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ABSTRACTThere is an ongoing burden of pneumococcal disease in children despite the use of pneumococcal conjugate vaccines (PCVs). This phase 3, open-label, single-arm, multisite, descriptive study was designed to evaluate the safety and immunogenicity of a 3 + 1 regimen of V114 (VAXNEUVANCE™), a 15-valent PCV, in South Korean infants and toddlers. Adverse events (AEs) were reported for 14 d following any vaccination, and throughout the study period for serious AEs. Serotype-specific immunoglobulin G (IgG) response rates (proportion of participants meeting an IgG threshold value of ≥0.35 μg/mL) and geometric mean concentrations (GMCs) for the 15 serotypes at 30 d postdose 3 (PD3) and at 30 d postdose 4 (PD4) were evaluated as endpoints. Healthy infants enrolled at 42–90 d after birth were vaccinated with V114 (N = 57). The most commonly reported AEs were those solicited in the trial. The majority of reported AEs were transient and of mild or moderate intensity. Few serious AEs were reported; none were vaccine related. No participants died nor discontinued the study vaccine because of an AE. V114 was immunogenic for all 15 serotypes contained in the vaccine, as assessed by IgG response rates at 30 d PD3 and IgG GMCs at 30 d PD3 and at 30 d PD4. V114 was well tolerated and immunogenic when administered as a 3 + 1 regimen in healthy South Korean infants and toddlers.

ABSTRACT Objective: To evaluate the role of being human immunodeficiency virus (HIV) positive for predicting the risk of recurrence in women with a cervical high grade squamous intraepithelial lesion (HSIL) diagnosis. Methods: Retrospective observational case-control study, comprising HIV positive (case) and HIV negative (control) women in a 1:4 ratio. Women assisted by the Erasto Gaertner Hospital, between 2009-2018, with cervical HSIL diagnosis, submitted to treatment by Loop electrosurgical excision procedure (LEEP), and with a minimum follow-up of 18 months, were included. The immunological status, number and time to recurrence were analyzed, with p

Voice preferences are an integral part of interpersonal interactions and shape how people connect with each other. While a large number of studies have investigated the mechanisms behind (speaking) voice attractiveness, very little research was dedicated to other types of vocalizations. In this Registered Report, we proposed to investigate voice preferences with an integrative approach. To this end, we used a newly recorded and validated stimulus set of contrasting vocalizations by 22 highly trained female singers speaking and singing the same material (in Brazilian Portuguese) in contrasting styles (sung as a lullaby, as a pop song or as an opera aria; and spoken aloud as if directed to an adult audience and as if directed to an infant). We asked 62 participants to rate these vocalizations in terms of how much they liked them; and we compared the amount of shared taste (that is, how much participants agreed in their preferences) across styles. We found highly idiosyncratic preferences across all styles. Our predictions concerning shared taste were not confirmed: although shared taste was higher for lullaby than for pop singing, it was unexpectedly higher for operatic than pop singing, and higher for infant-directed than adult-directed speech. Conversely, our prediction of limited consistency in average preferences for some singers across styles was confirmed, contradicting sexual selection-based ideas of singing and speaking as ‘backup’ signals of individual fitness. Our findings draw attention to the role of individual differences in voice preferences and highlight the need for a broader approach to understanding the underlying mechanisms of voice preferences. Stage 1 recommendation and review history: https://rr.peercommunityin.org/articles/rec?id=357. Stage 2 recommendation and review history: https://rr.peercommunityin.org/articles/rec?id=802.

This paper explores the pivotal transformations in postwar Portuguese architecture, tracing the oscillation between traditional styles and modernist influences from 1923 to 1953. During a period marked by ideological conflict and cultural reassessment, Portuguese architecture experienced a profound metamorphosis, mirroring the nation’s struggle between conservative nationalism and the burgeoning force of modernity. This study delves into the role of key figures such as Fernando Távora and the influence of international movements, notably from Italy and the CIAM, in shaping a new architectural ethos that navigated between heritage and innovation. Through a meticulous examination of architectural projects, periodicals (Arquitectura, Arquitectura portuguesa, Domus, Casabella), and ideological discourses, the paper illuminates how architects negotiated with political and cultural currents to forge the architectural language. A form characterized by its duality, attempted to reconcile the traditionalist values imposed by the Estado Novo regime with a modernist vision inspired by global trends. The transition from the “Português Suave” aesthetic to a more resistant form of modernism, underscored by a critique of superficial stylistic nationalism, encapsulates a broader narrative of resistance and adaptation. The findings underscore the importance of interdisciplinary approaches in understanding architectural evolution, revealing how shifts in political ideology, cultural identity, and international influences converge in the realm of architecture. The paper contributes to a deeper understanding on how the Portuguese architecture context surrounding Fernando Távora’s formative years not only reflected but also contested and reshaped the socio-political landscape of mid-20th century Portugal.

