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Proton pump inhibitors (PPIs) are among the most commonly and inappropriately prescribed drugs by general practitioners (GPs), resulting in increased risk of adverse outcomes for patients and in avoidable costs for Italy's National Health Service (NHS). This study aims to assess the effectiveness of a low-cost and easily implementable informative intervention directed at GPs to enhance the appropriate prescription of PPIs. The LAPTOP-PPI study is a pragmatic, cluster-randomized controlled trial designed to improve the appropriateness of PPI prescriptions among community-dwelling individuals aged ≥65 years. In June 2021, GPs in the Local Health Units (LHUs) of Bergamo (Northern Italy) and Caserta (Southern Italy) were randomly allocated to either an intervention group (summary reports on prescribing habits, scientific documents on the Italian Medicine Agency's therapeutic indications, strategies for PPI de-prescribing, along with educational materials for patients), and a control group (standard practice). PPI appropriateness was assessed through an algorithm specifically designed and based on NHS prescription appropriateness and reimbursement criteria. Intervention efficacy was evaluated by comparing data from the baseline period (July 1 to 31 December 2019) with those from the follow-up period (July 1 to 31 December 2021), 6 months after randomization. The analysis was performed on the intention-to-treat principle and according to GP level. To estimate the effectiveness of the intervention, we used a difference-in-differences (DID) approach. Overall, 942 GPs (540 from Bergamo and 402 from Caserta LHUs) were included in the analysis. At baseline, 171,978 patients aged ≥65 received drug prescriptions for acid-related diseases and were assessable for evaluation of appropriateness. At follow-up, this number was 137,699. The overall inappropriateness rate at baseline among GPs included in the analysis was 57.4% (std.dev. 8.4%) in the intervention arm and 57.6% (std.dev. 8.8%) in the control arm; 6 months after the intervention delivery, they were 59.2% (std.dev. 8.0%) and 58.5% (std.dev. 7.3%), respectively. Given their widespread use, improving the prescription quality of PPIs is a major concern. Educational interventions for GPs and patients are routine strategies to address inappropriateness, but they appear to be insufficient for independently improving prescribing practice, especially in a critical situation such as the post-pandemic period.

Background/Objectives: Childhood obesity represents a pressing global health challenge, demanding coordinated, long-term strategies. Schools and families are pivotal environments for shaping children’s lifestyle behaviors. The LIVELY project aimed to assess overweight/obesity prevalence and associated factors in primary school children, and to implement a multidimensional educational intervention promoting healthy, sustainable lifestyles. Methods: This single-arm study was conducted from October 2023 to October 2024 in a primary school in Milan. The intervention included age and culturally tailored lessons, games, and activities. Anthropometric measures, dietary adherence, and lifestyle habits were assessed before and after the intervention. Satisfaction surveys were administered to children, families, and teachers. Results: The project involved 227 children across 14 classes (mean age 8.9, SD 1.2 years). The prevalence of overweight/obesity was 23.4%. Adherence to the Mediterranean Diet was moderate, limited by low intake of vegetables, nuts, and dairy. Physical activity was low, screen time excessive, and sleep insufficient. No statistically significant improvements in anthropometrics or diet adherence were observed post-intervention, but positive trends emerged for physical activity, sleep, and hydration. Over half of the children passed the nutritional knowledge test. Despite these challenges, high satisfaction levels have been shared by children, parents, and teachers. Conclusions: The limited duration of the intervention and challenges engaging families in a low socio-economic context may have constrained the impact of the program, and caution is advised in generalizing the findings. The LIVELY project highlights the complexity of tackling childhood obesity in multicultural settings and emphasizes the need for longer, continuous, and culturally tailored programs that actively involve families to promote sustainable healthy behaviors.

Formation of primed single‐stranded DNA at stalled replication forks triggers activation of the replication checkpoint signalling cascade resulting in the ATR‐mediated phosphorylation of the Chk1 protein kinase, thus preventing genomic instability. By using siRNA‐mediated depletion in human cells and immunodepletion and reconstitution experiments in Xenopus egg extracts, we report that the Y‐family translesion (TLS) DNA polymerase kappa (Pol κ) contributes to the replication checkpoint response and is required for recovery after replication stress. We found that Pol κ is implicated in the synthesis of short DNA intermediates at stalled forks, facilitating the recruitment of the 9‐1‐1 checkpoint clamp. Furthermore, we show that Pol κ interacts with the Rad9 subunit of the 9‐1‐1 complex. Finally, we show that this novel checkpoint function of Pol κ is required for the maintenance of genomic stability and cell proliferation in unstressed human cells. A vertebrate translesion synthesis DNA polymerase broadly contributes to checkpoint‐activating primer synthesis at stalled replication forks, a role previously ascribed only to replicative polymerases.

