Modular and extendable 1D-simulation for microfluidic devices.

Microfluidic devices have been the subject of considerable attention in recent years. The development of novel microfluidic devices, their evaluation, and their validation requires simulations. While common methods based on Computational Fluid Dynamics (CFD) can be time-consuming, 1D simulation provides an appealing alternative that leads to efficient results with reasonable quality.

Sildenafil delays bone remodeling of fractured femora in aged mice by reducing the number and activity of osteoclasts within the callus tissue.

The elderly exhibit a reduced healing capacity after fracture, which is often associated with delayed or failed bone healing. This is due to a plethora of factors, such as an impaired bone vascular system and delayed angiogenesis. The phosphodiesterase-5 (PDE-5) inhibitor sildenafil exerts pro-angiogenic and pro-osteogenic effects.

Cilostazol Stimulates Angiogenesis and Accelerates Fracture Healing in Aged Male and Female Mice by Increasing the Expression of PI3K and RUNX2.

Fracture healing in the aged is associated with a reduced healing capacity, which often results in delayed healing or non-union formation. Many factors may contribute to this deterioration of bone regeneration, including a reduced 'angiogenic trauma response'. The phosphodiesterase-3 (PDE-3) inhibitor cilostazol has been shown to exert pro-angiogenic and pro-osteogenic effects in preclinical studies.

Late-Stage Metastatic Melanoma Emerges through a Diversity of Evolutionary Pathways.

Unlabelled: Understanding the evolutionary pathways to metastasis and resistance to immune-checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here, we present the most comprehensive intrapatient metastatic melanoma dataset assembled to date as part of the Posthumous Evaluation of Advanced Cancer Environment (PEACE) research autopsy program, including 222 exome sequencing, 493 panel-sequenced, 161 RNA sequencing, and 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen-presentation machinery.

Artificial intelligence in multi-objective drug design.

The factors determining a drug's success are manifold, making de novo drug design an inherently multi-objective optimisation (MOO) problem. With the advent of machine learning and optimisation methods, the field of multi-objective compound design has seen a rapid increase in developments and applications. Population-based metaheuris-tics and deep reinforcement learning are the most commonly used artificial intelligence methods in the field, but recently conditional learning methods are gaining popularity.

Dielectrophoretic separation of blood cells.

Microfluidic dielectrophoretic (DEP) devices enable the label-free separation and isolation of cells based on differences in their electrophysiological properties. The technique can serve as a tool in clinical diagnostics and medical research as it facilitates the analysis of patient-specific blood composition and the detection and isolation of pathogenic cells like circulating tumor cells or malaria-infected erythrocytes. This review compares different microfluidic DEP devices to separate platelets, erythrocytes and leukocytes including their cellular subclasses.

On the Construction of Pareto-Compliant Combined Indicators.

The most relevant property that a quality indicator (QI) is expected to have is Pareto compliance, which means that every time an approximation set strictly dominates another in a Pareto sense, the indicator must reflect this. The hypervolume indicator and its variants are the only unary QIs known to be Pareto-compliant but there are many commonly used weakly Pareto-compliant indicators such as R2, IGD+, and ε+. Currently, an open research area is related to finding new Pareto-compliant indicators whose preferences are different from those of the hypervolume indicator.

Biotransformation of Tetracyclines by Fungi: Challenges and Future Research Perspectives.

Tetracycline antibiotics are used worldwide in human and veterinary medicine. On the basis of low metabolization and through organic fertilizers, tetracyclines enter the environment in a biologically active form. This can have toxic effects on microbial communities and promote the selection of resistant strains.

DrugEx v2: de novo design of drug molecules by Pareto-based multi-objective reinforcement learning in polypharmacology.

In polypharmacology drugs are required to bind to multiple specific targets, for example to enhance efficacy or to reduce resistance formation. Although deep learning has achieved a breakthrough in de novo design in drug discovery, most of its applications only focus on a single drug target to generate drug-like active molecules. However, in reality drug molecules often interact with more than one target which can have desired (polypharmacology) or undesired (toxicity) effects.

Ventilator-associated pneumonia in patients on prolonged mechanical ventilation: description, risk factors for mortality, and performance of the SOFA score.

Objective: Ventilator-associated pneumonia (VAP) is a serious complication of mechanical ventilation (MV). However, data on VAP in patients on prolonged MV (PMV) are scarce. We aimed to describe the characteristics of VAP patients on PMV and to identify factors associated with mortality.

Targeting the ABC transporter ABCB5 sensitizes glioblastoma to temozolomide-induced apoptosis through a cell-cycle checkpoint regulation mechanism.

Glioblastoma multiforme (GBM) is a malignant brain tumor with a poor prognosis resulting from tumor resistance to anticancer therapy and a high recurrence rate. Compelling evidence suggests that this is driven by subpopulations of cancer stem cells (CSCs) with tumor-initiating potential. ABC subfamily B member 5 (ABCB5) has been identified as a molecular marker for distinct subsets of chemoresistant tumor-initiating cell populations in diverse human malignancies.

