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Engaging in extracurricular activities is known to affect both cognitive and non-cognitive outcomes, but there is social inequality in access to these activities. In this study, we examine the role of extracurricular activities in moderating the relationships between secondary school students' social background and their cognitive and non-cognitive outcomes. Secondly, we examine variations in these relationships among three European cities that represent different educational systems in managing student heterogeneity. Based on the study findings, the effects of extracurricular activities on academic outcomes varied with regard to measured skills and the city of study. Extracurricular activities were related to enhanced interpersonal skills in all cities studied. However, in Turku and Ghent, extracurricular activities buffered the socio-economic gradient in interpersonal skills, whereas in Barcelona, such activities increased it. Rather surprisingly, in all cities, engaging in extracurricular activities magnified the effect of socio-economic status on cognitive skills.

Abstract Extensive genetic studies have elucidated cardiomyocyte differentiation and associated gene networks using single-cell RNA-seq, yet the intricate transcriptional mechanisms governing cardiac conduction system (CCS) development and working cardiomyocyte differentiation remain largely unexplored. Here we show that mice deleted for Dhx36 (encoding the Dhx36 helicase) in the embryonic or neonatal heart develop overt dilated cardiomyopathy, surface ECG alterations related to cardiac impulse propagation, and (in the embryonic heart) a lack of a ventricular conduction system (VCS). Heart snRNA-seq and snATAC-seq reveal the role of Dhx36 in CCS development and in the differentiation of working cardiomyocytes. Dhx36 deficiency directly influences cardiomyocyte gene networks by disrupting the resolution of promoter G-quadruplexes in key cardiac genes, impacting cardiomyocyte differentiation and CCS morphogenesis, and ultimately leading to dilated cardiomyopathy and atrioventricular block. These findings further identify crucial genes and pathways that regulate the development and function of the VCS/Purkinje fiber (PF) network.

Abstract Wind speed and direction variations across the rotor affect power production. As utility‐scale turbines extend higher into the atmospheric boundary layer (ABL) with larger rotor diameters and hub heights, they increasingly encounter more complex wind speed and direction variations. We assess three models for power production that account for wind speed and direction shear. Two are based on actuator disc representations, and the third is a blade element representation. We also evaluate the predictions from a standard power curve model that has no knowledge of wind shear. The predictions from each model, driven by wind profile measurements from a profiling LiDAR, are compared to concurrent power measurements from an adjacent utility‐scale wind turbine. In the field measurements of the utility‐scale turbine, discrete combinations of speed and direction shear induce changes in power production of −19% to +34% relative to the turbine power curve for a given hub height wind speed. Positive speed shear generally corresponds to over‐performance and increasing magnitudes of direction shear to greater under‐performance, relative to the power curve. Overall, the blade element model produces both higher correlation and lower error relative to the other models, but its quantitative accuracy depends on induction and controller sub‐models. To further assess the influence of complex, non‐monotonic wind profiles, we also drive the models with best‐fit power law wind speed profiles and linear wind direction profiles. These idealized inputs produce qualitative and quantitative differences in power predictions from each model, demonstrating that time‐varying, non‐monotonic wind shear affects wind power production.

BACKGROUND: Adverse events induced by intravesical bacillus Calmette-Guérin (BCG) to treat high-grade non-muscle-invasive bladder cancer (NMIBC) often lead to treatment discontinuation. The EAU-RF NIMBUS trial found a reduced number of standard-dose BCG instillations to be inferior with the standard regimen. Nonetheless, it remains important to evaluate whether patients in the reduced BCG treatment arm had better quality of life (QoL) due to a possible reduction in toxicity or burden. OBJECTIVE: To evaluate whether patients in the EAU-RF NIMBUS trial experienced better QoL after a reduced BCG instillation frequency. DESIGN SETTING AND PARTICIPANTS: A total of 359 patients from 51 European sites were randomized to one of two treatment arms between December 2013 and July 2019. The standard frequency arm (n = 182) was 6 weeks of BCG induction followed by 3 weeks of maintenance at months 3, 6, and 12. The reduced frequency arm (n = 177) was BCG induction at weeks 1, 2, and 6, followed by maintenance instillations at weeks 1 and 3 of months 3, 6, and 12. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Analyses were performed using an intention-to-treat analysis and a per-protocol analysis. QoL was measured using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 version 3.0 (QLQ-C30 v.03) prior to the first and last instillations of each BCG cycle. Group differences were determined using linear regression corrected for QoL at baseline. Differences in QoL over time were tested for significance using a linear mixed model. Side effects were recorded by the treating physician using a standardized form. Chi-square tests were used to compare the side-effect frequency between the arms. RESULTS AND LIMITATIONS: There were no significant differences in the means of each QoL scale between the two arms. There were also no significant changes over time in all QoL domains for both arms. However, differences in the incidence of general malaise at T1 (before the last induction instillation), frequency, urgency, and dysuria at T7 (before the last maintenance instillation) were detected in favor of the reduced frequency arm. CONCLUSIONS: Reducing the BCG instillation frequency does not improve the QoL in NMIBC patients despite lower storage symptoms. PATIENT SUMMARY: In this study, we evaluated whether a reduction in the number of received bacillus Calmette-Guérin instillations led to better quality of life in patients with high-grade non-muscle-invasive bladder cancer. We found no difference in the quality of life between the standard and the reduced bacillus Calmette-Guérin instillation frequency. We conclude that reducing the number of instillations does not lead to better quality of life in patients with high-grade non-muscle-invasive bladder cancer.

