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National Research Data Infrastructure for Personal Health Data (NFDI4Health) : abstract

Seit 2007 arbeitet die Weltgesundheitsorganisation (WHO) an der 11. Revision zur Internationalen Klassifikation der Erkrankungen (ICD). Die ICD-11 unterscheidet sich in Umfang und Struktur deutlich von der ICD-10. Vor der Verabschiedung hatte die WHO daher Feldtests mit Kodierung von Diagnosen und Fallbeschreibungen vorgesehen. In der Arbeit sollen Hintergrund und Umsetzung der Feldtests in Deutschland beschrieben werden. Uber die Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) wurden interessierte Mitglieder zu Projektantragen aufgefordert. Die Koordination erfolgte durch die Technologie- und Methodenplattform fur die vernetzte medizinische Forschung e. V. (TMF) mit Unterstutzung des Deutschen Instituts fur Medizinische Dokumentation und Information (DIMDI). Zu untersuchen war eine Betaversion („draft for quality assurance“) der ICD-11 for Mortality and Morbidity Statistics (ICD-11-MMS), einer Fassung der ICD-11 zur Abbildung von Mortalitat und Morbiditat. Von Marz bis August 2017 konnten 11 Feldtests durchgefuhrt werden. Mit Ausnahme eines Tests uber die Diagnosenbezeichnungen aus dem Alphabetischen Verzeichnis zur ICD-10-GM fokussierten die Feldtests auf jeweils ein medizinisches Fachgebiet. Uber die 11 Feldtests wurden insgesamt 8 verschiedene Gutekriterien untersucht und 22 der 27 Kapitel der ICD-11-MMS zumindest anteilig einbezogen. Trotz engem Zeitrahmen liesen sich die Feldtests in Deutschland erfolgreich umsetzen. Weitestgehend wurde auf die Kodierwerkzeuge der WHO zuruckgegriffen. Ein Grosteil der Kapitel der ICD konnte anteilig abgedeckt werden. Erstmalig wurde demonstriert, dass Feldtests einen wertvollen Ansatz zu einer die Entwicklung begleitenden Evaluation der ICD darstellen. Die Feldtests sind allerdings noch in einen Methodenrahmen einzufugen, um alle relevanten Anforderungen bei einer Evaluation berucksichtigen zu konnen.

In the spirit of our common interest to build what could become an international beacon for sharing the benefits of high-quality research data and research data management, the signing NFDI consortia strongly support the idea that NFDI must build on a coordinated and inclusive effort fostering the FAIR data principles. Recalling the challenges that interoperability and sharing of data faces, the 21 consortia signing this declaration agreed on a common list of cross-cutting topics.

Hintergrund: Mit einer 9-monatigen Konzeptentwicklungsphase förderte das BMBF den Aufbau modellhafter Patientenregister in der Versorgungsforschung in 16 Vorhaben. Die Vorhaben wurden durch ein Begleitprojekt (Förderkennzeichen 01GY1720A) hinsichtlich der Einhaltung methodischer, organisatorischer[zum vollständigen Text gelangen Sie über die oben angegebene URL], 17. Deutscher Kongress für Versorgungsforschung (DKVF)

The World Health Organization (WHO) has been developing the 11th revision of the International Classification of Diseases (ICD) since 2007. ICD-11 is different from the ICD-10 in volume and structure. Therefore, the WHO planned field tests with a coding of diagnoses and cases.To describe the background of the field tests and their implementation in Germany.Interested parties were invited to submit proposals through a call to the Association of the Scientific Medical Societies (AWMF). The Technology, Methods, and Infrastructure for Networked Medical Research (TMF) was responsible for the coordination, supported by the German Institute for Medical Documentation and Information (DIMDI). The target was a beta version of the ICD-11 for Mortality and Morbidity Statistics (ICD-11-MMS), denoted as "draft for quality assurance".Eleven field tests were maintained between March and September 2017. With the exception of one field test analyzing diagnoses terms from the thesaurus of the ICD-10-GM, all field tests focused on a specific medical field. Eight different quality criteria were investigated over the 11 field tests, and 22 of the 27 chapters of the ICD-11-MMS were at least partially covered.Despite the strict time frame, the field tests were successfully implemented and concluded in Germany. Mostly, the ICD-11 tools from the WHO were used. A high percentage of the ICD chapters were partially covered. In summary, it has been demonstrated for the first time that field tests are a valuable approach to evaluate the ICD in parallel to its development. However, a methodological framework integrating the field tests should be developed, taking into account all relevant requirements.

