Filter and export

Publications

959 Publications visible to you, out of a total of 959
Polymorphisms at PRSS1-PRSS2 and CLDN2-MORC4 loci associate with alcoholic and non-alcoholic chronic pancreatitis in a European replication study.
Genetical Statistics and Systems Biology

Abstract (Expand)

OBJECTIVE: Several genetic risk factors have been identified for non-alcoholic chronic pancreatitis (NACP). A genome-wide association study reported an association of chronic pancreatitis (CP) with … variants in PRSS1-PRSS2 (rs10273639; near the gene encoding cationic trypsinogen) and CLDN2-MORC4 loci (rs7057398 in RIPPLY1 and rs12688220 in MORC4). We aimed to refine these findings in a large European cohort. DESIGN: We studied 3062 patients with alcohol-related CP (ACP) or NACP and 5107 controls. Also, 1559 German patients with alcohol-associated cirrhosis or alcohol dependence were included for comparison. We performed several meta-analyses to examine genotype-phenotype relationships. RESULTS: Association with ACP was found for rs10273639 (OR, 0.63; 95% CI 0.55 to 0.72). ACP was also associated with variants rs7057398 and rs12688220 in men (OR, 2.26; 95% CI 1.94 to 2.63 and OR, 2.66; 95% CI 2.21 to 3.21, respectively) and in women (OR, 1.57; 95% CI 1.14 to 2.18 and OR 1.71; 95% CI 1.41 to 2.07, respectively). Similar results were obtained when German patients with ACP were compared with those with alcohol-associated cirrhosis or alcohol dependence. In the overall population of patients with NACP, association with rs10273639 was absent (OR, 0.93; 95% CI 0.79 to 1.01), whereas rs7057398 of the X chromosomal single nucleotide polymorphisms was associated with NACP in women only (OR, 1.32; 95% CI 1.15 to 1.51). CONCLUSIONS: The single-nucleotide polymorphisms rs10273639 at the PRSS1-PRSS2 locus and rs7057398 and rs12688220 at the CLDN2-MORC4 locus are associated with CP and strongly associate with ACP, but only rs7057398 with NACP in female patients.

Authors: M. H. Derikx, P. Kovacs, M. Scholz, E. Masson, J. M. Chen, C. Ruffert, P. Lichtner, R. H. Te Morsche, G. M. Cavestro, C. Ferec, J. P. Drenth, H. Witt, J. Rosendahl

Date Published: 26th Sep 2014

Publication Type: Journal article

Frontomedian cortex is central for moral deficits in behavioural variant frontotemporal dementia.
LIFE Adult

Abstract

Not specified

Authors: M. L. Schroeter, D. Bzdok, S. B. Eickhoff, J. Neumann

Date Published: 25th Sep 2014

Publication Type: Not specified

Human Diseases: frontotemporal dementia

Assessing technical performance in differential gene expression experiments with external spike-in RNA control ratio mixtures.
LHA - Leipzig Health Atlas

Abstract (Expand)

There is a critical need for standard approaches to assess, report and compare the technical performance of genome-scale differential gene expression experiments. Here we assess technical performance … with a proposed standard 'dashboard' of metrics derived from analysis of external spike-in RNA control ratio mixtures. These control ratio mixtures with defined abundance ratios enable assessment of diagnostic performance of differentially expressed transcript lists, limit of detection of ratio (LODR) estimates and expression ratio variability and measurement bias. The performance metrics suite is applicable to analysis of a typical experiment, and here we also apply these metrics to evaluate technical performance among laboratories. An interlaboratory study using identical samples shared among 12 laboratories with three different measurement processes demonstrates generally consistent diagnostic power across 11 laboratories. Ratio measurement variability and bias are also comparable among laboratories for the same measurement process. We observe different biases for measurement processes using different mRNA-enrichment protocols.

Authors: S. A. Munro, S. P. Lund, P. S. Pine, H. Binder, D. A. Clevert, A. Conesa, J. Dopazo, M. Fasold, S. Hochreiter, H. Hong, N. Jafari, D. P. Kreil, P. P. Labaj, S. Li, Y. Liao, S. M. Lin, J. Meehan, C. E. Mason, J. Santoyo-Lopez, R. A. Setterquist, L. Shi, W. Shi, G. K. Smyth, N. Stralis-Pavese, Z. Su, W. Tong, C. Wang, J. Wang, J. Xu, Z. Ye, Y. Yang, Y. Yu, M. Salit

Date Published: 25th Sep 2014

Publication Type: Not specified

Incident subjective memory complaints and the risk of subsequent dementia.
LIFE Adult

Abstract (Expand)

