8ea6846239f068545aca9f41406edf58 301961.pdf 0c5830e048fce193561dc22711b5f10f64c634b5 301961.pdf 36b6de1ded8e755d2e082f9721599539cf7f726447031388c704ea88821b941d 301961.pdf Title: Blood gene expression biomarkers of response to anti-TNF drugs in pediatric inflammatory bowel diseases before initiation of treatment Subject: Biomedicine & Pharmacotherapy, 173 (2024) 116299. doi:10.1016/j.biopha.2024.116299 Keywords: RNA-seq,Pharmacogenomics,Inflammatory bowel disease,Anti-TNF drugs,Pediatrics Author: Sara Salvador-Martín Creator: Elsevier Producer: Acrobat Distiller 8.1.0 (Windows) CreationDate: Thu Mar 21 21:11:38 2024 CET ModDate: Thu Mar 21 21:57:04 2024 CET Custom Metadata: yes Metadata Stream: yes Tagged: yes UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 793.701 pts Page rot: 0 File size: 4897287 bytes Optimized: yes PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- RCOWKY+CharisSIL CID TrueType Identity-H yes yes yes 938 0 GRGVLF+TimesNewRomanPSMT CID TrueType Identity-H yes yes yes 943 0 VXCJFZ+Univers Type 1C Builtin yes yes yes 948 0 PVPCRS+STIXGeneral Type 1C Custom yes yes yes 952 0 BAFALN+TeX_CM_Roman Type 1C Builtin yes yes yes 957 0 GUJXOV+CharisSIL-Italic CID TrueType Identity-H yes yes yes 961 0 DLSJGZ+CharisSIL CID TrueType Identity-H yes yes yes 929 0 EDRAXC+CharisSIL-Bold CID TrueType Identity-H yes yes yes 381 0 VVCCGG+TeX_CM_Maths_Italic Type 1C Builtin yes yes yes 386 0 YLINFV+TeX_CM_Maths_Symbols Type 1C Builtin yes yes yes 390 0 NIGZKR+STIX-Regular Type 1C Custom yes yes yes 394 0 FYHUPI+CharisSIL-Italic CID TrueType Identity-H yes yes yes 374 0 LCRVWL+CharisSIL-BoldItalic CID TrueType Identity-H yes yes yes 92 0 GNZFDN+TeX_CM_Bold_Maths_Symbols Type 1C Builtin yes yes yes 97 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-11-09 02:40:05 CET RepresentationInformation: 301961.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-11-08 11:59:47 CET Size: 4897287 Format: PDF Version: 1.7 Status: Well-Formed, but not valid SignatureMatches: PDF-hul ErrorMessage: Invalid indirect destination - referenced object 'sec0115' cannot be found ID: PDF-HUL-149 ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'sec0115' cannot be found ID: PDF-HUL-122 Offset: 4843402 MIMEtype: application/pdf Profile: Linearized PDF, Tagged PDF PDFMetadata: Objects: 1100 FreeObjects: 1 IncrementalUpdates: 1 DocumentCatalog: PageLayout: SinglePage PageMode: UseOutlines Language: en Outlines: Item: Title: Blood gene expression biomarkers of response to anti-TNF drugs in pediatric inflammatory bowel diseases before initiation o ... Destination: mk:title Children: Item: Title: 1 Introduction Destination: mk:H1_1 Item: Title: 2 Material and methods Destination: mk:H1_2 Children: Item: Title: 2.1 Study design Destination: mk:H2_1 Item: Title: 2.2 Patients Destination: mk:H2_2 Item: Title: 2.3 Variables and data collection Destination: mk:H2_3 Item: Title: 2.4 Ethical considerations Destination: mk:H2_4 Item: Title: 2.5 Sample collection and RNA isolation Destination: mk:H2_5 Item: Title: 2.6 RNA sequencing Destination: mk:H2_6 Item: Title: 2.7 Differential expression (DE) analysis from RNA-seq data Destination: mk:H2_7 Item: Title: 2.8 Functional characterization of significant DE genes from RNA-seq experiments based on the fold change values Destination: mk:H2_8 Item: Title: 2.9 cDNA synthesis and real-time PCR validation Destination: mk:H2_9 Item: Title: 2.10 Statistical analysis Destination: mk:H2_10 Item: Title: 3 Results Destination: mk:H1_3 Children: Item: Title: 3.1 Patients Destination: mk:H2_11 Item: Title: 3.2 Genes associated with response to anti-TNF drugs Destination: mk:H2_12 Item: Title: 3.3 Functional analysis of differentially expressed genes Destination: mk:H2_13 Item: Title: 3.4 Validation of RNA-seq by semiquantitative real-time PCR Destination: mk:H2_14 Item: Title: 4 Discussion Destination: mk:H1_4 Item: Title: 5 Conclusion Destination: mk:H1_5 Item: Title: Funding Destination: mk:H1_6 Item: Title: CRediT authorship contribution statement Destination: mk:H1_7 Item: Title: Declaration of Competing Interest Destination: mk:HH1_29 Item: Title: Data availability Destination: datalink30 Item: Title: Acknowledgments Destination: mk:HH1_31 Item: Title: Appendix A Supporting information Destination: mk:H1_8 Item: Title: References Destination: mk:HH2_1 Info: Title: Blood gene expression biomarkers of response to anti-TNF drugs in pediatric inflammatory bowel diseases before initiation of treatment Author: Sara Salvador-Martín Subject: Biomedicine & Pharmacotherapy, 173 (2024) 116299. doi:10.1016/j.biopha.2024.116299 Keywords: RNA-seq,Pharmacogenomics,Inflammatory bowel disease,Anti-TNF drugs,Pediatrics Creator: Elsevier Producer: Acrobat Distiller 8.1.0 (Windows) CreationDate: Thu Mar 21 21:11:38 CET 2024 ModDate: Thu Mar 21 21:57:04 CET 2024 ID: 0x9d67f260e8cc7d132b5785658d243658, 0xec0191c545e4845e87cb42e8eeeab049 Filters: FilterPipeline: FlateDecode FilterPipeline: DCTDecode Images: Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 236 ImageHeight: 298 BitsPerSample: 8 BitsPerSampleUnit: integer Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 248 ImageHeight: 271 BitsPerSample: 8 BitsPerSampleUnit: integer Fonts: Type0: Font: BaseFont: GUJXOV+CharisSIL-Italic Encoding: Identity-H ToUnicode: true Font: BaseFont: RCOWKY+CharisSIL Encoding: Identity-H ToUnicode: true Font: BaseFont: LCRVWL+CharisSIL-BoldItalic Encoding: Identity-H ToUnicode: true Font: BaseFont: EDRAXC+CharisSIL-Bold Encoding: Identity-H ToUnicode: true Font: BaseFont: GRGVLF+TimesNewRomanPSMT Encoding: Identity-H ToUnicode: true Type1: Font: BaseFont: GNZFDN+TeX_CM_Bold_Maths_Symbols FontSubset: true FirstChar: 1 LastChar: 255 FontDescriptor: FontName: GNZFDN+TeX_CM_Bold_Maths_Symbols Flags: Symbolic, ForceBold FontBBox: -50, -180, 1000, 720 FontFile3: true ToUnicode: true Font: BaseFont: VVCCGG+TeX_CM_Maths_Italic FontSubset: true FirstChar: 1 LastChar: 127 FontDescriptor: FontName: VVCCGG+TeX_CM_Maths_Italic Flags: Symbolic FontBBox: -50, -180, 1000, 720 FontFile3: true ToUnicode: true Font: BaseFont: VXCJFZ+Univers FontSubset: true FirstChar: 32 LastChar: 251 FontDescriptor: FontName: VXCJFZ+Univers Flags: Symbolic FontBBox: -50, -180, 1000, 720 FontFile3: true ToUnicode: true Font: BaseFont: YLINFV+TeX_CM_Maths_Symbols FontSubset: true FirstChar: 1 LastChar: 138 FontDescriptor: FontName: YLINFV+TeX_CM_Maths_Symbols Flags: Symbolic FontBBox: -50, -180, 1000, 720 FontFile3: true ToUnicode: true Font: BaseFont: PVPCRS+STIXGeneral FontSubset: true FirstChar: 1 LastChar: 1 FontDescriptor: FontName: PVPCRS+STIXGeneral Flags: Nonsymbolic FontBBox: -178, -443, 2000, 1023 FontFile3: true EncodingDictionary: BaseEncoding: WinAnsiEncoding Differences: true ToUnicode: true Font: BaseFont: NIGZKR+STIX-Regular FontSubset: true FirstChar: 1 LastChar: 11 FontDescriptor: FontName: NIGZKR+STIX-Regular Flags: Nonsymbolic FontBBox: -970, -486, 2208, 1023 FontFile3: true EncodingDictionary: BaseEncoding: WinAnsiEncoding Differences: true ToUnicode: true Font: BaseFont: BAFALN+TeX_CM_Roman FontSubset: true FirstChar: 1 LastChar: 128 FontDescriptor: FontName: BAFALN+TeX_CM_Roman Flags: Symbolic FontBBox: -50, -180, 1000, 720 FontFile3: true ToUnicode: true CIDFontType2: Font: BaseFont: GRGVLF+TimesNewRomanPSMT CIDSystemInfo: Registry: Adobe Registry: Identity Supplement: 0 FontDescriptor: FontName: GRGVLF+TimesNewRomanPSMT Flags: Nonsymbolic FontBBox: -568, -307, 