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Title:          Noninvasive early detection of colorectal cancer by hypermethylation of the
Subject:        Clinical Epigenetics, https://doi.org/10.1186/s13148-022-01302-x
Keywords:       DNA methylation;;Cell-free DNA;Early detection;Colorectal cancer
Author:          Juan Ruiz-Bañobre
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     Item: 
      Title: Noninvasive early detection of colorectal cancer by hypermethylation of the LINC00473 promoter in plasma cell-free DNA
      Children: 
       Item: 
        Title: Abstract 
        Children: 
         Item: 
          Title: Background: 
         Item: 
          Title: Methods: 
         Item: 
          Title: Results: 
         Item: 
          Title: Conclusions: 
       Item: 
        Title: Background
       Item: 
        Title: Results
        Children: 
         Item: 
          Title: Epigenetic regulation of LINC00473 by promoter methylation in colorectal cancer
         Item: 
          Title: Methylation status of the LINC00473 promoter in colorectal tumors
         Item: 
          Title: Methylation status of the LINC00473 promoter in tissue from precancerous colorectal lesions
         Item: 
          Title: Diagnostic potential of methylation of the LINC00473 promoter to detect colorectal cancer and precancerous lesions in plasma cell-free DNA
         Item: 
          Title: Clinical utility of LINC00473 promoter methylation for the noninvasive detection of colorectal cancer during the follow-up of metastatic patients
       Item: 
        Title: Discussion
       Item: 
        Title: Conclusions
       Item: 
        Title: Methods
        Children: 
         Item: 
          Title: Cancer cell lines and treatments
         Item: 
          Title: Study participants
         Item: 
          Title: Blood sample collection and plasma isolation
         Item: 
          Title: Isolation of nucleic acids from cell lines, tissues and plasma samples
         Item: 
          Title: Bisulfite genomic sequencing
         Item: 
          Title: Gene expression analysis
         Item: 
          Title: DNA methylation analysis of 450K array data
         Item: 
          Title: Methylation analysis of the LINC00473 promoter in colorectal tissues by pyrosequencing
         Item: 
          Title: Methylation analysis of the LINC00473 promoter in cfDNA by qMSP
         Item: 
          Title: Methylation analysis of the LINC00473 promoter in cfDNA by ddPCR
         Item: 
          Title: Statistical analysis
       Item: 
        Title: Acknowledgements
       Item: 
        Title: References
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    Title: Noninvasive early detection of colorectal cancer by hypermethylation of the
    Author:  Juan Ruiz-Bañobre
    Subject: Clinical Epigenetics, https://doi.org/10.1186/s13148-022-01302-x
    Keywords: DNA methylation;;Cell-free DNA;Early detection;Colorectal cancer
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               <rdf:li>springer.com</rdf:li>
               <rdf:li>springerlink.com</rdf:li>
            </rdf:Seq>
         </pdfx:CrossMarkDomains>
         <xmpMM:DocumentID>uuid:3cb83f62-812b-484b-aba8-e33b53d8f804</xmpMM:DocumentID>
         <xmpMM:InstanceID>uuid:ed735089-174f-465f-856e-b3c3438f7263</xmpMM:InstanceID>
         <xmpMM:RenditionClass>default</xmpMM:RenditionClass>
         <xmpMM:VersionID>1</xmpMM:VersionID>
         <xmpMM:History>
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               <rdf:li rdf:parseType="Resource">
                  <stEvt:action>converted</stEvt:action>
                  <stEvt:instanceID>uuid:3cb83f62-812b-484b-aba8-e33b53d8f804</stEvt:instanceID>
                  <stEvt:parameters>converted to PDF/A-2b</stEvt:parameters>
                  <stEvt:softwareAgent>pdfToolbox</stEvt:softwareAgent>
                  <stEvt:when>2022-07-09T09:57:44Z</stEvt:when>
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         </xmpMM:History>
         <pdfaid:part>2</pdfaid:part>
         <pdfaid:conformance>B</pdfaid:conformance>
         <pdfaExtension:schemas>
            <rdf:Bag>
               <rdf:li rdf:parseType="Resource">
                  <pdfaSchema:namespaceURI>http://ns.adobe.com/pdfx/1.3/</pdfaSchema:namespaceURI>
                  <pdfaSchema:prefix>pdfx</pdfaSchema:prefix>
                  <pdfaSchema:schema>Adobe Document Info PDF eXtension Schema</pdfaSchema:schema>
                  <pdfaSchema:property>
                     <rdf:Seq>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>external</pdfaProperty:category>
                           <pdfaProperty:description>Mirrors crossmark:MajorVersionDate</pdfaProperty:description>
