg6jT_fXn_AEjt4KKVkl6tNMfunpoo2W_W3Vs7_ZJ2GiMMKnM_rAC_RvpFDgqPdeoi-X5zfnV7Nb75cXp9-vJmrqm7aeWeYEuW9nHKjGzCN5hUVkhjWiqoWQnLCCeGs49AtpOGLRWtaUMYoKbhmUB2id9tuiP7HBCn3o00KhkE68FPqqaAN55Q1daFv_qH3foqu3K6ompCWlk9Rb7dKRZ9SBNOHaEcZ1z0l_WZofdD9ZmhFvt71psUI-o_7PaUCjrfgwQ6w_l-n_3r2lPsFcwihhA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1940061400</pqid></control><display><type>article</type><title>Quantitation of nasal development in the early prenatal period using geometric morphometrics and MRI: a new insight into the critical period of Binder phenotype</title><source>Wiley</source><creator>Katsube, Motoki ; Yamada, Shigehito ; Miyazaki, Reina ; Yamaguchi, Yutaka ; Makishima, Haruyuki ; Takakuwa, Tetsuya ; Yamamoto, Akira ; Fujii, Yosuke ; Morimoto, Naoki ; Ito, Tsuyoshi ; Imai, Hirohiko ; Suzuki, Shigehiko</creator><creatorcontrib>Katsube, Motoki ; Yamada, Shigehito ; Miyazaki, Reina ; Yamaguchi, Yutaka ; Makishima, Haruyuki ; Takakuwa, Tetsuya ; Yamamoto, Akira ; Fujii, Yosuke ; Morimoto, Naoki ; Ito, Tsuyoshi ; Imai, Hirohiko ; Suzuki, Shigehiko</creatorcontrib><description>Objectives
Disturbance of the development of the nasal septum in the early prenatal period causes congenital facial anomalies characterized by a flat nose and defects of the anterior nasal spine (ANS), such as Binder phenotype. The present research aimed to assess the development of the nasal septum and the ANS with growth in the early prenatal period.
Methods
Magnetic resonance images were obtained from 56 specimens. Mid‐sagittal images were analyzed by using geometric morphometrics for the development of the nasal septum, and angle analysis was performed for the development of the ANS. Additionally, we calculated and visualized the ontogenetic allometry of the nasal septum.
Results
Our results showed that the nasal septum changed shape in the anteroposterior direction in smaller specimens, while it maintained an almost isometric shape in larger specimens. Furthermore, mathematical evidence revealed that the maturation periods of the shapes of the ANS and the nasal septum were around 12 and 14 weeks of gestation, respectively.
Conclusion
The anteroposterior development of the nasal septum is specific until 14 weeks of gestation, and it is important for nasal protrusion and the development of the ANS. Therefore, the disturbance of such development could induce low nasal deformity, including Binder phenotype. © 2017 John Wiley & Sons, Ltd.
What's already known about this topic?
When and how the anterior nasal spine (ANS) grows is unclear.
The disturbance of the development of the nasal septum during early prenatal period causes Binder phenotype. The critical period for this anomaly has been reported as 6 to 9 weeks of gestation by etiological research; however, embryological evidence regarding the same has not been presented.
What does this study add?
The nasal septum develops in the anteroposterior direction in the early prenatal period, which is important for nasal protrusion and the development of the ANS.
The shapes of the nasal septum and the ANS are matured at around the end of the first trimester of pregnancy.