The Break4Brain project aims to elucidate the effects of both acute and chronic physical activity (PA) on educational achievement in children with and without Attention Deficit Hyperactivity Disorder (ADHD). This study will be conducted in two phases: a cross-over design followed by a hybrid type 1 implementation-effectiveness trial, which includes both a cluster randomized controlled trial (RCT) and a qualitative study. In phase I, 60 children aged 10–12, with 30 each from ADHD and non-ADHD groups, will participate in a laboratory-based study over 4 days within 1 month. They will participate in three counterbalanced experimental conditions: (i) PA with cognitive engagement, (ii) PA without cognitive engagement, and (iii) a cognitively engaging control. This phase will assess acute changes in brain function, academic performance, working memory, inhibitory control, and sustained attention. Phase II will involve 600 children aged 10–12, randomly assigned to either a video-based PA program or a control group (300 children per group) in an 8-week cluster RCT. This phase will also incorporate a qualitative approach to explore the implementation context through pre- and post-intervention semi-structured interviews with teachers and school staff, and questionnaires for students. The outcomes of interest in this phase will include working memory, cognitive flexibility, selective attention, and academic performance. For the cross-over study, we hypothesize that PA conditions will enhance the studied outcomes compared to the control condition. In the RCT, we anticipate that the 8-week active breaks program will result in significant improvements in the selected outcomes compared to the control group. This study is expected to make pioneering contributions by including novel variables and focusing on the ADHD population. Furthermore, if the cluster RCT proves effective, it could offer a practical and cost-effective resource for integrating active breaks into daily school routines.

Summary: Background: Pseudomonas aeruginosa is a major cause of hospital-acquired and chronic infections, characterised by an extraordinary capacity to develop antimicrobial resistance through the selection of chromosomal mutations, leading to treatment failure. Here, we designed and tested a hybridisation-based capture system for the enrichment of genes of interest before sequencing to monitor resistant populations genomics directly from clinical samples. Methods: A panel for enrichment before sequencing of close to 200 genes related to P. aeruginosa antimicrobial resistance, multilocus sequence typing, mutability or virulence was designed, synthesised (KAPA HyperCap, Roche) and initially validated in vitro using a multidrug-resistant ST175 isolate and representative isolates from major P. aeruginosa clades. In vivo testing included ventilator associated pneumonia by MDR P. aeruginosa in ICU (3–10 sequential samples from 3 patients) and chronic respiratory infection by hypermutable P. aeruginosa in cystic fibrosis (8 sequential samples from a single patient covering a 4-year period). Results from direct sequencing with the enrichment panel were compared with those of whole genome sequencing (WGS) and phenotypic profiling of 10 isolated colonies per sample. Findings: In vitro assays confirmed the selectivity of the enrichment panel and the correct identification of the vast mutational resistome of ST175, including specific mutations even when introduced in a 1:100 proportion. In vivo performance was at least equivalent to sequencing 10 colonies per sample, including the accurate identification of the sequence types and the basal and acquired mutational resistome. To note, specific resistance mutations, such as those in ampC leading to resistance to novel β-lactams, could be traced even at frequencies of 1%. Moreover, the coselection of mutator populations and antibiotic resistance mutations, predicted in theoretical and in vitro studies, was evidenced in vivo. Interpretation: This proof-of-concept study demonstrates that resistance genomics of P. aeruginosa can be analysed directly from clinical samples, determining not only a considerable reduction in turnaround time and cost from a diagnostics perspective, but also an unprecedented potency for accurate monitoring of in vivo population dynamics in bacterial infections. Funding: Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea—NextGenerationEU.