Summary: Heterozygous mutations in SLC40A1, encoding a multi-pass membrane protein of the major facilitator superfamily known as ferroportin 1 (FPN1), are responsible for two distinct hereditary iron-overload diseases: ferroportin disease, which is associated with reduced FPN1 activity (i.e., decrease in cellular iron export), and SLC40A1-related hemochromatosis, which is associated with abnormally high FPN1 activity (i.e., resistance to hepcidin). Here, we report three SLC40A1 missense variants with opposite functional consequences. In cultured cells, the p.Arg40Gln and p.Ser47Phe substitutions partially reduced the ability of FPN1 to export iron and also partially reduced its sensitivity to hepcidin. The p.Ala350Val substitution had more profound effects, resulting in low FPN1 iron egress and weak FPN1/hepcidin interaction. Structural analyses helped to differentiate the first two substitutions, which are predicted to cause local instabilities, and the third, which is thought to prevent critical rigid-body movements that are essential to the iron transport cycle. The phenotypic traits observed in a total of 12 affected individuals are highly suggestive of ferroportin disease. Our findings dismantle the classical dualism of FPN1 loss versus gain of function, highlight some specific and unexpected functions of FPN1 transmembrane helices in the molecular mechanism of iron export and its regulation by hepcidin, and extend the spectrum of rare genetic variants that may cause ferroportin disease.

Background: Urinary tract infections (UTIs) are the most common bacterial infections in children. The high variability in pathogen susceptibility rates leads to the lack of clear guidelines for empiric and targeted therapies. In this view, local microbiological surveillance and locally adapted stewardship interventions need to be implemented. Objective: The study aims to describe the results of a pediatric antimicrobial stewardship program on antibiotic prescriptions for UTIs over 8 years in a pediatric general ward of a tertiary center. Design: This quasi-experimental study was conducted between 2015 and 2022, with two different implementations, one in 2018 and one in 2021. Methods: Demographic, clinical, microbiological, and therapeutic data were retrieved from the electronic clinical records of included patients. The primary outcomes were adherence to local guidelines for empiric therapies and the adequacy of targeted therapy. Secondary outcomes were evaluating antibiotic prescription patterns stratified by antibiotics during hospital stay and at discharge, and assessing the microbiological characteristics of UTI episodes. Results: During the study period, 7038 patients were admitted to the pediatric acute care unit (PACU), and 264 (3.7%) were included in this study. Adherence to local guidelines was highest immediately after the interventions, and it slightly decreased thereafter. Use of cephalosporins remained high throughout the 8 years but the changing microbiological scenario observed led to changing recommendations within the study period. An increase in E. coli strains resistant to co-amoxiclav was observed in the last years. Oral second-line agent consumption remained high but was adequate considering the prevalence of resistant bacteria. Conclusion: The variability of antimicrobial consumption reflects the changing resistance patterns for UTIs pathogens, underlying the importance of locally adapted, persevering antimicrobial stewardship interventions.

Epstein-Barr virus (EBV) uses latency programs to colonize the memory B-cell reservoir, and each program is associated with human malignancies. However, knowledge remains incomplete of epigenetic mechanisms that maintain the highly restricted latency I program, present in memory and Burkitt lymphoma cells, in which EBNA1 is the only EBV-encoded protein expressed. Given increasing appreciation that higher order chromatin architecture is an important determinant of viral and host gene expression, we investigated roles of Wings Apart-Like Protein Homolog (WAPL), a host factor that unloads cohesin to control DNA loop size and that was discovered as an EBNA2-associated protein. WAPL knockout (KO) in Burkitt cells de-repressed LMP1 and LMP2A expression, but not other EBV oncogenes, to yield a viral program reminiscent of EBV latency II, which is rarely observed in B-cells. WAPL KO also increased LMP1/2A levels in latency III lymphoblastoid cells. WAPL KO altered EBV genome architecture, triggering formation of DNA loops between the LMP promoter region and the EBV origins of lytic replication (oriLyt). Hi-C analysis further demonstrated that WAPL KO reprogrammed EBV genomic DNA looping. LMP1 and LMP2A de-repression correlated with decreased histone repressive marks at their promoters. We propose that EBV coopts WAPL to negatively regulate latent membrane protein expression to maintain Burkitt latency I.

