Macroporous click-elastin-like hydrogels for tissue engineering applications.

Elastin is a key extracellular matrix (ECM) protein that imparts functional elasticity to tissues and therefore an attractive candidate for bioengineering materials. Genetically engineered elastin-like recombinamers (ELRs) maintain inherent properties of the natural elastin (e.g.

Inflammatory markers and the risk of dementia and Alzheimer's disease: A meta-analysis.

Introduction: Inflammatory markers are often elevated in patients with dementia, including Alzheimer's disease (AD). However, it remains unclear whether inflammatory markers are associated with the risk of developing dementia.

Methods: We searched PubMed, Embase, and Cochrane library for prospective population-based studies reporting associations between inflammatory markers and all-cause dementia or AD.

Characterization of the Actinonin Biosynthetic Gene Cluster.

The hydroxamate moiety of the natural product actinonin mediates inhibition of metalloproteinases because of its chelating properties towards divalent cations in the active site of those enzymes. Owing to its antimicrobial activity, actinonin has served as a lead compound for the development of new antibiotic drug candidates. Recently, we identified a putative gene cluster for the biosynthesis of actinonin.

The importance of endpoint selection: How effective does a drug need to be for success in a clinical trial of a possible Alzheimer's disease treatment?

To date, Alzheimer's disease (AD) clinical trials have been largely unsuccessful. Failures have been attributed to a number of factors including ineffective drugs, inadequate targets, and poor trial design, of which the choice of endpoint is crucial. Using data from the Alzheimer's Disease Neuroimaging Initiative, we have calculated the minimum detectable effect size (MDES) in change from baseline of a range of measures over time, and in different diagnostic groups along the AD development trajectory.

Toward evidence-based severity assessment in rat models with repeated seizures: I. Electrical kindling.

Objective: Rodent epilepsy models can significantly contribute to our understanding of pathophysiological mechanisms and to validation of biomarker and target candidates. Evidence-based severity assessment is a presupposition for the ethical evaluation of animal experimentation allowances as well as for the development of efficacious refinement concepts.

Methods: Aiming to improve our understanding of the impact of experimental procedures and repeated seizures, we have completed a comprehensive behavioral and biochemical analysis assessing various parameters that can inform about the influence of an electrical kindling paradigm on well-being in rats.

Perineurial Barrier Glia Physically Respond to Alcohol in an Akap200-Dependent Manner to Promote Tolerance.

Ethanol is the most common drug of abuse. It exerts its behavioral effects by acting on widespread neural circuits; however, its impact on glial cells is less understood. We show that Drosophila perineurial glia are critical for ethanol tolerance, a simple form of behavioral plasticity.

SCANPY: large-scale single-cell gene expression data analysis.

SCANPY is a scalable toolkit for analyzing single-cell gene expression data. It includes methods for preprocessing, visualization, clustering, pseudotime and trajectory inference, differential expression testing, and simulation of gene regulatory networks. Its Python-based implementation efficiently deals with data sets of more than one million cells ( https://github.

Cerebral cortex dose sparing for glioblastoma patients: IMRT versus robust treatment planning.

Background: To date, patients with glioblastoma still have a bad median overall survival rate despite radiation dose-escalation and combined modality treatment. Neurocognitive decline is a crucial adverse event which may be linked to high doses to the cortex. In a planning study, we investigated the impact of dose constraints to the cerebral cortex and its relation to the organs at risk for glioblastoma patients.

The development of a stochastic mathematical model of Alzheimer's disease to help improve the design of clinical trials of potential treatments.

Alzheimer's disease (AD) is a neurodegenerative disorder characterised by a slow progressive deterioration of cognitive capacity. Drugs are urgently needed for the treatment of AD and unfortunately almost all clinical trials of AD drug candidates have failed or been discontinued to date. Mathematical, computational and statistical tools can be employed in the construction of clinical trial simulators to assist in the improvement of trial design and enhance the chances of success of potential new therapies.

VascuTrainer: A Mobile and Disposable Bioreactor System for the Conditioning of Tissue-Engineered Vascular Grafts.

In vitro tissue engineering of vascular grafts requires dynamic conditioning in a bioreactor system for in vitro tissue maturation and remodeling to receive a mechanically adequate and hemocompatible implant. The goal of the current work was to develop a bioreactor system for the conditioning of vascular grafts which is (i) able to create a wide range of flow, pressure and frequency conditions, including physiological ones; (ii) compact and easy to assemble; (iii) transportable; (iv) disposable. The system is driven by a small centrifugal pump controlled via a custom-made control unit, which can also be operated on batteries to allow for autonomous transportation.

Correction to: Clinical and endovascular practice in interventional radiology: a contemporary European analysis.

[This corrects the article DOI: 10.1186/s42155-018-0010-8.].

German general practitioners' self-reported management of patients with chronic depression.

Background: Patients with chronic depression (persisting symptoms for ≥2 years) are a clinically relevant group with extensive (co)morbidity, high functional impairment and associated costs in primary care. The General Practitioner (GP) is the main health professional attending to these patients. The aim of this study was to examine the GPs' perception on managing patients with chronic depression.

Warhead biosynthesis and the origin of structural diversity in hydroxamate metalloproteinase inhibitors.

