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190 Publications visible to you, out of a total of 190
Systemic and Ocular Determinants of Peripapillary Retinal Nerve Fiber Layer Thickness Measurements in the European Eye Epidemiology (E3) Population.
LIFE Adult

Abstract (Expand)

PURPOSE: To investigate systemic and ocular determinants of peripapillary retinal nerve fiber layer thickness (pRNFLT) in the European population. DESIGN: Cross-sectional meta-analysis. PARTICIPANTS: … A total of 16 084 European adults from 8 cohort studies (mean age range, 56.9+/-12.3-82.1+/-4.2 years) of the European Eye Epidemiology (E3) consortium. METHODS: We examined associations with pRNFLT measured by spectral-domain OCT in each study using multivariable linear regression and pooled results using random effects meta-analysis. MAIN OUTCOME MEASURES: Determinants of pRNFLT. RESULTS: Mean pRNFLT ranged from 86.8+/-21.4 mum in the Rotterdam Study I to 104.7+/-12.5 mum in the Rotterdam Study III. We found the following factors to be associated with reduced pRNFLT: Older age (beta = -0.38 mum/year; 95% confidence interval [CI], -0.57 to -0.18), higher intraocular pressure (IOP) (beta = -0.36 mum/mmHg; 95% CI, -0.56 to -0.15), visual impairment (beta = -5.50 mum; 95% CI, -9.37 to -1.64), and history of systemic hypertension (beta = -0.54 mum; 95% CI, -1.01 to -0.07) and stroke (beta = -1.94 mum; 95% CI, -3.17 to -0.72). A suggestive, albeit nonsignificant, association was observed for dementia (beta = -3.11 mum; 95% CI, -6.22 to 0.01). Higher pRNFLT was associated with more hyperopic spherical equivalent (beta = 1.39 mum/diopter; 95% CI, 1.19-1.59) and smoking (beta = 1.53 mum; 95% CI, 1.00-2.06 for current smokers compared with never-smokers). CONCLUSIONS: In addition to previously described determinants such as age and refraction, we found that systemic vascular and neurovascular diseases were associated with reduced pRNFLT. These may be of clinical relevance, especially in glaucoma monitoring of patients with newly occurring vascular comorbidities.

Authors: M. M. Mauschitz, P. W. M. Bonnemaijer, K. Diers, F. G. Rauscher, T. Elze, C. Engel, M. Loeffler, J. M. Colijn, M. A. Ikram, J. R. Vingerling, K. M. Williams, C. J. Hammond, C. Creuzot-Garcher, A. M. Bron, R. Silva, S. Nunes, C. Delcourt, A. Cougnard-Gregoire, F. G. Holz, C. C. W. Klaver, M. M. B. Breteler, R. P. Finger

Date Published: 3rd May 2018

Publication Type: Journal article

Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes.
GLA - German Lymphoma Alliance

Abstract (Expand)

Diffuse large B cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is a clinically and genetically heterogeneous disease that is further classified into transcriptionally defined … activated B cell (ABC) and germinal center B cell (GCB) subtypes. We carried out a comprehensive genetic analysis of 304 primary DLBCLs and identified low-frequency alterations, captured recurrent mutations, somatic copy number alterations, and structural variants, and defined coordinate signatures in patients with available outcome data. We integrated these genetic drivers using consensus clustering and identified five robust DLBCL subsets, including a previously unrecognized group of low-risk ABC-DLBCLs of extrafollicular/marginal zone origin; two distinct subsets of GCB-DLBCLs with different outcomes and targetable alterations; and an ABC/GCB-independent group with biallelic inactivation of TP53, CDKN2A loss, and associated genomic instability. The genetic features of the newly characterized subsets, their mutational signatures, and the temporal ordering of identified alterations provide new insights into DLBCL pathogenesis. The coordinate genetic signatures also predict outcome independent of the clinical International Prognostic Index and suggest new combination treatment strategies. More broadly, our results provide a roadmap for an actionable DLBCL classification.

