c02473418812e89c1a46e852a2dd9adb pmc_9572733.pdf ebd57c41c42ad508e5536aa3e986caa27c3a9038 pmc_9572733.pdf eb8ae15ff523ae2abd60992d15c40a420da148b836ec99b4d940ba373da75f9b pmc_9572733.pdf Title: Predictive Value of the Advanced Lipoprotein Profile and Glycated Proteins on Diabetic Retinopathy Subject: This study aimed to assess whether the advanced characteristics of serum lipoprotein subclasses could better predict the risk of developing diabetic retinopathy (DR) and its severity compared to other established risk factors in subjects with type 1 (T1D) and type 2 (T2D) diabetes. This observational, cross-sectional substudy analyzed DR-related data from 309 T1D and 264 T2D subjects. The advanced lipoprotein and glycoprotein profile was determined by nuclear magnetic resonance (NMR) spectroscopy (Liposcale test). NMR analysis of lipoproteins revealed that T1D subjects with DR showed standard non-HDL particles, despite higher IDL lipid concentrations. Notably, IDL lipids were elevated in T1D subjects with worsened DR. VLDL and LDL were smaller, whereas HDL triglycerides were increased in DR compared with non-DR. On the other hand, the T2D subjects with DR showed altered characteristics in the LDL fraction, mainly revealed by a significant decrease in smaller LDL and a reduction in LDL-C. Moreover, the glycoprotein profile did not reveal significant changes among DR groups, regardless of the type of diabetes. However, lipoprotein characteristics and glycoproteins unveiled by NMR analysis did not improve the predictive value of conventional lipids or other traditional, well-established biomarkers of DR in our cohorts. Keywords: diabetic retinopathy; lipoproteins; glycoproteins; triglycerides; remnants; nuclear magnetic resonance spectroscopy; type 1 diabetes; type 2 diabetes Author: Josep Julve, Joana Rossell, Eudald Correig, Marina Idalia Rojo-Lopez, Nuria Amigó, Marta Hernández, Alicia Traveset, Marc Carbonell, Nuria Alonso, Didac Mauricio and Esmeralda Castelblanco Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Sep 23 06:16:24 2022 CEST ModDate: Mon Oct 10 05:58:32 2022 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 4692521 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- ENXZUH+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 HHJTSL+VnURWPalladioL Type 1 Custom yes yes no 15 0 AMTOZY+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 NCMPNS+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 BSRMQA+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 HGMNRX+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 46 0 OHXQCJ+CMSY10 Type 1 Builtin yes yes no 68 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes no 78 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2022-12-14 02:25:59 CET RepresentationInformation: pmc_9572733.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-10-27 02:16:39 CEST Size: 4692521 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 326 FreeObjects: 3 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4923ab24 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Children: Item: Title: Clinical Assessment Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Assessment of Diabetes and Presence and Severity of Diabetic Retinopathy Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Nuclear Magnetic Resonance (NMR) Molecular Profiling Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Children: Item: Title: Clinical Characteristics in Diabetic Subjects with Diabetic Retinopathy Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Advanced Lipoprotein and Glycoprotein Characteristics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Contribution of