The specificity of glycosyltransferases is a major control factor in the biosynthesis of O-glycans. The enzyme that synthesizes O-glycan core 1, i.e., UDP-galactose:N-acetylgalactosamine-α-R β3-galactosyltransferase (β3-Gal-T; EC 2.4.1.122), was partially purified from rat liver. The enzyme preparation, free of pyrophosphatases, β4-galactosyltransferase, β-galactosidase, and N-acetylglucosaminyltransferase I, was used to study the specificity and inhibition of the β3-Gal-T. β3-Gal-T activity is sensitive to changes in the R-group of the GalNAcα-R acceptor substrate and is stimulated when the R-group is a peptide or an aromatic group. Derivatives of GalNAcα-benzyl were synthesized and tested as potential substrates and inhibitors. Removal or substitution of the 3-hydroxyl or removal of the 4-hydroxyl of GalNAc abolished β3-Gal-T activity. Compounds with modifications of the 3- or 4-hydroxyl of GalNAcα-benzyl did not show significant inhibition. Removal or substitution of the 6-hydroxyl of GalNAc reduced activity slightly and these derivatives acted as competitive substrates. Derivatives with epoxide groups attached to the 6-position of GalNAc acted as substrates and not as inhibitors, with the exception of the photosensitive 6-O-(4,4-azo)pentyl-GalNAcα-benzyl, which inhibited Gal incorporation into GalNAcα-benzyl. The results indicate that the enzyme does not require the 6-hydroxyl of GalNAc, but needs the 3- and the axial 4-hydroxyl as essential requirements for binding and activity. In the usual biochemical O-glycan pathway, core 2 (GlcNAcβ6[Galβ3]GalNAcα-) is formed from core 1 (Galβ3GalNAc-R). We have now demonstrated an alternate pathway that may be of importance in human tissues.Key words: β3-Gal-transferase, mucin synthesis, O-glycan core 1, enzyme specificity, enzyme inhibition.

The preferred conformations of the sequences of O-glycopeptides containing a beta-D-xylosyl group linked to an L-seryl residue, found in the N-terminus of proteodermatan sulfate, show an almost extended peptide chain with the sugar unit in a specific position. The results of force-field calculations with the AMBER program have been confirmed, by n.m.r.-spectroscopic experiments, for a minimum conformation.

The preferred conformations of eight O -glycopeptide sequences from the N -terminus of interleukin-2 containing two to ten amino acids, monoglycosylated at Thr 3 with a 2-acetamido-2-deoxy-α- d - galactopyranosyl group, were determined by means of n.m.r. spectroscopic methods. The preferred conformation of the N-terminal sequence, l -Ala- l -Pro-[α- d -Gal p NAc-(1→3)]- l -Thr- l -Ser, including the O -glycosidically linked 2-acetamido-deoxy-α- d -galactopyranosyl group is not substantially influenced by the linkage of additioinal amino acids at the C-terminal end. Extended conformations were observed for all peptide units. Measurements of the relaxation times of the 13 C atoms showed that the 2-acetamido-2-deoxy- d -galactose bound to the central amino acids has the lowest mobility, whereas the terminal amino acid residues and peptide side-chains are flexible. Calculations with the force-field program AMBER yielded conformations of minimized energies that were in good agreement with the n.m.r. spectroscopic data. This was only true when n.m.r. parameters that can be used as starting values for the calculations were available. Comparison with a nonglycosylated, N-terminal tetrapeptide sequence analog did not suggest changes in the peptide conformation when Thr 3 is glycosylated with a 2-acetamido-2-deoxy-α- d -galactopyranosyl group.

