f3a1df94b9c528eca07eaca63ec67b80 pmc_9737470.pdf a69e43549637d5e95d9bdeab7019a08926bda8d8 pmc_9737470.pdf 98cb532f384bc1b5b05a8d13336e219d1836c004b5dd209d623d808d3b41c79c pmc_9737470.pdf Title: Cord Blood Cardiovascular Biomarkers in Left-Sided Congenital Heart Disease Subject: Fetal echocardiography has limited prognostic ability in the evaluation of left-sided congenital heart defects (left heart defects). Cord blood cardiovascular biomarkers could improve the prognostic evaluation of left heart defects. A multicenter prospective cohort (2013–2019) including fetuses with left heart defects (aortic coarctation, aortic stenosis, hypoplastic left heart, and multilevel obstruction (complex left heart defects) subdivided according to their outcome (favorable vs. poor), and control fetuses were evaluated in the third trimester of pregnancy at three referral centers in Spain. Poor outcome was defined as univentricular palliation, heart transplant, or death. Cord blood concentrations of N-terminal precursor of B-type natriuretic peptide, Troponin I, transforming growth factor , placental growth factor, and soluble fms-like tyrosine kinase-1 were determined. A total of 45 fetuses with left heart defects (29 favorable and 16 poor outcomes) and 35 normal fetuses were included, with a median follow-up of 3.1 years (interquartile range 1.4–3.9). Left heart defects with favorable outcome showed markedly increased cord blood transforming growth factor (normal heart median 15.5 ng/mL (6.8–21.4) vs. favorable outcome 51.7 ng/mL (13.8–73.9) vs. poor outcome 25.1 ng/mL (6.9–39.0), p = 0.001) and decreased placental growth factor concentrations (normal heart 17.9 pg/mL (13.8–23.9) vs. favorable outcome 12.8 pg/mL (11.7–13.6) vs. poor outcome 11.0 pg/mL (8.8–15.4), p < 0.001). Poor outcome left heart defects had higher N-terminal precursor of B-type natriuretic peptide (normal heart 508.0 pg/mL (287.5–776.3) vs. favorable outcome 617.0 pg/mL (389.8–1087.8) vs. poor outcome 1450.0 pg/mL (919.0–1645.0), p = 0.001) and drastically reduced soluble fms-like tyrosine kinase-1 concentrations (normal heart 1929.7 pg/mL (1364.3–2715.8) vs. favorable outcome (1848.3 pg/mL (646.9–2313.6) vs. poor outcome 259.0 pg/mL (182.0–606.0), p < 0.001). Results showed that fetuses with left heart defects present a distinct cord blood biomarker profile according to their outcome. Keywords: congenital heart defects; fetal echocardiography; B-type natriuretic peptide; transforming growth factor beta; aortic stenosis; aortic coarctation; hypoplastic left heart syndrome; angiogenic factors; fetal cardiac remodeling Author: Iris Soveral, Laura Guirado, Maria C. Escobar-Diaz, María José Alcaide, Josep Maria Martínez, Víctor Rodríguez-Sureda, Bart Bijnens, Eugenia Antolin, Elisa Llurba, Jose L. Bartha, Olga Gómez and Fàtima Crispi Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Nov 30 12:58:43 2022 CET ModDate: Wed Nov 30 13:02:37 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1105825 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- CNRZPM+VnURWPalladioL Type 1 Custom yes yes no 10 0 QDCWHF+EURM10 Type 1 Builtin yes yes no 15 0 VOGLHG+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 WHQUWM+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 JJCXPT+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 ZSBPMM+VnURWPalladioL-Bold Type 1 Custom yes yes no 32 0 XPUSBJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 50 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 53 0 QMDDXF+CMSY10 Type 1 Builtin yes yes no 75 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes no 88 0 