Advanced Lipoprotein Characteristics and Glycoproteins to DR Prediction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Contribution of Advanced Lipoprotein Characteristics and Glycoproteins to DR Severity Prediction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Children: Item: Title: Mild DR vs. Severe DR Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: No DR vs. Severe DR Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: DR Stages Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Info: Title: Predictive Value of the Advanced Lipoprotein Profile and Glycated Proteins on Diabetic Retinopathy Author: Josep Julve, Joana Rossell, Eudald Correig, Marina Idalia Rojo-Lopez, Nuria Amigó, Marta Hernández, Alicia Traveset, Marc Carbonell, Nuria Alonso, Didac Mauricio and Esmeralda Castelblanco Subject: This study aimed to assess whether the advanced characteristics of serum lipoprotein subclasses could better predict the risk of developing diabetic retinopathy (DR) and its severity compared to other established risk factors in subjects with type 1 (T1D) and type 2 (T2D) diabetes. This observational, cross-sectional substudy analyzed DR-related data from 309 T1D and 264 T2D subjects. The advanced lipoprotein and glycoprotein profile was determined by nuclear magnetic resonance (NMR) spectroscopy (Liposcale test). NMR analysis of lipoproteins revealed that T1D subjects with DR showed standard non-HDL particles, despite higher IDL lipid concentrations. Notably, IDL lipids were elevated in T1D subjects with worsened DR. VLDL and LDL were smaller, whereas HDL triglycerides were increased in DR compared with non-DR. On the other hand, the T2D subjects with DR showed altered characteristics in the LDL fraction, mainly revealed by a significant decrease in smaller LDL and a reduction in LDL-C. Moreover, the glycoprotein profile did not reveal significant changes among DR groups, regardless of the type of diabetes. However, lipoprotein characteristics and glycoproteins unveiled by NMR analysis did not improve the predictive value of conventional lipids or other traditional, well-established biomarkers of DR in our cohorts. Keywords: diabetic retinopathy; lipoproteins; glycoproteins; triglycerides; remnants; nuclear magnetic resonance spectroscopy; type 1 diabetes; type 2 diabetes Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Sep 23 06:16:24 CEST 2022 ModDate: Mon Oct 10 05:58:32 CEST 2022 ID: 0x856b44f0a27ac7ba46864ae1238b2492, 0x856b44f0a27ac7ba46864ae1238b2492 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: AMTOZY+URWPalladioL-Bold FontSubset: true FirstChar: 2 LastChar: 134 FontDescriptor: FontName: AMTOZY+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: OHXQCJ+CMSY10 FontSubset: true FirstChar: 0 LastChar: 21 FontDescriptor: FontName: OHXQCJ+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: NCMPNS+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 243 FontDescriptor: FontName: NCMPNS+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: ENXZUH+VnURWPalladioL-Bold FontSubset: true FirstChar: 161 LastChar: 226 FontDescriptor: FontName: ENXZUH+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: BSRMQA+URWPalladioL-Ital FontSubset: true FirstChar: 2 LastChar: 121 FontDescriptor: FontName: BSRMQA+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: QLBIEB+URWPalladioL-BoldItal FontSubset: true FirstChar: 110 LastChar: 112 FontDescriptor: FontName: QLBIEB+URWPalladioL-BoldItal Flags: Symbolic FontBBox: -170, -300, 1073, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: HHJTSL+VnURWPalladioL FontSubset: true FirstChar: 160 LastChar: 226 FontDescriptor: FontName: HHJTSL+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 34, 323, 148, 332 Annotation: Subtype: Link Rect: 34, 164, 96, 186 Annotation: Subtype: Link Rect: 126, 90, 154, 99 Annotation: Subtype: Link Rect: 34, 78, 147, 87 Annotation: Subtype: Link Rect: 34, 756, 169, 792 Annotation: Subtype: Link Rect: 515, 756, 560, 792 Annotation: Subtype: Link Rect: 106, 660, 117, 674 Annotation: Subtype: Link Rect: 289, 660, 300, 674 Annotation: Subtype: Link Rect: 434, 660, 445, 674 Annotation: Subtype: Link Rect: 521, 660, 532, 674 Annotation: Subtype: Link Rect: 121, 649, 132, 661 Annotation: Subtype: Link Rect: 504, 649, 515, 661 Annotation: Subtype: Link Rect: 190, 638, 201, 649 Annotation: Subtype: Link Rect: 406, 69, 413, 78 ActionDest: 112 Annotation: Subtype: Link Rect: 120, 17, 254, 28 Annotation: Subtype: Link Rect: 404, 17, 560, 28 Annotation: Subtype: Link Rect: 34, 432, 87, 451 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 363, 736, 370, 744 ActionDest: 112 Annotation: Subtype: Link Rect: 371, 735, 378, 744 ActionDest: 112 Annotation: Subtype: Link Rect: 549, 685, 556, 694 ActionDest: 112 Annotation: Subtype: Link Rect: 232, 660, 239, 669 ActionDest: 112 Annotation: Subtype: Link Rect: 242, 660, 249, 669 ActionDest: 112 Annotation: Subtype: Link Rect: 446, 647, 458, 657 ActionDest: 115 Annotation: Subtype: Link Rect: 543, 648, 555, 657 ActionDest: 115 Annotation: Subtype: Link Rect: 337, 635, 349, 644 ActionDest: 115 Annotation: Subtype: Link Rect: 450, 635, 462, 644 ActionDest: 115 Annotation: Subtype: Link Rect: 265, 610, 277, 619 ActionDest: 115 Annotation: Subtype: Link Rect: 277, 610, 289, 619 ActionDest: 115 Annotation: Subtype: Link Rect: 412, 610, 424, 619 ActionDest: 115 Annotation: Subtype: Link Rect: 427, 610, 439, 619 ActionDest: 115 Annotation: Subtype: Link Rect: 335, 572, 347, 581 ActionDest: 115 Annotation: Subtype: Link Rect: 380, 560, 391, 569 ActionDest: 115 Annotation: Subtype: Link Rect: 394, 560, 406, 569 ActionDest: 115 Annotation: Subtype: Link Rect: 257, 535, 269, 544 ActionDest: 115 Annotation: Subtype: Link Rect: 270, 535, 282, 544 ActionDest: 115 Annotation: Subtype: Link Rect: 329, 535, 341, 544 ActionDest: 115 Annotation: Subtype: Link Rect: 344, 535, 356, 544 ActionDest: 115 Annotation: Subtype: Link Rect: 344, 510, 356, 519 ActionDest: 115 Annotation: Subtype: Link Rect: 321, 484, 333, 493 ActionDest: 115 Annotation: Subtype: Link Rect: 283, 422, 295, 431 ActionDest: 115 Annotation: Subtype: Link Rect: 495, 409, 507, 418 ActionDest: 115 Annotation: Subtype: Link Rect: 277, 396, 289, 406 ActionDest: 115 Annotation: Subtype: Link Rect: 204, 271, 216, 280 ActionDest: 115 Annotation: Subtype: Link Rect: 217, 271, 228, 280 ActionDest: 115 Annotation: Subtype: Link Rect: 263, 95, 275, 104 ActionDest: 115 Annotation: Subtype: Link Rect: 347, 82, 359, 91 ActionDest: 118 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 545, 735, 556, 744 ActionDest: 118 Annotation: Subtype: Link Rect: 202, 597, 213, 606 ActionDest: 118 Annotation: Subtype: Link Rect: 267, 572, 279, 581 ActionDest: 118 Annotation: Subtype: Link Rect: 543, 534, 555, 543 ActionDest: 115 Annotation: Subtype: Link Rect: 304, 459, 316, 468 ActionDest: 118 Annotation: Subtype: Link Rect: 186, 408, 198, 417 ActionDest: 118 Annotation: Subtype: Link Rect: 333, 408, 345, 417 ActionDest: 118 Annotation: Subtype: Link Rect: 249, 295, 261, 305 ActionDest: 118 Annotation: Subtype: Link Rect: 530, 220, 542, 229 ActionDest: 118 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 466, 710, 478, 719 ActionDest: 118 Annotation: Subtype: Link Rect: 436, 535, 448, 544 ActionDest: 118 Annotation: Subtype: Link Rect: 376, 418, 383, 430 ActionDest: 82 