A European aerosol phenomenology - 9: Light absorption properties of carbonaceous aerosol particles across surface Europe.

Carbonaceous aerosols (CA), composed of black carbon (BC) and organic matter (OM), significantly impact the climate. Light absorption properties of CA, particularly of BC and brown carbon (BrC), are crucial due to their contribution to global and regional warming. We present the absorption properties of BC (b) and BrC (b) inferred using Aethalometer data from 44 European sites covering different environments (traffic (TR), urban (UB), suburban (SUB), regional background (RB) and mountain (M)).

Misfolding of transthyretin in vivo is controlled by the redox environment and macromolecular crowding.

Transthyretin (TTR) amyloidosis is a progressive disorder characterized by peripheral neuropathy, autonomic dysfunction, and cardiomyopathy. The precise mechanism by which TTR misfolds and forms fibrils in vivo remains incompletely understood, posing challenges to the development of effective therapeutics. In this study, we reveal that the recently identified nonnative pathological species of TTR (NNTTR), which is enriched in the plasma of ttr-val30met gene carriers, exhibits strong amyloidogenic properties, making it a promising therapeutic target.

Candesartan Has No Clinically Meaningful Effect on the Plasma Concentrations of Cytochrome P450 2C8 Substrate Repaglinide in Humans.

In vitro evidence shows that the acyl--D-glucuronide metabolite of candesartan inhibits cytochrome P450 (CYP) 2C8 with an inhibition constant of 7.12 M. We investigated the effect of candesartan on the plasma concentrations and glucose-lowering effect of repaglinide, a sensitive clinical CYP2C8 index substrate.

A burden of rare copy number variants in obsessive-compulsive disorder.

Current genetic research on obsessive-compulsive disorder (OCD) supports contributions to risk specifically from common single nucleotide variants (SNVs), along with rare coding SNVs and small insertion-deletions (indels). The contribution to OCD risk from rare copy number variants (CNVs), however, has not been formally assessed at a similar scale. Here we describe an analysis of rare CNVs called from genotype array data in 2248 deeply phenotyped OCD cases and 3608 unaffected controls from Sweden and Norway.

Joint testing of rare variant burden scores using non-negative least squares.

Gene-based burden tests are a popular and powerful approach for analysis of exome-wide association studies. These approaches combine sets of variants within a gene into a single burden score that is then tested for association. Typically, a range of burden scores are calculated and tested across a range of annotation classes and frequency bins.

Yield of genetic association signals from genomes, exomes and imputation in the UK Biobank.

Whole-genome sequencing (WGS), whole-exome sequencing (WES) and array genotyping with imputation (IMP) are common strategies for assessing genetic variation and its association with medically relevant phenotypes. To date, there has been no systematic empirical assessment of the yield of these approaches when applied to hundreds of thousands of samples to enable the discovery of complex trait genetic signals. Using data for 100 complex traits from 149,195 individuals in the UK Biobank, we systematically compare the relative yield of these strategies in genetic association studies.

Early change in specific depression symptoms and later outcome in internet-delivered psychotherapy for depression: A cohort study and cross-lagged network analysis.

Background: Symptom reduction occurring early in depression treatment is associated with favourable post-treatment outcome, but it is not known how early reduction in specific depression symptoms affect treatment outcome. We aimed to determine the impact of symptom-specific change from pre-treatment to week four during internet-delivered CBT (ICBT) on overall and symptom-specific depression severity at post-treatment. We hypothesized that change in mood and emotional involvement would be most strongly associated with later overall depression severity.

In vitro assessment of inhibitory effects of kinase inhibitors on CYP2C9, 3A and 1A2: Prediction of drug-drug interaction risk with warfarin and direct oral anticoagulants.

Objective: This study aimed to evaluate the cytochrome P450 (CYP)-mediated drug-drug interaction (DDI) potential of kinase inhibitors with warfarin and direct oral anticoagulants (DOACs).

Methods: An in vitro CYP probe substrate cocktail assay was used to study the inhibitory effects of fifteen kinase inhibitors on CYP2C9, 3A, and 1A2. Then, DDI predictions were performed using both mechanistic static and physiologically-based pharmacokinetic (PBPK) models.

Seasonal migration patterns of Siberian Rubythroat (Calliope calliope) facing the Qinghai-Tibet Plateau.

