The effect of minimum volume standards in hospitals (MIVOS) - protocol of a systematic review.

Background: The volume-outcome relationship, i.e., higher hospital volume results in better health outcomes, has been established for different surgical procedures as well as for certain nonsurgical medical interventions.

Low serum albumin is an independent risk factor in elderly patients with aggressive B-cell lymphoma: Results from prospective trials of the German High-Grade Non-Hodgkin's Lymphoma Study Group.

Serum albumin a well-known risk factor predicting outcome in many solid tumors. We explore the role of low serum albumin (≤3.5 g/dL) as an independent risk factor in elderly patients with aggressive B-cell lymphoma.

EGFR/Ras-induced CCL20 production modulates the tumour microenvironment.

Background: The activation of the EGFR/Ras-signalling pathway in tumour cells induces a distinct chemokine repertoire, which in turn modulates the tumour microenvironment.

Methods: The effects of EGFR/Ras on the expression and translation of CCL20 were analysed in a large set of epithelial cancer cell lines and tumour tissues by RT-qPCR and ELISA in vitro. CCL20 production was verified by immunohistochemistry in different tumour tissues and correlated with clinical data.

Consensus in determining the resectability of locally progressed pancreatic ductal adenocarcinoma - results of the Conko-007 multicenter trial.

Background: One critical step in the therapy of patients with localized pancreatic cancer is the determination of local resectability. The decision between primary surgery versus upfront local or systemic cancer therapy seems especially to differ between pancreatic cancer centers. In our cohort study, we analyzed the independent judgement of resectability of five experienced high volume pancreatic surgeons in 200 consecutive patients with borderline resectable or locally advanced pancreatic cancer.

Structural brain anomalies in patients with FOXG1 syndrome and in Foxg1+/- mice.

Objective: FOXG1 syndrome is a rare neurodevelopmental disorder associated with heterozygous variants or chromosomal microaberrations in 14q12. The study aimed at assessing the scope of structural cerebral anomalies revealed by neuroimaging to delineate the genotype and neuroimaging phenotype associations.

Methods: We compiled 34 patients with a heterozygous (likely) pathogenic variant.

Reaction-diffusion model for STIM-ORAI interaction: The role of ROS and mutations.

Release of Ca from endoplasmatic retriculum (ER) Ca stores causes stromal interaction molecules (STIM) in the ER membrane and ORAI proteins in the plasma membrane (PM) to interact and form the Ca release activated Ca (CRAC) channels, which represent a major Ca entry route in non-excitable cells and thus control various cell functions. It is experimentally possible to mutate ORAI1 proteins and therefore modify, especially block, the Ca influx into the cell. On the basis of the model of Hoover and Lewis (2011), we formulate a reaction-diffusion model to quantify the STIM1-ORAI1 interaction during CRAC channel formation and analyze different ORAI1 channel stoichiometries and different ratios of STIM1 and ORAI1 in comparison with experimental data.

Approach and Avoidance Biases Toward Sexual Stimuli and Their Association with the Dual Control Model of Sexual Response in Heterosexual Men.

Many models of human behavior work in an interaction of a dual system. While one system usually represents controlled and reflective behavioral responses, the other system reflects automatic and impulsive actions. In the impulsive system, positive stimuli initiate approach reactions and negative cues avoidance reactions.

A Yin and Yang in Epithelial Immunology: The Roles of the α(CD103)β Integrin in T Cells.

The proper function(s) of cell-surface receptors is crucial for the regulation of adaptive immune responses. One such receptor is the α(CD103)β integrin, whose history in science is closely linked with the evolution of our knowledge of immune regulation. Initially described as a marker of intraepithelial T-lymphocytes, this leukocyte integrin is now seen as a dynamically regulated receptor involved in the functional differentiation of some cytotoxic T cells as well as regulatory T cells, thus presumably contributing to the fine-tuning of immune reactions in epithelial compartments.

RNA sequencing of bipolar disorder lymphoblastoid cell lines implicates the neurotrophic factor HRP-3 in lithium's clinical efficacy.

Lithium remains the oldest and most effective treatment for mood stabilisation in bipolar disorder (BD), even though at least half of patients are only partially responsive or do not respond. This study aimed to identify biomarkers associated with lithium response in BD, based on comparing RNA sequencing information derived from lymphoblastoid cell lines (LCLs) of lithium-responsive (LR) versus lithium non-responsive (LNR) BD patients, to assess gene expression variations that might bear on treatment outcome. RNA sequencing was carried out on 24 LCLs from female BD patients (12 LR and 12 LNR) followed by qPCR validation in two additional independent cohorts (41 and 17 BD patients, respectively).

The utilization of multidisciplinary tumor boards (MDT) in clinical routine: results of a health care research study focusing on patients with metastasized colorectal cancer.

Purpose: Multidisciplinary tumor boards (MDT) have been advocated as standard of care in modern oncology. German guidelines for metastasized colorectal cancer (mCRC) recommend MDT discussion of colon cancer patients after completion of primary tumor therapy but stage IV colon cancer as well as rectal cancer patients prior to any therapy. In this health care research study, we evaluated application and decisional consequences of this approach in clinical routine.

Necrotizing enterocolitis in premature infants and newborns.

Necrotizing enterocolitis (NEC) is the most common acquired disease of the gastrointestinal tract (GIT) in premature infants and newborns. It is defined as an ulcerative inflammation of the intestinal wall. The clinical signs of incipient NEC are often very discrete, and range from localized intestinal symptoms to generalized signs of sepsis.

