Hepatotoxicity of antipsychotics: an exploratory pharmacoepidemiologic and pharmacodynamic study integrating FAERS data and receptor-binding affinities.

Introduction: Antipsychotic psychopharmacotherapy is associated with the risk of drug-induced liver injury (DILI). However, understanding specific risk factors remains challenging due to limited data. This study investigates the relationship between receptor binding affinities and occupancies of antipsychotics and their associated hepatotoxic risks.

Exploiting WEE1 Kinase Activity as FUS::DDIT3-Dependent Therapeutic Vulnerability in Myxoid Liposarcoma.

Purpose: The pathognomonic FUS::DDIT3 fusion protein drives myxoid liposarcoma (MLS) tumorigenesis via aberrant transcriptional activation of oncogenic signaling. As FUS::DDIT3 has so far not been pharmacologically tractable to selectively target MLS cells, this study investigated the functional role of the cell cycle regulator WEE1 as novel FUS::DDIT3-dependent therapeutic vulnerability in MLS.

Experimental Design: Immunohistochemical evaluation of the cell cycle regulator WEE1 was performed in a large cohort of MLS specimens.

Pig manure degradation and carbon emission: Measuring and modeling combined aerobic-anaerobic transformations.

Greenhouse gas emissions from liquid livestock manure storage significantly contribute to global warming. Accurate farm-scale models are essential for predicting these emissions and evaluating manure management strategies, but they rely on multiple parameters describing carbon loss dynamics. Surface respiration may significantly influence carbon loss and methane emission, yet it is not explicitly included in current models.

Multicolor, Cell-Impermeable, and High Affinity BACE1 Inhibitor Probes Enable Superior Endogenous Staining and Imaging of Single Molecules.

The prevailing but not undisputed amyloid cascade hypothesis places the β-site of APP cleaving enzyme 1 (BACE1) center stage in Alzheimer's Disease pathogenesis. Here, we investigated functional properties of BACE1 with novel tag- and antibody-free labeling tools, which are conjugates of the BACE1-inhibitor IV (also referred to as C3) linked to different impermeable Alexa Fluor dyes. We show that these fluorescent small molecules bind specifically to BACE1, with a 1:1 labeling stoichiometry at their orthosteric site.

Idiopathic generalized epilepsies in the epilepsy monitoring unit: Systematic quantification of focal EEG and semiological signs.

Objective: Focal seizure symptoms (FSS) and focal interictal epileptiform discharges (IEDs) are common in patients with idiopathic generalized epilepsies (IGEs), but dedicated studies systematically quantifying them both are lacking. We used automatic IED detection and localization algorithms and correlated these EEG findings with clinical FSS for the first time in IGE patients.

Methods: 32 patients with IGEs undergoing long-term video EEG monitoring were systematically analyzed regarding focal vs.

Ribosomal RNA 2'-O-methylation dynamics impact cell fate decisions.

Translational regulation impacts both pluripotency maintenance and cell differentiation. To what degree the ribosome exerts control over this process remains unanswered. Accumulating evidence has demonstrated heterogeneity in ribosome composition in various organisms.

Association of hypertension, type 2 diabetes mellitus and dyslipidemia with the duration of inpatient treatments and recurrence of schizophrenia.

Objective: People with schizophrenia have an increased cardiovascular risk with higher mortality than the general population. Only a few studies have investigated the impact of cardiovascular risk on the later course of schizophrenia. This study aims to explore the association of cardiovascular risk factors, as detected during an index inpatient treatment for schizophrenia, with the duration of psychiatric inpatient treatments and number of inpatient admissions in the subsequent 10 years, in patients with schizophrenia.

Complement and platelets: prothrombotic cell activation requires membrane attack complex-induced release of danger signals.

Complement activation in the diseases paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) results in cytolysis and fatal thrombotic events, which are largely refractory to anticoagulation and/or antiplatelet therapy. Anticomplement therapy, however, efficiently prevents thrombotic events in PNH and aHUS, but the underlying mechanisms remain unresolved. We show that complement-mediated hemolysis in whole blood induces platelet activation similarly to activation by adenosine 5'-diphosphate (ADP).

Effect of anaerobic digestion on odor and ammonia emission from land-applied cattle manure.

High ammonia (NH) and odor emission can occur after land application of liquid animal manure. This study was aimed at evaluating NH loss and odor nuisance after field application of cattle manure and how it is affected by two anaerobic digestion strategies: i) digestion of cattle manure alone and ii) digestion with catch crops and dilution by water. A system of dynamic chambers with online measurements of NH and odorous compounds (summarized as odor activity value, OAV) was used.

Optimized genetic code expansion technology for time-dependent induction of adhesion GPCR-ligand engagement.

The introduction of an engineered aminoacyl-tRNA synthetase/tRNA pair enables site-specific incorporation of unnatural amino acids (uAAs) with functionalized side chains into proteins of interest. Genetic Code Expansion (GCE) via amber codon suppression confers functionalities to proteins but can also be used to temporally control the incorporation of genetically encoded elements into proteins. Here, we report an optimized GCE system (GCEXpress) for efficient and fast uAA incorporation.