2000, 1007 FontFile2: true Font: BaseFont: GUJXOV+CharisSIL-Italic CIDSystemInfo: Registry: Adobe Registry: Identity Supplement: 0 FontDescriptor: FontName: GUJXOV+CharisSIL-Italic Flags: Nonsymbolic, Italic FontBBox: -716, -533, 1627, 1318 FontFile2: true Font: BaseFont: RCOWKY+CharisSIL CIDSystemInfo: Registry: Adobe Registry: Identity Supplement: 0 FontDescriptor: FontName: RCOWKY+CharisSIL Flags: Nonsymbolic FontBBox: -692, -533, 1623, 1319 FontFile2: true Font: BaseFont: LCRVWL+CharisSIL-BoldItalic CIDSystemInfo: Registry: Adobe Registry: Identity Supplement: 0 FontDescriptor: FontName: LCRVWL+CharisSIL-BoldItalic Flags: Nonsymbolic, Italic, ForceBold FontBBox: -741, -533, 1795, 1320 FontFile2: true Font: BaseFont: EDRAXC+CharisSIL-Bold CIDSystemInfo: Registry: Adobe Registry: Identity Supplement: 0 FontDescriptor: FontName: EDRAXC+CharisSIL-Bold Flags: Nonsymbolic, ForceBold FontBBox: -720, -533, 1759, 1320 FontFile2: true XMP: application/pdf 10.1016/j.biopha.2024.116299 Elsevier Masson SAS Biomedicine & Pharmacotherapy, 173 (2024) 116299. doi:10.1016/j.biopha.2024.116299 RNA-seq Pharmacogenomics Inflammatory bowel disease Anti-TNF drugs Pediatrics Blood gene expression biomarkers of response to anti-TNF drugs in pediatric inflammatory bowel diseases before initiation of treatment Sara Salvador-Martín Gianluca Rubbini Perceval Vellosillo Paula Zapata-Cobo Marta Velasco Laura M. Palomino Susana Clemente Oscar Segarra Ana Moreno-Álvarez Ana Fernández-Lorenzo Begoña Pérez-Moneo Montserrat Montraveta Cesar Sánchez Mar Tolín Inés Loverdos María José Fobelo Victor Manuel Navas-López Lorena Magallares Ruth García-Romero Ricardo Torres-Peral Alejandro Rodríguez Ferrán Bossacoma Vicente Merino-Bohórquez Enrique Salcedo Rebeca Álvarez Ana Dopazo María Sanjurjo-Sáez Luis A. López-Fernández journal Biomedicine & Pharmacotherapy © 2024 The Authors. Published by Elsevier Masson SAS. 0753-3322 173 1 April 2024 2024-04-01 116299 116299 10.1016/j.biopha.2024.116299 https://doi.org/10.1016/j.biopha.2024.116299 2010-04-23 true 10.1016/j.biopha.2024.116299 elsevier.com sciencedirect.com http://creativecommons.org/licenses/by-nc-nd/4.0/ VoR 10.1016/j.biopha.2024.116299 noindex 2010-04-23 true 22nd March 2024 sciencedirect.com elsevier.com Elsevier 2024-03-21T20:57:04 2024-03-21T20:11:38 2024-03-21T20:57:04 True 22nd March 2024 Acrobat Distiller 8.1.0 (Windows) RNA-seq,Pharmacogenomics,Inflammatory bowel disease,Anti-TNF drugs,Pediatrics uuid:1b499bed-4ce8-4c0c-b682-0d58baae1cbe uuid:b6ed5266-03cb-4855-90c0-636283357f42 Pages: Page: Label: 1 Annotations: Annotation: Subtype: Link Rect: 138, 576, 145, 587 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 145, 571, 240, 582 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 240, 576, 246, 587 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 247, 571, 347, 582 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 347, 576, 353, 587 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 353, 576, 360, 587 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 361, 571, 462, 582 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 462, 571, 469, 582 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 105, 558, 293, 569 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 293, 558, 477, 569 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 477, 558, 483, 569 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 150, 545, 261, 556 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 261, 545, 380, 556 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 380, 545, 459, 556 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 459, 545, 466, 556 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 86, 532, 162, 543 