Serotonin receptor 5-HT7 modulates inflammatory-associated functions of macrophages.

The hormone and neurotransmitter serotonin regulates numerous physiological functions within the central nervous system and in the periphery upon binding to specific receptors. In the periphery, the serotonin receptor 7 (5-HT7R) is expressed on different immune cells including monocytes and macrophages. To investigate the impact of 5-HT7R-mediated signaling on macrophage properties, we used human THP-1 cells and differentiated them into pro-inflammatory M1- and anti-inflammatory M2-like macrophages.

Impact of calreticulin mutations on treatment and survival outcomes in myelofibrosis during ruxolitinib therapy.

Calreticulin (CALR) mutations are detected in around 20% of patients with primary and post-essential thrombocythemia myelofibrosis (MF). Regardless of driver mutations, patients with splenomegaly and symptoms are generally treated with JAK2-inhibitors, most commonly ruxolitinib. Recently, new therapies specifically targeting the CALR mutant clone have entered clinical investigation.

AA-Stacked Hydrogen-Substituted Graphdiyne for Enhanced Lithium Storage.

Graphdiyne (GDY) has been considered a promising electrode material for application in electrochemical energy storage. However, studies on GDY featuring an ordered interlayer stacking are lacking, which is supposed to be another effective way to increase lithium binding sites and diffusion pathways. Herein, we synthesized a hydrogen-substituted GDY (HsGDY) with a highly-ordered AA-stacking structure via a facile alcohol-thermal method.

Photogenerated charge carrier dynamics on Pt-loaded SrTiO nanoparticles studied transient-absorption spectroscopy.

Loading cocatalysts on semiconductor-based photocatalysts to create active reaction sites is a preferable method to enhance photocatalytic activity and a widely adopted strategy to achieve effective photocatalytic applications. Although theoretical calculations suggest that the broad density of states of noble metal cocatalysts, such as Pt, act as a recombination center, this has never been experimentally demonstrated. Herein, we employed pico-nano and nano-micro second transient absorption spectroscopy to investigate the often overlooked photogenerated holes, instead of the widely studied electrons on Pt- and Ni-loaded SrTiO to evaluate the effects of cocatalysts as a recombination center.

Validity and Accuracy of the Derived Left Ventricular End-Diastolic Pressure in Impella 5.5.

Background: Consensus regarding on-support evaluation and weaning concepts from Impella 5.5 support is scarce. The derived left ventricular end-diastolic pressure (dLVEDP), estimated by device algorithms, is a rarely reported tool for monitoring the weaning process.

Informed circular fields: a global reactive obstacle avoidance framework for robotic manipulators.

In this paper, we present a global reactive motion planning framework designed for robotic manipulators navigating in complex dynamic environments. Utilizing local minima-free circular fields, our methodology generates reactive control commands while also leveraging global environmental information from arbitrary configuration space motion planners to identify promising trajectories around obstacles. Furthermore, we extend the virtual agents framework introduced in Becker et al.

3D multiscale characterization of the human placenta: Bridging anatomy and histology by X-ray phase-contrast tomography.

The human placenta exhibits a complex three-dimensional (3D) structure with a interpenetrating vascular tree and large internal interfacial area. In a unique and yet insufficiently explored way, this parenchymal structure enables its multiple functions as a respiratory, renal, and gastrointestinal multiorgan. The histopathological states are highly correlated with complications and health issues of mother, and fetus or newborn.

The Impact of Idiopathic Intracranial Hypertension on Cardiovascular Disease Risk Among UK Women: An Obesity-Adjusted Analysis.

Introduction: Idiopathic intracranial hypertension (IIH) is known to elevate cardiovascular disease (CVD) risk, but the extent to which obesity and IIH-specific factors contribute to this risk is not well understood. WE aim to separate the effects of obesity from IIH-specific factors on the risk of stroke and CVD, building on previous findings that indicate a two-fold increase in cardiovascular events in women with IIH compared to BMI-matched controls.

Methods: An obesity-adjusted risk analysis was conducted using Indirect Standardization based on data from a cohort study by Adderley et al.

