The German Communities That Care Youth Survey: dimensionality and validity of risk factors.

Background: Communities That Care (CTC) is an evidence-based community change strategy for supporting healthy youth development. One of its key elements is the development of a community profile to identify and prioritise risk factors for health and behavioural problems in adolescents based on the CTC Youth Survey. The strategy was originally developed and evaluated in the United States.

Anchoring Vignettes: A Useful Tool to Measure and Correct for Cultural Bias in Parent Reports on Their Child's Mental Health?

Parent report measures developed in the Western world are commonly used to assess children's mental health, but their cross-cultural comparability is questionable. The present study examines the use of anchoring vignettes to assess and adjust for bias in five countries: the United States, Mexico, Germany, China, and Russia. Parents ( = 500) rated their child's mental health and vignettes depicting internalizing and externalizing problem behaviors in an online survey.

Burden and satisfaction with social support in families with a history of problematic substance use or dementia - a comparison.

Background: Living in a family with a history of problematic substance use or dementia is a major stressful experience for family members and results often in an impaired health condition. Seeking and receiving social support has been emphasized as a major resource while coping with this stress. However, especially family members of people with problematic substance use often refrain from help-seeking.

Targeting fatty acid synthase in preclinical models of TNBC brain metastases synergizes with SN-38 and impairs invasion.

Fatty acid synthesis (FAS) has been shown to play a key role in the survival of brain-metastatic (BM) breast cancer. We demonstrate that the fatty acid synthase inhibitor TVB-2640 synergizes with the topoisomerase inhibitor SN-38 in triple-negative breast cancer (TNBC) BM cell lines, upregulates FAS and downregulates cell cycle progression gene expression, and slows the motility of TNBC BM cell lines. The combination of SN-38 and TVB-2640 warrants further consideration as a potential therapeutic option in TNBC BMs.

Selective and Potent PROTAC Degraders of c-Src Kinase.

Using dasatinib linked to E3 ligase ligands, we identified a potent and selective dual Csk/c-Src PROTAC degrader. We then replaced dasatinib, the c-Src-directed ligand, with a conformation-selective analogue that stabilizes the αC-helix-out conformation of c-Src. Using the αC-helix-out ligand, we identified a PROTAC that is potent and selective for c-Src.

Contextual effects of community capacity as a predictor for adolescent alcohol, tobacco, and illicit drug use: A multi-level analysis.

Adolescent substance use is a major public health issue that can result in enduring physical, psychological, and social consequences. This study seeks to examine the relationship between community capacity for prevention and the 4-week prevalence rate of substance use, including tobacco, alcohol, other drugs, and binge-drinking, among students in Germany ranging from grades 5 to 11. This study employed a cross-sectional design and used baseline data from 28 communities participating in the CTC-EFF study.

The effectiveness of workplace interventions for the prevention of alcohol use: A meta-analysis.

Background And Aims: Previous research has pointed to the potential of workplace interventions addressing alcohol consumption. However, there is still no systematic overview of the effects of these interventions. Therefore, we aimed to quantify the effectiveness of workplace interventions addressing alcohol use by conducting a meta-analysis.

Optimizing Precision Medicine for Breast Cancer Brain Metastases with Functional Drug Response Assessment.

Unlabelled: The development of novel therapies for brain metastases is an unmet need. Brain metastases may have unique molecular features that could be explored as therapeutic targets. A better understanding of the drug sensitivity of live cells coupled to molecular analyses will lead to a rational prioritization of therapeutic candidates.

Integrative multi-omics analysis reveals novel idiopathic pulmonary fibrosis endotypes associated with disease progression.

Background: Idiopathic pulmonary fibrosis (IPF) is characterized by the accumulation of extracellular matrix in the pulmonary interstitium and progressive functional decline. We hypothesized that integration of multi-omics data would identify clinically meaningful molecular endotypes of IPF.

Methods: The IPF-PRO Registry is a prospective registry of patients with IPF.

TMPRSS2 Inhibitor Discovery Facilitated through an and Biochemical Screening Platform.

The COVID-19 pandemic has highlighted the need for new antiviral approaches because many of the currently approved drugs have proven ineffective against mitigating SARS-CoV-2 infections. The host transmembrane serine protease TMPRSS2 is a promising antiviral target because it plays a role in priming the spike protein before viral entry occurs for the most virulent variants. Further, TMPRSS2 has no established physiological role, thereby increasing its attractiveness as a target for antiviral agents.

QSAR via multisite λ-dynamics in the orphaned TSSK1B kinase.

Multisite λ-dynamics (MSλD) is a novel method for the calculation of relative free energies of binding for ligands to their targeted receptors. It can be readily used to examine a large number of molecules with multiple functional groups at multiple sites around a common core. This makes MSλD a powerful tool in structure-based drug design.

Cultural Bias in Parent Reports: The Role of Socialization Goals When Parents Report on Their Child's Problem Behavior.

