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Fungal dysbiosis predicts the diagnosis of pediatric Crohn's disease
To investigate the accuracy of fungal dysbiosis in mucosa and stool for predicting the diagnosis of Crohn's disease (CD). Children were prospectively enrolled in two medical centers: one university hospital and one private gastroenterology clinic in the city of Riyadh, Kingdom of Saudi Arabia....
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| Published in: | World journal of gastroenterology : WJG 2018-10, Vol.24 (39), p.4510-4516 |
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| container_title | World journal of gastroenterology : WJG |
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| creator | El Mouzan, Mohammad I Korolev, Kirill S Al Mofarreh, Mohammad A Menon, Rajita Winter, Harland S Al Sarkhy, Ahmad A Dowd, Scot E Al Barrag, Ahmad M Assiri, Asaad A |
| description | To investigate the accuracy of fungal dysbiosis in mucosa and stool for predicting the diagnosis of Crohn's disease (CD).
Children were prospectively enrolled in two medical centers: one university hospital and one private gastroenterology clinic in the city of Riyadh, Kingdom of Saudi Arabia. The children with confirmed diagnosis of CD by standard guidelines were considered cases, and the others were considered non-inflammatory bowel disease controls. Mucosal and stool samples were sequenced utilizing Illumina MiSeq chemistry following the manufacturer's protocols, and abundance and diversity of fungal taxa in mucosa and stool were analyzed. Sparse logistic regression was used to predict the diagnosis of CD. The accuracy of the classifier was tested by computing the receiver operating characteristic curves with 5-fold stratified cross-validation under 100 permutations of the training data partition and the mean area under the curve (AUC) was calculated.
All the children were Saudi nationals. There were 15 children with CD and 20 controls. The mean age was 13.9 (range: 6.7-17.8) years for CD children and 13.9 (3.25-18.6) years for controls, and 10/15 (67%) of the CD and 13/20 (65%) of the control subjects were boys. CD locations at diagnosis were ileal (L1) in 4 and colonic (L3) in 11 children, while CD behavior was non-stricturing and non-penetrating (B1) in 12 and stricturing (B2) in 3 children. The mean AUC for the fungal dysbiosis classifier was significantly higher in stools (AUC = 0.85 ± 0.057) than in mucosa (AUC = 0.71 ± 0.067) (
< 0.001). Most fungal species were significantly more depleted in stools than mucosal samples, except for
and
, which were significantly more abundant. Diversity was significantly more reduced in stools than in mucosa.
We found high AUC of fungal dysbiosis in fecal samples of children with CD, suggesting high accuracy in predicting diagnosis of CD. |
| doi_str_mv | 10.3748/wjg.v24.i39.4510 |
| format | article |
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Children were prospectively enrolled in two medical centers: one university hospital and one private gastroenterology clinic in the city of Riyadh, Kingdom of Saudi Arabia. The children with confirmed diagnosis of CD by standard guidelines were considered cases, and the others were considered non-inflammatory bowel disease controls. Mucosal and stool samples were sequenced utilizing Illumina MiSeq chemistry following the manufacturer's protocols, and abundance and diversity of fungal taxa in mucosa and stool were analyzed. Sparse logistic regression was used to predict the diagnosis of CD. The accuracy of the classifier was tested by computing the receiver operating characteristic curves with 5-fold stratified cross-validation under 100 permutations of the training data partition and the mean area under the curve (AUC) was calculated.
All the children were Saudi nationals. There were 15 children with CD and 20 controls. The mean age was 13.9 (range: 6.7-17.8) years for CD children and 13.9 (3.25-18.6) years for controls, and 10/15 (67%) of the CD and 13/20 (65%) of the control subjects were boys. CD locations at diagnosis were ileal (L1) in 4 and colonic (L3) in 11 children, while CD behavior was non-stricturing and non-penetrating (B1) in 12 and stricturing (B2) in 3 children. The mean AUC for the fungal dysbiosis classifier was significantly higher in stools (AUC = 0.85 ± 0.057) than in mucosa (AUC = 0.71 ± 0.067) (
< 0.001). Most fungal species were significantly more depleted in stools than mucosal samples, except for
and
, which were significantly more abundant. Diversity was significantly more reduced in stools than in mucosa.