Background: Small songbirds respond and adapt to various geographical barriers during their annual migration. Global flyways reveal the diverse migration strategies in response to different geographical barriers, among which are high-elevation plateaus. However, few studies have been focused on the largest and highest plateau in the world, the Qinghai-Tibet Plateau (QTP) which poses a significant barrier to migratory passerines.

Automated data transfer for digital twin applications: Two case studies.

Digital twins have been gaining an immense interest in various fields over the last decade. Bringing conventional process simulation models into (near) real time are thought to provide valuable insights for operators, decision makers, and stakeholders in many industries. The objective of this paper is to describe two methods for implementing digital twins at water resource recovery facilities and highlight and discuss their differences and preferable use situations, with focus on the automated data transfer from the real process.

Examining the role of the visuospatial sketchpad in children's math calculation skills using Baddeley and Hitch's model of working memory.

Math difficulties (MDs) occur in about 3-7 % of children and have been associated with academic, health, and occupational challenges. To date, findings about the role of working memory in MDs have been conflicting. The Automated Working Memory Assessment Battery (AWMA), which assesses all components of Baddeley and Hitch's model of working memory, was used to investigate which component of the model was most related to math calculation skills in elementary-school children.

Liver stiffness predicts progression to liver-related events in patients with chronic liver disease - A cohort study of 14 414 patients.

Background & Aims: Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) is a non-invasive diagnostic biomarker of liver fibrosis. It is uncertain if LSM can predict risk for future liver-related outcomes in large, heterogenous populations.

Methods: This Swedish multi-centre cohort study included patients (n = 14 414) from 16 sites who underwent LSM by VCTE between 2008 and 2020.

Non-targeted metabolomics for the identification of plasma metabolites associated with organic anion transporting polypeptide 1B1 function.

Our aim was to evaluate biomarkers for organic anion transporting polypeptide 1B1 (OATP1B1) function using a hypothesis-free metabolomics approach. We analyzed fasting plasma samples from 356 healthy volunteers using non-targeted metabolite profiling by liquid chromatography high-resolution mass spectrometry. Based on SLCO1B1 genotypes, we stratified the volunteers to poor, decreased, normal, increased, and highly increased OATP1B1 function groups.

The effect of hydroxychloroquine on cholesterol synthesis depends on the profile of cholesterol metabolism. A controlled clinical study.

Background And Aims: Hydroxychloroquine (HCQ) has a variable effect on cholesterol synthesis. To clarify this, we assessed the effect of HCQ on the cholesterol-synthesis pathway in individuals with low and high cholesterol absorption efficiency.

Method: A total of 53 acute myocardial infarction patients with a constant statin dose randomized to receive HCQ or placebo for six months in a double-blind manner, were classified further into low (n = 26) and high (n = 27) cholesterol absorbers based on the median baseline serum cholestanol level.

Screening of 16 major drug glucuronides for time-dependent inhibition of nine drug-metabolizing CYP enzymes - detailed studies on CYP3A inhibitors.

Time-dependent inhibition of cytochrome P450 (CYP) enzymes has been observed for a few glucuronide metabolites of clinically used drugs. Here, we investigated the inhibitory potential of 16 glucuronide metabolites towards nine major CYP enzymes in vitro. Automated substrate cocktail methods were used to screen time-dependent inhibition of CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2J2 and 3A in human liver microsomes.

Posaconazole-ibrutinib interaction cannot be avoided by staggered dosing: How to optimize ibrutinib dose during posaconazole treatment.

Aims: Ibrutinib is used in the treatment of certain B-cell malignancies. Due to its CYP3A4-mediated metabolism and highly variable pharmacokinetics, it is prone to potentially harmful drug-drug interactions.

Methods: In a randomized, placebo-controlled, three-phase crossover study, we examined the effect of the CYP3A4-inhibiting antifungal posaconazole on ibrutinib pharmacokinetics.

Drug-related deaths in a university hospital: Comparison to previous decades.

The incidence of fatal adverse drug reactions (ADRs) in hospitals varies widely, and ADRs are often underreported. The impact of medical safety processes is not easily evaluated, and although medical practice changes constantly, little is known about ADR trends. This study concentrated on the current incidence and properties of fatal ADRs occurring in a university hospital and compared the results with two previous studies performed in the same hospital.