The implausibility of response shifts in dementia patients.

Dementia patients may express wishes that do not conform to or contradict earlier expressed preferences. Our understanding of the difference between their prior preferences and current wishes has important consequences for the way we deal with advance directives. Some bioethicists and gerontologists have argued that dementia patients change because they undergo a 'response shift'.

No reactivation of JCV and CMV infections in the temporal cortex and cerebellum of sporadic Creutzfeldt-Jakob disease patients.

Sporadic Creutzfeldt-Jakob disease (sCJD) is characterized by great phenotypic variability regarding clinical course and neuropathology. The most prominent disease modifiers are a polymorphism in Codon 129 of the prion protein gene and conformational variations of the misfolded prion protein. The cellular form of the prion protein restricts replication of viruses and may be involved in viral host defense, and viral infections influence the presentation and neuropathology in prion diseased mice.

Concept for linking de-identified biomedical research data using a study participant management system.

Biomedical research projects show an increasing demand of large numbers of participants from different recruiting centers to achieve statistically significant results. The collected types of data are stored in distributed databases and are linked to the participant by different non-resolvable identifiers (layered pseudonyms) for de-identification. To ensure the quality of the gathered data, regular quality assurance analyses are required at each local center.

Doxycycline in Creutzfeldt-Jakob disease: a phase 2, randomised, double-blind, placebo-controlled trial.

Background: Creutzfeldt-Jakob disease (CJD) is a fatal, untreatable prion encephalopathy. Previous studies showed that doxycycline is effective in in-vitro and in-vivo models of disease, and patients with CJD who received compassionate treatment with doxycycline showed increased survival time compared with historical series. We therefore did a randomised, double-blind study of doxycycline versus placebo in CJD.

Subtype-specific synaptic proteome alterations in sporadic Creutzfeldt-Jakob disease.

Sporadic Creutzfeldt-Jakob disease (sCJD) is characterized by wide clinical and pathological variability, which is mainly influenced by the conformation of the misfolded prion protein (PrPSc) and by methionine and valine polymorphism at codon 129 of the gene encoding PrP. This heterogeneity likely implies differences in the molecular cascades that lead to the development of certain disease phenotypes. Here, we investigated synaptic proteome patterns in two most common sCJD subtypes (MM1 and VV2) using 2D DIGE and mass spectrometry.

The four and a half LIM-domain 2 controls early cardiac cell commitment and expansion via regulating β-catenin-dependent transcription.

The multiphasic regulation of the Wnt/β-catenin canonical pathway is essential for cardiogenesis in vivo and in vitro. To achieve tight regulation of the Wnt/β-catenin signaling, tissue- and cell-specific coactivators and repressors need to be recruited. The identification of such factors may help to elucidate mechanisms leading to enhanced cardiac differentiation efficiency in vitro as well as promote regeneration in vivo.

Low-abundant cerebrospinal fluid proteome alterations in dementia with Lewy bodies.

Dementia with Lewy bodies (DLB) is one of the most common neurodegenerative diseases and shares multiple clinical and neuropathological parallels with Alzheimer's (AD) and Parkinson's disease (PD). A variety of clinical signs are suggestive for the diagnosis, and imaging (βCIT SPECT) contributes substantially to the diagnosis. The study reported here was performed in search for a biomarker in the cerebrospinal fluid (CSF) of these patients.

Sporadic Creutzfeldt-Jakob disease subtype-specific alterations of the brain proteome: impact on Rab3a recycling.

Sporadic Creutzfeldt-Jakob disease (sCJD) is characterized by wide clinical and pathological variability, which is mainly influenced by the conformation of the misfolded prion protein, and by the methionine and valine polymorphism at codon 129 of the prion protein gene. This heterogeneity likely implies differences in the molecular cascade that leads to the development of certain disease phenotypes. In this study, we investigated the proteome of the frontal cortex of patients with the two most common sCJD subtypes (MM1 and VV2) using 2D-DIGE and MS.

Desmoplakin as a potential candidate for cerebrospinal fluid marker to rule out 14-3-3 false positive rates in sporadic Creutzfeldt-Jakob disease differential diagnosis.

Background: The detection of a 14-3-3 elevated level in cerebrospinal fluid (CSF) is a part of the diagnostic criteria for probable sporadic Creutzfeldt-Jakob disease (sCJD), as defined by the WHO. However, some pathological conditions associated with acute neuronal damage may result in a positive 14-3-3 test and thereby reduce test specificity in sCJD.

Objective: Desmoplakin has been previously identified as up-regulated CSF protein in sCJD and these studies aimed to investigate its diagnostic utility and compare it with two known CSF markers, 14-3-3 and tau.

Codon 129 polymorphism specific cerebrospinal fluid proteome pattern in sporadic Creutzfeldt-Jakob disease and the implication of glycolytic enzymes in prion-induced pathology.

Cerebrospinal fluid (CSF) contains a dynamic and complex mixture of proteins, which can reflect a physiological and pathological state of the central nervous system. In our present study, we show CSF protein patterns from patients with the two most frequent subtypes of sporadic Creutzfeldt-Jakob disease (sCJD) defined by the codon 129 genotype (MM, MV, and VV) and the protease-resistant form of prion protein (type 1 and type 2). The densitometric analysis of 2D gels showed up-regulation of 27 and down-regulation of 3 proteins in the MM-sCJD as well as the up-regulation of 24 proteins in the VV-sCJD as compared to nondemented control.