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 162, 532, 261, 543 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 261, 532, 401, 543 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 401, 532, 406, 543 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 125, 519, 234, 530 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 234, 519, 341, 530 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 341, 519, 453, 530 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 453, 519, 460, 530 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 124, 507, 262, 517 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 262, 507, 350, 517 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 350, 507, 435, 517 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 435, 507, 441, 517 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 96, 494, 201, 504 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 201, 498, 335, 509 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 336, 501, 340, 506 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 336, 494, 340, 504 Flags: Print Destination: 914 Annotation: Subtype: Link Rect: 104, 190, 185, 197 Flags: Print Annotation: Subtype: Link Rect: 258, 190, 342, 197 Flags: Print Annotation: Subtype: Link Rect: 390, 190, 486, 197 Flags: Print Annotation: Subtype: Link Rect: 538, 190, 557, 197 Flags: Print Annotation: Subtype: Link Rect: 37, 181, 97, 188 Flags: Print Annotation: Subtype: Link Rect: 164, 181, 254, 188 Flags: Print Annotation: Subtype: Link Rect: 307, 181, 434, 188 Flags: Print Annotation: Subtype: Link Rect: 499, 181, 557, 188 Flags: Print Annotation: Subtype: Link Rect: 37, 171, 83, 178 Flags: Print Annotation: Subtype: Link Rect: 136, 171, 229, 178 Flags: Print Annotation: Subtype: Link Rect: 278, 171, 375, 178 Flags: Print Annotation: Subtype: Link Rect: 450, 171, 557, 178 Flags: Print Annotation: Subtype: Link Rect: 37, 162, 65, 169 Flags: Print Annotation: Subtype: Link Rect: 150, 162, 259, 169 Flags: Print Annotation: Subtype: Link Rect: 325, 162, 449, 169 Flags: Print Annotation: Subtype: Link Rect: 512, 162, 557, 169 Flags: Print Annotation: Subtype: Link Rect: 37, 152, 123, 159 Flags: Print Annotation: Subtype: Link Rect: 171, 152, 279, 159 Flags: Print Annotation: Subtype: Link Rect: 319, 152, 381, 159 Flags: Print Annotation: Subtype: Link Rect: 430, 152, 557, 159 Flags: Print Annotation: Subtype: Link Rect: 87, 142, 216, 150 Flags: Print Annotation: Subtype: Link Rect: 289, 142, 408, 150 Flags: Print Annotation: Subtype: Link Rect: 466, 142, 557, 150 Flags: Print Annotation: Subtype: Link Rect: 107, 133, 199, 140 Flags: Print Annotation: Subtype: Link Rect: 264, 133, 419, 140 Flags: Print Annotation: Subtype: Link Rect: 478, 133, 557, 140 Flags: Print Annotation: Subtype: Link Rect: 96, 123, 229, 130 Flags: Print Annotation: Subtype: Link Rect: 318, 123, 449, 130 Flags: Print Annotation: Subtype: Link Rect: 504, 123, 557, 130 Flags: Print Annotation: Subtype: Link Rect: 80, 114, 134, 121 Flags: Print Annotation: Subtype: Link Rect: 180, 114, 286, 121 Flags: Print Annotation: Subtype: Link Rect: 352, 114, 423, 121 Flags: Print Annotation: Subtype: Link Rect: 321, 722, 369, 730 Flags: Print Annotation: Subtype: Link Rect: 274, 667, 397, 675 Flags: Print Annotation: Subtype: Link Rect: 37, 87, 188, 94 Flags: Print Annotation: Subtype: Link Rect: 297, 749, 300, 757 Flags: Print Annotation: Subtype: Link Rect: 212, 748, 381, 760 Annotation: Subtype: Link Rect: 499, 616, 528, 645 Annotation: Subtype: Link Rect: 40, 48, 206, 59 Page: Label: 2 Annotations: Annotation: Subtype: Link Rect: 129, 470, 140, 478 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 129, 460, 140, 468 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 