Psychometric validation of the Vaccination Attitudes Examination (VAX) scale in German pre-pandemic and mid-pandemic samples.

Despite the public health value of immunizations, vaccine hesitancy is a widespread phenomenon and received special attention during the global COVID-19 pandemic. The Vaccination Attitudes Examination (VAX) Scale aims to identify anti-vaccination attitudes for understanding vaccine hesitancy. The present study is the validation of the German version of the VAX scale in pre-/mid-pandemic samples.

Maintenance therapy with trofosfamide, idarubicin and etoposide in patients with rhabdomyosarcoma and other high-risk soft tissue sarcomas (CWS-2007-HR): a multicentre, open-label, randomised controlled phase 3 trial.

Background: Rhabdomyosarcoma and other soft tissue sarcomas (STS) with high-risk features are still associated with an unsatisfactory outcome. We evaluated the efficacy of oral maintenance therapy added at the end of standard therapy in patients with high-risk rhabdomyosarcoma and STS.

Methods: CWS-2007-HR was a multicentre, open-label, randomised controlled, phase 3 trial done at 87 centers in 5 countries.

CRISPR-StAR enables high-resolution genetic screening in complex in vivo models.

Pooled genetic screening with CRISPR-Cas9 has enabled genome-wide, high-resolution mapping of genes to phenotypes, but assessing the effect of a given genetic perturbation requires evaluation of each single guide RNA (sgRNA) in hundreds of cells to counter stochastic genetic drift and obtain robust results. However, resolution is limited in complex, heterogeneous models, such as organoids or tumors transplanted into mice, because achieving sufficient representation requires impractical scaling. This is due to bottleneck effects and biological heterogeneity of cell populations.

Advancing the personalized advantage index (PAI): a systematic review and application in two large multi-site samples in anxiety disorders.

Background: The Personalized Advantage Index (PAI) shows promise as a method for identifying the most effective treatment for individual patients. Previous studies have demonstrated its utility in retrospective evaluations across various settings. In this study, we explored the effect of different methodological choices in predictive modelling underlying the PAI.

Longitudinal Associations of Experiential and Reflective Dimensions of Meaning in Life With Psychopathological Symptoms.

Background: Rather than being rooted in deliberate reflection, the experience of meaning has been shown to evolve from intuitive processes (Heintzelman & King, 2013b, https://doi.org/10.1007/978-94-007-6527-6_7).

Influence of pleural invasion on survival in pathologic T3-4N0M0 non-small cell lung cancer: a propensity score matching study based on the Surveillance, Epidemiology, and End Results database.

Background: Pleural invasion (PI) is considered to be an adverse prognostic factor in non-small cell lung cancer (NSCLC). However, the prognostic roles of PI in pathologic (p)T3-4N0M0 NSCLC remain controversial. Therefore, this study aimed to evaluate the predictive value of PI in patients with pT3-4N0M0 NSCLC.

Does sleep help children to generalise features like adults?

Children and adults have been shown to benefit from sleep with regard to the consolidation of declarative memories. Especially during childhood, the generalisation of information from social and non-social contexts is important for adaptable behaviour in new situations and might show specific features in children. Here, we investigated whether adults (n = 18) and children (n = 19) differ in their generalisation of features assessed in wake and sleep conditions.

Long-term safety and efficacy of fitusiran prophylaxis, and perioperative management in people with hemophilia A or B.

Fitusiran is an investigational small interfering RNA therapeutic that targets antithrombin (AT) to rebalance hemostasis in people with hemophilia. Here we present the results of the completed Phase 2 open-label extension study, which evaluated the long-term safety and efficacy of fitusiran in participants with moderate or severe hemophilia A or B, with or without inhibitors. Male participants who had completed the Phase 1 study (NCT02035605) were enrolled.

Arthroscopic Autologous Minced Cartilage Implantation of Cartilage Defects in the Knee: A 2-Year Follow-up of 62 Patients.

Background: Symptomatic cartilage defects of the knee joint are frequently diagnosed and can be treated with different available surgical methods. Nevertheless, there is currently no gold standard treatment for all indications. Minced cartilage implantation is increasingly coming into focus as a refined surgical technique.

Seipin governs phosphatidic acid homeostasis at the inner nuclear membrane.

The nuclear envelope is a specialized subdomain of the endoplasmic reticulum and comprises the inner and outer nuclear membranes. Despite the crucial role of the inner nuclear membrane in genome regulation, its lipid metabolism remains poorly understood. Phosphatidic acid (PA) is essential for membrane growth as well as lipid storage.

Cancer cells impair monocyte-mediated T cell stimulation to evade immunity.

The tumour microenvironment is programmed by cancer cells and substantially influences anti-tumour immune responses. Within the tumour microenvironment, CD8 T cells undergo full effector differentiation and acquire cytotoxic anti-tumour functions in specialized niches. Although interactions with type 1 conventional dendritic cells have been implicated in this process, the underlying cellular players and molecular mechanisms remain incompletely understood.

Vitamin D Is Associated with Lipid Metabolism: A Sex- and Age-Dependent Analysis of a Large Outpatient Cohort.

Vitamin D is a fat-soluble steroid that influences cardiovascular health by affecting lipid metabolism. Since dyslipidemia is a key risk factor for cardiovascular disease (CVD), our study aimed to explore the relationship between vitamin D levels and lipid parameters, considering the effects of age and gender. : In this cross-sectional study of 47,778 outpatients, we analyzed correlations between two forms of vitamin D-25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)D)-and lipid parameters, including low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol (TC).

Non-Invasive Monitoring of Corticosterone Levels in Mouse Urine with Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry.