The critical period for Binder phenotype could be extended to 14 weeks of gestation.</description><identifier>ISSN: 0197-3851</identifier><identifier>EISSN: 1097-0223</identifier><identifier>DOI: 10.1002/pd.5106</identifier><identifier>PMID: 28675493</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Allometry ; Anomalies ; Critical period ; Deformation mechanisms ; Disturbance ; Etiology ; Female ; Genotype & phenotype ; Gestation ; Gestational Age ; Humans ; Isometric ; Magnetic Resonance Imaging ; Maturation ; Morphometry ; Nasal Septum - embryology ; Nose ; Nose - abnormalities ; Ontogeny ; Phenotype ; Pregnancy ; Quantitation ; Respiratory therapy ; Septum ; Spine</subject><ispartof>Prenatal diagnosis, 2017-09, Vol.37 (9), p.907-915</ispartof><rights>2017 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3456-7f2c9019818fd5ef5d8319a0f2693499a808008278e7baf8bb6f6ecffca98d2e3</citedby><cites>FETCH-LOGICAL-c3456-7f2c9019818fd5ef5d8319a0f2693499a808008278e7baf8bb6f6ecffca98d2e3</cites><orcidid>0000-0002-5674-109X ; 0000-0001-7711-2439 ; 0000-0002-8194-6927</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28675493$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Katsube, Motoki</creatorcontrib><creatorcontrib>Yamada, Shigehito</creatorcontrib><creatorcontrib>Miyazaki, Reina</creatorcontrib><creatorcontrib>Yamaguchi, Yutaka</creatorcontrib><creatorcontrib>Makishima, Haruyuki</creatorcontrib><creatorcontrib>Takakuwa, Tetsuya</creatorcontrib><creatorcontrib>Yamamoto, Akira</creatorcontrib><creatorcontrib>Fujii, Yosuke</creatorcontrib><creatorcontrib>Morimoto, Naoki</creatorcontrib><creatorcontrib>Ito, Tsuyoshi</creatorcontrib><creatorcontrib>Imai, Hirohiko</creatorcontrib><creatorcontrib>Suzuki, Shigehiko</creatorcontrib><title>Quantitation of nasal development in the early prenatal period using geometric morphometrics and MRI: a new insight into the critical period of Binder phenotype</title><title>Prenatal diagnosis</title><addtitle>Prenat Diagn</addtitle><description>Objectives
Disturbance of the development of the nasal septum in the early prenatal period causes congenital facial anomalies characterized by a flat nose and defects of the anterior nasal spine (ANS), such as Binder phenotype. The present research aimed to assess the development of the nasal septum and the ANS with growth in the early prenatal period.
Methods
Magnetic resonance images were obtained from 56 specimens. Mid‐sagittal images were analyzed by using geometric morphometrics for the development of the nasal septum, and angle analysis was performed for the development of the ANS. Additionally, we calculated and visualized the ontogenetic allometry of the nasal septum.
Results
Our results showed that the nasal septum changed shape in the anteroposterior direction in smaller specimens, while it maintained an almost isometric shape in larger specimens. Furthermore, mathematical evidence revealed that the maturation periods of the shapes of the ANS and the nasal septum were around 12 and 14 weeks of gestation, respectively.
Conclusion
The anteroposterior development of the nasal septum is specific until 14 weeks of gestation, and it is important for nasal protrusion and the development of the ANS. Therefore, the disturbance of such development could induce low nasal deformity, including Binder phenotype. © 2017 John Wiley & Sons, Ltd.
What's already known about this topic?
When and how the anterior nasal spine (ANS) grows is unclear.
The disturbance of the development of the nasal septum during early prenatal period causes Binder phenotype. The critical period for this anomaly has been reported as 6 to 9 weeks of gestation by etiological research; however, embryological evidence regarding the same has not been presented.
What does this study add?
The nasal septum develops in the anteroposterior direction in the early prenatal period, which is important for nasal protrusion and the development of the ANS.
The shapes of the nasal septum and the ANS are matured at around the end of the first trimester of pregnancy.