Authors: B. Chapuy, C. Stewart, A. J. Dunford, J. Kim, A. Kamburov, R. A. Redd, M. S. Lawrence, M. G. M. Roemer, A. J. Li, M. Ziepert, A. M. Staiger, J. A. Wala, M. D. Ducar, I. Leshchiner, E. Rheinbay, A. Taylor-Weiner, C. A. Coughlin, J. M. Hess, C. S. Pedamallu, D. Livitz, D. Rosebrock, M. Rosenberg, A. A. Tracy, H. Horn, P. van Hummelen, A. L. Feldman, B. K. Link, A. J. Novak, J. R. Cerhan, T. M. Habermann, R. Siebert, A. Rosenwald, A. R. Thorner, M. L. Meyerson, T. R. Golub, R. Beroukhim, G. G. Wulf, G. Ott, S. J. Rodig, S. Monti, D. S. Neuberg, M. Loeffler, M. Pfreundschuh, L. Trumper, G. Getz, M. A. Shipp

Date Published: 2nd May 2018

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

Genetic Regulation of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Plasma Levels and Its Impact on Atherosclerotic Vascular Disease Phenotypes
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND Inhibition of PCSK9 (proprotein convertase subtilisin/kexin type 9) is a novel strategy to treat hypercholesterolemia and reduce cardiovascular events. However, the potential role of circulating …g plasma PCSK9 concentrations as a diagnostic and predictive biomarker remains uncertain as of now. Here, we aimed to identify genetic variants associated with plasma PCSK9 and investigate possible causal effects on atherosclerotic vascular disease phenotypes. METHODS We performed the first genome-wide association study of plasma PCSK9 levels in a cohort of suspected and confirmed coronary artery disease (LIFE-Heart; n=3290). RESULTS Several independent variants at the PCSK9 gene locus were associated with circulating PCSK9 levels at genome-wide significance (lead SNP rs11591147, PCSK9-R46L; P=1.94\times10-17). We discovered 4 independent PCSK9 SNPs explaining 4.4% of the variance of plasma PCSK9. In addition, we identified a genome-wide significant locus at chromosome 7p22.1 (rs6957201; P=7.01\times10-9) and 7 suggestive hits (P\textless1\times10-6). Using MR (Mendelian Randomization), we detected significant causal effects of circulating PCSK9 on coronary artery disease status and severity, carotid plaques, and intima-media thickness. CONCLUSIONS Variants at the PCSK9 gene locus seem to be the major genetic determinants of plasma PCSK9 levels with 4 independent variants at the PCSK9 gene locus expressing allelic heterogeneity. The detected MR estimates support the hypothesis of a causal effect of PCSK9 on coronary artery disease and other vascular phenotypes. Other observed genetic associations for PCSK9 require validation in independent cohorts. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00497887.

Authors: Janne Pott, Valentin Schlegel, Andrej Teren, Katrin Horn, Holger Kirsten, Christina Bluecher, Juergen Kratzsch, Markus Loeffler, Joachim Thiery, Ralph Burkhardt, Markus Scholz

Date Published: 1st May 2018

Publication Type: Journal article

3000PA-Towards a National Reference Corpus of German Clinical Language
SMITH - Smart Medical Information Technology for Healthcare

Abstract (Expand)

We introduce 3000PA, a clinical document corpus composed of 3,000 EPRs from three different clinical sites, which will serve as the backbone of a national reference language resource for German clinical … NLP. We outline its design principles, results from a medication annotation campaign and the evaluation of a first medication information extraction prototype using a subset of 3000PA.