                           <pdfaProperty:name>CrossmarkMajorVersionDate</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>external</pdfaProperty:category>
                           <pdfaProperty:description>Mirrors crossmark:CrossmarkDomainExclusive</pdfaProperty:description>
                           <pdfaProperty:name>CrossmarkDomainExclusive</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>Mirrors crossmark:DOI</pdfaProperty:description>
                           <pdfaProperty:name>doi</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>external</pdfaProperty:category>
                           <pdfaProperty:description>Mirrors crossmark:CrosMarkDomains</pdfaProperty:description>
                           <pdfaProperty:name>CrossMarkDomains</pdfaProperty:name>
                           <pdfaProperty:valueType>seq Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>A name object indicating whether the document has been modified to include trapping information</pdfaProperty:description>
                           <pdfaProperty:name>robots</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>ID of PDF/X standard</pdfaProperty:description>
                           <pdfaProperty:name>GTS_PDFXVersion</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>Conformance level of PDF/X standard</pdfaProperty:description>
                           <pdfaProperty:name>GTS_PDFXConformance</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>Company creating the PDF</pdfaProperty:description>
                           <pdfaProperty:name>Company</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>Date when document was last modified</pdfaProperty:description>
                           <pdfaProperty:name>SourceModified</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                     </rdf:Seq>
                  </pdfaSchema:property>
               </rdf:li>
               <rdf:li rdf:parseType="Resource">
                  <pdfaSchema:namespaceURI>http://crossref.org/crossmark/1.0/</pdfaSchema:namespaceURI>
                  <pdfaSchema:prefix>crossmark</pdfaSchema:prefix>
                  <pdfaSchema:schema>Crossmark Schema</pdfaSchema:schema>
                  <pdfaSchema:property>
                     <rdf:Seq>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>Usual same as prism:doi</pdfaProperty:description>
                           <pdfaProperty:name>DOI</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>external</pdfaProperty:category>
                           <pdfaProperty:description>The date when a publication was publishe.</pdfaProperty:description>
                           <pdfaProperty:name>MajorVersionDate</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>CrossmarkDomainExclusive</pdfaProperty:description>
                           <pdfaProperty:name>CrossmarkDomainExclusive</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>CrossMarkDomains</pdfaProperty:description>
                           <pdfaProperty:name>CrossMarkDomains</pdfaProperty:name>
                           <pdfaProperty:valueType>seq Text</pdfaProperty:valueType>
                        </rdf:li>
                     </rdf:Seq>
                  </pdfaSchema:property>
               </rdf:li>
               <rdf:li rdf:parseType="Resource">
                  <pdfaSchema:namespaceURI>http://prismstandard.org/namespaces/basic/2.0/</pdfaSchema:namespaceURI>
                  <pdfaSchema:prefix>prism</pdfaSchema:prefix>
                  <pdfaSchema:schema>Prism Schema</pdfaSchema:schema>
                  <pdfaSchema:property>
                     <rdf:Seq>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>external</pdfaProperty:category>
                           <pdfaProperty:description>This element provides the url for an article or unit of content. The attribute platform is optionally allowed for situations in which multiple URLs must be specified. PRISM recommends that a subset of the PCV platform values, namely “mobile” and “web”, be used in conjunction with this element. NOTE: PRISM recommends against the use of the #other value allowed in the PRISM Platform controlled vocabulary. In lieu of using #other please reach out to the PRISM group at prism-wg@yahoogroups.com to request addition of your term to the Platform Controlled Vocabulary.</pdfaProperty:description>
                           <pdfaProperty:name>url</pdfaProperty:name>
                           <pdfaProperty:valueType>URI</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>external</pdfaProperty:category>
                           <pdfaProperty:description>The Digital Object Identifier for the article.