KJKHHF+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 97 0 KJKHHH+PalatinoLinotype TrueType WinAnsi yes yes no 100 0 KJKHHJ+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 103 0 KJKKGJ+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 106 0 ZYYJXI+EURB10 Type 1 Builtin yes yes no 119 0 KJKHHF+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 126 0 KJKHHG+PalatinoLinotype CID TrueType Identity-H yes yes yes 129 0 KJKHHH+PalatinoLinotype TrueType WinAnsi yes yes no 135 0 KJKHHJ+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 138 0 KJKHHF+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 149 0 KJKHHG+PalatinoLinotype CID TrueType Identity-H yes yes yes 152 0 KJKHHH+PalatinoLinotype TrueType WinAnsi yes yes no 158 0 KJKHHJ+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 161 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-09-07 02:29:25 CEST RepresentationInformation: pmc_9737470.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-08-03 02:25:14 CEST Size: 1105825 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 342 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Study Population Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Fetal Standard Ultrasound and Echocardiography Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Cord Blood Biomarkers Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Children: Item: Title: Study Populations Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Cord Blood Biomarkers Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Info: Title: Cord Blood Cardiovascular Biomarkers in Left-Sided Congenital Heart Disease Author: Iris Soveral, Laura Guirado, Maria C. Escobar-Diaz, María José Alcaide, Josep Maria Martínez, Víctor Rodríguez-Sureda, Bart Bijnens, Eugenia Antolin, Elisa Llurba, Jose L. Bartha, Olga Gómez and Fàtima Crispi Subject: Fetal echocardiography has limited prognostic ability in the evaluation of left-sided congenital heart defects (left heart defects). Cord blood cardiovascular biomarkers could improve the prognostic evaluation of left heart defects. A multicenter prospective cohort (2013 2019) including fetuses with left heart defects (aortic coarctation, aortic stenosis, hypoplastic left heart, and multilevel obstruction (complex left heart defects) subdivided according to their outcome (favorable vs. poor), and control fetuses were evaluated in the third trimester of pregnancy at three referral centers in Spain. Poor outcome was defined as univentricular palliation, heart transplant, or death. Cord blood concentrations of N-terminal precursor of B-type natriuretic peptide, Troponin I, transforming growth factor , placental growth factor, and soluble fms-like tyrosine kinase-1 were determined. A total of 45 fetuses with left heart defects (29 favorable and 16 poor outcomes) and 35 normal fetuses were included, with a median follow-up of 3.1 years (interquartile range 1.4 3.9). Left heart defects with favorable outcome showed markedly increased cord blood transforming growth factor (normal heart median 15.5 ng/mL (6.8 21.4) vs. favorable outcome 51.7 ng/mL (13.8 73.9) vs. poor outcome 25.1 ng/mL (6.9 39.0), p = 0.001) and decreased placental growth factor concentrations (normal heart 17.9 pg/mL (13.8 23.9) vs. favorable outcome 12.8 pg/mL (11.7 13.6) vs. poor outcome 11.0 pg/mL (8.8 15.4), p < 0.001). Poor outcome left heart defects had higher N-terminal precursor of B-type natriuretic peptide (normal heart 508.0 pg/mL (287.5 776.3) vs. favorable outcome 617.0 pg/mL (389.8 1087.8) vs. poor outcome 1450.0 pg/mL (919.0 1645.0), p = 0.001) and drastically