Naturally occurring variation in a cytochrome P450 modifies thiabendazole responses independently of beta-tubulin.

Widespread anthelmintic resistance has complicated the management of parasitic nematodes. Resistance to the benzimidazole (BZ) drug class is nearly ubiquitous in many species and is associated with mutations in beta-tubulin genes. However, mutations in beta-tubulin alone do not fully explain all BZ resistance.

FLI1 and GATA1 govern transcription: new insights into FLI1-related platelet disorders.

Germline variants of FLI1, essential for megakaryopoiesis, are linked to bleeding disorders, platelet aggregation defects and mild thrombocytopenia. However, the mechanisms behind these abnormalities remain unclear. This study aims to elucidate the impact of FLI1 variants on human megakaryocytes and platelets.

The long and short of hyperdivergent regions.

The increasing prevalence of genome sequencing and assembly has uncovered evidence of hyperdivergent genomic regions - loci with excess genetic diversity - in species across the tree of life. Hyperdivergent regions are often enriched for genes that mediate environmental responses, such as immunity, parasitism, and sensory perception. Especially in self-fertilizing species where the majority of the genome is homozygous, the existence of hyperdivergent regions might imply the historical action of evolutionary forces such as introgression and/or balancing selection.

Single-Molecule Multivalent Interactions Revealed by Plasmon-Enhanced Fluorescence.

Multivalency as an interaction principle is widely utilized in nature. It enables specific and strong binding by multiple weak interactions through enhanced avidity and is a core process in immune recognition and cellular signaling, which is also a current concept in drug design. Here, we use the high signals from plasmon-enhanced fluorescence of nanoparticles to extract binding kinetics and dynamics of multivalent interactions on the single-molecule level and in real time.

Monitoring performance of clinical artificial intelligence in health care: a scoping review.

Objective: The objective of this review was to provide an overview of the diverse methods described, tested, or implemented for monitoring performance of clinical artificial intelligence (AI) systems, while also summarizing the arguments given for or against these methods.

Introduction: The integration of AI in clinical decision-making is steadily growing. Performances of AI systems evolve over time, necessitating ongoing performance monitoring.

Integrating metabolomics into the diagnosis and investigation of anthelmintic resistance.

Anthelmintic resistance (AR) in parasitic nematodes poses a global health problem in livestock and domestic animals and is an emerging problem in humans. Consequently, we must understand the mechanisms of AR, including target-site resistance (TSR), in which mutations affect drug binding, and non-target site resistance (NTSR), which involves alterations in drug metabolism and detoxification processes. Because much of the focus has been on TSR, NTSR has received less attention.

BCL11A intellectual developmental disorder: defining the clinical spectrum and genotype-phenotype correlations.

An increasing number of individuals with intellectual developmental disorder (IDD) and heterozygous variants in BCL11A are identified, yet our knowledge of manifestations and mutational spectrum is lacking. To address this, we performed detailed analysis of 42 individuals with BCL11A-related IDD (BCL11A-IDD, a.k.

Non-averaged single-molecule tertiary structures reveal RNA self-folding through individual-particle cryo-electron tomography.

Large-scale and continuous conformational changes in the RNA self-folding process present significant challenges for structural studies, often requiring trade-offs between resolution and observational scope. Here, we utilize individual-particle cryo-electron tomography (IPET) to examine the post-transcriptional self-folding process of designed RNA origami 6-helix bundle with a clasp helix (6HBC). By avoiding selection, classification, averaging, or chemical fixation and optimizing cryo-ET data acquisition parameters, we reconstruct 120 three-dimensional (3D) density maps from 120 individual particles at an electron dose of no more than 168 eÅ, achieving averaged resolutions ranging from 23 to 35 Å, as estimated by Fourier shell correlation (FSC) at 0.

Construction of Small Genes with Repetitive Elements Using Oligo Extension and Golden Gate Assembly.

Gene synthesis efficiency has greatly improved in recent years but is limited when it comes to repetitive sequences and results in synthesis failure or delays by DNA synthesis vendors. Here, we describe a method for the assembly of small synthetic genes with repetitive elements: First, a gene of interest is split in silico into small synthons of up to 80 base pairs flanked by Golden Gate-compatible overhangs. Then synthons are made by oligo extension and finally assembled into a synthetic gene by Golden Gate assembly.

Fostering health behaviour change in overweight male football fans through the European Fans in Training (EuroFIT) program: A Self-Determination Theory perspective.

The European Fans in Training (EuroFIT) program integrated need-supportive motivational strategies from Self-Determination Theory (SDT) in the design of a healthy lifestyle program delivered to overweight or obese male football fans (n = 1113; mean age of 45.9 [SD = 9.0] years old and BMI of 33.

Transposon-mediated genic rearrangements underlie variation in small RNA pathways.

Transposable elements (TEs) can alter host gene structure and expression, whereas host organisms develop mechanisms to repress TE activities. In the nematode , a small interfering RNA pathway dependent on the helicase ERI-6/7 primarily silences retrotransposons and recent genes of likely viral origin. By studying gene expression variation among wild strains, we found that structural variants and transposon remnants likely underlie expression variation in and the pathway targets.