268, 439, 286, 447 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 168, 386, 186, 394 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 114, 345, 125, 352 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 251, 324, 262, 332 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 179, 282, 190, 290 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 234, 271, 250, 279 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 69, 188, 96, 196 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 172, 177, 201, 185 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 177, 156, 206, 164 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 37, 104, 53, 112 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 366, 407, 423, 415 Flags: Print Destination: null Annotation: Subtype: Link Rect: 429, 333, 557, 341 Flags: Print Annotation: Subtype: Link Rect: 306, 323, 417, 331 Flags: Print Annotation: Subtype: Link Rect: 343, 113, 359, 121 Flags: Print Destination: 182 Page: Label: 3 Annotations: Annotation: Subtype: Link Rect: 118, 416, 134, 424 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 40, 312, 272, 320 Flags: Print Annotation: Subtype: Link Rect: 37, 301, 52, 309 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 37, 249, 53, 257 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 172, 228, 188, 236 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 227, 217, 242, 225 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 128, 165, 144, 173 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 62, 134, 77, 142 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 363, 730, 379, 738 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 381, 709, 396, 717 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 437, 709, 453, 717 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 504, 668, 520, 676 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 382, 657, 398, 665 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 482, 657, 498, 665 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 468, 647, 484, 655 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 424, 594, 440, 602 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 509, 479, 557, 487 Flags: Print Annotation: Subtype: Link Rect: 306, 469, 548, 477 Flags: Print Annotation: Subtype: Link Rect: 306, 458, 374, 466 Flags: Print Annotation: Subtype: Link Rect: 505, 458, 532, 466 Flags: Print Destination: 24 Page: Label: 4 Annotations: Annotation: Subtype: Link Rect: 164, 406, 190, 414 Flags: Print Destination: 52 Annotation: Subtype: Link Rect: 241, 364, 257, 372 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 210, 343, 237, 351 Flags: Print Destination: 69 Annotation: Subtype: Link Rect: 177, 228, 203, 236 Flags: Print Destination: 69 Annotation: Subtype: Link Rect: 236, 165, 262, 173 Flags: Print Destination: 86 Annotation: Subtype: Link Rect: 96, 60, 151, 68 Flags: Print Destination: null Annotation: Subtype: Link Rect: 348, 234, 374, 242 Flags: Print Destination: 86 Annotation: Subtype: Link Rect: 386, 165, 405, 173 Flags: Print Destination: 101 Annotation: Subtype: Link Rect: 411, 92, 466, 100 Flags: Print Destination: null Annotation: Subtype: Link Rect: 535, 60, 557, 68 Flags: Print Destination: null Annotation: Subtype: Link Rect: 306, 50, 326, 58 Flags: Print Destination: null Page: Label: 5 Annotations: Annotation: Subtype: Link Rect: 175, 188, 218, 196 Flags: Print Destination: null Annotation: Subtype: Link Rect: 234, 188, 288, 196 Flags: Print Destination: null Annotation: Subtype: Link Rect: 132, 146, 175, 154 Flags: Print Destination: null Annotation: Subtype: Link Rect: 99, 104, 154, 112 Flags: Print Destination: null Annotation: Subtype: Link Rect: 