Abstract Early life conditions may influence the gut microbiome and contribute to health status in adulthood. We examined the impact of maternal obesity and/or obesogenic diet on the gut microbiome of mothers (at weaning) and their adult offspring, along with the effects of leptin supplementation during suckling. Three groups of rats were studied: control (C) dams, fed with standard diet (SD); western diet (WD) dams, fed with WD (a high‐fat, high‐sucrose diet) before gestation and during gestation and lactation; and reversion (REV) dams, fed as WD‐dams but with SD during lactation. Offspring were supplemented throughout suckling with leptin/vehicle and weaned on an SD. WD‐dams showed lower microbial diversity and an altered microbiome compared to C‐ and REV‐dams, widely normalized by diet improvement during lactation. WD‐ and REV‐offspring (males) displayed lower microbiome diversity and greater dominance compared to C‐offspring. Taxonomic group differences (Proteobacteria phylum and Bacteroides, Parasutterella, and Phocea genera) were observed in WD‐ and REV‐offspring. WD‐offspring, but not REV‐offspring, had a greater abundance of the phylum Firmicutes and Lachnospiraceae family and a lower abundance of the family Tannerellaceae compared to C‐offspring. Leptin supplementation led to decreased abundance of the phylum Actinobacteria (family Eggerthellaceae and genera Enterorhabdus and Adlercreutzia (females)), and the genera Lachnospiraceae UCG‐008 group, Roseburia and Limosilactobacillus, and increased abundance of the genus Dellaglioa, compared to vehicle‐treated groups. Therefore, maternal consumption of an obesogenic diet during the perinatal period results in microbiome changes in dams, alleviated by dietary improvement during lactation. Maternal conditions and leptin supplementation during suckling modestly influenced the microbiome in adulthood, which might partially contribute to the adverse/beneficial effects, respectively, of these conditions on programmed metabolic health.

Abstract Placental leptin may impact foetal development. Maternal overnutrition has been linked to increased plasma leptin levels and adverse effects on offspring, whereas choline, an essential nutrient for foetal development, has shown promise in mitigating some negative impacts of maternal obesity. Here, we investigate whether a maternal obesogenic diet alters foetal growth and leptin levels in the foetal stomach, amniotic fluid (AF), and placenta in late gestation and explore the potential modulating effects of maternal choline supplementation. Female rats were fed a control (CD) or a western diet (WD) four weeks before mating and during gestation, half of them supplemented with choline (pregnancy days 11–17). Leptin levels (in foetal stomach, AF, and placenta) and leptin gene expression (in placenta) were assessed on gestation days 20 and 21. At day 20, maternal WD feeding resulted in greater leptin levels in foetal stomach, placenta, and AF. The increased AF leptin levels were associated with a premature increase in foetal weight in both sexes. Maternal choline supplementation partially prevented these alterations, but effects differed in CD dams, causing increased AF leptin levels and greater weight in male foetuses at day 20. Maternal choline supplementation effectively mitigates premature foetal overgrowth induced by an obesogenic diet, potentially linked to increased AF leptin levels. Further research is needed to explore the sex-specific effects.

The main purpose of this paper is to investigate the impact of the thermal processing of natural fibers on the strength of what is considered fiber-reinforced concrete. Natural fibers extracted from palm trees and bamboo residues were collected and pyrolyzed. The investigation of the morphological alterations that occur during the pyrolysis of natural fibers at a temperature of 200°C showed the impact of the cementitious environment on this process. In addition, the mechanical characteristics of fiber-reinforced concrete were conducted on different dosages (1, 1.5, 2, and 5% wt.) of treated and untreated palm oil, date kernel, and bamboo fibers. The results demonstrated that the inclusion of fibers up to 1.5% wt. enhanced the concrete mixes mechanical properties, which included pyrolyzed fibers. Analyzes of the concrete microstructure revealed that the treated fibers were not damaged. The 1.5% wt. addition of fibers after pyrolysis process can effectively improve their adhesion to the matrix and reduce the width and number of cracks. The analysis of variance results for flexural strength indicated that all sources had no significant impact on the flexural strength of untreated or pyrolysis treated natural fiber reinforced concrete.

This narrative review aims to provide an overview of medical pleurodesis techniques, and their indications and potential adverse effects. Pleurodesis is a procedure performed with the aim of obliterating the pleural space. It has indications in the management of both malignant and benign pleural effusions and pneumothorax. Various nonsurgical techniques exist to perform pleurodesis. The scope of this work is to review the different nonsurgical techniques and their indications. This narrative review was performed checking scientific databases for medical literature, focusing especially on the data derived from randomised controlled trials. Pleurodesis is an effective method to manage pleural effusions and pneumothorax, and minimally invasive techniques are now frequently used with good results. Further research is needed to assess the efficacy of new treatments and the possibility of using different techniques in association.