Annotation: Subtype: Link Rect: 405, 393, 412, 405 ActionDest: 82 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 194, 470, 201, 482 ActionDest: 82 Annotation: Subtype: Link Rect: 335, 457, 342, 469 ActionDest: 82 Annotation: Subtype: Link Rect: 491, 445, 497, 457 ActionDest: 82 Annotation: Subtype: Link Rect: 261, 357, 268, 369 ActionDest: 82 Annotation: Subtype: Link Rect: 257, 332, 264, 344 ActionDest: 82 Annotation: Subtype: Link Rect: 359, 307, 366, 319 ActionDest: 82 Annotation: Subtype: Link Rect: 230, 231, 237, 243 ActionDest: 85 Annotation: Subtype: Link Rect: 494, 181, 501, 193 ActionDest: 85 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 464, 70, 471, 82 ActionDest: 85 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 329, 695, 336, 707 ActionDest: 85 Annotation: Subtype: Link Rect: 315, 594, 322, 606 ActionDest: 91 Annotation: Subtype: Link Rect: 216, 569, 223, 581 ActionDest: 91 Annotation: Subtype: Link Rect: 407, 557, 414, 569 ActionDest: 91 Annotation: Subtype: Link Rect: 253, 469, 260, 481 ActionDest: 91 Annotation: Subtype: Link Rect: 199, 444, 206, 456 ActionDest: 91 Page: Sequence: 8 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 532, 219, 544, 228 ActionDest: 115 Annotation: Subtype: Link Rect: 544, 219, 556, 228 ActionDest: 118 Annotation: Subtype: Link Rect: 211, 206, 223, 216 ActionDest: 115 Annotation: Subtype: Link Rect: 224, 206, 235, 216 ActionDest: 118 Annotation: Subtype: Link Rect: 346, 119, 358, 128 ActionDest: 118 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 528, 736, 540, 744 ActionDest: 118 Annotation: Subtype: Link Rect: 543, 735, 555, 744 ActionDest: 118 Annotation: Subtype: Link Rect: 479, 723, 491, 732 ActionDest: 118 Annotation: Subtype: Link Rect: 523, 610, 535, 619 ActionDest: 115 Annotation: Subtype: Link Rect: 191, 597, 198, 606 ActionDest: 112 Annotation: Subtype: Link Rect: 198, 597, 210, 606 ActionDest: 115 Annotation: Subtype: Link Rect: 211, 597, 223, 606 ActionDest: 118 Annotation: Subtype: Link Rect: 272, 572, 283, 581 ActionDest: 118 Annotation: Subtype: Link Rect: 284, 572, 296, 581 ActionDest: 118 Annotation: Subtype: Link Rect: 363, 560, 375, 569 ActionDest: 118 Annotation: Subtype: Link Rect: 323, 535, 335, 544 ActionDest: 121 Annotation: Subtype: Link Rect: 378, 484, 390, 493 ActionDest: 121 Annotation: Subtype: Link Rect: 483, 409, 495, 418 ActionDest: 121 Annotation: Subtype: Link Rect: 366, 246, 378, 255 ActionDest: 121 Annotation: Subtype: Link Rect: 483, 221, 495, 230 ActionDest: 121 Annotation: Subtype: Link Rect: 251, 158, 263, 167 ActionDest: 121 Annotation: Subtype: Link Rect: 201, 83, 213, 92 ActionDest: 121 Annotation: Subtype: Link Rect: 214, 83, 226, 92 ActionDest: 121 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 496, 710, 508, 719 ActionDest: 115 Annotation: Subtype: Link Rect: 193, 685, 205, 694 ActionDest: 121 Annotation: Subtype: Link Rect: 319, 673, 331, 682 ActionDest: 115 Annotation: Subtype: Link Rect: 265, 660, 277, 669 ActionDest: 115 Annotation: Subtype: Link Rect: 544, 622, 556, 631 ActionDest: 121 Annotation: Subtype: Link Rect: 452, 610, 464, 619 ActionDest: 121 Annotation: Subtype: Link Rect: 485, 597, 497, 606 ActionDest: 118 Annotation: Subtype: Link Rect: 497, 597, 509, 606 ActionDest: 118 Annotation: Subtype: Link Rect: 261, 572, 273, 581 ActionDest: 118 Annotation: Subtype: Link Rect: 492, 434, 504, 443 ActionDest: 121 Annotation: Subtype: Link Rect: 536, 207, 560, 218 Annotation: Subtype: Link Rect: 165, 195, 375, 206 Page: Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 471, 272, 508, 283 Annotation: Subtype: Link Rect: 515, 272, 551, 283 Annotation: Subtype: Link Rect: 416, 249, 