265, 73, 286, 81 Flags: Print Destination: 111 Annotation: Subtype: Link Rect: 37, 63, 92, 71 Flags: Print Destination: null Annotation: Subtype: Link Rect: 344, 261, 389, 269 Flags: Print Destination: null Annotation: Subtype: Link Rect: 411, 229, 432, 237 Flags: Print Destination: 128 Annotation: Subtype: Link Rect: 539, 135, 557, 143 Flags: Print Destination: null Annotation: Subtype: Link Rect: 306, 125, 338, 133 Flags: Print Destination: null Annotation: Subtype: Link Rect: 318, 51, 364, 59 Flags: Print Destination: null Page: Label: 6 Page: Label: 7 Annotations: Annotation: Subtype: Link Rect: 106, 236, 122, 244 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 40, 152, 60, 160 Flags: Print Destination: 148 Annotation: Subtype: Link Rect: 229, 121, 283, 129 Flags: Print Destination: null Page: Label: 8 Annotations: Annotation: Subtype: Link Rect: 163, 252, 178, 260 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 125, 220, 140, 228 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 37, 199, 53, 207 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 350, 252, 366, 260 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 306, 189, 333, 197 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 348, 178, 375, 186 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 487, 126, 502, 134 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 460, 95, 476, 103 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 385, 74, 401, 82 Flags: Print Destination: 261 Page: Label: 9 Annotations: Annotation: Subtype: Link Rect: 103, 306, 119, 314 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 149, 233, 164, 241 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 37, 212, 53, 220 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 50, 159, 66, 167 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 409, 327, 425, 335 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 483, 327, 499, 335 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 453, 295, 469, 303 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 484, 264, 500, 272 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 378, 243, 393, 251 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 474, 201, 489, 209 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 344, 159, 360, 167 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 480, 86, 496, 94 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 306, 65, 322, 73 Flags: Print Destination: 261 Page: Label: 10 Page: Label: 11 Annotations: Annotation: Subtype: Link Rect: 140, 730, 156, 738 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 37, 699, 53, 707 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 78, 605, 93, 613 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 165, 584, 181, 592 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 77, 542, 92, 550 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 156, 511, 172, 519 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 220, 448, 236, 456 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 202, 406, 217, 414 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 188, 396, 203, 404 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 126, 343, 142, 351 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 162, 302, 178, 309 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 37, 260, 64, 268 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 37, 239, 53, 247 Flags: Print Destination: 182 Annotation: Subtype: Link Rect: 110, 207, 126, 215 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 202, 207, 218, 215 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 243, 165, 259, 173 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 259, 103, 286, 111 