The DOI may also be used as the dc:identifier. If used as a dc:identifier, the URI form should be captured, and the bare identifier should also be captured using prism:doi. If an alternate unique identifier is used as the required dc:identifier, then the DOI should be specified as a bare identifier within prism:doi only. If the URL associated with a DOI is to be specified, then prism:url may be used in conjunction with prism:doi in order to provide the service endpoint (i.e. the URL). </pdfaProperty:description>
                           <pdfaProperty:name>doi</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>external</pdfaProperty:category>
                           <pdfaProperty:description>ISSN for an electronic version of the issue in which the resource occurs. Permits publishers to include a second ISSN, identifying an electronic version of the issue in which the resource occurs (therefore e(lectronic)Issn. If used, prism:eIssn MUST contain the ISSN of the electronic version.</pdfaProperty:description>
                           <pdfaProperty:name>issn</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>Volume number</pdfaProperty:description>
                           <pdfaProperty:name>volume</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>Issue number</pdfaProperty:description>
                           <pdfaProperty:name>number</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>Starting page</pdfaProperty:description>
                           <pdfaProperty:name>startingPage</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>Ending page</pdfaProperty:description>
                           <pdfaProperty:name>endingPage</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>external</pdfaProperty:category>
                           <pdfaProperty:description>The aggregation type specifies the unit of aggregation for a content collection. Comment PRISM recommends that the PRISM Aggregation Type Controlled Vocabulary be used to provide values for this element. Note: PRISM recommends against the use of the #other value currently allowed in this controlled vocabulary. In lieu of using #other please reach out to the PRISM group at info@prismstandard.org to request addition of your term to the Aggregation Type Controlled Vocabulary. </pdfaProperty:description>
                           <pdfaProperty:name>aggregationType</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>external</pdfaProperty:category>
                           <pdfaProperty:description>Title of the magazine, or other publication, in which a resource was/will be published. Typically this will be used to provide the name of the magazine an article appeared in as metadata for the article, along with information such as the article title, the publisher, volume, number, and cover date. Note: Publication name can be used to differentiate between a print magazine and the online version if the names are different such as “magazine” and “magazine.com.”</pdfaProperty:description>
                           <pdfaProperty:name>publicationName</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>external</pdfaProperty:category>
                           <pdfaProperty:description>Copyright</pdfaProperty:description>
                           <pdfaProperty:name>copyright</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                     </rdf:Seq>
                  </pdfaSchema:property>
               </rdf:li>
               <rdf:li rdf:parseType="Resource">
                  <pdfaSchema:namespaceURI>http://ns.adobe.com/pdf/1.3/</pdfaSchema:namespaceURI>
                  <pdfaSchema:prefix>pdf</pdfaSchema:prefix>
                  <pdfaSchema:schema>Adobe PDF Schema</pdfaSchema:schema>
                  <pdfaSchema:property>
                     <rdf:Seq>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>A name object indicating whether the document has been modified to include trapping information</pdfaProperty:description>
                           <pdfaProperty:name>Trapped</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                     </rdf:Seq>
                  </pdfaSchema:property>
               </rdf:li>
               <rdf:li rdf:parseType="Resource">
                  <pdfaSchema:namespaceURI>http://ns.adobe.com/xap/1.0/mm/</pdfaSchema:namespaceURI>
                  <pdfaSchema:prefix>xmpMM</pdfaSchema:prefix>
                  <pdfaSchema:schema>XMP Media Management Schema</pdfaSchema:schema>
                  <pdfaSchema:property>
                     <rdf:Seq>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>UUID based identifier for specific incarnation of a document</pdfaProperty:description>
                           <pdfaProperty:name>InstanceID</pdfaProperty:name>
                           <pdfaProperty:valueType>URI</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>The common identifier for all versions and renditions of a document.</pdfaProperty:description>
                           <pdfaProperty:name>DocumentID</pdfaProperty:name>
                           <pdfaProperty:valueType>URI</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>The common identifier for all versions and renditions of a document.</pdfaProperty:description>
                           <pdfaProperty:name>OriginalDocumentID</pdfaProperty:name>