453, 260 Annotation: Subtype: Link Rect: 459, 249, 495, 260 Annotation: Subtype: Link Rect: 458, 214, 495, 225 Annotation: Subtype: Link Rect: 501, 214, 537, 225 Annotation: Subtype: Link Rect: 220, 192, 258, 202 Annotation: Subtype: Link Rect: 433, 168, 470, 179 Annotation: Subtype: Link Rect: 108, 146, 146, 156 Annotation: Subtype: Link Rect: 407, 111, 444, 122 Annotation: Subtype: Link Rect: 520, 88, 557, 99 Annotation: Subtype: Link Rect: 401, 65, 438, 76 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 109, 711, 146, 721 Annotation: Subtype: Link Rect: 228, 676, 265, 687 Annotation: Subtype: Link Rect: 347, 641, 385, 652 Annotation: Subtype: Link Rect: 59, 607, 96, 617 Annotation: Subtype: Link Rect: 254, 572, 291, 583 Annotation: Subtype: Link Rect: 440, 549, 477, 560 Annotation: Subtype: Link Rect: 240, 514, 277, 525 Annotation: Subtype: Link Rect: 59, 481, 96, 491 Annotation: Subtype: Link Rect: 131, 446, 168, 456 Annotation: Subtype: Link Rect: 332, 422, 370, 433 Annotation: Subtype: Link Rect: 330, 399, 367, 410 Annotation: Subtype: Link Rect: 59, 377, 96, 387 Annotation: Subtype: Link Rect: 463, 353, 501, 364 Annotation: Subtype: Link Rect: 256, 320, 293, 330 Annotation: Subtype: Link Rect: 239, 296, 277, 307 Annotation: Subtype: Link Rect: 283, 296, 319, 307 Annotation: Subtype: Link Rect: 256, 273, 294, 284 Annotation: Subtype: Link Rect: 300, 273, 336, 284 Annotation: Subtype: Link Rect: 118, 228, 155, 238 Annotation: Subtype: Link Rect: 161, 228, 197, 238 Annotation: Subtype: Link Rect: 378, 204, 416, 215 Annotation: Subtype: Link Rect: 422, 204, 458, 215 Annotation: Subtype: Link Rect: 434, 181, 472, 192 Annotation: Subtype: Link Rect: 467, 146, 505, 157 Annotation: Subtype: Link Rect: 462, 112, 500, 123 Annotation: Subtype: Link Rect: 186, 78, 224, 88 Page: Sequence: 14 Annotations: Annotation: Subtype: Link Rect: 487, 722, 524, 733 Annotation: Subtype: Link Rect: 454, 699, 492, 710 Annotation: Subtype: Link Rect: 371, 664, 409, 675 Annotation: Subtype: Link Rect: 203, 630, 240, 640 Annotation: Subtype: Link Rect: 190, 595, 228, 606 Annotation: Subtype: Link Rect: 59, 561, 96, 571 Annotation: Subtype: Link Rect: 140, 527, 177, 537 Annotation: Subtype: Link Rect: 192, 491, 230, 502 Annotation: Subtype: Link Rect: 168, 468, 205, 479 Annotation: Subtype: Link Rect: 148, 445, 261, 456 Annotation: Subtype: Link Rect: 318, 411, 356, 422 Annotation: Subtype: Link Rect: 428, 388, 465, 399 Annotation: Subtype: Link Rect: 59, 354, 96, 364 Annotation: Subtype: Link Rect: 304, 330, 341, 341 Annotation: Subtype: Link Rect: 231, 296, 268, 307 Annotation: Subtype: Link Rect: 59, 262, 96, 272 Annotation: Subtype: Link Rect: 472, 238, 509, 249 Annotation: Subtype: Link Rect: 284, 215, 322, 226 Annotation: Subtype: Link Rect: 520, 192, 557, 203 Annotation: Subtype: Link Rect: 59, 159, 96, 169 Annotation: Subtype: Link Rect: 319, 123, 357, 134 Annotation: Subtype: Link Rect: 363, 123, 399, 134 Annotation: Subtype: Link Rect: 519, 89, 557, 100 Annotation: Subtype: Link Rect: 59, 78, 95, 88 Page: Sequence: 15 Annotations: Annotation: Subtype: Link Rect: 113, 711, 150, 721 Annotation: Subtype: Link Rect: 156, 711, 192, 721 Annotation: Subtype: Link Rect: 108, 676, 146, 687 Annotation: Subtype: Link Rect: 513, 652, 550, 664 Annotation: Subtype: Link Rect: 270, 629, 307, 640 Annotation: Subtype: Link Rect: 277, 606, 314, 617 Annotation: Subtype: Link Rect: 477, 595, 515, 606 Annotation: Subtype: Link Rect: 510, 572, 548, 583 Annotation: Subtype: Link Rect: 286, 549, 323, 560 Checksum: 9dad5f7b Type: CRC32 Checksum: c02473418812e89c1a46e852a2dd9adb Type: MD5 Checksum: ebd57c41c42ad508e5536aa3e986caa27c3a9038 Type: SHA-1