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 306, 720, 322, 728 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 418, 709, 434, 717 Flags: Print Destination: 261 Annotation: Subtype: Link Rect: 391, 668, 407, 676 Flags: Print Destination: 182 Page: Label: 12 Annotations: Annotation: Subtype: Link Rect: 99, 481, 223, 489 Flags: Print Annotation: Subtype: Link Rect: 180, 433, 257, 439 Flags: Print Annotation: Subtype: Link Rect: 53, 425, 104, 431 Flags: Print Annotation: Subtype: Link Rect: 89, 385, 231, 391 Flags: Print Annotation: Subtype: Link Rect: 165, 369, 284, 375 Flags: Print Annotation: Subtype: Link Rect: 82, 345, 261, 351 Flags: Print Annotation: Subtype: Link Rect: 241, 329, 286, 336 Flags: Print Annotation: Subtype: Link Rect: 53, 321, 150, 328 Flags: Print Annotation: Subtype: Link Rect: 220, 297, 265, 304 Flags: Print Annotation: Subtype: Link Rect: 53, 289, 139, 296 Flags: Print Annotation: Subtype: Link Rect: 147, 218, 248, 224 Flags: Print Annotation: Subtype: Link Rect: 53, 194, 175, 200 Flags: Print Annotation: Subtype: Link Rect: 253, 178, 286, 184 Flags: Print Annotation: Subtype: Link Rect: 53, 170, 182, 176 Flags: Print Annotation: Subtype: Link Rect: 82, 106, 213, 112 Flags: Print Annotation: Subtype: Link Rect: 253, 74, 286, 80 Flags: Print Annotation: Subtype: Link Rect: 54, 66, 151, 73 Flags: Print Annotation: Subtype: Link Rect: 382, 724, 515, 730 Flags: Print Annotation: Subtype: Link Rect: 427, 684, 499, 690 Flags: Print Annotation: Subtype: Link Rect: 323, 676, 380, 682 Flags: Print Annotation: Subtype: Link Rect: 493, 636, 538, 643 Flags: Print Annotation: Subtype: Link Rect: 323, 628, 408, 635 Flags: Print Annotation: Subtype: Link Rect: 365, 588, 488, 595 Flags: Print Annotation: Subtype: Link Rect: 387, 557, 517, 563 Flags: Print Annotation: Subtype: Link Rect: 493, 509, 538, 515 Flags: Print Annotation: Subtype: Link Rect: 323, 501, 407, 507 Flags: Print Annotation: Subtype: Link Rect: 533, 437, 555, 443 Flags: Print Annotation: Subtype: Link Rect: 323, 429, 442, 435 Flags: Print Annotation: Subtype: Link Rect: 522, 389, 555, 396 Flags: Print Annotation: Subtype: Link Rect: 323, 381, 405, 388 Flags: Print Annotation: Subtype: Link Rect: 369, 349, 495, 356 Flags: Print Annotation: Subtype: Link Rect: 385, 333, 518, 340 Flags: Print Annotation: Subtype: Link Rect: 531, 317, 553, 324 Flags: Print Annotation: Subtype: Link Rect: 323, 309, 428, 316 Flags: Print Annotation: Subtype: Link Rect: 323, 286, 451, 292 Flags: Print Annotation: Subtype: Link Rect: 435, 270, 553, 276 Flags: Print Annotation: Subtype: Link Rect: 533, 238, 555, 244 Flags: Print Annotation: Subtype: Link Rect: 323, 230, 423, 236 Flags: Print Annotation: Subtype: Link Rect: 422, 142, 527, 148 Flags: Print Annotation: Subtype: Link Rect: 381, 118, 492, 125 Flags: Print Annotation: Subtype: Link Rect: 478, 94, 554, 101 Flags: Print Annotation: Subtype: Link Rect: 323, 86, 375, 93 Flags: Print Annotation: Subtype: Link Rect: 518, 70, 551, 77 Flags: Print Annotation: Subtype: Link Rect: 323, 62, 424, 69 Flags: Print Page: Label: 13 Annotations: Annotation: Subtype: Link Rect: 145, 700, 257, 706 Flags: Print Annotation: Subtype: Link Rect: 234, 652, 279, 658 Flags: Print Annotation: Subtype: Link Rect: 54, 644, 114, 651 Flags: Print Annotation: Subtype: Link Rect: 54, 612, 163, 619 Flags: Print Annotation: Subtype: Link Rect: 156, 588, 228, 595 Flags: Print Annotation: Subtype: Link Rect: 54, 580, 125, 587 Flags: Print Annotation: Subtype: Link Rect: 238, 549, 283, 555 Flags: Print Annotation: Subtype: Link Rect: 54, 541, 135, 547 Flags: Print Annotation: Subtype: Link Rect: 264, 525, 286, 531 Flags: Print Annotation: Subtype: Link Rect: 54, 517, 133, 523 Flags: Print