OBJECTIVE: In this study, we aimed to analyze the association between new-incident-subjective memory complaints (SMC) and risk of subsequent dementia in a general population sample aged 75+ years. … METHOD: Data were derived from follow-up (FUP) waves I-V of the population-based Leipzig Longitudinal Study of the Aged (LEILA75+). We used the Kaplan-Meier survival method to estimate dementia-free survival times of individuals with and without incident SMC and multivariable Cox proportional hazards regression to assess the association between incident SMC and risk of subsequent dementia, controlled for covariates. RESULTS: Of 443 non-demented individuals, 58 (13.1%) developed dementia during a subsequent 5.4-year follow-up period. Participants with incident SMC showed a significantly higher progression to dementia (18.5% vs. 10.0%; P=0.010) and a significantly shorter mean dementia-free survival time than those without (6.2 vs. 6.8 years; P=0.008). The association between incident SMC and risk of subsequent dementia remained significant in the multivariable Cox analysis (adjusted hazard ratio=1.8; P=0.028). CONCLUSION: Our findings suggest higher progression to dementia and shorter dementia-free survival in older individuals with incident SMC. These findings support the notion that such subjective complaints should be taken seriously in clinical practice as possible early indicators of incipient dementia.

Authors: T. Luck, M. Luppa, H. Matschinger, F. Jessen, M. C. Angermeyer, S. G. Riedel-Heller

Date Published: 10th Sep 2014

Publication Type: Not specified

Human Diseases: dementia

A systems biology approach for defining the molecular framework of the hematopoietic stem cell niche.
LHA - Leipzig Health Atlas

Abstract (Expand)

Despite progress in identifying the cellular composition of hematopoietic stem/progenitor cell (HSPC) niches, little is known about the molecular requirements of HSPC support. To address this issue, … we used a panel of six recognized HSPC-supportive stromal lines and less-supportive counterparts originating from embryonic and adult hematopoietic sites. Through comprehensive transcriptomic meta-analyses, we identified 481 mRNAs and 17 microRNAs organized in a modular network implicated in paracrine signaling. Further inclusion of 18 additional cell strains demonstrated that this mRNA subset was predictive of HSPC support. Our gene set contains most known HSPC regulators as well as a number of unexpected ones, such as Pax9 and Ccdc80, as validated by functional studies in zebrafish embryos. In sum, our approach has identified the core molecular network required for HSPC support. These cues, along with a searchable web resource, will inform ongoing efforts to instruct HSPC ex vivo amplification and formation from pluripotent precursors.

Authors: P. Charbord, C. Pouget, H. Binder, F. Dumont, G. Stik, P. Levy, F. Allain, C. Marchal, J. Richter, B. Uzan, F. Pflumio, F. Letourneur, H. Wirth, E. Dzierzak, D. Traver, T. Jaffredo, C. Durand

Date Published: 4th Sep 2014

Publication Type: Not specified

Cellular Adhesion Gene SELP Is Associated with Rheumatoid Arthritis and Displays Differential Allelic Expression // Cellular adhesion gene SELP is associated with rheumatoid arthritis and displays differential allelic expression
Genetical Statistics and Systems Biology

Abstract (Expand)

In rheumatoid arthritis (RA), a key event is infiltration of inflammatory immune cells into the synovial lining, possibly aggravated by dysregulation of cellular adhesion molecules. Therefore, single … nucleotide polymorphisms of 14 genes involved in cellular adhesion processes (CAST, ITGA4, ITGB1, ITGB2, PECAM1, PTEN, PTPN11, PTPRC, PXN, SELE, SELP, SRC, TYK2, and VCAM1) were analyzed for association with RA. Association analysis was performed consecutively in three European RA family sample groups (Nfamilies = 407). Additionally, we investigated differential allelic expression, a possible functional consequence of genetic variants. SELP (selectin P, CD62P) SNP-allele rs6136-T was associated with risk for RA in two RA family sample groups as well as in global analysis of all three groups (ptotal = 0.003). This allele was also expressed preferentially (p\textless10-6) with a two- fold average increase in regulated samples. Differential expression is supported by data from Genevar MuTHER (p1 = 0.004; p2 = 0.0177). Evidence for influence of rs6136 on transcription factor binding was also found in silico and in public datasets reporting in vitro data. In summary, we found SELP rs6136-T to be associated with RA and with increased expression of SELP mRNA. SELP is located on the surface of endothelial cells and crucial for recruitment, adhesion, and migration of inflammatory cells into the joint. Genetically determined increased SELP expression levels might thus be a novel additional risk factor for RA. In rheumatoid arthritis (RA), a key event is infiltration of inflammatory immune cells into the synovial lining, possibly aggravated by dysregulation of cellular adhesion molecules. Therefore, single nucleotide polymorphisms of 14 genes involved in cellular adhesion processes (CAST, ITGA4, ITGB1, ITGB2, PECAM1, PTEN, PTPN11, PTPRC, PXN, SELE, SELP, SRC, TYK2, and VCAM1) were analyzed for association with RA. Association analysis was performed consecutively in three European RA family sample groups (Nfamilies = 407). Additionally, we investigated differential allelic expression, a possible functional consequence of genetic variants. SELP (selectin P, CD62P) SNP-allele rs6136-T was associated with risk for RA in two RA family sample groups as well as in global analysis of all three groups (ptotal = 0.003). This allele was also expressed preferentially (p\textless10-6) with a two- fold average increase in regulated samples. Differential expression is supported by data from Genevar MuTHER (p1 = 0.004; p2 = 0.0177). Evidence for influence of rs6136 on transcription factor binding was also found in silico and in public datasets reporting in vitro data. In summary, we found SELP rs6136-T to be associated with RA and with increased expression of SELP mRNA. SELP is located on the surface of endothelial cells and crucial for recruitment, adhesion, and migration of inflammatory cells into the joint. Genetically determined increased SELP expression levels might thus be a novel additional risk factor for RA.

