ebca82b99c1e59cc55e2cc73270be1cd  pmc_10805832.pdf
d76057e524a82b7c46e08a3b77ac5b91ee2c8df2  pmc_10805832.pdf
3ab2ad1d344bfc5dfcd984583cb7c32315010f6d7ff6ed76665e465b6eef8c26  pmc_10805832.pdf

Title:           PD-1/PD-L1 immune checkpoint therapy demonstrates favorable safety profile in patients with autoimmune and cholestatic liver disease
Subject:         Introduction: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of many malignancies in recent years.
Keywords:        autoimmune disease (AID), immune checkpoint inhibitors (ICI), autoimmune liver diseases (AILD), immune related adverse effects (irAEs), PD-1/PD-L1 immune checkpoint inhibitors, autoimmune hepatitis (AIH), primary sclerosing cholangites (PSC), primary biliary cholangitis (PBC)
Author:          Lorenz Kocheise
CreationDate:    Tue Jan 23 10:07:11 2024 CET
ModDate:         Tue Jan 23 10:07:20 2024 CET
Custom Metadata: no
Metadata Stream: yes
Tagged:          no
UserProperties:  no
Suspects:        no
Form:            none
JavaScript:      no
Pages:           9
Encrypted:       no
Page size:       595.389 x 841.663 pts (A4)
Page rot:        0
File size:       535382 bytes
Optimized:       yes
PDF version:     1.4


name                                 type              encoding         emb sub uni object ID
------------------------------------ ----------------- ---------------- --- --- --- ---------
PDGOOI+AdvTTd3a5f740                 Type 1C           WinAnsi          yes yes no     490  0
PDGPHF+AdvTTd3a5f740+fb              Type 1C           Custom           yes yes yes    491  0
PDGPHG+AdvPSA18C                     Type 1C           WinAnsi          yes yes no     492  0
PDGPHH+AdvTTd3a5f740+20              Type 1C           WinAnsi          yes yes no     493  0
PDGPHI+AdvTT9b12cd41                 Type 1C           WinAnsi          yes yes no     494  0
PDGPHJ+AdvPSA323                     Type 1C           WinAnsi          yes yes no     495  0
PDGPHK+AdvTT9b12cd41+20              Type 1C           WinAnsi          yes yes no     505  0
PDGPIL+AdvTT2c8ce45a                 Type 1C           WinAnsi          yes yes no     507  0
PDGPJM+AdvTT9b12cd41+22              Type 1C           Custom           yes yes yes    508  0
PDGPJN+AdvTT9b12cd41+fb              Type 1C           Custom           yes yes yes    509  0
PDHAPF+AdvTTd168d80a.I               Type 1C           WinAnsi          yes yes no     520  0
PDHBCF+AdvOT1ef757c0                 Type 1C           WinAnsi          yes yes no     172  0
PDHBCG+AdvOT1ef757c0+fb              Type 1C           Custom           yes yes yes    165  0
PDHBCH+AdvOT1ef757c0+20              Type 1C           WinAnsi          yes yes no     167  0
PDHBDH+AdvOT1ef757c0+22              Type 1C           Custom           yes yes yes    169  0
PDHBGH+Arial-BoldMT                  Type 1C           WinAnsi          yes yes no     180  0
PDHBJH+ArialMT                       Type 1C           WinAnsi          yes yes no     181  0
PDHCED+AdvTT749c1f5a.I               Type 1C           WinAnsi          yes yes no     187  0
ArialNarrow                          Type 1C           WinAnsi          yes no  no     189  0
HelveticaNeueLTStd-Bd                Type 1C           WinAnsi          yes no  no     188  0
PDHDAC+AdvOT7d6df7ab.I               Type 1C           WinAnsi          yes yes no     191  0
PDHDAD+AdvTT58d178b9+03              Type 1C           Custom           yes yes yes    190  0


Jhove (Rel. 1.28.0, 2023-05-18)
 Date: 2025-02-06 02:51:37 CET
 RepresentationInformation: pmc_10805832.pdf
  ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16)
  LastModified: 2024-12-17 02:35:46 CET
  Size: 535382
  Format: PDF
  Version: 1.4
  Status: Well-Formed and valid
  SignatureMatches:
   PDF-hul
  MIMEtype: application/pdf
  Profile: Linearized PDF
  PDFMetadata: 
   Objects: 575
   FreeObjects: 1
   IncrementalUpdates: 1
   DocumentCatalog: 
    PageLayout: SinglePage
    PageMode: UseOutlines