Formation of primed single-stranded DNA at stalled replication forks triggers activation of the replication checkpoint signalling cascade resulting in the ATR-mediated phosphorylation of the Chk1 protein kinase, thus preventing genomic instability. By using siRNA-mediated depletion in human cells and immunodepletion and reconstitution experiments in Xenopus egg extracts, we report that the Y-family translesion (TLS) DNA polymerase kappa (Pol κ) contributes to the replication checkpoint response and is required for recovery after replication stress. We found that Pol κ is implicated in the synthesis of short DNA intermediates at stalled forks, facilitating the recruitment of the 9-1-1 checkpoint clamp. Furthermore, we show that Pol κ interacts with the Rad9 subunit of the 9-1-1 complex. Finally, we show that this novel checkpoint function of Pol κ is required for the maintenance of genomic stability and cell proliferation in unstressed human cells. [PUBLICATION ABSTRACT]

ABSTRACT DNA polymerase kappa (Pol κ) has been well documented thus far for its specialized DNA synthesis activity during translesion replication, progression of replication forks through regions difficult to replicate and replication checkpoint at stalled forks. Here we unveiled an unexpected role for Pol κ in controlling the stability and abundance of Chk1, the major mediator of the replication checkpoint. We found that loss of Pol κ decreased the Chk1 protein level in the nucleus of four human cell lines. Pol κ and not the other Y‐family polymerase members is required to maintain the Chk1 protein pool all along the cell cycle. We showed that Pol κ depletion affected the protein stability of Chk1 and protected it from proteasome degradation and the replication recovery defects observed in Pol κ-depleted cells could be overcome by the re-expression of Chk1. Importantly, this new function of Pol κ does not require its catalytic activity, revealing that in addition to its known roles in the replication process, Pol κ can contribute to the maintenance of genome stability independently of its DNA synthesis activity. Competing Interest Statement The authors have declared no competing interest.

A bstract We present results from a state-of-the-art fit of electroweak precision observables and Higgs-boson signal-strength measurements performed using 7 and 8 TeV data from the Large Hadron Collider. Based on the HEPfit package, our study updates the traditional fit of electroweak precision observables and extends it to include Higgs-boson measurements. As a result we obtain constraints on new physics corrections to both electroweak observables and Higgs-boson couplings. We present the projected accuracy of the fit taking into account the expected sensitivities at future colliders.

Much hope for finding new physics phenomena at microscopic scale relies on the observations obtained from High Energy Physics experiments, like the ones performed at the Large Hadron Collider (LHC). However, current experiments do not indicate clear signs of new physics that could guide the development of additional Beyond Standard Model (BSM) theories. Identifying signatures of new physics out of the enormous amount of data produced at the LHC falls into the class of anomaly detection and constitutes one of the greatest computational challenges. In this article, we propose a novel strategy to perform anomaly detection in a supervised learning setting, based on the artificial creation of anomalies through a random process. For the resulting supervised learning problem, we successfully apply classical and quantum support vector classifiers (CSVC and QSVC respectively) to identify the artificial anomalies among the SM events. Even more promising, we find that employing an SVC trained to identify the artificial anomalies, it is possible to identify realistic BSM events with high accuracy. In parallel, we also explore the potential of quantum algorithms for improving the classification accuracy and provide plausible conditions for the best exploitation of this novel computational paradigm.

Background Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive respiratory rare disease characterized by an irreversible loss of lung function, with unknown etiology and poor prognosis. Methods A population registry-based study was conducted to provide estimates of prevalence, incidence and survival of IPF. The study included all cases diagnosed with IPF in the years 2000–2022 and residing in Tuscany, Italy. Prevalence as of December 31, 2022, was calculated by sex and age class. Incidence was calculated across the period 2018–2022. Survival at 1, 5 and 10 years from diagnosis with 95% confidence intervals (CI) was estimated by sex and age class using the Kaplan-Meyer method. The independent effect of sex and age at diagnosis on survival was estimated by Cox proportional hazard model. Results A total of 1,388 subjects with IPF were diagnosed during the study period. The prevalence as of 31st December 2022 was 21.5 cases (95%CI: 20.0–23.0) per 100,000 inhabitants, with a significantly higher frequency in men and in 70–79 years age group ( p  < 0.0001). The average annual incidence was 4.6 cases per 100,000 inhabitants, with significantly higher incident cases among males ( p  < 0.0001). Survival at 1, 5 and 10 years from diagnosis was 91.3%, 51.4% and 22.2%, respectively. Women exhibited a longer survival than men (34.8% vs. 17.3% at 10 years), while patients under 70 had the highest survival rate at 58.2% (95% CI: 52.5–63.4) at five years. Cox regression model confirmed a higher risk of mortality for men (adjusted Hazard Ratio – adjHR = 1.52, 95%CI: 1.25–1.84, p  < 0.0001) and with age at diagnosis (adjHR = 1.04, 95%CI: 1.03–1.05, p  < 0.0001). Conclusions The higher prevalence and incidence rates of IPF among men, as indicated by this population registry-based study, align with recent data reported in Europe. Furthermore, IPF is consistently identified as a disease with a poor prognosis, especially in male patients. Therefore, early and accurate diagnosis, coupled with timely management, is essential to improve the care and treatment outcomes for these patients.

