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1004 Publications visible to you, out of a total of 1004
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

The role of radiotherapy and intrathecal CNS prophylaxis in extralymphatic craniofacial aggressive B-cell lymphomas.
GLA - German Lymphoma Alliance

Abstract (Expand)

To define the role of radiotherapy and intrathecal prophylaxis in extralymphatic craniofacial involvement (ECFI) of aggressive B-cell lymphoma, we analyzed 11 consecutive German High-Grade Non-Hodgkin … Lymphoma Study Group trials. ECFI occurred in 290/4155 (7.0%) patients (orbita, 31; paranasal sinuses, 93; main nasal cavity, 38; tongue, 27; remaining oral cavity, 99; salivary glands, 54). In a multivariable analysis adjusted for International Prognostic Index rituximab improved event-free and overall survival both in patients with and without ECFI. Three-year event-free (79% vs 79%; P = .842) and overall survival (86% vs 88%; P = .351) rates were similar in 145 patients receiving and 57 not receiving radiotherapy. Without rituximab, the 2-year cumulative rate of central nervous system (CNS) disease was increased in 205 ECFI patients compared with 2586 non-ECFI patients (4.2% vs 2.8%; P = .038), whereas this was not observed with rituximab (1.6% in 83 ECFI vs 3.4% in 1252 non-ECFI patients; P = .682). In 88 ECFI patients who received intrathecal prophylaxis with methotrexate, the 2-year rate of CNS disease was 4.2% compared with 2.3% in 191 patients who did not (P = .981). In conclusion, rituximab eliminates the increased risk for CNS disease in patients with ECFI. This retrospective analysis does not support intrathecal prophylaxis or radiotherapy to ECFI patients in complete remission/unconfirmed complete remission. These findings should be confirmed in a prospective study.

Authors: N. Murawski, G. Held, M. Ziepert, B. Kempf, A. Viardot, M. Hanel, M. Witzens-Harig, R. Mahlberg, C. Rube, J. Fleckenstein, C. Zwick, B. Glass, N. Schmitz, S. Zeynalova, M. Pfreundschuh

Date Published: 31st Jul 2014

Publication Type: Not specified

Human Diseases: B-cell lymphoma

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