    Outlines: 
     Item: 
      Title: PD-1/PD-L1 immune checkpoint therapy demonstrates favorable safety profile in patients with autoimmune and cholestatic liver disease
      Destination: bmark_-322177956
      Children: 
       Item: 
        Title: Introduction
        Destination: s1
       Item: 
        Title: Patients and methods
        Destination: s2
        Children: 
         Item: 
          Title: Patients
          Destination: s2_1
         Item: 
          Title: Study design
          Destination: s2_2
         Item: 
          Title: Statistical analysis
          Destination: s2_3
       Item: 
        Title: Results
        Destination: s3
        Children: 
         Item: 
          Title: Patient characteristics
          Destination: s3_1
         Item: 
          Title: Baseline immunosuppression
          Destination: s3_2
         Item: 
          Title: Immune-related adverse events and changes in immunosuppressive treatment
          Destination: s3_3
         Item: 
          Title: Liver function during immune checkpoint inhibitor treatment
          Destination: s3_4
       Item: 
        Title: Discussion
        Destination: s4
       Item: 
        Title: Data availability statement
        Destination: s5
       Item: 
        Title: Ethics statement
        Destination: s6
       Item: 
        Title: Author contributions
        Destination: s7
       Item: 
        Title: Funding
        Destination: bmark_1865464027
       Item: 
        Title: Acknowledgments
        Destination: bmark_-366698314
       Item: 
        Title: Conflict of interest
        Destination: bmark_1089982005
       Item: 
        Title: Publisher’s note
        Destination: bmark_-1256977648
       Item: 
        Title: References
        Destination: bmark_2090415954
   Info: 
    Title: PD-1/PD-L1 immune checkpoint therapy demonstrates favorable safety profile in patients with autoimmune and cholestatic liver disease
    Author: Lorenz Kocheise
    Subject: Introduction: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of many malignancies in recent years.
    Keywords: autoimmune disease (AID), immune checkpoint inhibitors (ICI), autoimmune liver diseases (AILD), immune related adverse effects (irAEs), PD-1/PD-L1 immune checkpoint inhibitors, autoimmune hepatitis (AIH), primary sclerosing cholangites (PSC), primary biliary cholangitis (PBC)
    CreationDate: Tue Jan 23 10:07:11 CET 2024
    ModDate: Tue Jan 23 10:07:20 CET 2024
   ID: 0xbcae6cc827d6bba2fe49bc5eae9e6ff8, 0xf0d724f1c69b654b82ef510a71fb7b26
   Filters: 
    FilterPipeline: FlateDecode
    FilterPipeline: DCTDecode
   Images: 
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 2919
      ImageHeight: 577
      BitsPerSample: 8
      BitsPerSampleUnit: integer
    Image: 
     NisoImageMetadata: 
      FormatName: image/png
      ImageWidth: 902
      ImageHeight: 167
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Filter: FlateDecode
    Image: 
     NisoImageMetadata: 
      FormatName: image/png
      ImageWidth: 990
      ImageHeight: 309
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Filter: FlateDecode
    Image: 
     NisoImageMetadata: 
      FormatName: image/png
      ImageWidth: 906
      ImageHeight: 167
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Filter: FlateDecode
    Image: 
     NisoImageMetadata: 
      FormatName: image/png
      ImageWidth: 906
      ImageHeight: 290
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Filter: FlateDecode
    Image: 
     NisoImageMetadata: 
      FormatName: image/png
      ImageWidth: 906
      ImageHeight: 361
      BitsPerSample: 8
      BitsPerSampleUnit: integer
     Filter: FlateDecode
   Fonts: 
    Type1: 
     Font: 
      BaseFont: PDHBCG+AdvOT1ef757c0+fb
      FontSubset: true
      FirstChar: 1
      LastChar: 3
      FontDescriptor: 
       FontName: PDHBCG+AdvOT1ef757c0+fb
       Flags: Symbolic
       FontBBox: 0, -10, 781, 708