PurposeSocial life cycle assessment (S-LCA) applications have been growing during the last years. Most of the scientific articles published so far have addressed the applicability of S-LCA, focusing on selecting suitable indicators, and only recently, the developments in the area of impact pathway are increasing. However, a critical analysis of how to set an S-LCA study, in particular the goal and scope and inventory phase, is missing. This article critically analyses the most important elements affecting the goal and scope and inventory phase of S-LCA, with a focus on the automotive sector, with the ultimate goal of developing a structured approach to guide practitioners in the critical application of S-LCA.MethodsThe literature review covers 67 publications from 2006 to 2015, including all the case studies published so far, to the best knowledge of the authors, in several sectors and the automotive one. The reviewed works have been structured along the key elements affecting the goal and scope and inventory phases of the S-LCA.Results and discussionThe methodological and practical issues affecting S-LCA have been organized into a conceptual map, in which all the elements are sequentially placed. This sequence is an orderly procedure consisting of several nodes representing crucial points where a decision needs to be taken or a further reflection is necessary. The case studies of the automotive sector and the corporate-related documents have been used also for the discussion of the conceptual map nodes to identify which aspects are already covered by the literature and which ones need further research.ConclusionsFacing the inventory phase of S-LCA needs also to set specific elements of the goal and scope phase which are fundamental for approaching coherently the product system at hand and for supporting the selection of stakeholders, indicators, and data. Moreover, in order to foster S-LCA applications and make it a robust decision-support tool, the authors suggest to re-define its framework and approach according to the organizational perspective, as laid down in the recent Organisation Environmental Footprint and Organizational LCA. This implies that social aspects will be evaluated both in relation to the organization behavior and to the basket of products, thus reconciling the need to keep together the conduct-of-a-company perspective, typical of social evaluations, and the product-oriented approach, inherent to the life cycle and in particular to the functional unit concept.

Background Congenital anomalies are the leading cause of perinatal, neonatal and infant mortality in developed countries. Large long-term follow-up studies investigating survival beyond the first year of life in children with rare congenital anomalies are costly and sufficiently large standardized cohorts are difficult to obtain due to the rarity of some anomalies. This study aimed to investigate the survival up to 10 years of age of children born with a rare structural congenital anomaly in the period 1995–2014 in Western Europe. Methods Live births from thirteen EUROCAT (European network for the epidemiological surveillance of congenital anomalies) population-based registries were linked to mortality records. Survival for 12,685 live births with one of the 31 investigated rare structural congenital anomalies (CAs) was estimated at 1 week, 4 weeks and 1, 5 and 10 years of age within each registry and combined across Europe using random effects meta-analyses. Differences between registries were evaluated for the eight rare CAs with at least 500 live births. Results Amongst the investigated CAs, arhinencephaly/holoprosencephaly had the lowest survival at all ages (58.1%, 95% Confidence Interval (CI): 44.3–76.2% at 1 week; 47.4%, CI: 36.4–61.6% at 1 year; 35.6%, CI: 22.2–56.9% at 10 years). Overall, children with rare CAs of the digestive system had the highest survival (> 95% at 1 week, > 84% at 10 years). Most deaths occurred within the first four weeks of life, resulting in a 10-year survival conditional on surviving 4 weeks of over 95% for 17 out of 31 rare CAs. A moderate variability in survival between participating registries was observed for the eight selected rare CAs. Conclusions Pooling standardised data across 13 European CA registries and the linkage to mortality data enabled reliable survival estimates to be obtained at five ages up to ten years. Such estimates are useful for clinical practice and parental counselling.