Drug interactions in patients with alcohol use disorder: results from a real-world study on an addiction-specific ward.

Background: The majority of patients with alcohol use disorder (AUD) regularly take medication. Alcohol interacts negatively with many commonly prescribed drugs. However, little is known about the characteristics and frequency of potential alcohol-medication and drug-drug interactions in patients with AUD.

Deep learning helps discriminate between autoimmune hepatitis and primary biliary cholangitis.

Background & Aims: Biliary abnormalities in autoimmune hepatitis (AIH) and interface hepatitis in primary biliary cholangitis (PBC) occur frequently, and misinterpretation may lead to therapeutic mistakes with a negative impact on patients. This study investigates the use of a deep learning (DL)-based pipeline for the diagnosis of AIH and PBC to aid differential diagnosis.

Methods: We conducted a multicenter study across six European referral centers, and built a library of digitized liver biopsy slides dating from 1997 to 2023.

Frankenstein matrices: Among-population life history variation affects the reliability and predictions of demographic models.

Population matrix models are routinely used to study the demography of wild populations and to guide management choices. When vital rates are unknown for a specific population or life history stage, researchers often replace them with estimates from other populations of the same species. Such 'hybrid' matrices might ignore among-population life history variation and lead to incorrect inferences.

A multicenter Phase II randomized, placebo-controlled single-blind trial with the SV2A ligand seletracetam in photosensitive epilepsy patients.

The objective of this study was to evaluate the effect of seletracetam (SEL), a potent modulator of synaptic vesicle glycoprotein 2A (SV2A), in patients with photoparoxysmal EEG response (PPR) to intermittent photic stimulation (IPS) as proof-of-principle of efficacy in patients with epilepsy. In this multicenter, single-blind Phase II study, adults with photosensitive epilepsy, with/without concomitant antiseizure medication therapy, underwent IPS under 3 eye conditions (at eye closure, eyes closed and eyes open) after a single oral dose of placebo (day - 1) or SEL (day 1; 0.5, 1, 2, 4, 10, or 20 mg).

Reverse mutational scanning of SARS-CoV-2 spike BA.2.86 identifies epitopes contributing to immune escape from polyclonal sera.

The recently detected Omicron BA.2.86 lineage contains more than 30 amino acid mutations relative to BA.

Quantifying the influence of combined lung and kidney support using a cardiovascular model and sensitivity analysis-informed parameter identification.

The combination of extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) pose complex hemodynamic challenges in intensive care. In this study, a comprehensive lumped parameter model (LPM) is developed to simulate the cardiovascular system, incorporating ECMO and CRRT circuit dynamics. A parameter identification framework based on global sensitivity analysis (GSA) and multi-start gradient-based optimization was developed and tested on 30 clinical data points from eight veno-arterial ECMO patients.

Reciprocal relationships between adolescent mental health difficulties and alcohol consumption.

The directionality of the relationship between adolescent alcohol consumption and mental health difficulties remains poorly understood. This study investigates the longitudinal relationship between alcohol use frequency, internalizing and externalizing symptoms from the ages of 11 to 17. We conducted a random-intercept cross-lagged panel model across three timepoints (ages: 11yrs, 14yrs, 17yrs; 50.

Obesity and hypoxia have differential effects on myocardial innervation in the right ventricle of the male mouse heart.

Obesity, along with hypoxia, is known to be a risk factor for pulmonary hypertension (PH), which can lead to right ventricular hypertrophy and eventually heart failure. Both obesity and PH influence the autonomic nervous system (ANS), potentially aggravating changes in the right ventricle (RV). This study investigates the combined effects of obesity and hypoxia on the autonomic innervation of the RV in a mouse model.

A four-level model of political polarization over science: Evidence from 10 European countries.

Citizens' trust in science increasingly depends on their political leaning. Structural equation models on survey data from 10 European countries ( = 5306) demonstrate that this can be captured by a model with four levels of generalization. Voters of populist parties distrust the in general, which indirectly fuels a broad science skepticism.

