5-Fluorouracil treatment induces characteristic T>G mutations in human cancer.

5-Fluorouracil (5-FU) is a chemotherapeutic drug commonly used for the treatment of solid cancers. It is proposed that 5-FU interferes with nucleotide synthesis and incorporates into DNA, which may have a mutational impact on both surviving tumor and healthy cells. Here, we treat intestinal organoids with 5-FU and find a highly characteristic mutational pattern that is dominated by T>G substitutions in a CTT context.

Preferences and beliefs of Dutch orthopaedic surgeons and patients reduce the implementation of "Choosing Wisely" recommendations in degenerative knee disease.

Purpose: The purpose of this study was to assess which factors were associated with the implementation of "Choosing Wisely" recommendations to refrain from routine MRI and arthroscopy use in degenerative knee disease.

Methods: Cross-sectional surveys were sent to 123 patients (response rate 95%) and 413 orthopaedic surgeons (response rate 62%) fulfilling the inclusion criteria. Univariate and multivariate logistic regression analyses were used to identify factors associated with implementation of "Choosing Wisely" recommendations.

Effect of reimbursement restriction policy on the use of benzodiazepines in the Netherlands: an interrupted time series analysis.

Objectives: Use of benzodiazepines has health risks. Reimbursement was restricted in the Netherlands from January 2009 onwards with the goal to reduce chronic use and healthcare expenditures. The aim of this study is to assess the initial and long-term effects of this policy on benzodiazepine use.

Current State of Care for Pediatric ACL Ruptures in the Netherlands: A Survey.

The management of anterior cruciate ligament (ACL) injuries in the skeletally immature patient is an area of controversy. The purpose of this survey is to inventory the current state of care for pediatric ACL injuries in the Netherlands. This survey was conveyed by e-mail among all members of the Dutch Arthroscopy Society (Nederlandse Vereniging van Arthroscopie [NVA]) and promoted on the Web site of the NVA.

Correction to: Validity and reliability of serratus anterior hand held dynamometry.

Following publication of the original article [1], the authors reported that the headers in Table 2 in their paper were omitted.

Twenty Years of Ferroportin Disease: A Review or An Update of Published Clinical, Biochemical, Molecular, and Functional Features.

Iron overloading disorders linked to mutations in ferroportin have diverse phenotypes in vivo, and the effects of mutations on ferroportin in vitro range from loss of function (LOF) to gain of function (GOF) with hepcidin resistance. We reviewed 359 patients with 60 ferroportin variants. Overall, macrophage iron overload and low/normal transferrin saturation (TSAT) segregated with mutations that caused LOF, while GOF mutations were linked to high TSAT and parenchymal iron accumulation.

Potential for Reducing Time to Referral for Colorectal Cancer Patients in Primary Care.

Purpose: An optimal diagnostic process in primary care is pivotal for reducing cancer-related disease burden. This study aims to explore reasons for long times to referral for Dutch colorectal cancer (CRC) patients in primary care.

Methods: A retrospective cohort study of anonymized free-text primary care records from the Julius General Practitioners' Network database, linked to the Netherlands Cancer Registry.

Alumina-Doped Zirconia Submicro-Particles: Synthesis, Thermal Stability, and Microstructural Characterization.

Zirconia nanoceramics are interesting materials for numerous high-temperature applications. Because their beneficial properties are mainly governed by the crystal and microstructure, it is essential to understand and control these features. The use of co-stabilizing agents in the sol-gel synthesis of zirconia submicro-particles should provide an effective tool for adjusting the particles' size and shape.

Severity of degenerative lumbar spinal stenosis affects pelvic rigidity during walking.

Background Context: To understand the role of compensation mechanisms in the development and treatment of symptomatic degenerative lumbar spinal stenosis (DLSS), pelvic stability during walking should be objectively assessed in the context of clinical parameters.

Purpose: To determine the association among duration of symptoms, lumbar muscle atrophy, disease severity, pelvic stability during walking, and surgical outcome in patients with DLSS scheduled for decompression surgery.

Study Design/setting: Prospective observational study with intervention.

An artificial neural network and Random Forest identify glyphosate-impacted brackish communities based on 16S rRNA amplicon MiSeq read counts.

Machine learning algorithms can be trained on complex data sets to detect, predict, or model specific aspects. Aim of this study was to train an artificial neural network in comparison to a Random Forest model to detect induced changes in microbial communities, in order to support environmental monitoring efforts of contamination events. Models were trained on taxon count tables obtained via next-generation amplicon sequencing of water column samples originating from a lab microcosm incubation experiment conducted over 140 days to determine the effects of glyphosate on succession within brackish-water microbial communities.

Immunogenicity and safety of a 2-dose hepatitis B vaccine, HBsAg/CpG 1018, in persons with diabetes mellitus aged 60-70 years.

Background: Hepatitis B virus (HBV) remains a major public health issue, although it is a vaccine-preventable disease. Adults with diabetes are at greater risk of contracting HBV than the general population. Commonly used 3-dose HBV vaccines have reduced immunogenicity in older individuals and in those with diabetes mellitus.

Weak biases emerging from vocal tract anatomy shape the repeated transmission of vowels.