The critical period for Binder phenotype could be extended to 14 weeks of gestation.</description><subject>Allometry</subject><subject>Anomalies</subject><subject>Critical period</subject><subject>Deformation mechanisms</subject><subject>Disturbance</subject><subject>Etiology</subject><subject>Female</subject><subject>Genotype & phenotype</subject><subject>Gestation</subject><subject>Gestational Age</subject><subject>Humans</subject><subject>Isometric</subject><subject>Magnetic Resonance Imaging</subject><subject>Maturation</subject><subject>Morphometry</subject><subject>Nasal Septum - embryology</subject><subject>Nose</subject><subject>Nose - abnormalities</subject><subject>Ontogeny</subject><subject>Phenotype</subject><subject>Pregnancy</subject><subject>Quantitation</subject><subject>Respiratory therapy</subject><subject>Septum</subject><subject>Spine</subject><issn>0197-3851</issn><issn>1097-0223</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNp10d1qFDEYgOFQLHatxTuQgAcKZWuS-Us80_5DRS31eMgmX3ZTZpKYZCx7N71Us91VQfBkMoGHNwkfQq8oOaGEsPdBnzSUtHtoRono5oSx6hmaEVr-K97QA_QipfsCORPdc3TAeNs1tahm6PHbJF22WWbrHfYGO5nkgDX8hMGHEVzG1uG8AgwyDmscIjiZiwgQrdd4StYt8RL8CDlahUcfw2q3SVg6jT_fXn_AEjt4KKVkl6tNMfunpoo2W_W3Vs7_ZJ2GiMMKnM_rAC_RvpFDgqPdeoi-X5zfnV7Nb75cXp9-vJmrqm7aeWeYEuW9nHKjGzCN5hUVkhjWiqoWQnLCCeGs49AtpOGLRWtaUMYoKbhmUB2id9tuiP7HBCn3o00KhkE68FPqqaAN55Q1daFv_qH3foqu3K6ompCWlk9Rb7dKRZ9SBNOHaEcZ1z0l_WZofdD9ZmhFvt71psUI-o_7PaUCjrfgwQ6w_l-n_3r2lPsFcwihhA</recordid><startdate>201709</startdate><enddate>201709</enddate><creator>Katsube, Motoki</creator><creator>Yamada, Shigehito</creator><creator>Miyazaki, Reina</creator><creator>Yamaguchi, Yutaka</creator><creator>Makishima, Haruyuki</creator><creator>Takakuwa, Tetsuya</creator><creator>Yamamoto, Akira</creator><creator>Fujii, Yosuke</creator><creator>Morimoto, Naoki</creator><creator>Ito, Tsuyoshi</creator><creator>Imai, Hirohiko</creator><creator>Suzuki, Shigehiko</creator><general>Wiley Subscription Services, Inc</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>7QP</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-5674-109X</orcidid><orcidid>https://orcid.org/0000-0001-7711-2439</orcidid><orcidid>https://orcid.org/0000-0002-8194-6927</orcidid></search><sort><creationdate>201709</creationdate><title>Quantitation of nasal development in the early prenatal period using geometric morphometrics and MRI: a new insight into the critical period of Binder phenotype</title><author>Katsube, Motoki ; Yamada, Shigehito ; Miyazaki, Reina ; Yamaguchi, Yutaka ; Makishima, Haruyuki ; Takakuwa, Tetsuya ; Yamamoto, Akira ; Fujii, Yosuke ; Morimoto, Naoki ; Ito, Tsuyoshi ; Imai, Hirohiko ; Suzuki, Shigehiko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3456-7f2c9019818fd5ef5d8319a0f2693499a808008278e7baf8bb6f6ecffca98d2e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Allometry</topic><topic>Anomalies</topic><topic>Critical period</topic><topic>Deformation mechanisms</topic><topic>Disturbance</topic><topic>Etiology</topic><topic>Female</topic><topic>Genotype & phenotype</topic><topic>Gestation</topic><topic>Gestational Age</topic><topic>Humans</topic><topic>Isometric</topic><topic>Magnetic Resonance Imaging</topic><topic>Maturation</topic><topic>Morphometry</topic><topic>Nasal Septum - embryology</topic><topic>Nose</topic><topic>Nose - abnormalities</topic><topic>Ontogeny</topic><topic>Phenotype</topic><topic>Pregnancy</topic><topic>Quantitation</topic><topic>Respiratory therapy</topic><topic>Septum</topic><topic>Spine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Katsube, Motoki</creatorcontrib><creatorcontrib>Yamada, Shigehito</creatorcontrib><creatorcontrib>Miyazaki, Reina</creatorcontrib><creatorcontrib>Yamaguchi, Yutaka</creatorcontrib><creatorcontrib>Makishima, Haruyuki</creatorcontrib><creatorcontrib>Takakuwa, Tetsuya</creatorcontrib><creatorcontrib>Yamamoto, Akira</creatorcontrib><creatorcontrib>Fujii, Yosuke</creatorcontrib><creatorcontrib>Morimoto, Naoki</creatorcontrib><creatorcontrib>Ito, Tsuyoshi</creatorcontrib><creatorcontrib>Imai, Hirohiko</creatorcontrib><creatorcontrib>Suzuki, Shigehiko</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Prenatal diagnosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Katsube, Motoki</au><au>Yamada, Shigehito</au><au>Miyazaki, Reina</au><au>Yamaguchi, Yutaka</au><au>Makishima, Haruyuki</au><au>Takakuwa, Tetsuya</au><au>Yamamoto, Akira</au><au>Fujii, Yosuke</au><au>Morimoto, Naoki</au><au>Ito, Tsuyoshi</au><au>Imai, Hirohiko</au><au>Suzuki, Shigehiko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Quantitation of nasal development in the early prenatal period using geometric morphometrics and MRI: a new insight into the critical period of Binder phenotype</atitle><jtitle>Prenatal diagnosis</jtitle><addtitle>Prenat Diagn</addtitle><date>2017-09</date><risdate>2017</risdate><volume>37</volume><issue>9</issue><spage>907</spage><epage>915</epage><pages>907-915</pages><issn>0197-3851</issn><eissn>1097-0223</eissn><abstract>Objectives
Disturbance of the development of the nasal septum in the early prenatal period causes congenital facial anomalies characterized by a flat nose and defects of the anterior nasal spine (ANS), such as Binder phenotype. The present research aimed to assess the development of the nasal septum and the ANS with growth in the early prenatal period.
