Search

In the present work, we addressed the relationship between parental leave policies and social norms. Using a pre-registered, cross-national approach, we examined the relationship between parental leave policies and the perception of social norms for the gender division of childcare. In this study, 19,259 students (11,924 women) from 48 countries indicated the degree to which they believe childcare is (descriptive norm) and should be (prescriptive norm) equally divided among mothers and fathers. Policies were primarily operationalized as the existence of parental leave options in the respective country. The descriptive and prescriptive norms of equal division of childcare were stronger when parental leave was available in a country - also when controlling for potential confounding variables. Moreover, analyses of time since policy change suggested that policy change may initially affect prescriptive norms and then descriptive norms at a later point. However, due to the cross-sectional nature of the data, drawing causal inferences is difficult., (© 2024 British Psychological Society.)

Background: Scabies, an infestation of the mite Sarcoptes scabiei, has seen an increase in clinical diagnoses in the Netherlands since 2011. This study aimed to analyse PCR-positive S. scabiei skin samples through partial genome sequencing and to link findings to patient epidemiological characteristics., Methods: Skin samples were collected from individuals in the Netherlands between January 2016 and January 2023. On the PCR-positive S. scabiei skin samples, partial mitochondrial cytochrome c oxidase subunit 1 gene (cox1) sequencing was performed to assess genetic variability. Epidemiological information was collected through interviews. We examined associations between cox1 subtypes, epidemiological factors and treatment outcomes., Results: Sequencing results were obtained from 128 patients, with epidemiological information available for 55 (43%) of these patients. Fifteen distinct cox1 subtypes were identified. Subtype 01 was most prevalent (45%) and present across all age groups and social settings. The remaining subtypes were less common and not consistently found in all contexts. Five clusters were identified, each with identical cox1 subtypes. Comparative analysis with GenBank sequences revealed genetic similarities with strains from Australia, the USA and China, suggesting the global distribution and transmission of specific subtypes. A substantial proportion (73%) of patients with scabies required multiple treatments to eradicate the infestation, with no subtype-related differences., Conclusions: This is the first study linking S. scabiei sequencing results to patient epidemiological data. Several subtypes clustered in specific geographic regions and social contexts, underscoring localised transmission patterns. Further research with larger sample sizes is needed to enhance our understanding of the transmission of this mite. This study provides valuable insights that will strengthen scabies control efforts., (© 2024. The Author(s).)

Purpose: Apalutamide plus androgen-deprivation therapy (ADT) improved outcomes in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). Nevertheless real-world data are limited. The aim of this multicenter study was to generate real-world data from nmCRPC patients treated with ADT plus apalutamide., Methods: In this observational cohort based investigator initiated trial data of nmCRPC patients receiving apalutamide plus ADT were collected focusing on patient demographic data, prostate-specific antigen (PSA) declines, safety profile including dose modification/discontinuation as well as subsequent therapy and metastasis-free survival (MFS)., Results: Data from a total of 31 nmCRPC patients were documented. Compared to the Phase III study Spartan real-world patients are older, showed a higher ECOG-PS and more aggressive tumors. In the cohort PSA decreased about 98.1%, 74% of patients showed a PSA decrease over 90% and 54.8% reached a PSA-level < 0.2ng/ml. Apalutamide was well tolerated in real world patients: adverse events occurred in 67.7% but were in the majority mild (≥ grade 3: 6.5%). Dose reduction was necessary in 38.7% and 32.2% discontinued apalutamide treatment. MFS was 43 months and majority of patients were subsequently treated with abiraterone., Conclusion: In real world more comorbid nmCRPC patients with a higher ECOG-PS and more aggressive tumors are treated with apalutamide plus ADT. Nevertheless efficacy results as well as side effects are similar in real-world compared to Spartan trial showing also a rapid, durable and deep PSA response with a median MFS of 43 months., (© 2024. The Author(s).)

The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas13d system was adapted as a powerful tool for targeting viral RNA sequences, making it a promising approach for antiviral strategies. Understanding the influence of template RNA structure on Cas13d binding and cleavage efficiency is crucial for optimizing its therapeutic potential. In this study, we investigated the effect of local RNA secondary structure on Cas13d activity. To do so, we varied the stability of a hairpin structure containing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) target sequence, allowing us to determine the threshold RNA stability at which Cas13d activity is affected. Our results demonstrate that Cas13d possesses the ability to effectively bind and cleave highly stable RNA structures. Notably, we only observed a decrease in Cas13d activity in the case of exceptionally stable RNA hairpins with completely base-paired stems, which are rarely encountered in natural RNA molecules. A comparison of Cas13d and RNA interference (RNAi)-mediated cleavage of the same RNA targets demonstrated that RNAi is more sensitive for local target RNA structures than Cas13d. These results underscore the suitability of the CRISPR-Cas13d system for targeting viruses with highly structured RNA genomes., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Objective: Altered B cell receptor (BCR) signaling has been implicated in the pathogenesis of rheumatoid arthritis (RA). Here we aimed to identify signaling aberrations in autoantibody-positive and autoantibody-negative RA patients by performing a comprehensive analysis of the BCR signaling cascade in different B cell subsets., Methods: We first optimized phosphoflow cytometry for an in-depth analysis of BCR signaling across immunoglobulin isotypes in healthy donors. Subsequently, we compared BCR signaling in circulating B cell subsets from treatment-naïve, newly-diagnosed autoantibody-positive RA and autoantibody-negative RA patients and healthy controls (HCs)., Results: We observed subset-specific phosphorylation patterns of the BCR signalosome in circulating B cells from healthy donors. Compared with HCs, autoantibody-positive RA patients displayed enhanced responses to BCR stimulation for multiple signaling proteins, specifically in naïve and IgA + memory B cells. Whereas in unstimulated healthy donor B cells, the phosphorylation status of individual signaling proteins showed only limited correlation, BCR stimulation enhanced the interconnectivity in phosphorylation within the BCR signalosome. However, this strong interconnectivity within the BCR signalosome in stimulated B cells from HCs was lost in RA, especially in autoantibody-positive RA patients. Finally, we observed strong correlations between SYK and BTK protein expression, and IgA and IgG anti-citrullinated protein antibody concentrations in serum from autoantibody-positive RA patients., Conclusion: Collectively, the isotype-specific analysis of multiple key components of the BCR signalosome identified aberrant BCR signaling responses in treatment-naïve autoantibody-positive RA patients, particularly in naïve B cells and IgA + memory B cells. Our findings support differential involvement of dysregulated BCR signaling in the pathogenesis of autoantibody-positive and autoantibody-negative RA., (Copyright © 2024. Published by Elsevier Ltd.)

