Safety and tolerability of the M2 muscarinic acetylcholine receptor modulator BAY 2413555 in heart failure with reduced ejection fraction in the REMOTE-HF study.

BAY 2413555 is a novel selective and reversible positive allosteric modulator of the type 2 muscarinic acetylcholine (M2) receptor, aimed at enhancing parasympathetic signaling and restoring cardiac autonomic balance for the treatment of heart failure (HF). This study tested the safety, tolerability and pharmacokinetics of this novel therapeutic option. REMOTE-HF was a multicenter, double-blind, randomized, placebo-controlled, phase Ib dose-titration study with two active arms.

The impact of antioxidant-ciprofloxacin combinations on the evolution of antibiotic resistance in Pseudomonas aeruginosa biofilms.

The evolution of antimicrobial resistance (AMR) in biofilms, driven by mechanisms like oxidative stress, is a major challenge. This study investigates whether antioxidants (AOs) such as N-acetyl-cysteine (NAC) and Edaravone (ED) can reduce AMR in Pseudomonas aeruginosa biofilms exposed to sub-inhibitory concentrations of ciprofloxacin (CIP). In vitro experimental evolution studies were conducted using flow cells and glass beads biofilm models.

Environmental Conditions Modulate Warming Effects on Plant Litter Decomposition Globally.

Empirical studies worldwide show that warming has variable effects on plant litter decomposition, leaving the overall impact of climate change on decomposition uncertain. We conducted a meta-analysis of 109 experimental warming studies across seven continents, using natural and standardised plant material, to assess the overarching effect of warming on litter decomposition and identify potential moderating factors. We determined that at least 5.

Cardiogenic shock in women: From risk factors to therapy.

Cardiogenic shock (CS) in women is a serious cardiovascular (CV) event associated with a high mortality rate. Non-ischemic etiologies are the most common etiologies in women, such as stress-induced cardiomyopathy, peripartum/postpartum cardiomyopathy, heart failure-related CS, or CS due to myocarditis or valvular heart disease. Although not being the most common etiology in women, acute myocardial infarction is still an important one.

Maternal postpartum infection risk following induction of labor: A Danish national cohort study.

Introduction: Induction of labor is a common procedure, and in Denmark, approximately one in four vaginal deliveries are induced. The association between induction and maternal postpartum infections such as endometritis, surgical site infection after cesarean section, urinary tract infection, and sepsis has been sparsely investigated. Our objective was to investigate the association between induction of labor and risk of maternal postpartum infection and to identify potential risk factors for infection.

Expanding the phenotype and genotype spectrum of TAOK1 neurodevelopmental disorder and delineating TAOK2 neurodevelopmental disorder.

Purpose: The TAOK proteins are a group of serine/threonine-protein kinases involved in signalling pathways, cytoskeleton regulation, and neuronal development. TAOK1 variants are associated with a neurodevelopmental disorder (NDD) characterized by distinctive facial features, hypotonia and feeding difficulties. TAOK2 variants have been reported to be associated with autism and early-onset obesity.

Mandatory surveillance of bacteremia conducted by automated monitoring.

Except for a few countries, comprehensive all-cause surveillance for bacteremia is not part of mandatory routine public health surveillance. We argue that time has come to include automated surveillance for bacteremia in the national surveillance systems, and explore diverse approaches and challenges in establishing bacteremia monitoring. Assessed against proposed criteria, surveillance for bacteremia should be given high priority.

A sex-specific effect of M muscarinic cholinergic autoreceptor deletion on locomotor stimulation by cocaine and scopolamine.

Objective: Acetylcholine modulates the activity of the direct and indirect pathways within the striatum through interaction with muscarinic M and M receptors. M receptors are uniquely positioned to regulate plasticity within the direct pathway and play a substantial role in reward and addiction-related behaviors. However, the role of M receptors on cholinergic neurons has been less explored.

Incredibly emotional: interpreting trustworthiness in Danish courtrooms.

This paper explores how Danish legal professionals assess the trustworthiness of victims in criminal cases based on emotional expressions. It focuses on the alignment of these expressions with the nature of the crime, the social context, and the victims' social identities, and is based on findings from several ethnographic projects involving extensive observations of crime cases and interviews with criminal justice professionals. The research analyzes how victims' emotional expressions are scrutinized and interpreted within the context of Danish cultural norms, which favor "calm and quiet" behavior.

The burden of headache disorders in the adult population of Morocco: estimates, and a health-care needs assessment, from a cross-sectional population-based door-to-door survey.

Background: We have previously shown headache disorders to be prevalent in in the adult general population of Morocco, especially migraine (30.8%) and headache on ≥ 15 days/month (H15+; 10.5%).

The cysteine protease legumain decreases glucose metabolism and enhances fatty acid uptake in human myotubes.

Skeletal muscle has an important role in whole body energy metabolism and various proteases are involved in skeletal muscle functions. We have previously identified the cysteine protease legumain in cultured human skeletal muscle cells. However, the potential role of legumain in regulation of energy metabolism remains unexplored.

Towards safe and reliable deep learning for lung nodule malignancy estimation using out-of-distribution detection.