reduced soluble fms-like tyrosine kinase-1 concentrations (normal heart 1929.7 pg/mL (1364.3 2715.8) vs. favorable outcome (1848.3 pg/mL (646.9 2313.6) vs. poor outcome 259.0 pg/mL (182.0 606.0), p < 0.001). Results showed that fetuses with left heart defects present a distinct cord blood biomarker profile according to their outcome. Keywords: congenital heart defects; fetal echocardiography; B-type natriuretic peptide; transforming growth factor beta; aortic stenosis; aortic coarctation; hypoplastic left heart syndrome; angiogenic factors; fetal cardiac remodeling Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Nov 30 12:58:43 CET 2022 ModDate: Wed Nov 30 13:02:37 CET 2022 ID: 0x7db9d5310bec23d83ce0b04ee2853221, 0x7db9d5310bec23d83ce0b04ee2853221 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: ZSBPMM+VnURWPalladioL-Bold FontSubset: true FirstChar: 160 LastChar: 226 FontDescriptor: FontName: ZSBPMM+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: VOGLHG+URWPalladioL-Bold FontSubset: true FirstChar: 2 LastChar: 135 FontDescriptor: FontName: VOGLHG+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: ZYYJXI+EURB10 FontSubset: true FirstChar: 12 LastChar: 12 FontDescriptor: FontName: ZYYJXI+EURB10 Flags: Symbolic FontBBox: -30, -247, 1178, 723 FontFile: true Font: BaseFont: WHQUWM+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: WHQUWM+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 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: CNRZPM+VnURWPalladioL FontSubset: true FirstChar: 129 LastChar: 243 FontDescriptor: FontName: CNRZPM+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: QMDDXF+CMSY10 FontSubset: true FirstChar: 0 LastChar: 14 FontDescriptor: FontName: QMDDXF+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: JJCXPT+URWPalladioL-Ital FontSubset: true FirstChar: 46 LastChar: 121 FontDescriptor: FontName: JJCXPT+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: QDCWHF+EURM10 FontSubset: true FirstChar: 11 LastChar: 12 FontDescriptor: FontName: QDCWHF+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 121, 335, 152, 344 Annotation: Subtype: Link Rect: 34, 323, 128, 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, 176, 792 Annotation: Subtype: Link Rect: 515, 756, 560, 792 Annotation: Subtype: Link Rect: 299, 661, 310, 674 Annotation: Subtype: Link Rect: 412, 661, 423, 674 Annotation: Subtype: Link Rect: 418, 648, 429, 662 Annotation: Subtype: Link Rect: 125, 636, 136, 649 Annotation: Subtype: Link Rect: 130, 17, 267, 28 Annotation: Subtype: Link Rect: 424, 17, 560, 28 Annotation: Subtype: Link Rect: 34, 432, 87, 451 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 501, 707, 508, 716 ActionDest: 169 Annotation: Subtype: Link Rect: 449, 695, 456, 704 ActionDest: 169 Annotation: Subtype: Link Rect: 269, 619, 276, 629 ActionDest: 169 Annotation: Subtype: Link Rect: 549, 620, 556, 629 ActionDest: 169 Annotation: Subtype: Link Rect: 472, 607, 479, 616 ActionDest: 169 Annotation: Subtype: Link Rect: 214, 582, 221, 591 ActionDest: 169 Annotation: Subtype: Link Rect: 350, 569, 357, 578 ActionDest: 169 Annotation: Subtype: Link Rect: 358, 569, 365, 578 ActionDest: 169 Annotation: Subtype: Link Rect: 250, 532, 257, 541 ActionDest: 169 Annotation: Subtype: Link Rect: 260, 532, 271, 541 ActionDest: 169 Annotation: Subtype: Link Rect: 259, 481, 271, 490 ActionDest: 169 Annotation: Subtype: Link Rect: 274, 481, 286, 490 ActionDest: 173 Annotation: Subtype: Link Rect: 324, 456, 336, 465 ActionDest: 173 Annotation: Subtype: Link Rect: 287, 444, 299, 453 ActionDest: 173 Annotation: Subtype: Link Rect: 319, 