The analysis of the nitrogen (N) isotopic composition of organic matter bound to fossil biomineral structures (BB-δ 15 N) using the oxidation-denitrifier (O-D) method provides a novel tool to study past changes in N cycling processes., Methods: We report a set of methodological improvements to the O-D method, including (a) a method for sealing the reaction vials in which the oxidation of organic N to NO 3 - takes place, (b) a recipe for bypassing the pH adjustment step before the bacterial conversion of NO 3 - to N 2 O, and (c) a method for storing recrystallized dipotassium peroxodisulfate (K 2 S 2 O 8 ) under Ar atmosphere., Results: The new sealing method eliminates the occasional contamination and vial breakage that occurred previously while increasing sample throughput. The protocol for bypassing pH adjustment does not affect BB-δ 15 N, and it significantly reduces the processing time. Storage of K 2 S 2 O 8 reagent under Ar atmosphere produces stable oxidation blanks over more than 3.5 years. We report analytical blanks, accuracy, and precision for this methodology from eight users over the course of ~3.5 years of analyses at the Max Planck Institute for Chemistry. Our method produces analytical blanks characterized by low N content (0.30 ± 0.13 nmol N, 1σ, n = 195) and stable δ 15 N (-2.20 ± 3.13‰, n = 195). The analysis of reference amino acid standards USGS 40 and USGS 65 indicates an overall accuracy of -0.23 ± 0.35‰ (1σ, n = 891). The analysis of in-house fossil standards gives similar analytical precision (1σ) across a range of BB-δ 15 N values and biominerals: zooxanthellate coral standard PO-1 (6.08 ± 0.21‰, n = 267), azooxanthellate coral standard LO-1 (10.20 ± 0.28‰, n = 258), foraminifera standard MF-1 (5.92 ± 0.28‰, n = 243), and tooth enamel AG-Lox (4.06 ± 0.49‰, n = 78)., Conclusions: The methodological improvements significantly increase sample throughput without compromising analytical precision or accuracy down to 1 nmol of N., (© 2023 The Authors. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd.)

Background: FOLFIRINOX chemotherapy has improved outcomes for pancreatic cancer patients, but poor long-term survival outcomes and high toxicity remain challenges. This study investigates the impact of FOLFIRINOX on plasma proteins and peripheral immune cells to guide immune-based combination therapies and, ideally, to identify a potential biomarker to predict early disease progression during FOLFIRINOX., Methods: Blood samples were collected from 86 pancreatic cancer patients before and two weeks after the first FOLFIRINOX cycle and subjected to comprehensive immune cell and proteome profiling. Principal Component Analysis and Linear Mixed Effect Regression models were used for data analysis. FOLFIRINOX efficacy was radiologically evaluated after the fourth cycle., Results: One cycle of FOLFIRINOX diminished tumour-cell-related pathways and enhanced pathways related to immune activation, illustrated by an increase in pro-inflammatory IL-18, IL-15, and TNFRSF4. Similarly, FOLFIRINOX promoted the activation of CD4 + and CD8 + T cells, the proliferation of NK(T), and the activation of antigen-presenting cells. Furthermore, high pre-treatment levels of VEGFA and PRDX3 and an elevation in FCRL3 levels after one cycle predicted early progression under FOLFIRINOX. Finally, patients with progressive disease exhibited high levels of inhibitory markers on B cells and CD8 + T cells, while responding patients exhibited high levels of activation markers on CD4 + and CD8 + T cell subsets., Conclusion: FOLFIRINOX has immunomodulatory effects, providing a foundation for clinical trials exploring immune-based combination therapies that harness the immune system to treat pancreatic cancer. In addition, several plasma proteins hold potential as circulating predictive biomarkers for early prediction of FOLFIRINOX response in patients with pancreatic cancer., Competing Interests: Declaration of Competing Interest J.G.J.V. Aerts reports personal fees and nonfinancial support from MSD, personal fees from BMS, Boehringer Ingelheim, Amphera, Eli‐Lilly, Takeda, Bayer, Roche, Astra Zeneca outside the submitted work; in addition, J.G.J.V. Aerts holds ownership interest (including patients) in Amphera BV and is a consultant/advisory board member for Amphera. The other authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)