We found high AUC of fungal dysbiosis in fecal samples of children with CD, suggesting high accuracy in predicting diagnosis of CD.</description><identifier>ISSN: 1007-9327</identifier><identifier>EISSN: 2219-2840</identifier><identifier>DOI: 10.3748/wjg.v24.i39.4510</identifier><identifier>PMID: 30356965</identifier><language>eng</language><publisher>United States: Baishideng Publishing Group Inc</publisher><subject>Adolescent ; Case-Control Studies ; Child ; Crohn Disease - diagnosis ; Crohn Disease - epidemiology ; Crohn Disease - microbiology ; Crohn Disease - pathology ; DNA, Fungal - genetics ; DNA, Fungal - isolation & purification ; Dysbiosis - epidemiology ; Dysbiosis - microbiology ; Feces - microbiology ; Female ; Fungi - genetics ; Fungi - isolation & purification ; Gastrointestinal Microbiome - genetics ; Humans ; Incidence ; Intestinal Mucosa - microbiology ; Intestinal Mucosa - pathology ; Male ; Observational Study ; Prognosis ; Prospective Studies ; Saudi Arabia - epidemiology</subject><ispartof>World journal of gastroenterology : WJG, 2018-10, Vol.24 (39), p.4510-4516</ispartof><rights>The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved. 2018</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c396t-db5599660e493988b3dbf771f13644472cd8a7f314111bb1785bb5d739fc0f6a3</citedby><cites>FETCH-LOGICAL-c396t-db5599660e493988b3dbf771f13644472cd8a7f314111bb1785bb5d739fc0f6a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196340/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196340/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,733,786,790,891,27957,27958,53827,53829</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30356965$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>El Mouzan, Mohammad I</creatorcontrib><creatorcontrib>Korolev, Kirill S</creatorcontrib><creatorcontrib>Al Mofarreh, Mohammad A</creatorcontrib><creatorcontrib>Menon, Rajita</creatorcontrib><creatorcontrib>Winter, Harland S</creatorcontrib><creatorcontrib>Al Sarkhy, Ahmad A</creatorcontrib><creatorcontrib>Dowd, Scot E</creatorcontrib><creatorcontrib>Al Barrag, Ahmad M</creatorcontrib><creatorcontrib>Assiri, Asaad A</creatorcontrib><title>Fungal dysbiosis predicts the diagnosis of pediatric Crohn's disease</title><title>World journal of gastroenterology : WJG</title><addtitle>World J Gastroenterol</addtitle><description>To investigate the accuracy of fungal dysbiosis in mucosa and stool for predicting the diagnosis of Crohn's disease (CD).
Children were prospectively enrolled in two medical centers: one university hospital and one private gastroenterology clinic in the city of Riyadh, Kingdom of Saudi Arabia. The children with confirmed diagnosis of CD by standard guidelines were considered cases, and the others were considered non-inflammatory bowel disease controls. Mucosal and stool samples were sequenced utilizing Illumina MiSeq chemistry following the manufacturer's protocols, and abundance and diversity of fungal taxa in mucosa and stool were analyzed. Sparse logistic regression was used to predict the diagnosis of CD. The accuracy of the classifier was tested by computing the receiver operating characteristic curves with 5-fold stratified cross-validation under 100 permutations of the training data partition and the mean area under the curve (AUC) was calculated.
All the children were Saudi nationals. There were 15 children with CD and 20 controls. The mean age was 13.9 (range: 6.7-17.8) years for CD children and 13.9 (3.25-18.6) years for controls, and 10/15 (67%) of the CD and 13/20 (65%) of the control subjects were boys. CD locations at diagnosis were ileal (L1) in 4 and colonic (L3) in 11 children, while CD behavior was non-stricturing and non-penetrating (B1) in 12 and stricturing (B2) in 3 children. The mean AUC for the fungal dysbiosis classifier was significantly higher in stools (AUC = 0.85 ± 0.057) than in mucosa (AUC = 0.71 ± 0.067) (
< 0.001). Most fungal species were significantly more depleted in stools than mucosal samples, except for
and
, which were significantly more abundant. Diversity was significantly more reduced in stools than in mucosa.