254, 331, 263 ActionDest: 173 Annotation: Subtype: Link Rect: 341, 129, 353, 138 ActionDest: 173 Annotation: Subtype: Link Rect: 271, 91, 283, 100 ActionDest: 173 Annotation: Subtype: Link Rect: 517, 66, 529, 75 ActionDest: 173 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 346, 673, 358, 682 ActionDest: 173 Annotation: Subtype: Link Rect: 215, 472, 227, 481 ActionDest: 173 Annotation: Subtype: Link Rect: 230, 472, 242, 481 ActionDest: 173 Annotation: Subtype: Link Rect: 333, 472, 345, 481 ActionDest: 173 Annotation: Subtype: Link Rect: 345, 472, 357, 481 ActionDest: 173 Annotation: Subtype: Link Rect: 450, 472, 462, 481 ActionDest: 173 Annotation: Subtype: Link Rect: 539, 472, 551, 481 ActionDest: 173 Annotation: Subtype: Link Rect: 328, 384, 340, 393 ActionDest: 173 Annotation: Subtype: Link Rect: 397, 384, 409, 393 ActionDest: 173 Annotation: Subtype: Link Rect: 230, 371, 242, 380 ActionDest: 173 Annotation: Subtype: Link Rect: 320, 358, 332, 368 ActionDest: 173 Annotation: Subtype: Link Rect: 544, 346, 556, 355 ActionDest: 173 Annotation: Subtype: Link Rect: 381, 321, 393, 330 ActionDest: 173 Annotation: Subtype: Link Rect: 512, 308, 524, 317 ActionDest: 173 Annotation: Subtype: Link Rect: 525, 308, 537, 317 ActionDest: 173 Annotation: Subtype: Link Rect: 239, 296, 251, 305 ActionDest: 173 Annotation: Subtype: Link Rect: 432, 296, 444, 305 ActionDest: 173 Annotation: Subtype: Link Rect: 191, 283, 203, 292 ActionDest: 173 Annotation: Subtype: Link Rect: 362, 283, 374, 292 ActionDest: 173 Annotation: Subtype: Link Rect: 374, 283, 386, 292 ActionDest: 176 Annotation: Subtype: Link Rect: 203, 233, 215, 242 ActionDest: 176 Annotation: Subtype: Link Rect: 330, 233, 342, 242 ActionDest: 176 Annotation: Subtype: Link Rect: 525, 233, 537, 242 ActionDest: 176 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 206, 635, 217, 644 ActionDest: 176 Annotation: Subtype: Link Rect: 549, 229, 556, 241 ActionDest: 85 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 309, 372, 317, 384 ActionDest: 85 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 395, 126, 402, 138 ActionDest: 113 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 200, 177, 207, 189 ActionDest: 116 Annotation: Subtype: Link Rect: 256, 177, 263, 189 ActionDest: 116 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 327, 57, 334, 69 ActionDest: 143 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 517, 327, 529, 336 ActionDest: 176 Annotation: Subtype: Link Rect: 532, 327, 544, 336 ActionDest: 176 Annotation: Subtype: Link Rect: 401, 289, 408, 298 ActionDest: 169 Annotation: Subtype: Link Rect: 401, 276, 408, 285 ActionDest: 169 Annotation: Subtype: Link Rect: 268, 264, 275, 273 ActionDest: 169 Annotation: Subtype: Link Rect: 249, 176, 261, 185 ActionDest: 176 Annotation: Subtype: Link Rect: 261, 176, 273, 185 ActionDest: 176 Annotation: Subtype: Link Rect: 274, 176, 285, 185 ActionDest: 176 Annotation: Subtype: Link Rect: 508, 151, 520, 160 ActionDest: 176 Annotation: Subtype: Link Rect: 490, 88, 502, 97 ActionDest: 176 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 488, 723, 500, 732 ActionDest: 176 Annotation: Subtype: Link Rect: 500, 723, 512, 732 ActionDest: 176 Annotation: Subtype: Link Rect: 290, 647, 297, 657 ActionDest: 169 Annotation: Subtype: Link Rect: 297, 647, 309, 657 ActionDest: 169 Annotation: Subtype: Link Rect: 310, 647, 322, 657 ActionDest: 176 Annotation: Subtype: Link Rect: 376, 560, 388, 569 ActionDest: 176 Annotation: Subtype: Link Rect: 251, 535, 263, 544 ActionDest: 176 Annotation: Subtype: Link Rect: 264, 535, 276, 544 ActionDest: 176 Annotation: Subtype: Link Rect: 419, 509, 431, 519 ActionDest: 173 Annotation: Subtype: Link Rect: 312, 221, 324, 229 ActionDest: 176 Annotation: Subtype: Link Rect: 324, 220, 336, 229 ActionDest: 176 Annotation: Subtype: Link Rect: 337, 220, 349, 229 ActionDest: 176 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 268, 328, 305, 338 Annotation: Subtype: Link Rect: 430, 304, 467, 315 Annotation: Subtype: Link Rect: 501, 281, 539, 292 Annotation: Subtype: Link Rect: 375, 246, 413, 257 Annotation: Subtype: Link Rect: 109, 224, 146, 234 Annotation: Subtype: Link Rect: 433, 200, 470, 211 Annotation: Subtype: Link Rect: 487, 166, 525, 177 Annotation: Subtype: Link Rect: 519, 143, 557, 154 Annotation: Subtype: Link Rect: 182, 97, 220, 108 Annotation: Subtype: Link Rect: 356, 62, 393, 73 Page: Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 439, 722, 477, 733 Annotation: Subtype: Link Rect: 131, 699, 168, 710 Annotation: Subtype: Link Rect: 520, 687, 557, 698 Annotation: Subtype: Link Rect: 59, 653, 96, 664 Annotation: Subtype: Link Rect: 504, 629, 542, 640 Annotation: Subtype: Link Rect: 59, 596, 96, 606 Annotation: Subtype: Link Rect: 441, 572, 479, 583 Annotation: Subtype: Link Rect: 59, 538, 96, 548 Annotation: Subtype: Link Rect: 131, 504, 168, 514 Annotation: Subtype: Link Rect: 175, 504, 211, 514 Annotation: Subtype: Link Rect: 397, 481, 434, 491 Annotation: Subtype: Link Rect: 440, 481, 476, 491 Annotation: Subtype: Link Rect: 466, 468, 503, 479 Annotation: Subtype: Link Rect: 122, 435, 159, 445 Annotation: Subtype: Link Rect: 264, 411, 301, 422 Annotation: Subtype: Link Rect: 517, 388, 555, 399 Annotation: Subtype: Link Rect: 163, 354, 201, 364 Annotation: Subtype: Link Rect: 446, 330, 484, 341 Annotation: Subtype: Link Rect: 411, 307, 449, 318 Annotation: Subtype: Link Rect: 95, 274, 133, 284 Annotation: Subtype: Link Rect: 59, 239, 96, 249 Annotation: Subtype: Link Rect: 102, 239, 138, 249 Annotation: Subtype: Link Rect: 59, 216, 96, 226 Annotation: Subtype: Link Rect: 102, 216, 138, 226 Annotation: Subtype: Link Rect: 284, 192, 321, 203 Annotation: Subtype: Link Rect: 147, 170, 184, 180 Annotation: Subtype: Link Rect: 165, 123, 203, 134 Annotation: Subtype: Link Rect: 281, 89, 318, 100 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 152, 711, 189, 721 Annotation: Subtype: Link Rect: 277, 676, 315, 687 Annotation: Subtype: Link Rect: 460, 664, 497, 675 Annotation: Subtype: Link Rect: 282, 629, 319, 640 Annotation: Subtype: Link Rect: 104, 596, 141, 606 Annotation: Subtype: Link Rect: 460, 572, 498, 583 Annotation: Subtype: Link Rect: 504, 572, 540, 583 Annotation: Subtype: Link Rect: 248, 537, 285, 548 Annotation: Subtype: Link Rect: 291, 537, 327, 548 Annotation: Subtype: Link Rect: 281, 503, 318, 514 Annotation: Subtype: Link Rect: 325, 503, 361, 514 Annotation: Subtype: Link Rect: 385, 481, 422, 491 Annotation: Subtype: Link Rect: 428, 481, 464, 491 Annotation: Subtype: Link Rect: 274, 445, 311, 456 Annotation: Subtype: Link Rect: 520, 434, 557, 445 Annotation: Subtype: Link Rect: 131, 400, 168, 410 Annotation: Subtype: Link Rect: 286, 377, 323, 387 Annotation: Subtype: Link Rect: 469, 353, 507, 364 Annotation: Subtype: Link Rect: 135, 320, 173, 330 Annotation: Subtype: Link Rect: 179, 320, 215, 330 Annotation: Subtype: Link Rect: 381, 296, 418, 307 Annotation: Subtype: Link Rect: 425, 296, 461, 307 Annotation: Subtype: Link Rect: 81, 274, 119, 284 Annotation: Subtype: Link Rect: 125, 274, 161, 284 Checksum: 975a7348 Type: CRC32 Checksum: f3a1df94b9c528eca07eaca63ec67b80 Type: MD5 Checksum: a69e43549637d5e95d9bdeab7019a08926bda8d8 Type: SHA-1