Environmental pH and compound structure affect the activity of short-chain carboxylic acids against planktonic growth, biofilm formation, and eradication of the food pathogen .

Short-chain carboxylic acids (SCCAs) that are naturally produced by microbial fermentation play an essential role in delaying microbial spoilage. SCCAs are structurally diverse, but only a few of them are routinely used in food biopreservation. This study investigated the effects of environmental pH and intrinsic properties of 21 structurally different SCCAs on the antimicrobial and antibiofilm activity against .

Antipsychotic exposure and infection risk in people with schizophrenia spectrum disorders during the COVID-19 pandemic: a Danish nationwide registry study.

Background: Infection risk and mortality are increased in schizophrenia spectrum disorders, which was corroborated during the COVID-19 pandemic. However, evidence is lacking regarding the additional impact of antipsychotic drugs, and the highly debated safety of clozapine treatment during large-scale infection outbreaks. Therefore, we aimed to investigate risk of COVID-19 and non-COVID respiratory infections during exposure to antipsychotics.

The thyroid hormone system disrupting potential of resorcinol in fish.

Environmental pollutants capable of interfering with the thyroid hormone (TH) system increasingly raise concern for both human and environmental health. Recently, resorcinol has received attention as a compound of concern due to its endocrine disrupting properties. It is a known inhibitor of thyroperoxidase (TPO), an enzyme required in TH synthesis, and therapeutic use of resorcinol exposure has led to hypothyroidism in humans.

Teaching Atraumatic Soft Tissue Handling in the Simulation Laboratory: Development of a Novel Training System.

Atraumatic soft issue handling is essential for optimal wound healing. Simulation is a safe and effective way to improve surgical skills outside the operating room. Our primary aim was the development of a pressure-sensing forceps that measures the force applied to a given tissue and provides real-time biofeedback.

Lack of correlation between parasite burden and key weight metrics in poultry infected with intestinal ascarids.

and are the most common and economically impactful nematode parasites of commercial poultry. These infections rarely cause clinical disease, but reduction in feed conversion efficiency is detected. To determine if feed conversion efficiency reductions correlate with any physiological measures independent of clinical disease, we determined if ascarid infections correlate with changes in the weights of the small intestine, liver, or total animal weight (quantitative measures of animal health).

Success factors for interventions to reduce low-value imaging. Six crucial lessons learned from a practical case study in Norway.

Background: Substantial overuse of health care services is identified and intensified efforts are incited to reduce low-value services in general and in imaging in particular.

Objective: To report crucial success factors for developing and implementing interventions to reduce specific low-value imaging examinations based on a case study in Norway.

Materials And Methods: Mixed methods design including one systematic review, one scoping review, implementation science, qualitative interviews, content analysis of stakeholders' input, and stakeholder deliberations.

Direct inference of the distribution of fitness effects of spontaneous mutations from recombinant inbred Caenorhabditis elegans mutation accumulation lines.

The distribution of fitness effects of new mutations plays a central role in evolutionary biology. Estimates of the distribution of fitness effect from experimental mutation accumulation lines are compromised by the complete linkage disequilibrium between mutations in different lines. To reduce the linkage disequilibrium, we constructed 2 sets of recombinant inbred lines from a cross of 2 Caenorhabditis elegans mutation accumulation lines.

Machine learning in diagnostic support in medical emergency departments.

Diagnosing patients in the medical emergency department is complex and this is expected to increase in many countries due to an ageing population. In this study we investigate the feasibility of training machine learning algorithms to assist physicians handling the complex situation in the medical emergency departments. This is expected to reduce diagnostic errors and improve patient logistics and outcome.

Impact of MRI radiomic feature normalization for prognostic modelling in uterine endometrial and cervical cancers.

Widespread clinical use of MRI radiomic tumor profiling for prognostication and treatment planning in cancers faces major obstacles due to limitations in standardization of radiomic features. The purpose of the current work was to assess the impact of different MRI scanning- and normalization protocols for the statistical analyses of tumor radiomic data in two patient cohorts with uterine endometrial-(EC) (n = 136) and cervical (CC) (n = 132) cancer. 1.

Reducing low-value imaging-A qualitative evaluation of a pilot intervention in Norway.

Rational: Low-value radiological imaging threatens patient safety and efficient use of limited health resources. It is important to evaluate measures for reducing low-value utilisation, to learn and to improve. Accordingly, the objective of this study was to qualitatively evaluate a pilot intervention for reducing low-value imaging in Norway.

Quantitative tests of albendazole resistance in Caenorhabditis elegans beta-tubulin mutants.

Benzimidazole (BZ) anthelmintics are among the most important treatments for parasitic nematode infections in the developing world. Widespread BZ resistance in veterinary parasites and emerging resistance in human parasites raise major concerns for the continued use of BZs. Knowledge of the mechanisms of resistance is necessary to make informed treatment decisions and circumvent resistance.