An innovative method for the quantification of corticosterone in the urine of C57BL/6J mice by liquid chromatography-electrospray ionization-tandem mass spectrometry was developed. Unconjugated and glucuronidated corticosterone was detected in the urine samples using enzymatic hydrolysis following liquid-liquid extraction. After optimization of the extraction protocol and LC-MS/MS parameters, we performed a validation study using a representative urine pool of C57BL/6J and Naval Medical Research Institute mice.

Psychometric properties of the Maternal Postnatal Attachment Scale and the Postpartum Bonding Questionnaire in three German samples.

Background: Forming an emotional bond towards the infant is an important developmental aspect of the mother-child relationship. Two questionnaires frequently used for the assessment of mother-infant bonding, namely the Maternal Postnatal Attachment Scale (MPAS) and the Postpartum Bonding Questionnaire (PBQ), have shown inconclusive psychometric properties. To ensure comparability of results across studies, it is crucial to examine the replicability of psychometric properties and previously proposed factor structures of measurements when adapted to other languages.

Mitochondrial DNA abundance and circulating metabolomic profiling: Multivariable-adjusted and Mendelian randomization analyses in UK Biobank.

Background: Low leukocyte mitochondrial DNA (mtDNA) abundance has been associated with a higher risk of atherosclerotic cardiovascular disease, but through unclear mechanisms. We aimed to investigate whether low mtDNA abundance is associated with worse metabolomic profiling, as being potential intermediate phenotypes, using cross-sectional and genetic studies.

Methods: Among 61,186 unrelated European participants from UK Biobank, we performed multivariable-adjusted linear regression analyses to examine the associations between mtDNA abundance and 168 NMR-based circulating metabolomic measures and nine metabolomic principal components (PCs) that collectively covered 91.

When softer sounds are more distracting: Task-irrelevant whispered speech causes disruption of serial recall.

Two competing accounts propose that the disruption of short-term memory by irrelevant speech arises either due to interference-by-process (e.g., changing-state effect) or attentional capture, but it is unclear how whispering affects the irrelevant speech effect.

A genome-wide screen identifies silencers with distinct chromatin properties and mechanisms of repression.

Differential gene transcription enables development and homeostasis in all animals and is regulated by two major classes of distal cis-regulatory DNA elements (CREs): enhancers and silencers. Although enhancers have been thoroughly characterized, the properties and mechanisms of silencers remain largely unknown. By an unbiased genome-wide functional screen in Drosophila melanogaster S2 cells, we discover a class of silencers that bind one of three transcription factors (TFs) and are generally not included in chromatin-defined CRE catalogs as they mostly lack detectable DNA accessibility.

An expanded view of cell competition.

Cell competition arises in heterogeneous tissues when neighbouring cells sense their relative fitness and undergo selection. It has been a challenge to define contexts in which cell competition is a physiologically relevant phenomenon and to understand the cellular features that underlie fitness and fitness sensing. Drawing on examples across a range of contexts and length scales, we illuminate molecular and cellular features that could underlie fitness in diverse tissue types and processes to promote and reinforce long-term maintenance of tissue function.

Molecular profiles, sources and lineage restrictions of stem cells in an annelid regeneration model.

Regeneration of missing body parts can be observed in diverse animal phyla, but it remains unclear to which extent these capacities rely on shared or divergent principles. Research into this question requires detailed knowledge about the involved molecular and cellular principles in suitable reference models. By combining single-cell RNA sequencing and mosaic transgenesis in the marine annelid Platynereis dumerilii, we map cellular profiles and lineage restrictions during posterior regeneration.

Effects of Tirzepatide on the Clinical Trajectory of Patients with Heart Failure, a Preserved Ejection Fraction, and Obesity.

Background: Patients with heart failure, a preserved ejection fraction (HFpEF), and obesity have significant disability and suffer frequent exacerbations of heart failure. We hypothesized that tirzepatide, a long-acting agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, would improve a comprehensive suite of clinical endpoints, including measures of health status, functional capacity, quality of life, exercise tolerance, patient well-being, and medication burden in these patients.

Methods: 731 patients in class II-IV heart failure, ejection fraction ≥50%, and body mass index ≥30 kg/m were randomized(double-blind) to tirzepatide(titrated up to 15mg subcutaneously weekly)(n=364) or placebo(n=367), added to background therapy for a median of 104 weeks (Q1=66, Q3=126 weeks).

Alternative lengthening of telomere-based immortalization renders H3G34R -mutant diffuse hemispheric glioma hypersensitive to PARP inhibitor combination regimens.

Background: Diffuse hemispheric glioma, H3G34R/V-mutant (DHG-H3G34) is characterized by poor prognosis and lack of effective treatment options. DHG-H3G34R further harbor deactivation of Alpha-Thalassemia/Mental Retardation Syndrome X-linked protein (ATRX; DHG-H3G34R_ATRX) suggesting a unique interaction of these two oncogenic alterations. In this study, we dissect their cell biological interplay, investigate the impact on telomere stabilization and, consequently, validate a targeted therapy approach.

Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity.

Background: Obesity increases the risk of heart failure with preserved ejection fraction. Tirzepatide, a long-acting agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, causes considerable weight loss, but data are lacking with respect to its effects on cardiovascular outcomes.

Methods: In this international, double-blind, randomized, placebo-controlled trial, we randomly assigned, in a 1:1 ratio, 731 patients with heart failure, an ejection fraction of at least 50%, and a body-mass index (the weight in kilograms divided by the square of the height in meters) of at least 30 to receive tirzepatide (up to 15 mg subcutaneously once per week) or placebo for at least 52 weeks.