A photoswitchable inhibitor of TREK channels controls pain in wild-type intact freely moving animals.

By endowing light control of neuronal activity, optogenetics and photopharmacology are powerful methods notably used to probe the transmission of pain signals. However, costs, animal handling and ethical issues have reduced their dissemination and routine use. Here we report LAKI (Light Activated K channel Inhibitor), a specific photoswitchable inhibitor of the pain-related two-pore-domain potassium TREK and TRESK channels.

Simple Management Changes Drastically Reduce Pig House Methane Emission in Combined Experimental and Modeling Study.

Reducing methane from livestock slurry is one of the quickest ways to counteract global warming. A straightforward strategy is to reduce slurry retention time inside pig houses by frequent transfer to outside storages, where temperature and therefore microbial activity are lower. We demonstrate three frequent slurry removal strategies in pig houses in a year-round continuous measurement campaign.

FUS regulates a subset of snoRNA expression and modulates the level of rRNA modifications.

FUS is a multifunctional protein involved in many aspects of RNA metabolism, including transcription, splicing, translation, miRNA processing, and replication-dependent histone gene expression. In this work, we show that FUS depletion results in the differential expression of numerous small nucleolar RNAs (snoRNAs) that guide 2'-O methylation (2'-O-Me) and pseudouridylation of specific positions in ribosomal RNAs (rRNAs) and small nuclear RNAs (snRNAs). Using RiboMeth-seq and HydraPsiSeq for the profiling of 2'-O-Me and pseudouridylation status of rRNA species, we demonstrated considerable hypermodification at several sites in HEK293T and SH-SY5Y cells with FUS knockout (FUS KO) compared to wild-type cells.

Development and validation of the ASKFV-SE tool to measure children's self-efficacy for requesting fruits and vegetables.

The aim of the present study was to develop the ASKFV-SE tool to measure self-efficacy (SE) towards requesting fruits and vegetables (FV) in the home and school environment with school-age children (grades 4-5) from urban, ethnically diverse, low-income households. Cognitive interviews reduced the tool from eleven items to seven. The 7-item questionnaire was tested with 444 children.

Transportable clock laser system with an instability of 1.6 × 10.

We present a transportable ultra-stable clock laser system based on a Fabry-Perot cavity with crystalline AlGaAs/GaAs mirror coatings, fused silica (FS) mirror substrates, and a 20 cm-long ultra-low expansion (ULE) glass spacer with a predicted thermal noise floor of mod σ = 7 × 10 in modified Allan deviation at one second averaging time. The cavity has a cylindrical shape and is mounted at 10 points. Its measured sensitivity of the fractional frequency to acceleration for the three Cartesian directions are 2(1) × 10 /(ms), 3(3) × 10 /(ms), and 3(1) × 10 /(ms), which belong to the lowest acceleration sensitivities published for transportable systems.

Intimate Partner Violence, Economic Insecurity, and Health Outcomes Among American Indian and Alaska Native Men and Women: Findings From a National Sample.

Limited data are available on experiences of intimate partner violence (IPV) and sexual violence (SV) and health outcomes among American Indian and Alaska Native (AIAN) populations. This study explores the relationship between IPV and SV, food insecurity, housing insecurity, healthcare access, and self-reported physical and mental health status in a nationally representative sample of AIAN adults ( = 3,634). IPV and SV were associated with poorer physical and mental health at the bivariate level, but not in multivariate analyses.

Effectiveness of mechanical separation for reducing ammonia loss from field-applied slurry: Assessment through literature review and model calculations.

To assess solid-liquid separation as a technology to reduce ammonia (NH) emission from storage and field application of animal slurry, it is necessary to consider a possible higher NH loss from the solid fraction after application than from raw slurry, as well as losses during storage. A literature review was conducted, and a case study was developed for Denmark, including cattle slurry, pig slurry, and biogas digestate applied by trailing hose, trailing shoe, or open slot injection at five different periods of the year. Standard storage emission factors were used and emission factors after field application were estimated using the ALFAM2 model with input data for dry matter (DM), pH, total ammoniacal nitrogen (TAN), and separation efficiency all from the literature compilation.

Drug-Associated Liver Injury Related to Antipsychotics: Exploratory Analysis of Pharmacovigilance Data.

Background: Drug-associated liver injury is one of the most common causes for acute liver failure and market withdrawal of approved drugs. In addition, the potential for hepatotoxicity related to specific substances has to be considered in psychopharmacotherapy. However, systematic evaluations of hepatotoxicity related to antipsychotics are limited.

SS18-SSX drives CREB activation in synovial sarcoma.

Purpose: Synovial sarcoma (SySa) is a rare soft tissue tumor characterized by a reciprocal t(X;18) translocation. The chimeric SS18-SSX fusion protein represents the major driver of the disease, acting as aberrant transcriptional dysregulator. Oncogenic mechanisms whereby SS18-SSX mediates sarcomagenesis are incompletely understood, and strategies to selectively target SySa cells remain elusive.