Authors: Jana Burkhardt, Mechthild Blume, Elisabeth Petit-Teixeira, Vitor Hugo Teixeira, Anke Steiner, Elfi Quente, Grit Wolfram, Markus Scholz, Céline Pierlot, Paola Migliorini, Stefano Bombardieri, Alejandro Balsa, René Westhovens, Pilar Barrera, Timothy R D J Radstake, Helena Alves, Thomas Bardin, Bernard Prum, Frank Emmrich, François Cornelis, Peter Ahnert, Holger Kirsten

Date Published: 22nd Aug 2014

Publication Type: Journal article

A specialized post anaesthetic care unit improves fast-track management in cardiac surgery: a prospective randomized trial
Genetical Statistics and Systems Biology

Abstract (Expand)

INTRODUCTION Fast-track treatment in cardiac surgery has become the global standard of care. We compared the efficacy and safety of a specialised post-anaesthetic care unit (PACU) to a conventional …l intensive care unit (ICU) in achieving defined fast-track end-points in adult patients after elective cardiac surgery. METHODS In a prospective, single blinded, randomized study, 200 adult patients undergoing elective cardiac surgery (coronary artery bypass graft (CABG), valve surgery or combined CABG and valve surgery), were selected to receive their postoperative treatment either in the ICU (n = 100), or in the PACU (n = 100). Patients who, at the time of surgery, were in cardiogenic shock, required renal dialysis, or had an additive EuroSCORE of more than 10 were excluded from the study. The primary end points were: time to extubation (ET), and length of stay in the PACU or ICU (PACU/ICU LOS respectively). Secondary end points analysed were the incidences of: surgical re-exploration, development of haemothorax, new onset cardiac arrhythmia, low cardiac output syndrome, need for cardio-pulmonary resuscitation, stroke, acute renal failure, and death. RESULTS Median time to extubation was 90 [50; 140] min in the PACU vs. 478 [305; 643] min in the ICU group (P \textless 0.001). Median length of stay in PACU was 3.3 [2.7; 4.0] hours vs. 17.9 [10.3; 24.9] hours in the ICU (P \textless 0.001). Of the adverse events examined, only the incidence of new onset cardiac arrhythmia (25 in PACU vs. 41 in ICU, P = 0.02) was statistically different between groups. CONCLUSIONS Treatment in a specialised PACU rather than an ICU, after elective cardiac surgery leads to earlier extubation and quicker discharge to a step down unit, without compromising patient safety. TRIAL REGISTRATION ISRCTN71768341. Registered 11 March 2014.

Authors: Stefan Probst, Christof Cech, Dirk Haentschel, Markus Scholz, Joerg Ender

Date Published: 1st Aug 2014

Publication Type: Journal article

Navigate

Health Atlas - Local Data Hub/Leipzig

The Health Atlas - Local Data Hub/Leipzig is an alliance of medical ontologists, medical systems biologists and clinical trials groups to design and implement a multi-functional and quality-assured atlas. It provides models, data and metadata on specific use cases from medical research fields.

Registered Repository

re3data.org Badge
Powered by
 (v.1.13.0-master)
Health Atlas | Funding and Programmes | Credits | Terms & Conditions | Privacy Policy | Imprint
Copyright © 2008 - 2021 The University of Manchester and HITS gGmbH
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig

By continuing to use this site you agree to the use of cookies