                           <pdfaProperty:valueType>URI</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>A reference to the original document from which this one is derived. It is a minimal reference; missing components can be assumed to be unchanged. For example, a new version might only need to specify the instance ID and version number of the previous version, or a rendition might only need to specify the instance ID and rendition class of the original.</pdfaProperty:description>
                           <pdfaProperty:name>DerivedFrom</pdfaProperty:name>
                           <pdfaProperty:valueType>ResourceRef</pdfaProperty:valueType>
                        </rdf:li>
                     </rdf:Seq>
                  </pdfaSchema:property>
                  <pdfaSchema:valueType>
                     <rdf:Seq>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaType:description>Identifies a portion of a document. This can be a position at which the document has been changed since the most recent event history (stEvt:changed). For a resource within an xmpMM:Ingredients list, the ResourceRef uses this type to identify both the portion of the containing document that refers to the resource, and the portion of the referenced resource that is referenced.</pdfaType:description>
                           <pdfaType:namespaceURI>http://ns.adobe.com/xap/1.0/sType/Part#</pdfaType:namespaceURI>
                           <pdfaType:prefix>stPart</pdfaType:prefix>
                           <pdfaType:type>Part</pdfaType:type>
                        </rdf:li>
                     </rdf:Seq>
                  </pdfaSchema:valueType>
               </rdf:li>
               <rdf:li rdf:parseType="Resource">
                  <pdfaSchema:namespaceURI>http://www.aiim.org/pdfa/ns/id/</pdfaSchema:namespaceURI>
                  <pdfaSchema:prefix>pdfaid</pdfaSchema:prefix>
                  <pdfaSchema:schema>PDF/A ID Schema</pdfaSchema:schema>
                  <pdfaSchema:property>
                     <rdf:Seq>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>Part of PDF/A standard</pdfaProperty:description>
                           <pdfaProperty:name>part</pdfaProperty:name>
                           <pdfaProperty:valueType>Integer</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>Amendment of PDF/A standard</pdfaProperty:description>
                           <pdfaProperty:name>amd</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>Conformance level of PDF/A standard</pdfaProperty:description>
                           <pdfaProperty:name>conformance</pdfaProperty:name>
                           <pdfaProperty:valueType>Text</pdfaProperty:valueType>
                        </rdf:li>
                     </rdf:Seq>
                  </pdfaSchema:property>
               </rdf:li>
               <rdf:li rdf:parseType="Resource">
                  <pdfaSchema:schema>Springer Nature ORCID Schema</pdfaSchema:schema>
                  <pdfaSchema:namespaceURI>http://springernature.com/ns/xmpExtensions/2.0/</pdfaSchema:namespaceURI>
                  <pdfaSchema:prefix>sn</pdfaSchema:prefix>
                  <pdfaSchema:property>
                     <rdf:Seq>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:name>authorInfo</pdfaProperty:name>
                           <pdfaProperty:valueType>Bag AuthorInformation</pdfaProperty:valueType>
                           <pdfaProperty:category>external</pdfaProperty:category>
                           <pdfaProperty:description>Author information: contains the name of each author and his/her ORCiD (ORCiD: Open Researcher and Contributor ID). An ORCiD is a persistent identifier (a non-proprietary alphanumeric code) to uniquely identify scientific and other academic authors.</pdfaProperty:description>
                        </rdf:li>
                     </rdf:Seq>
                  </pdfaSchema:property>
                  <pdfaSchema:valueType>
                     <rdf:Seq>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaType:type>AuthorInformation</pdfaType:type>
                           <pdfaType:namespaceURI>http://springernature.com/ns/xmpExtensions/2.0/authorInfo/</pdfaType:namespaceURI>
                           <pdfaType:prefix>author</pdfaType:prefix>
                           <pdfaType:description>Specifies the types of author information: name and ORCID of an author.</pdfaType:description>
                           <pdfaType:field>
                              <rdf:Seq>
                                 <rdf:li rdf:parseType="Resource">
                                    <pdfaField:name>name</pdfaField:name>
                                    <pdfaField:valueType>Text</pdfaField:valueType>
                                    <pdfaField:description>Gives the name of an author.</pdfaField:description>
                                 </rdf:li>
                                 <rdf:li rdf:parseType="Resource">
                                    <pdfaField:name>orcid</pdfaField:name>
                                    <pdfaField:valueType>URI</pdfaField:valueType>
                                    <pdfaField:description>Gives the ORCID of an author.</pdfaField:description>
                                 </rdf:li>
                              </rdf:Seq>
                           </pdfaType:field>
                        </rdf:li>
                     </rdf:Seq>
                  </pdfaSchema:valueType>
               </rdf:li>
            </rdf:Bag>
         </pdfaExtension:schemas>
      </rdf:Description>
   </rdf:RDF>
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