       FontFile3: true
      EncodingDictionary: 
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: PDHBCH+AdvOT1ef757c0+20
      FontSubset: true
      FirstChar: 146
      LastChar: 150
      FontDescriptor: 
       FontName: PDHBCH+AdvOT1ef757c0+20
       Flags: Nonsymbolic
       FontBBox: -135, -187, 1010, 833
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: PDHAPF+AdvTTd168d80a.I
      FontSubset: true
      FirstChar: 46
      LastChar: 117
      FontDescriptor: 
       FontName: PDHAPF+AdvTTd168d80a.I
       Flags: Serif, Nonsymbolic
       FontBBox: -145, -208, 968, 875
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: PDHBDH+AdvOT1ef757c0+22
      FontSubset: true
      FirstChar: 2
      LastChar: 21
      FontDescriptor: 
       FontName: PDHBDH+AdvOT1ef757c0+22
       Flags: Symbolic
       FontBBox: -135, -166, 697, 916
       FontFile3: true
      EncodingDictionary: 
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: PDGOOI+AdvTTd3a5f740
      FontSubset: true
      FirstChar: 35
      LastChar: 252
      FontDescriptor: 
       FontName: PDGOOI+AdvTTd3a5f740
       Flags: Serif, Nonsymbolic
       FontBBox: -52, -208, 916, 885
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: PDGPHF+AdvTTd3a5f740+fb
      FontSubset: true
      FirstChar: 1
      LastChar: 3
      FontDescriptor: 
       FontName: PDGPHF+AdvTTd3a5f740+fb
       Flags: Symbolic
       FontBBox: 0, 0, 906, 708
       FontFile3: true
      EncodingDictionary: 
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: PDGPHG+AdvPSA18C
      FontSubset: true
      FirstChar: 136
      LastChar: 180
      FontDescriptor: 
       FontName: PDGPHG+AdvPSA18C
       Flags: Nonsymbolic
       FontBBox: -156, -208, 1125, 802
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: PDHBCF+AdvOT1ef757c0
      FontSubset: true
      FirstChar: 35
      LastChar: 246
      FontDescriptor: 
       FontName: PDHBCF+AdvOT1ef757c0
       Flags: Serif, Nonsymbolic
       FontBBox: -20, -250, 947, 854
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: PDGPHH+AdvTTd3a5f740+20
      FontSubset: true
      FirstChar: 134
      LastChar: 150
      FontDescriptor: 
       FontName: PDGPHH+AdvTTd3a5f740+20
       Flags: Nonsymbolic
       FontBBox: -114, -166, 1062, 864
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: PDGPHI+AdvTT9b12cd41
      FontSubset: true
      FirstChar: 38
      LastChar: 252
      FontDescriptor: 
       FontName: PDGPHI+AdvTT9b12cd41
       Flags: Serif, Nonsymbolic
       FontBBox: -52, -208, 906, 875
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: PDGPHJ+AdvPSA323
      FontSubset: true
      FirstChar: 136
      LastChar: 180
      FontDescriptor: 
       FontName: PDGPHJ+AdvPSA323
       Flags: Nonsymbolic
       FontBBox: -156, -239, 1104, 770
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: PDHBGH+Arial-BoldMT
      FontSubset: true
      FirstChar: 32
      LastChar: 121
      FontDescriptor: 
       FontName: PDHBGH+Arial-BoldMT
       Flags: Nonsymbolic
       FontBBox: -628, -376, 2000, 1056
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: PDHBJH+ArialMT
      FontSubset: true
      FirstChar: 40
      LastChar: 149
      FontDescriptor: 
       FontName: PDHBJH+ArialMT
       Flags: Nonsymbolic
       FontBBox: -665, -325, 2000, 1040
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: PDGPHK+AdvTT9b12cd41+20
      FontSubset: true
      FirstChar: 134
      LastChar: 150
      FontDescriptor: 
       FontName: PDGPHK+AdvTT9b12cd41+20
       Flags: Nonsymbolic
       FontBBox: -114, -166, 1010, 864
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: PDGPIL+AdvTT2c8ce45a
      FontSubset: true
      FirstChar: 40
      LastChar: 121
      FontDescriptor: 
       FontName: PDGPIL+AdvTT2c8ce45a
       Flags: Nonsymbolic
       FontBBox: -52, -208, 947, 895
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: PDHCED+AdvTT749c1f5a.I
      FontSubset: true