A multiple classifier system identifies novel cannabinoid CB2 receptor ligands.

Drugs have become an essential part of our lives due to their ability to improve people's health and quality of life. However, for many diseases, approved drugs are not yet available or existing drugs have undesirable side effects, making the pharmaceutical industry strive to discover new drugs and active compounds. The development of drugs is an expensive process, which typically starts with the detection of candidate molecules (screening) after a protein target has been identified.

British Association of Dermatologists (BAD) National Audit on Non-Melanoma Skin Cancer Excision 2016 in collaboration with the Royal College of Pathologists.

Background: We conducted a re-audit of the surgical practice of UK dermatologists for the treatment of nonmelanoma skin cancer and examined changes with reference to our previous audit in 2014. The audit was supplemented by a detailed assessment of completeness of the histopathology reports for each tumour.

Methods: UK dermatologists collected data on 10 consecutive nonmicrographic excisions for basal cell carcinoma (BCC) and 5 for squamous cell carcinoma (SCC).

Mirrored Orthogonal Sampling for Covariance Matrix Adaptation Evolution Strategies.

Generating more evenly distributed samples in high dimensional search spaces is the major purpose of the recently proposed technique for evolution strategies. The diversity of the mutation samples is enlarged and the convergence rate is therefore improved by the mirrored sampling. Motivated by the mirrored sampling technique, this article introduces a new derandomized sampling technique called .

The Set-Based Hypervolume Newton Method for Bi-Objective Optimization.

In this paper, we propagate the use of a set-based Newton method that enables computing a finite size approximation of the Pareto front (PF) of a given twice continuously differentiable bi-objective optimization problem (BOP). To this end, we first derive analytically the Hessian matrix of the hypervolume indicator, a widely used performance indicator for PF approximation sets. Based on this, we propose the hypervolume Newton method (HNM) for hypervolume maximization of a given set of candidate solutions.

Search Dynamics on Multimodal Multiobjective Problems.

We continue recent work on the definition of multimodality in multiobjective optimization (MO) and the introduction of a test bed for multimodal MO problems. This goes beyond well-known diversity maintenance approaches but instead focuses on the landscape topology induced by the objective functions. More general multimodal MO problems are considered by allowing ellipsoid contours for single-objective subproblems.

A tutorial on multiobjective optimization: fundamentals and evolutionary methods.

In almost no other field of computer science, the idea of using bio-inspired search paradigms has been so useful as in solving multiobjective optimization problems. The idea of using a population of search agents that collectively approximate the Pareto front resonates well with processes in natural evolution, immune systems, and swarm intelligence. Methods such as NSGA-II, SPEA2, SMS-EMOA, MOPSO, and MOEA/D became standard solvers when it comes to solving multiobjective optimization problems.

Dynamic vehicle routing with time windows in theory and practice.

The vehicle routing problem is a classical combinatorial optimization problem. This work is about a variant of the vehicle routing problem with dynamically changing orders and time windows. In real-world applications often the demands change during operation time.

Horizontal Ridge Augmentation with a Novel Resorbable Collagen Membrane: A Retrospective Analysis of 36 Consecutive Patients.

The aim of this investigation was to evaluate a new resorbable, monolayer, noncross-linked collagen barrier membrane for immobilizing bone augmentation material during horizontal guided bone regeneration (GBR) procedures. GBR was performed on 36 consecutive patients in 49 sites, with 103 implants placed either simultaneously or after a healing period. Healing time, suture retention, postoperative complications, and functional outcome after GBR, implant placement, and prosthesis loading were assessed.

Major aging-associated RNA expressions change at two distinct age-positions.

Background: Genome-wide expression profiles are altered during biological aging and can describe molecular regulation of tissue degeneration. Age-regulated mRNA expression trends from cross-sectional studies could describe how aging progresses. We developed a novel statistical methodology to identify age-regulated expression trends in cross-sectional datasets.

Cesarean section in a patient with non-compaction cardiomyopathy managed with ECMO.

Isolated ventricular non-compaction is a rare cardiomyopathy associated with left heart failure, severe arrhythmias and thromboembolism. We report about our interdisciplinary strategy in a patient with severe isolated ventricular non-compaction cardiomyopathy scheduled for caesarean section in general anaesthesia. Monitoring included placement of an arterial line, a central venous catheter and a pulmonary artery catheter with pacing option.

[Postoperative assessment of daily energy expenditure. Comparison of two methods].

Background: The reference method for determining resting energy expenditure (REE) in clinical nutrition practice is measurement by indirect calorimetry; however, indirect calorimetry has some limitations, is expensive and not widely available. Therefore, the most used methods to estimate the caloric requirements in intensive care patients are predictive equations. The Harris-Benedict equations (HBE) are the most common formulae in the clinical setting.