Authors: U. Hahn, F. Matthies, C. Lohr, Markus Löffler

Date Published: 24th Apr 2018

Publication Type: InProceedings

Linking stem cell function and growth pattern of intestinal organoids.
ProstataCA

Abstract (Expand)

Intestinal stem cells (ISCs) require well-defined signals from their environment in order to carry out their specific functions. Most of these signals are provided by neighboring cells that form a stem … cell niche, whose shape and cellular composition self-organize. Major features of this self-organization can be studied in ISC-derived organoid culture. In this system, manipulation of essential pathways of stem cell maintenance and differentiation results in well-described growth phenotypes. We here provide an individual cell-based model of intestinal organoids that enables a mechanistic explanation of the observed growth phenotypes. In simulation studies of the 3D structure of expanding organoids, we investigate interdependences between Wnt- and Notch-signaling which control the shape of the stem cell niche and, thus, the growth pattern of the organoids. Similar to in vitro experiments, changes of pathway activities alter the cellular composition of the organoids and, thereby, affect their shape. Exogenous Wnt enforces transitions from branched into a cyst-like growth pattern; known to occur spontaneously during long term organoid expansion. Based on our simulation results, we predict that the cyst-like pattern is associated with biomechanical changes of the cells which assign them a growth advantage. The results suggest ongoing stem cell adaptation to in vitro conditions during long term expansion by stabilizing Wnt-activity. Our study exemplifies the potential of individual cell-based modeling in unraveling links between molecular stem cell regulation and 3D growth of tissues. This kind of modeling combines experimental results in the fields of stem cell biology and cell biomechanics constituting a prerequisite for a better understanding of tissue regeneration as well as developmental processes.

Authors: T. Thalheim, M. Quaas, M. Herberg, U. D. Braumann, C. Kerner, M. Loeffler, G. Aust, J. Galle

Date Published: 15th Jan 2018

Publication Type: Not specified

Human Diseases: colonic disease

Ontology-Based Modelling of Web Content: Example Leipzig Health Atlas
Onto-Med Research Group

Abstract (Expand)

The realisation of a complex web portal, including the modelling of content, is a challenging process. The contents describe different interconnected entities that form a complex structure. The entities … and their relations have to be systematically analysed, and the content has to be specified and integrated into a content management system (CMS). Ontologies provide a suitable solution for modelling and specifying complex entities and their relations. However, the functionality for automated import of ontologies is not available in current content management systems. In order to describe the content of a web portal, we developed an ontology. Based on this ontology, we implemented a pipeline that allows the specification of the portal’s content and its import into the CMS Drupal. Our method is generic. It enables the development of web portals with the focus on a suitable representation of structured knowledge (entities, their properties and relations). Furthermore, it makes it possible to represent existing ontologies in such a way that their content can be understood by users without knowledge of ontologies and their semantics. Our approach has successfully been applied in building the LHA (Leipzig Health Atlas) portal, which provides access to metadata, data, publications and methods from various research projects at the University of Leipzig.

Authors: A. Uciteli, C. Beger, C. Rillich, F. A. Meineke, M. Loffler, H. Herre

Date Published: 2018

Publication Type: InBook

Smart Medical Information Technology for Healthcare (SMITH): Data Integration based on Interoperability Standards
Management of health information systems

Abstract

Not specified

Authors: Alfred Winter, Sebastian Stäubert, Danny Ammon, Stephan Aiche, Oya Beyan, Verena Bischoff, Philipp Daumke, Stefan Decker, Gert Funkat, Jan Erik Gewehr, Armin de Greiff, Silke Haferkamp, Udo Hahn, Andreas Henkel, Toralf Kirsten, Thomas Klöss, Jörg Lippert, Matthias Löbe, Volker Lowitsch, Oliver Maassen, Jens Maschmann, Sven Meister, Rafael Mikolajczyk, Matthias Nüchter, Mathias W. Pletz, Erhard Rahm, Morris Riedel, Kutaiba Saleh, Andreas Schuppert, Stefan Smers, André Stollenwerk, Stefan Uhlig, Thomas Wendt, Sven Zenker, Wolfgang Fleig, Gernot Marx, André Scherag, Markus Löffler

Date Published: 2018

Publication Type: Journal article

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