      FirstChar: 37
      LastChar: 116
      FontDescriptor: 
       FontName: PDHCED+AdvTT749c1f5a.I
       Flags: Serif, Nonsymbolic
       FontBBox: -145, -208, 989, 885
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: PDGPJM+AdvTT9b12cd41+22
      FontSubset: true
      FirstChar: 2
      LastChar: 21
      FontDescriptor: 
       FontName: PDGPJM+AdvTT9b12cd41+22
       Flags: Symbolic
       FontBBox: 0, -156, 552, 697
       FontFile3: true
      EncodingDictionary: 
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: HelveticaNeueLTStd-Bd
      FirstChar: 0
      LastChar: 255
      FontDescriptor: 
       FontName: HelveticaNeueLTStd-Bd
       Flags: Nonsymbolic, ForceBold
       FontBBox: -166, -218, 1078, 975
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: PDGPJN+AdvTT9b12cd41+fb
      FontSubset: true
      FirstChar: 1
      LastChar: 3
      FontDescriptor: 
       FontName: PDGPJN+AdvTT9b12cd41+fb
       Flags: Symbolic
       FontBBox: 0, 0, 854, 697
       FontFile3: true
      EncodingDictionary: 
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: ArialNarrow
      FirstChar: 0
      LastChar: 255
      FontDescriptor: 
       FontName: ArialNarrow
       Flags: Nonsymbolic
       FontBBox: -182, -307, 1000, 1086
       FontFile3: true
      Encoding: WinAnsiEncoding
     Font: 
      BaseFont: PDHDAD+AdvTT58d178b9+03
      FontSubset: true
      FirstChar: 0
      LastChar: 0
      FontDescriptor: 
       FontName: PDHDAD+AdvTT58d178b9+03
       Flags: Symbolic
       FontBBox: -645, -354, 916, 895
       FontFile3: true
      EncodingDictionary: 
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: PDHDAC+AdvOT7d6df7ab.I
      FontSubset: true
      FirstChar: 40
      LastChar: 119
      FontDescriptor: 
       FontName: PDHDAC+AdvOT7d6df7ab.I
       Flags: Serif, Nonsymbolic
       FontBBox: -135, -250, 1000, 854
       FontFile3: true
      Encoding: WinAnsiEncoding
   XMP: <x:xmpmeta xmlns:x="adobe:ns:meta/" x:xmptk="3.1-701">
   <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
      <rdf:Description rdf:about=""
            xmlns:dc="http://purl.org/dc/elements/1.1/">
         <dc:format>application/pdf</dc:format>
         <dc:creator>
            <rdf:Seq>
               <rdf:li>Lorenz Kocheise</rdf:li>
               <rdf:li>Ignazio Piseddu</rdf:li>
               <rdf:li>Joscha Vonderlin</rdf:li>
               <rdf:li>Eric T. Tjwa</rdf:li>
               <rdf:li>Gustav Buescher</rdf:li>
               <rdf:li>Lucy Meunier</rdf:li>
               <rdf:li>Pia Goeggelmann</rdf:li>
               <rdf:li>Francesca Fianchi</rdf:li>
               <rdf:li>Jérôme Dumortier</rdf:li>
               <rdf:li>Mar Riveiro Barciela</rdf:li>
               <rdf:li>Tom J. G. Gevers</rdf:li>
               <rdf:li>Benedetta Terziroli Beretta-Piccoli</rdf:li>
               <rdf:li>Maria-Carlota Londoño</rdf:li>
               <rdf:li>Sona Frankova</rdf:li>
               <rdf:li>Thomas Roesner</rdf:li>
               <rdf:li>Vincent Joerg</rdf:li>
               <rdf:li>Constantin Schmidt</rdf:li>
               <rdf:li>Fabian Glaser</rdf:li>
               <rdf:li>Jan P. Sutter</rdf:li>
               <rdf:li>Thorben W. Fründt</rdf:li>
               <rdf:li>Ansgar W. Lohse</rdf:li>
               <rdf:li>Samuel Huber</rdf:li>
               <rdf:li>Johann von Felden</rdf:li>
               <rdf:li>Marcial Sebode</rdf:li>
               <rdf:li>Kornelius Schulze</rdf:li>
            </rdf:Seq>
         </dc:creator>
         <dc:description>
            <rdf:Alt>
               <rdf:li xml:lang="x-default">Introduction: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of many malignancies in recent years.</rdf:li>
            </rdf:Alt>
         </dc:description>
         <dc:rights>
            <rdf:Alt>