Artificial Intelligence (AI) models may fail or suffer from reduced performance when applied to unseen data that differs from the training data distribution, referred to as dataset shift. Automatic detection of out-of-distribution (OOD) data contributes to safe and reliable clinical implementation of AI models. In this study, we propose a recognized OOD detection method that utilizes the Mahalanobis distance (MD) and compare its performance to widely known classical methods.

Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.

Possible scenarios for the spread of mpox outside the endemic focus in Africa.

The recent expansion of mpox in Africa is characterized by a dramatic increase in zoonotic transmission (clade Ia) and the emergence of a new clade Ib that is transmitted from human-to-human (H2H) by close contact. Clade Ia does not pose a threat in areas without zoonotic reservoir. But clade Ib may spread widely, as did the clade IIb that since 2022 has spread globally among MSM.

Electromembrane extraction of multi-class prohibited/restricted veterinary drugs from food samples - Exploring liquid membrane composition.

Effective monitoring of veterinary drug residues in food is essential for legislation compliance and food safety, yet remains challenging due to low concentrations and complex matrices. This study introduced a miniaturized 96-well electromembrane extraction (EME) technique for pre-concentration and isolation 80 prohibited/restricted veterinary drugs from honey samples. Three liquid membranes were developed and characterized: V1 ("V" for veterinary), a mixture of 2-undecanone and 0.

Dimethyltryptamine (DMT) and ibogaine elicit membrane effects in HEK cells transiently transfected with the human 5-HT2A receptor.

Psychedelics show promise in treating psychiatric disorders. Therapeutic effects appear to involve activation of the 5-Hydroxytryptamine 2A receptor (5-HTR), a G protein-coupled receptor (GPCR). Several SNPs of the 5-HTR naturally occur, which are associated with differences in receptor function and altered responsiveness to treatments.

The rhythm of horse gaits.

What makes animal gaits so audibly rhythmic? To answer this question, we recorded the footfall sound of 19 horses and quantified the rhythmic differences in the temporal structure of three natural gaits: walk, trot, and canter. Our analyses show that each gait displays a strikingly specific rhythmic pattern and that all gaits are organized according to small-integer ratios, those found when adjacent temporal intervals are related by a mathematically simple relationship of integer numbers. Walk and trot exhibit an isochronous structure (1:1)-similar to a ticking clock-while canter is characterized by three small-integer ratios (1:1, 1:2, 2:1).

Long-term effects of petroleum mulch on concentration, health, and ecological risks of polycyclic aromatic hydrocarbons in sand dune soils of Khuzestan province, Iran.

Environmental consequences of petroleum mulch application are crucial in regions prone to wind erosion and desertification. This study aimed to assess the long-term effects of petroleum mulching on soil polycyclic aromatic hydrocarbon (PAH) concentrations and the associated human and ecological risk indices. These indices include incremental lifetime cancer risk (ILCR), hazard index (HI), toxic equivalent concentration (TEQ), toxic unit (TU), and risk quotient (RQ) in soil samples from Khuzestan province, Iran.

Gender-stratified national mental health norms of BSI-53, BSI-18, SCL-10, ADHD-9, and ADHD-6 for Denmark.

Background: Reliable gender-sensitive normative data is needed to facilitate mental health research and clinical utility of commonly used symptoms scales. This study establishes Danish gender-stratified norms for the 53-item and 18-item Brief Symptom Inventory (BSI-53, BSI-18), proposed attention deficit hyperactivity disorder (ADHD) symptomatology scales from the BSI-53, and the 10-item Symptom Checklist (SCL-10). This study also examines gender-differences in symptom reporting of the ADHD and SCL-10 scales, and assesses potential bias in recent SCL-10 norms.

Potential Evolutionary Convergence in Trophic Adaptations of Two Booidean Snake Lineages as Evidenced by Skull Morphology.

Booidean snakes are a diverse and widespread lineage with an intriguing evolutionary and biogeographic history. By means of cranial morphology and osteology, this study investigates the evolutionary convergence in the Neotropical genera Boa and Corallus on the one hand and the Malagasy clade comprising Acrantophis and Sanzinia on the other. We hypothesize that the mostly arboreal Corallus and Sanzinia present larger jaws and longer teeth to keep hold of the prey and resist gravity and torsional forces acting on their skull while hanging from branches, while terrestrial genera such as Acrantophis show thinner jaws with shorter teeth because they can rely on the full length of their coils to immobilize and constrict the prey together with a substrate that supports the whole of their body.

Ecological and anthropogenic effects on the genomic diversity of lemurs in Madagascar.

Ecological variation and anthropogenic landscape modification have had key roles in the diversification and extinction of mammals in Madagascar. Lemurs represent a radiation with more than 100 species, constituting roughly one-fifth of the primate order. Almost all species of lemurs are threatened with extinction, but little is known about their genetic diversity and demographic history.

Source-tracing of industrial and municipal wastewater effluent in river water via fluorescence fingerprinting.

Fluorescence fingerprinting is a technique to uniquely characterize water samples based on their distinct composition of dissolved organic matter (DOM) measured via 3D fluorescence spectroscopy. It is an effective tool for monitoring the chemical composition of various water systems. This study examines a river affected by several municipal and industrial wastewater treatment plant (WWTP) effluents and aims to source-tracing them via fluorescence fingerprints based on parallel factor analysis (PARAFAC) components.