Quantifying spatial and dynamic lung abnormalities with 3D PREFUL FLORET UTE imaging: A feasibility study.

Purpose: Pulmonary MRI faces challenges due to low proton density, rapid transverse magnetization decay, and cardiac and respiratory motion. The fermat-looped orthogonally encoded trajectories (FLORET) sequence addresses these issues with high sampling efficiency, strong signal, and motion robustness, but has not yet been applied to phase-resolved functional lung (PREFUL) MRI-a contrast-free method for assessing pulmonary ventilation during free breathing. This study aims to develop a reconstruction pipeline for FLORET UTE, enhancing spatial resolution for three-dimensional (3D) PREFUL ventilation analysis.

Naturally russeted and wound russeted skins of mango (cv. 'Apple') show no differences in anatomy, chemical composition or gene expression.

The mango cultivar 'Apple' is commercially important in Kenya but highly susceptible to russeting. Russeting refers to an area of fruit skin where the primary (epidermal) surface has been replaced by a secondary (peridermal) surface. The objective was to establish histologies, gene expressions and chemical compositions of a natural periderm, a wound-induced periderm and of cuticles of an un-russeted skin.

Regulatory workshop on standardisation of clinical procedures, endpoints and data robustness of human challenge studies - A stakeholder meeting report.

Inno4Vac, a public-private partnership funded by the IMI2/EU/EFPIA Joint Undertaking (IMI2 JU), brings together academic institutions, SMEs, and pharmaceutical companies to accelerate and de-risk vaccine development. The project has made significant strides in the selection and production of challenge agents for influenza, respiratory syncytial virus (RSV), and toxigenic Clostridioides difficile for controlled human infection model studies (CHIMs). A regulatory workshop held on March 20, 2024, addressed the standardisation of clinical procedures, ethical considerations, endpoints, and data integrity, highlighting the ongoing initiatives related to these CHIMs.

The vacuolar phosphatases PAP26 and HIIA2.1 hydrolyze 5'-, 3'-, and 2'-nucleotides derived from RNA degradation.

The vacuole is an important site for RNA degradation. Autophagy delivers RNA to the vacuole, where the vacuolar T2 RNase Ribonuclease 2 (RNS2) plays a major role in RNA catabolism. The presumed products of RNS2 activity are 3'-nucleoside monophosphates (3'-NMPs).

Disease characteristics and outcomes of acute myeloid leukemia in germline deficiency (Familial Platelet Disorder with associated Myeloid Malignancy).

Familial Platelet Disorder with associated Myeloid Malignancy (FPDMM, FPD/AML, -FPD), caused by monoallelic deleterious germline variants, is characterized by bleeding diathesis and predisposition for hematologic malignancies, particularly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Clinical data on FPDMM-associated AML (FPDMM-AML) are limited, complicating evidence-based clinical decision-making. Here, we present retrospective genetic and clinical data of the largest cohort of FPDMM patients reported to date.

Beating Cardiac Cell Cultures From Different Developmental Stages of Rainbow Trout as a Novel Approach for Replication of Cardiac Fish Viruses.

Piscine orthoreovirus-1 and 3 (PRV-1, PRV-3) cause highly prevalent infection in cultured salmonids and can induce heart and skeletal muscle inflammation (HSMI) resulting in economic losses in aquaculture. However, to date, PRV-1 and PRV-3 have withstood replication in continuous cell lines. In this study, we used beating heart cell cultures obtained from different developmental stages of rainbow trout (Oncorhynchus mykiss) (RTC-L and RTC-A) and tested their ability to sustain replication of PRV-1 and PRV-3.

Treatment of Venous Thromboembolism with Edoxaban over 18 Months: Results from ETNA-VTE Europe.

Background:  The benefits and risks of extending anticoagulant treatment beyond the first 3 to 6 months in patients with venous thromboembolism (VTE) in clinical practice are not well understood.

Methods:  ETNA-VTE Europe is a prospective, noninterventional, post-authorization study in unselected patients with VTE treated with edoxaban in eight European countries for up to 18 months. Recurrent VTE, major bleeding, and all-cause death were the primary study outcomes.