               <rdf:li xml:lang="x-default">Copyright © 2024 Kocheise, Piseddu, Vonderlin, Tjwa, Buescher, Meunier, Goeggelmann, Fianchi, Dumortier, Riveiro Barciela, Gevers, Terziroli Beretta-Piccoli, Londoño, Frankova, Roesner, Joerg, Schmidt, Glaser, Sutter, Fründt, Lohse, Huber, von Felden, Sebode and Schulze. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</rdf:li>
            </rdf:Alt>
         </dc:rights>
         <dc:title>
            <rdf:Alt>
               <rdf:li xml:lang="x-default">PD-1/PD-L1 immune checkpoint therapy demonstrates favorable safety profile in patients with autoimmune and cholestatic liver disease</rdf:li>
            </rdf:Alt>
         </dc:title>
         <dc:subject>
            <rdf:Bag>
               <rdf:li>autoimmune disease (AID)</rdf:li>
               <rdf:li>immune checkpoint inhibitors (ICI)</rdf:li>
               <rdf:li>autoimmune liver diseases (AILD)</rdf:li>
               <rdf:li>immune related adverse effects (irAEs)</rdf:li>
               <rdf:li>PD-1/PD-L1 immune checkpoint inhibitors</rdf:li>
               <rdf:li>autoimmune hepatitis (AIH)</rdf:li>
               <rdf:li>primary sclerosing cholangites (PSC)</rdf:li>
               <rdf:li>primary biliary cholangitis (PBC)</rdf:li>
            </rdf:Bag>
         </dc:subject>
      </rdf:Description>
      <rdf:Description rdf:about=""
            xmlns:pdf="http://ns.adobe.com/pdf/1.3/">
         <pdf:Keywords>autoimmune disease (AID), immune checkpoint inhibitors (ICI), autoimmune liver diseases (AILD), immune related adverse effects (irAEs), PD-1/PD-L1 immune checkpoint inhibitors, autoimmune hepatitis (AIH), primary sclerosing cholangites (PSC), primary biliary cholangitis (PBC)</pdf:Keywords>
      </rdf:Description>
      <rdf:Description rdf:about=""
            xmlns:xapRights="http://ns.adobe.com/xap/1.0/rights/">
         <xapRights:Marked>True</xapRights:Marked>
         <xapRights:WebStatement>https://www.frontiersin.org/legal/copyright-statement</xapRights:WebStatement>
      </rdf:Description>
      <rdf:Description rdf:about=""
            xmlns:xap="http://ns.adobe.com/xap/1.0/">
         <xap:ModifyDate>2024-01-23T17:07:20+08:00</xap:ModifyDate>
         <xap:CreateDate>2024-01-23T17:07:11+08:00</xap:CreateDate>
         <xap:MetadataDate>2024-01-23T17:07:20+08:00</xap:MetadataDate>
      </rdf:Description>
      <rdf:Description rdf:about=""
            xmlns:xapMM="http://ns.adobe.com/xap/1.0/mm/">
         <xapMM:DocumentID>uuid:093ecfe8-4707-4a57-a11d-82640122ffa8</xapMM:DocumentID>
         <xapMM:InstanceID>uuid:4ae6c039-b811-43d5-aed3-43091ce77434</xapMM:InstanceID>
      </rdf:Description>
   </rdf:RDF>
</x:xmpmeta>
   Pages: 
    Page: 
     Label: 1
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 221, 693, 537, 714
      Annotation: 
       Subtype: Link
       Rect: 221, 668, 529, 689
      Annotation: 
       Subtype: Link
       Rect: 221, 643, 502, 664
      Annotation: 
       Subtype: Link
       Rect: 221, 618, 498, 639
      Annotation: 
       Subtype: Link
       Rect: 221, 593, 338, 614
      Annotation: 
       Subtype: Link
       Rect: 49, 33, 129, 40
      Annotation: 
       Subtype: Link
       Rect: 500, 33, 545, 40
      Annotation: 
       Subtype: Link
       Rect: 49, 690, 125, 705
      Annotation: 
       Subtype: Link
       Rect: 60, 528, 118, 535
      Annotation: 
       Subtype: Link
       Rect: 49, 329, 159, 336
      Annotation: 
       Subtype: Link
       Rect: 101, 243, 194, 250
      Annotation: 
       Subtype: Link
       Rect: 49, 234, 99, 241
      Annotation: 
       Subtype: Link
       Rect: 450, 802, 506, 809
      Annotation: 
       Subtype: Link
       Rect: 466, 793, 519, 800
      Annotation: 
       Subtype: Link
       Rect: 446, 783, 539, 790
      Annotation: 
       Subtype: Link
       Rect: 49, 789, 233, 806
    Page: 
     Label: 2
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 52, 309, 56, 318
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 61, 309, 65, 318
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 207, 222, 211, 231