Vestibular sensory epithelia contain type I and type II sensory hair cells (HCI and HCII). Recent studies have revealed molecular markers for the identification of these cells, but the precise composition of each vestibular epithelium (saccule, utricle, lateral crista, anterior crista, posterior crista) and their postnatal maturation have not been described in detail. Moreover, in vitro methods to study this maturation are not well developed. We obtained total HCI and HCII counts in adult rats and studied the maturation of the epithelia from birth (P0) to postnatal day 28 (P28). Adult vestibular epithelia hair cells were found to comprise ∼65% HCI expressing osteopontin and PMCA2, ∼30% HCII expressing calretinin, and ∼4% HCII expressing SOX2 but neither osteopontin nor calretinin. At birth, immature HCs express both osteopontin and calretinin. P28 epithelia showed an almost adult-like composition but still contained 1.3% of immature HCs. In addition, we obtained free-floating 3D cultures of the epithelia at P1, which formed a fluid-filled cyst, and studied their survival and maturation in vitro up to day 28 (28 DIV). These cultures showed good HC resiliency and maturation. Using an enriched medium for the initial 4 days, a HCI/calretinin+-HCII ratio close to the in vivo ratio was obtained. These cultures are suitable to study HC maturation and mature HCs in pharmacological, toxicological and molecular research.

Cell-free massive MIMO (CF-mMIMO) emerges as a pivotal technology in the landscape of beyond-5G and 6G wireless networks, addressing the ever-increasing demand for seamless connectivity and unprecedented data throughput. This paper undertakes a comprehensive exploration of scalable usercentric (UC) CF-mMIMO systems, focusing on critical aspects of downlink (DL) channel state information (CSI) acquisition and its intricate interactions with both distributed and centralized precoding strategies. The paper delves into the crucial role of DL CSI acquisition, particularly in scenarios of weak channel hardening arising from sparse subsets of access points (APs) serving specific mobile stations (MS) in UC strategies, and transmission over spatially correlated multiple keyhole Ricean fading channels. The main contributions of this research work include in-depth analyses of different detection schemes under varying precoding scenarios, offering valuable insights for practical deployment. The pivotal role of DL CSI acquisition in optimizing the performance of UC CF-mMIMO networks is fully assessed, dismissing the use of DL pilot-based detection approaches and advocating for either centralized precoding architectures with statistical CSI-based decoding strategies at the MSs or distributed precoding schemes with DL blind channel estimation-based decoders at the MSs.

Abstract The incorporation of waste materials into cementitious binders serves as a strategy to diminish waste volume and lower carbon emissions. This study presents an in-depth evaluation of calcium carbide residue and coal fly ash as alternative binders. The assessment of raw materials emphasized their chemical composition and potential for pozzolanic reactions. Based on these factors, the optimal ratio of Ca/(SiO2 + Al2O3) in the raw materials was determined to be 1.5. Therefore, this study was designed to vary the raw material composition with a CaO/(SiO2 + Al2O3) ratio ranging from 1.7 to 0.9. Upon investigating the effect of the raw material proportion on the compressive strength of pastes and mortars, the composition yielding the highest compressive strength was selected for its potential application as a stabilizer for loess soil. A mixture of calcium carbide residue and coal fly ash with a Ca/(SiO2 + Al2O3) ratio of 1.5 resulted in the highest compressive strength at long curing periods in both pastes and mortars. Mineralogical and microstructural analyses revealed several products, beyond those formed from the pozzolanic reactions, that occurred and enhanced the compressive strength of samples. The highest performing mixture of carbide residue and coal fly ash was then used to stabilize loess soil at 10–25 wt%. The unconfined compressive strength, along with mass and strength loss due to wetting and drying cycles, was also studied. It was observed that the unconfined compressive strength of the stabilized soils remained consistent after six wet-dry cycles but decreased after twelve cycles due to microcracks. The findings suggest that carefully designed mixtures based on the chemical interactions of calcium carbide residue and coal fly ash can offer a sustainable, efficient approach for soil stabilization, potentially revolutionizing construction practices.

This paper introduces a novel dynamic spectrum sharing (DSS) scheme designed for cell-free massive MIMO (CF-mMIMO) networks. The motivation behind this work arises from the urgent need to enhance spectrum utilization in modern wireless communication systems. Traditional spectrum allocation methods often struggle to meet the diverse spectrum demands of different wireless operators. The proposed approach addresses these challenges by enabling the spectrum provider (SP) to flexibly allocate and sell its spectrum resources, empowering wireless virtual operators to acquire bandwidth efficiently based on their specific needs. In our framework, each wireless operator is represented by a CF-mMIMO network, characterized by an average spectral efficiency metric that quantifies the potential value of additional spectrum acquisition. Leveraging a Stackelberg game formulation, our DSS policy achieves an equilibrium point that optimally allocates bandwidths to operators and determines corresponding prices. This approach not only enhances spectrum utilization but also fosters fair competition among operators. A key innovation of our work lies in the utilization of blockchain technology, where all spectrum transactions are managed through a smart contract. This ensures transparency, integrity, and auditability throughout the spectrum trading process. The novel protocol facilitates seamless information exchange, orchestrates the Stackelberg game dynamics, and delivers conclusive outcomes to both the SP and the CF-mMIMO operators.