Metalloproteinase inhibitors often feature hydroxamate moieties to facilitate the chelation of metal ions in the catalytic center of target enzymes. Actinonin and matlystatins are  potent metalloproteinase inhibitors that comprise rare N-hydroxy-2-pentyl-succinamic acid warheads. Here we report the identification and characterization of their biosynthetic pathways.

Application of probabilistic risk assessment: Evaluating remedial alternatives at the Portland Harbor Superfund Site, Portland, Oregon, USA.

A probabilistic risk assessment (PRA) was performed to evaluate the range of potential baseline and postremedy health risks to fish consumers at the Portland Harbor Superfund Site (the "Site"). The analysis focused on risks of consuming fish resident to the Site containing polychlorinated biphenyls (PCBs), given that this exposure scenario and contaminant are the primary basis for US Environmental Protection Agency's (USEPA's) selected remedy per the January 2017 Record of Decision (ROD). The PRA used probability distributions fit to the same data sets used in the deterministic baseline human health risk assessment (BHHRA) as well as recent sediment and fish tissue data to evaluate the range and likelihood of current baseline cancer risks and noncancer hazards for anglers.

Temporal association patterns and dynamics of amyloid-β and tau in Alzheimer's disease.

The elusive relationship between underlying pathology and clinical disease hampers diagnosis of Alzheimer's disease (AD) and preventative intervention development. We seek to understand the relationship between two classical AD biomarkers, amyloid-β (Aβ) and total-tau (t-tau), and define their trajectories across disease development, as defined by disease onset at diagnosis of mild cognitive impairment (MCI). Using longitudinal data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we performed a correlation analysis of biomarkers CSF Aβ and t-tau, and longitudinal quantile analysis.

Drug coated balloons in the superficial femoral artery.

Despite the progress in endovascular treatment of patients with peripheral arterial disease, restenosis remains the major drawback, especially in patients with femoropopliteal lesions. To reduce neointimal proliferation and subsequent restenosis the use of antiproliferative drug eluting devices was implemented in the endovascular treatment of femoropopliteal disease. Aiming to use the favorable effects of these antiproliferative agents and to reduce foreign body exposure in affected arteries, drug coated balloons (DCB) have been developed.

Reconstructing cell cycle and disease progression using deep learning.

We show that deep convolutional neural networks combined with nonlinear dimension reduction enable reconstructing biological processes based on raw image data. We demonstrate this by reconstructing the cell cycle of Jurkat cells and disease progression in diabetic retinopathy. In further analysis of Jurkat cells, we detect and separate a subpopulation of dead cells in an unsupervised manner and, in classifying discrete cell cycle stages, we reach a sixfold reduction in error rate compared to a recent approach based on boosting on image features.

A Systematic Review of Longitudinal Studies Which Measure Alzheimer's Disease Biomarkers.

Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disease, with no effective treatment or cure. A gold standard therapy would be treatment to slow or halt disease progression; however, knowledge of causation in the early stages of AD is very limited. In order to determine effective endpoints for possible therapies, a number of quantitative surrogate markers of disease progression have been suggested, including biochemical and imaging biomarkers.

An IGRT margin concept for pelvic lymph nodes in high-risk prostate cancer.

Purpose: Gold-marker-based image-guided radiation therapy (IGRT) of the prostate allows to correct for inter- and intrafraction motion and therefore to safely reduce margins for the prostate planning target volume (PTV). However, pelvic PTVs, when coadministered in a single plan (registered to gold markers [GM]), require reassessment of the margin concept since prostate movement is independent from the pelvic bony anatomy to which the lymphatics are usually referenced to.

Methods: We have therefore revisited prostate translational movement relative to the bony anatomy to obtain adequate margins for the pelvic PTVs compensating mismatch resulting from referencing pelvic target volumes to GMs in the prostate.

Model-based branching point detection in single-cell data by K-branches clustering.

Motivation: The identification of heterogeneities in cell populations by utilizing single-cell technologies such as single-cell RNA-Seq, enables inference of cellular development and lineage trees. Several methods have been proposed for such inference from high-dimensional single-cell data. They typically assign each cell to a branch in a differentiation trajectory.

International infectious diseases teaching to undergraduate medical students: A successful European collaborative experience.

Context: The emerging global-health paradigm requires medical teaching to be continuously redefined and updated; to this end, transnational approaches should be encouraged and medical training harmonized. Infectious diseases (ID) teaching in the current context of emerging infections, fast-increasing bacterial resistance and large-scale human migration, was chosen to develop a common international course.

Objective: We report the successful implementation of a joint European undergraduate course aiming to (i) develop a common ID core curriculum among European medical schools; (ii) promote mobility among teachers and students (iii) promote international cooperation among European teachers.

Flexible information routing by transient synchrony.

Perception, cognition and behavior rely on flexible communication between microcircuits in distinct cortical regions. The mechanisms underlying rapid information rerouting between such microcircuits are still unknown. It has been proposed that changing patterns of coherence between local gamma rhythms support flexible information rerouting.

In Vitro Quantification of Luminal Denudation After Crimping and Balloon Dilatation of Endothelialized Covered Stents.

Purpose: Covered stents have been demonstrated to reduce restenosis; however, the membrane's limited biocompatibility can still lead to thrombus formation. To obtain optimal surface hemocompatibility, endothelialization of the luminal surface has been proposed. However, the effect of delivery procedures, such as crimping and balloon dilatation, on the endothelial layer has not been quantified.