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 216, 222, 220, 231
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 202, 184, 206, 193
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 211, 184, 215, 193
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 200, 134, 208, 143
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 213, 134, 222, 143
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 281, 109, 285, 118
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 152, 84, 160, 93
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 166, 84, 174, 93
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 381, 350, 389, 359
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 394, 350, 402, 359
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 381, 287, 390, 296
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 394, 287, 403, 296
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 307, 225, 316, 234
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 418, 72, 449, 81
       Destination: 24
      Annotation: 
       Subtype: Link
       Rect: 449, 799, 545, 806
      Annotation: 
       Subtype: Link
       Rect: 49, 33, 129, 40
      Annotation: 
       Subtype: Link
       Rect: 500, 33, 545, 40
    Page: 
     Label: 3
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 52, 206, 154, 215
      Annotation: 
       Subtype: Link
       Rect: 490, 560, 517, 569
       Destination: 49
      Annotation: 
       Subtype: Link
       Rect: 499, 118, 527, 127
       Destination: 49
      Annotation: 
       Subtype: Link
       Rect: 497, 105, 527, 114
       Destination: 58
      Annotation: 
       Subtype: Link
       Rect: 449, 799, 545, 806
      Annotation: 
       Subtype: Link
       Rect: 49, 33, 129, 40
      Annotation: 
       Subtype: Link
       Rect: 500, 33, 545, 40
    Page: 
     Label: 4
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 147, 197, 174, 206
       Destination: 49
      Annotation: 
       Subtype: Link
       Rect: 449, 799, 545, 806
      Annotation: 
       Subtype: Link
       Rect: 49, 33, 129, 40
      Annotation: 
       Subtype: Link
       Rect: 500, 33, 545, 40
    Page: 
     Label: 5
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 350, 411, 376, 420
       Destination: 70
      Annotation: 
       Subtype: Link
       Rect: 426, 98, 457, 107
       Destination: 91
      Annotation: 
       Subtype: Link
       Rect: 449, 799, 545, 806
      Annotation: 
       Subtype: Link
       Rect: 49, 33, 129, 40
      Annotation: 
       Subtype: Link
       Rect: 500, 33, 545, 40
    Page: 
     Label: 6
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 137, 157, 146, 166
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 151, 157, 160, 166
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 164, 157, 173, 166
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 179, 107, 188, 116
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 307, 756, 316, 765
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 373, 706, 383, 715
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 389, 706, 399, 715
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 377, 681, 386, 690
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 519, 619, 528, 628
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 532, 619, 540, 628
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 406, 581, 415, 590
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 420, 581, 429, 590
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 434, 581, 442, 590
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 532, 544, 540, 553
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 369, 494, 377, 503
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 449, 799, 545, 806
      Annotation: 
       Subtype: Link
       Rect: 49, 33, 129, 40
      Annotation: 
       Subtype: Link
       Rect: 500, 33, 545, 40
    Page: 
     Label: 7