We found high AUC of fungal dysbiosis in fecal samples of children with CD, suggesting high accuracy in predicting diagnosis of CD.</description><subject>Adolescent</subject><subject>Case-Control Studies</subject><subject>Child</subject><subject>Crohn Disease - diagnosis</subject><subject>Crohn Disease - epidemiology</subject><subject>Crohn Disease - microbiology</subject><subject>Crohn Disease - pathology</subject><subject>DNA, Fungal - genetics</subject><subject>DNA, Fungal - isolation & purification</subject><subject>Dysbiosis - epidemiology</subject><subject>Dysbiosis - microbiology</subject><subject>Feces - microbiology</subject><subject>Female</subject><subject>Fungi - genetics</subject><subject>Fungi - isolation & purification</subject><subject>Gastrointestinal Microbiome - genetics</subject><subject>Humans</subject><subject>Incidence</subject><subject>Intestinal Mucosa - microbiology</subject><subject>Intestinal Mucosa - pathology</subject><subject>Male</subject><subject>Observational Study</subject><subject>Prognosis</subject><subject>Prospective Studies</subject><subject>Saudi Arabia - epidemiology</subject><issn>1007-9327</issn><issn>2219-2840</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNpVkDtPwzAQxy0EouWxM6FssKT47XhBQoUCUiUWmC07cVJXaRLspKjfHpeWCqaT7v-40w-AKwQnRNDs7mtZTdaYThyRE8oQPAJjjJFMcUbhMRgjCEUqCRYjcBbCEkJMCMOnYEQgYVxyNgaPs6GpdJ0Um2BcG1xIOm8Ll_ch6Rc2KZyump91WyZdFHTvXZ5MfbtobkKUg9XBXoCTUtfBXu7nOfiYPb1PX9L52_Pr9GGe5kTyPi0MY1JyDi2VRGaZIYUphUAlIpxSKnBeZFqUBFGEkDFIZMwYVggiyxyWXJNzcL_r7QazskVum97rWnXerbTfqFY79V9p3EJV7VpxJDmhMBbc7gt8-znY0KuVC7mta93YdggKI8ywZFzwaIU7a-7bELwtD2cQVFv4KsJXEb6K8NUWfoxc_33vEPilTb4BWgSCGQ</recordid><startdate>20181021</startdate><enddate>20181021</enddate><creator>El Mouzan, Mohammad I</creator><creator>Korolev, Kirill S</creator><creator>Al Mofarreh, Mohammad A</creator><creator>Menon, Rajita</creator><creator>Winter, Harland S</creator><creator>Al Sarkhy, Ahmad A</creator><creator>Dowd, Scot E</creator><creator>Al Barrag, Ahmad M</creator><creator>Assiri, Asaad A</creator><general>Baishideng Publishing Group 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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20181021</creationdate><title>Fungal dysbiosis predicts the diagnosis of pediatric Crohn's disease</title><author>El Mouzan, Mohammad I ; Korolev, Kirill S ; Al Mofarreh, Mohammad A ; Menon, Rajita ; Winter, Harland S ; Al Sarkhy, Ahmad A ; Dowd, Scot E ; Al Barrag, Ahmad M ; Assiri, Asaad A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c396t-db5599660e493988b3dbf771f13644472cd8a7f314111bb1785bb5d739fc0f6a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adolescent</topic><topic>Case-Control Studies</topic><topic>Child</topic><topic>Crohn Disease - diagnosis</topic><topic>Crohn Disease - epidemiology</topic><topic>Crohn Disease - microbiology</topic><topic>Crohn Disease - pathology</topic><topic>DNA, Fungal - genetics</topic><topic>DNA, Fungal - isolation & purification</topic><topic>Dysbiosis - epidemiology</topic><topic>Dysbiosis - microbiology</topic><topic>Feces - microbiology</topic><topic>Female</topic><topic>Fungi - genetics</topic><topic>Fungi - isolation & purification</topic><topic>Gastrointestinal Microbiome - genetics</topic><topic>Humans</topic><topic>Incidence</topic><topic>Intestinal Mucosa - microbiology</topic><topic>Intestinal Mucosa - pathology</topic><topic>Male</topic><topic>Observational Study</topic><topic>Prognosis</topic><topic>Prospective Studies</topic><topic>Saudi Arabia - epidemiology</topic><toplevel>online_resources</toplevel><creatorcontrib>El Mouzan, Mohammad I</creatorcontrib><creatorcontrib>Korolev, Kirill S</creatorcontrib><creatorcontrib>Al Mofarreh, Mohammad A</creatorcontrib><creatorcontrib>Menon, Rajita</creatorcontrib><creatorcontrib>Winter, Harland S</creatorcontrib><creatorcontrib>Al Sarkhy, Ahmad A</creatorcontrib><creatorcontrib>Dowd, Scot E</creatorcontrib><creatorcontrib>Al Barrag, Ahmad M</creatorcontrib><creatorcontrib>Assiri, Asaad A</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>World journal of gastroenterology : WJG</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>El Mouzan, Mohammad I</au><au>Korolev, Kirill