The preferred conformations of eight O-glycopeptide sequences from the N-terminus of interleukin-2 containing two to ten amino acids, monoglycosylated at Thr3 with a 2-acetamido-2-deoxy-alpha-D-galactopyranosyl group, were determined by means of n.m.r. spectroscopic methods. The preferred conformation of the N-terminal sequence, L-Ala-L-Pro-[alpha-D-GalpNAc-(1----3)]-L-Thr-L-Ser, including the O-glycosidically linked 2-acetamido-2-deoxy-alpha-D-galactopyranosyl group is not substantially influenced by the linkage of additional amino acids at the C-terminal end. Extended conformations were observed for all peptide units. Measurements of the relaxation times of the 13C atoms showed that the 2-acetamido-2-deoxy-D-galactose bound to the central amino acids has the lowest mobility, whereas the terminal amino acid residues and peptide side-chains are flexible. Calculations with the force-field program AMBER yielded conformations of minimized energies that were in good agreement with the n.m.r. spectroscopic data. This was only true when n.m.r. parameters that can be used as starting values for the calculations were available. Comparison with a nonglycosylated, N-terminal tetrapeptide sequence analog did not suggest changes in the peptide conformation when Thr3 is glycosylated with a 2-acetamido-2-deoxy-alpha-D-galactopyranosyl group.

The preferred conformations of the sequences of O-glycopeptides containing a beta-D-xylosyl group linked to an L-seryl residue, found in the N-terminus of proteodermatan sulfate, show an almost extended peptide chain with the sugar unit in a specific position. The results of force-field calculations with the AMBER program have been confirmed, by n.m.r.-spectroscopic experiments, for a minimum conformation.

Malignant transformation of rodent cell lines by polyoma virus and by activated ras genes is associated with increased UDP-GlcNAc:Man alpha-R beta-1,6-N-acetylglucosaminyltransferase V (GlcNAc-transferase V) activity and it product -GlcNAc beta 1-6Man alpha 1-6Man beta 1-branched Asn-linked oligosaccharides. In this report, we have compared beta 1-6GlcNAc branching of core O- and N-linked oligosaccharides in three experimental models of malignancy, namely (a) rat2 fibroblasts and their malignant T24H-ras-transfected counterpart; (b) benign SP1 mammary carcinoma cells and two metastic sublines of SP1; and (c) the metastatic MDAY-D2 lymphoma cell line and its poorly metastatic glycosylation mutant KBL-1. In addition to the previously reported increase in GlcNAc-transferase V activity, UDP-GlcNAc:Gal beta 1-3GalNAc alpha-R (GlcNAc to GalNAc) beta-1,6-N-acetylglucosaminyltransferase (core 2 GlcNAc-transferase, EC 2.4.1.102) activity was found to be elevated by 70% in the malignant rat2 and SP1 cell lines while several other glycosyltransferase activities were not significantly different. The action of core 2 GlcNAc-transferase followed by beta 1-4Gal-transferase provides an N-acetyllactosamine antenna that can be extended with polylactosamine (i.e. repeating Gal beta 1-4GlcNAc beta 1-3) provided UDP-GlcNAc:Gal beta-R beta 1-3GlcNAc-transferase (GlcNAc-transferase) (i)) activity is present. Polylactosamine content in microsomal membrane glycoproteins was quantitated by labeling the GlcNAc termini resulting from the action of Escherichia freundii endo-beta-galactosidase with bovine galactosyltransferase/UDP-[3H] Gal. Glycopeptidase F- sensitive and -insensitive fractions were measured to assess the N- and O-linked components. In the SP1 tumor model, the metastatic sublines showed increased core 2 GlcNAc-transferase and GlcNAc-transferase V activities but no change in GlcNAc-transferase (i) activity, yet polylactosamine was increased in both O- and N-linked oligosaccharides. In rat2 cells, down-regulation of GlcNAc-transferase (i) following transformation was associated with decreased polyactosamine even though core 2 GlcNAc-transferase and GlcNAc-transferase V were elevated in the cells. Finally, a 3-fold decrease in GlcNAc-transferase V in KBL-1, the glycosylation mutant of MDAY-D2 cells, resulted in complete loss of polylactosamine in N-linked but no change in O-linked polylactosamine content. These results suggest that, provided GlcNAc-transferase (i) is not limiting, the beta 1-6-branching enzymes core 2 GlcNAc-transferase and GlcNAc-transferase V regulate the levels of polyactosamine in O- and N-linked oligosaccharides, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)