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 156, 223, 160, 232
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 166, 223, 170, 232
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 84, 123, 93, 132
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 140, 73, 149, 82
       Destination: 117
      Annotation: 
       Subtype: Link
       Rect: 449, 799, 545, 806
      Annotation: 
       Subtype: Link
       Rect: 49, 33, 129, 40
      Annotation: 
       Subtype: Link
       Rect: 500, 33, 545, 40
    Page: 
     Label: 8
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 479, 343, 545, 352
      Annotation: 
       Subtype: Link
       Rect: 304, 331, 410, 340
      Annotation: 
       Subtype: Link
       Rect: 449, 799, 545, 806
      Annotation: 
       Subtype: Link
       Rect: 49, 33, 129, 40
      Annotation: 
       Subtype: Link
       Rect: 500, 33, 545, 40
    Page: 
     Label: 9
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 139, 707, 243, 714
      Annotation: 
       Subtype: Link
       Rect: 166, 680, 237, 687
      Annotation: 
       Subtype: Link
       Rect: 166, 653, 237, 660
      Annotation: 
       Subtype: Link
       Rect: 105, 626, 177, 633
      Annotation: 
       Subtype: Link
       Rect: 112, 599, 182, 606
      Annotation: 
       Subtype: Link
       Rect: 62, 572, 132, 579
      Annotation: 
       Subtype: Link
       Rect: 62, 545, 133, 552
      Annotation: 
       Subtype: Link
       Rect: 229, 518, 286, 525
      Annotation: 
       Subtype: Link
       Rect: 126, 491, 207, 498
      Annotation: 
       Subtype: Link
       Rect: 196, 464, 273, 471
      Annotation: 
       Subtype: Link
       Rect: 205, 445, 288, 452
      Annotation: 
       Subtype: Link
       Rect: 175, 426, 249, 433
      Annotation: 
       Subtype: Link
       Rect: 85, 391, 175, 398
      Annotation: 
       Subtype: Link
       Rect: 149, 364, 227, 371
      Annotation: 
       Subtype: Link
       Rect: 95, 337, 176, 344
      Annotation: 
       Subtype: Link
       Rect: 221, 310, 284, 317
      Annotation: 
       Subtype: Link
       Rect: 208, 283, 257, 290
      Annotation: 
       Subtype: Link
       Rect: 99, 256, 177, 263
      Annotation: 
       Subtype: Link
       Rect: 304, 699, 384, 706
      Annotation: 
       Subtype: Link
       Rect: 359, 664, 430, 671
      Annotation: 
       Subtype: Link
       Rect: 417, 629, 467, 636
      Annotation: 
       Subtype: Link
       Rect: 469, 594, 540, 601
      Annotation: 
       Subtype: Link
       Rect: 521, 567, 545, 574
      Annotation: 
       Subtype: Link
       Rect: 304, 559, 371, 566
      Annotation: 
       Subtype: Link
       Rect: 304, 524, 375, 531
      Annotation: 
       Subtype: Link
       Rect: 414, 489, 507, 496
      Annotation: 
       Subtype: Link
       Rect: 456, 462, 518, 469
      Annotation: 
       Subtype: Link
       Rect: 519, 435, 545, 442
      Annotation: 
       Subtype: Link
       Rect: 304, 427, 374, 434
      Annotation: 
       Subtype: Link
       Rect: 443, 400, 514, 407
      Annotation: 
       Subtype: Link
       Rect: 352, 373, 423, 380
      Annotation: 
       Subtype: Link
       Rect: 441, 346, 505, 353
      Annotation: 
       Subtype: Link
       Rect: 520, 319, 545, 326
      Annotation: 
       Subtype: Link
       Rect: 304, 311, 358, 318
      Annotation: 
       Subtype: Link
       Rect: 474, 284, 545, 291
      Annotation: 
       Subtype: Link
       Rect: 439, 257, 513, 264
      Annotation: 
       Subtype: Link
       Rect: 449, 799, 545, 806
      Annotation: 
       Subtype: Link
       Rect: 49, 33, 129, 40
      Annotation: 
       Subtype: Link
       Rect: 500, 33, 545, 40
  Checksum: ca396e35
   Type: CRC32
  Checksum: ebca82b99c1e59cc55e2cc73270be1cd
   Type: MD5
  Checksum: d76057e524a82b7c46e08a3b77ac5b91ee2c8df2
   Type: SHA-1
  Checksum: 3ab2ad1d344bfc5dfcd984583cb7c32315010f6d7ff6ed76665e465b6eef8c26
   Type: SHA-256