It has been called into question whether widely used screening instruments for child mental health can provide comparable results across countries and cultures. Socialization goals can influence whether and to what extent a parent considers a behavior to be problematic and thus might influence parental reports on their child's behavior. We tested comparability of parental reports between native German (N = 116) and Turkish origin (N = 77) parents in Germany in an online study using a vignette approach.

Reply to Correspondence on "Synergy and Antagonism between Allosteric and Active-Site Inhibitors of Abl Tyrosine Kinase".

Manley and co-workers provide data demonstrating that, at super-pharmacological concentrations (300 μM), a ternary complex between Abl, asciminib, and ATP-competitive inhibitors is possible. The work in our manuscript concerns the interplay of asciminib (and GNF-2) with ATP-competitive inhibitors at pharmacologically relevant concentrations (C =1.6-3.

Motive perception pathways to the release of personal information to healthcare organizations.

Background: The goal of the study is to assess the downstream effects of who requests personal information from individuals for artificial intelligence-(AI) based healthcare research purposes-be it a pharmaceutical company (as an example of a for-profit organization) or a university hospital (as an example of a not-for-profit organization)-as well as their boundary conditions on individuals' likelihood to release personal information about their health. For the latter, the study considers two dimensions: the tendency to self-disclose (which is aimed to be high so that AI applications can reach their full potential) and the tendency to falsify (which is aimed to be low so that AI applications are based on both valid and reliable data).

Methods: Across three experimental studies with Amazon Mechanical Turk workers from the U.

Insights into the modular design of kinase inhibitors and application to Abl and Axl.

Scaffold hopping is a common strategy for generating kinase inhibitors that bind to the DFG-out inactive conformation. Small structural differences in inhibitor scaffolds can have significant effects on potency and selectivity across the kinome, however, these effects are often not studied in detail. Herein, we outline a design strategy to generate an array of DFG-out conformation inhibitors with three different hinge-binders and two DFG-pocket groups.

Conformation-tunable ATP-competitive kinase inhibitors.

Small molecule kinase inhibitors have shown immense clinical utility for diverse indications. While >60 kinase inhibitors have been approved (and many more in clinical trials), it remains unclear whether the clinical efficacy of a kinase inhibitor is solely dependent on enzymatic inhibition, or whether non-catalytic functions play a role in the efficacy of some kinase inhibitors. Here, we designed and synthesized a series of pyrazolopyrimidine kinase inhibitors that modulate the global kinase conformation of c-Src kinase.

Study protocol: a non-randomised community trial to evaluate the effectiveness of the communities that care prevention system in Germany.

Background: The Communities That Care (CTC) prevention planning and implementation system trains communities throughout a five-phase cycle to (1) build capacity for prevention, (2) adopt science-based prevention, (3) assess the prevention needs of adolescents living in the community, (4) select, and (5) implement evidence-based programs according to their needs. After CTC proved to be effective and cost-effective in the U.S.

Compliance with medical recommendations depending on the use of artificial intelligence as a diagnostic method.

Background: Advanced analytics, such as artificial intelligence (AI), increasingly gain relevance in medicine. However, patients' responses to the involvement of AI in the care process remains largely unclear. The study aims to explore whether individuals were more likely to follow a recommendation when a physician used AI in the diagnostic process considering a highly (vs.

Synergy and Antagonism between Allosteric and Active-Site Inhibitors of Abl Tyrosine Kinase.

Allosteric inhibitors of Abl kinase are being explored in the clinic, often in combination with ATP-site inhibitors of Abl kinase. However, there are conflicting data on whether both ATP-competitive inhibitors and myristoyl-site allosteric inhibitors can simultaneously bind Abl kinase. Here, we determine whether there is synergy or antagonism between ATP-competitive inhibitors and allosteric inhibitors of Abl.

gagCEST imaging at 3 T MRI in patients with articular cartilage lesions of the knee and intraoperative validation.

Objective: The aim of this study was to compare glycosaminoglycan chemical exchange saturation transfer (gagCEST) of knee cartilage with intraoperative results for the assessment of early osteoarthritis (OA) and to define gagCEST values for the differentiation between healthy and degenerated cartilage.

Design: Twenty-one patients with cartilage lesions or moderate OA were examined using 3 T Magnetic Resonance Imaging (MRI). In this prospective study, regions of interest (ROIs) were examined by a sagittal gagCEST analysis and a morphological high-resolution three-dimensional, fat-saturated proton-density space sequence.

TMPRSS2 inhibitor discovery facilitated through an and biochemical screening platform.

The COVID-19 pandemic has highlighted the need for new antiviral targets, as many of the currently approved drugs have proven ineffective against mitigating SARS-CoV-2 infections. The host transmembrane serine protease TMPRSS2 is a highly promising antiviral target, as it plays a direct role in priming the spike protein before viral entry occurs. Further, unlike other targets such as ACE2, TMPRSS2 has no known biological role.