Linguistic diversity is affected by multiple factors, but it is usually assumed that variation in the anatomy of our speech organs plays no explanatory role. Here we use realistic computer models of the human speech organs to test whether inter-individual and inter-group variation in the shape of the hard palate (the bony roof of the mouth) affects acoustics of speech sounds. Based on 107 midsagittal MRI scans of the hard palate of human participants, we modelled with high accuracy the articulation of a set of five cross-linguistically representative vowels by agents learning to produce speech sounds.

Polynomial-Time Algorithms for Phylogenetic Inference Problems involving duplication and reticulation.

A common problem in phylogenetics is to try to infer a species phylogeny from gene trees. We consider different variants of this problem. The first variant, called Unrestricted Minimal Episodes Inference, aims at inferring a species tree based on a model with speciation and duplication where duplications are clustered in duplication episodes.

Validity and reliability of serratus anterior hand held dynamometry.

Background: Strength testing of the serratus anterior muscle with hand held dynamometry (HDD) in supine subjects has low reproducibility, and is influenced by compensatory activity of other muscles like the pectoralis major and upper trapezius. Previously, two manual maximum voluntary isometric contraction tests of the serratus anterior muscle were reported that recruited optimal surface electromyography (sEMG) activity in a sitting position. We adapted three manual muscle tests to make them suitable for HHD and investigated their validity and reliability.

Transparency induced in opals via nanometer thick conformal coating.

Self-assembled periodic structures out of monodisperse spherical particles, so-called opals, are a versatile approach to obtain 3D photonic crystals. We show that a thin conformal coating of only several nanometers can completely alter the reflection properties of such an opal. Specifically, a coating with a refractive index larger than that of the spherical particles can eliminate the first photonic band gap of opals.

Low Vitamin K Status Is Associated with Increased Elastin Degradation in Chronic Obstructive Pulmonary Disease.

Elastin degradation is accelerated in chronic obstructive pulmonary disease (COPD) and is partially regulated by Matrix Gla Protein (MGP), via a vitamin K-dependent pathway. The aim was to assess vitamin K status in COPD as well as associations between vitamin K status, elastin degradation, lung function parameters and mortality. A total of 192 COPD patients and 186 age-matched controls were included.

Co-creating a program for teams to maintain and reflect on their flexibility.

To prevent rigidity within teams in health care and to support teams in detecting early warning signs of decreasing flexibility, a program has been co-created in collaboration with mental healthcare teams. This program is intended to systematically monitor team behavior, and by doing so to facilitate team intervention. We aim to lay foundations for the further development of methods that can help teams to recognize and respond to processes going on under the surface.

Phylogenetic analysis and embryonic expression of panarthropod Dmrt genes.

Background: One set of the developmentally important Doublesex and Male-abnormal-3 Related Transcription factors (Dmrt) is subject of intense research, because of their role in sex-determination and sexual differentiation. This likely non-monophyletic group of Dmrt genes is represented by the gene (), the () gene, and vertebrate Dmrt1 genes. However, other members of the Dmrt family are much less well studied, and in arthropods, including the model organism , data on these genes are virtually absent with respect to their embryonic expression and function.

Reconstructing Tree-Child Networks from Reticulate-Edge-Deleted Subnetworks.

Network reconstruction lies at the heart of phylogenetic research. Two well-studied classes of phylogenetic networks include tree-child networks and level-k networks. In a tree-child network, every non-leaf node has a child that is a tree node or a leaf.

Scalable Workflows and Reproducible Data Analysis for Genomics.

Biological, clinical, and pharmacological research now often involves analyses of genomes, transcriptomes, proteomes, and interactomes, within and between individuals and across species. Due to large volumes, the analysis and integration of data generated by such high-throughput technologies have become computationally intensive, and analysis can no longer happen on a typical desktop computer.In this chapter we show how to describe and execute the same analysis using a number of workflow systems and how these follow different approaches to tackle execution and reproducibility issues.

Embryonic expression of priapulid Wnt genes.

Posterior elongation of the developing embryo is a common feature of animal development. One group of genes that is involved in posterior elongation is represented by the Wnt genes, secreted glycoprotein ligands that signal to specific receptors on neighbouring cells and thereby establish cell-to-cell communication. In segmented animals such as annelids and arthropods, Wnt signalling is also likely involved in segment border formation and regionalisation of the segments.

Outcome Expectations of Total Knee Arthroplasty Patients: The Influence of Demographic Factors, Pain, Personality Traits, Physical and Psychological Status.

Unfulfilled preoperative expectations have a strong influence on the outcome after total knee arthroplasty (TKA). More insight into determinants of the level of expectations is useful in identifying patients at risk for having expectations of the treatment result that are too high or too low. This information can be used in optimizing preoperative expectation management.

Author Correction: The gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Conserved NPPB+ Border Zone Switches From MEF2- to AP-1-Driven Gene Program.

Background: Surviving cells in the postinfarction border zone are subjected to intense fluctuations of their microenvironment. Recently, border zone cardiomyocytes have been specifically implicated in cardiac regeneration. Here, we defined their unique transcriptional and regulatory properties, and comprehensively validated new molecular markers, including Nppb, encoding B-type natriuretic peptide, after infarction.