Annotation: Subtype: Link Rect: 86, 485, 220, 491 Flags: Print Annotation: Subtype: Link Rect: 238, 461, 283, 467 Flags: Print Annotation: Subtype: Link Rect: 54, 453, 153, 459 Flags: Print Annotation: Subtype: Link Rect: 100, 413, 202, 419 Flags: Print Annotation: Subtype: Link Rect: 234, 397, 279, 403 Flags: Print Annotation: Subtype: Link Rect: 54, 389, 134, 396 Flags: Print Annotation: Subtype: Link Rect: 190, 373, 266, 380 Flags: Print Annotation: Subtype: Link Rect: 54, 365, 114, 372 Flags: Print Annotation: Subtype: Link Rect: 231, 341, 276, 348 Flags: Print Annotation: Subtype: Link Rect: 54, 333, 114, 340 Flags: Print Annotation: Subtype: Link Rect: 100, 301, 210, 308 Flags: Print Annotation: Subtype: Link Rect: 54, 294, 279, 300 Flags: Print Annotation: Subtype: Link Rect: 54, 286, 283, 292 Flags: Print Annotation: Subtype: Link Rect: 54, 278, 286, 284 Flags: Print Annotation: Subtype: Link Rect: 54, 270, 214, 276 Flags: Print Annotation: Subtype: Link Rect: 224, 238, 269, 244 Flags: Print Annotation: Subtype: Link Rect: 54, 230, 108, 236 Flags: Print Annotation: Subtype: Link Rect: 100, 190, 205, 196 Flags: Print Annotation: Subtype: Link Rect: 89, 166, 204, 172 Flags: Print Annotation: Subtype: Link Rect: 82, 142, 212, 148 Flags: Print Annotation: Subtype: Link Rect: 264, 118, 286, 125 Flags: Print Annotation: Subtype: Link Rect: 54, 110, 161, 117 Flags: Print Annotation: Subtype: Link Rect: 431, 732, 523, 738 Flags: Print Annotation: Subtype: Link Rect: 323, 724, 380, 730 Flags: Print Annotation: Subtype: Link Rect: 323, 668, 428, 674 Flags: Print Annotation: Subtype: Link Rect: 455, 644, 527, 651 Flags: Print Annotation: Subtype: Link Rect: 323, 636, 364, 643 Flags: Print Annotation: Subtype: Link Rect: 452, 620, 524, 627 Flags: Print Annotation: Subtype: Link Rect: 323, 612, 369, 619 Flags: Print Annotation: Subtype: Link Rect: 440, 572, 552, 579 Flags: Print Annotation: Subtype: Link Rect: 533, 549, 555, 555 Flags: Print Annotation: Subtype: Link Rect: 323, 541, 407, 547 Flags: Print Annotation: Subtype: Link Rect: 323, 533, 554, 539 Flags: Print Annotation: Subtype: Link Rect: 323, 525, 551, 531 Flags: Print Annotation: Subtype: Link Rect: 323, 517, 404, 523 Flags: Print Annotation: Subtype: Link Rect: 447, 493, 554, 499 Flags: Print Annotation: Subtype: Link Rect: 323, 485, 346, 491 Flags: Print Annotation: Subtype: Link Rect: 393, 453, 519, 459 Flags: Print Annotation: Subtype: Link Rect: 502, 421, 548, 427 Flags: Print Annotation: Subtype: Link Rect: 323, 413, 409, 419 Flags: Print Annotation: Subtype: Link Rect: 358, 381, 502, 388 Flags: Print Annotation: Subtype: Link Rect: 498, 365, 543, 372 Flags: Print Annotation: Subtype: Link Rect: 323, 357, 386, 364 Flags: Print Annotation: Subtype: Link Rect: 337, 333, 468, 340 Flags: Print Annotation: Subtype: Link Rect: 422, 309, 527, 316 Flags: Print Annotation: Subtype: Link Rect: 373, 286, 508, 292 Flags: Print Annotation: Subtype: Link Rect: 409, 262, 526, 268 Flags: Print Annotation: Subtype: Link Rect: 433, 214, 540, 220 Flags: Print Annotation: Subtype: Link Rect: 323, 206, 346, 212 Flags: Print Annotation: Subtype: Link Rect: 483, 174, 555, 180 Flags: Print Annotation: Subtype: Link Rect: 323, 166, 394, 172 Flags: Print Annotation: Subtype: Link Rect: 483, 142, 555, 148 Flags: Print Annotation: Subtype: Link Rect: 323, 134, 384, 140 Flags: Print Annotation: Subtype: Link Rect: 434, 118, 509, 125 Flags: Print Annotation: Subtype: Link Rect: 323, 110, 380, 117 Flags: Print Checksum: bf3c51b1 Type: CRC32 Checksum: 8ea6846239f068545aca9f41406edf58 Type: MD5 Checksum: 0c5830e048fce193561dc22711b5f10f64c634b5 Type: SHA-1 Checksum: 36b6de1ded8e755d2e082f9721599539cf7f726447031388c704ea88821b941d Type: SHA-256