S</au><au>Al Mofarreh, Mohammad A</au><au>Menon, Rajita</au><au>Winter, Harland S</au><au>Al Sarkhy, Ahmad A</au><au>Dowd, Scot E</au><au>Al Barrag, Ahmad M</au><au>Assiri, Asaad A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fungal dysbiosis predicts the diagnosis of pediatric Crohn's disease</atitle><jtitle>World journal of gastroenterology : WJG</jtitle><addtitle>World J Gastroenterol</addtitle><date>2018-10-21</date><risdate>2018</risdate><volume>24</volume><issue>39</issue><spage>4510</spage><epage>4516</epage><pages>4510-4516</pages><issn>1007-9327</issn><eissn>2219-2840</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><notes>Correspondence to: Mohammad I El Mouzan, MD, Professor and Consultant Pediatrician, Department of Pediatrics, Gastroenterology Unit, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia. drmouzan@gmail.com</notes><notes>Author contributions: El Mouzan MI and Winter HS contributed to the conception and design of the study; Al Mofarreh MA, Al Sarkhy AA, Assiri AA and Al Barrag AM contributed to data acquisition and samples’ storage; Dowd SE performed DNA extraction and fungal sequencing; Korolev KS and Menon R performed the biostatistics and bioinformatics; El Mouzan MI drafted the manuscript and all co-authors contributed to reviewing, editing and giving approval of the final manuscript.</notes><notes>Telephone: +966-55-5479281 Fax: +966-11-4679364</notes><abstract>To investigate the accuracy of fungal dysbiosis in mucosa and stool for predicting the diagnosis of Crohn's disease (CD).
Children were prospectively enrolled in two medical centers: one university hospital and one private gastroenterology clinic in the city of Riyadh, Kingdom of Saudi Arabia. The children with confirmed diagnosis of CD by standard guidelines were considered cases, and the others were considered non-inflammatory bowel disease controls. Mucosal and stool samples were sequenced utilizing Illumina MiSeq chemistry following the manufacturer's protocols, and abundance and diversity of fungal taxa in mucosa and stool were analyzed. Sparse logistic regression was used to predict the diagnosis of CD. The accuracy of the classifier was tested by computing the receiver operating characteristic curves with 5-fold stratified cross-validation under 100 permutations of the training data partition and the mean area under the curve (AUC) was calculated.
All the children were Saudi nationals. There were 15 children with CD and 20 controls. The mean age was 13.9 (range: 6.7-17.8) years for CD children and 13.9 (3.25-18.6) years for controls, and 10/15 (67%) of the CD and 13/20 (65%) of the control subjects were boys. CD locations at diagnosis were ileal (L1) in 4 and colonic (L3) in 11 children, while CD behavior was non-stricturing and non-penetrating (B1) in 12 and stricturing (B2) in 3 children. The mean AUC for the fungal dysbiosis classifier was significantly higher in stools (AUC = 0.85 ± 0.057) than in mucosa (AUC = 0.71 ± 0.067) (
< 0.001). Most fungal species were significantly more depleted in stools than mucosal samples, except for
and
, which were significantly more abundant. Diversity was significantly more reduced in stools than in mucosa.
We found high AUC of fungal dysbiosis in fecal samples of children with CD, suggesting high accuracy in predicting diagnosis of CD.</abstract><cop>United States</cop><pub>Baishideng Publishing Group Inc</pub><pmid>30356965</pmid><doi>10.3748/wjg.v24.i39.4510</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Case-Control Studies Child Crohn Disease - diagnosis Crohn Disease - epidemiology Crohn Disease - microbiology Crohn Disease - pathology DNA, Fungal - genetics DNA, Fungal - isolation & purification Dysbiosis - epidemiology Dysbiosis - microbiology Feces - microbiology Female Fungi - genetics Fungi - isolation & purification Gastrointestinal Microbiome - genetics Humans Incidence Intestinal Mucosa - microbiology Intestinal Mucosa - pathology Male Observational Study Prognosis Prospective Studies Saudi Arabia - epidemiology |
| title | Fungal dysbiosis predicts the diagnosis of pediatric Crohn's disease |
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