Methods
Magnetic resonance images were obtained from 56 specimens. Mid‐sagittal images were analyzed by using geometric morphometrics for the development of the nasal septum, and angle analysis was performed for the development of the ANS. Additionally, we calculated and visualized the ontogenetic allometry of the nasal septum.
Results
Our results showed that the nasal septum changed shape in the anteroposterior direction in smaller specimens, while it maintained an almost isometric shape in larger specimens. Furthermore, mathematical evidence revealed that the maturation periods of the shapes of the ANS and the nasal septum were around 12 and 14 weeks of gestation, respectively.
Conclusion
The anteroposterior development of the nasal septum is specific until 14 weeks of gestation, and it is important for nasal protrusion and the development of the ANS. Therefore, the disturbance of such development could induce low nasal deformity, including Binder phenotype. © 2017 John Wiley & Sons, Ltd.
What's already known about this topic?
When and how the anterior nasal spine (ANS) grows is unclear.
The disturbance of the development of the nasal septum during early prenatal period causes Binder phenotype. The critical period for this anomaly has been reported as 6 to 9 weeks of gestation by etiological research; however, embryological evidence regarding the same has not been presented.
What does this study add?
The nasal septum develops in the anteroposterior direction in the early prenatal period, which is important for nasal protrusion and the development of the ANS.
The shapes of the nasal septum and the ANS are matured at around the end of the first trimester of pregnancy.
The critical period for Binder phenotype could be extended to 14 weeks of gestation.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28675493</pmid><doi>10.1002/pd.5106</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-5674-109X</orcidid><orcidid>https://orcid.org/0000-0001-7711-2439</orcidid><orcidid>https://orcid.org/0000-0002-8194-6927</orcidid></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0197-3851 |
ispartof | Prenatal diagnosis, 2017-09, Vol.37 (9), p.907-915 |
issn | 0197-3851 1097-0223 |
language | eng |
recordid | cdi_proquest_miscellaneous_1915881254 |
source | Wiley |
subjects | Allometry Anomalies Critical period Deformation mechanisms Disturbance Etiology Female Genotype & phenotype Gestation Gestational Age Humans Isometric Magnetic Resonance Imaging Maturation Morphometry Nasal Septum - embryology Nose Nose - abnormalities Ontogeny Phenotype Pregnancy Quantitation Respiratory therapy Septum Spine |
title | Quantitation of nasal development in the early prenatal period using geometric morphometrics and MRI: a new insight into the critical period of Binder phenotype |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-27T16%3A36%3A01IST&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=Quantitation%20of%20nasal%20development%20in%20the%20early%20prenatal%20period%20using%20geometric%20morphometrics%20and%20MRI:%20a%20new%20insight%20into%20the%20critical%20period%20of%20Binder%20phenotype&rft.jtitle=Prenatal%20diagnosis&rft.au=Katsube,%20Motoki&rft.date=2017-09&rft.volume=37&rft.issue=9&rft.spage=907&rft.epage=915&rft.pages=907-915&rft.issn=0197-3851&rft.eissn=1097-0223&rft_id=info:doi/10.1002/pd.5106&rft_dat=%3Cproquest_cross%3E1915881254%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c3456-7f2c9019818fd5ef5d8319a0f2693499a808008278e7baf8bb6f6ecffca98d2e3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1940061400&rft_id=info:pmid/28675493&rfr_iscdi=true |