Several coronaviruses infect humans, with three, including the SARS-CoV2, causing diseases. While coronaviruses are especially prone to induce pandemics, we know little about their evolutionary history, host-to-host transmissions, and biogeography. One of the difficulties lies in dating the origination of the family, a particularly challenging task for RNA viruses in general. Previous cophylogenetic tests of virus-host associations, including in the Coronaviridae family, have suggested a virus-host codiversification history stretching many millions of years. Here, we establish a framework for robustly testing scenarios of ancient origination and codiversification versus recent origination and diversification by host switches. Applied to coronaviruses and their mammalian hosts, our results support a scenario of recent origination of coronaviruses in bats and diversification by host switches, with preferential host switches within mammalian orders. Hotspots of coronavirus diversity, concentrated in East Asia and Europe, are consistent with this scenario of relatively recent origination and localized host switches. Spillovers from bats to other species are rare, but have the highest probability to be towards humans than to any other mammal species, implicating humans as the evolutionary intermediate host. The high host-switching rates within orders, as well as between humans, domesticated mammals, and non-flying wild mammals, indicates the potential for rapid additional spreading of coronaviruses across the world. Our results suggest that the evolutionary history of extant mammalian coronaviruses is recent, and that cases of long-term virus–host codiversification have been largely over-estimated.

French Guiana, located in the Guiana Shield, is a natural reservoir for many zoonotic pathogens that are of considerable medical or veterinary importance. Until now, there has been limited data available on the description of parasites circulating in this area, especially on protozoan belonging to the phylum Apicomplexa; conversely, the neighbouring countries describe a high parasitic prevalence in animals and humans. Epidemiological surveillance is necessary, as new potentially virulent strains may emerge from these forest ecosystems, such as Amazonian toxoplasmosis. However, there is no standard tool for detecting protozoa in wildlife. In this study, we developed Meat-Borne-Parasite, a high-throughput meta-barcoding workflow for detecting Apicomplexa based on the Oxford Nanopore Technologies sequencing platform using the 18S gene of 14 Apicomplexa positive samples collected in French Guiana. Sequencing reads were then analysed with MetONTIIME pipeline. Thanks to a scoring rule, we were able to classify 10 samples out of 14 as Apicomplexa positive and reveal the presence of co-carriages. The same samples were also sequenced with the Illumina platform for validation purposes. For samples identified as Apicomplexa positive by both platforms, a strong positive correlation at up to the genus level was reported. Overall, the presented workflow represents a reliable method for Apicomplexa detection, which may pave the way for more comprehensive biomonitoring of zoonotic pathogens.

Background and Clinical Significance: Biliary tract injuries are a recognized complication of laparoscopic cholecystectomy. Early diagnosis and prompt management are crucial to minimize complications such as bile leaks, strictures, and fistula formation. This case report highlights the use of a biodegradable biliary stent in managing a complex biliary injury and discusses the impact of delayed diagnosis on treatment outcomes. Case Presentation: We present the case of a 30-year-old male who sustained a Strasberg E2 biliary tract injury during a laparoscopic cholecystectomy. Initially misdiagnosed, the injury was only recognized on the fourth postoperative day. The patient underwent a Roux-en-Y hepaticojejunostomy and subsequently developed a postoperative biliary fistula, which was managed with percutaneous drainage. A biodegradable biliary stent was later placed to address a stricture and minimize the need for future interventions. One year later, the patient presented with symptoms of cholangitis, and radiological findings revealed a narrowing of the biliary lumen. The stricture was resolved and an endoscopic gastrojejunal shunt was placed to prevent further complications. The patient is currently in good condition with no signs of further complications. Conclusions: This case emphasizes the importance of early diagnosis in managing biliary tract injuries and highlights the potential of biodegradable stents to reduce the need for repeat interventions. Despite a delayed diagnosis necessitating complex surgical procedures, the use of a biodegradable stent proved effective in managing postoperative complications. Further studies are needed to evaluate the long-term efficacy of biodegradable stents in similar clinical scenarios.

IntroductionExcessive daytime sleepiness (EDS) is a common and debilitating symptom in both forms of myotonic dystrophy (DM), significantly impacting patients’ quality of life. The review focuses on the purpose of examining the current understanding of EDS in these conditions, the difficulty in correctly accessing it, the recent findings related to its etiology and prevalence, and a summary of potential therapeutic implications.MethodsWe conducted a comprehensive search through PubMed, selecting studies that provided significant insights into the mechanisms, prevalence, and management of EDS in DM1 and DM2.Results and discussionEDS is highly prevalent in both DM1 and DM2. Polysomnographic studies have revealed prominent dysregulation of REM sleep in DM1, suggesting a possible narcoleptic-like phenotype and alterations in NREM sleep that contributes to daytime sleepiness. Other factors have been proposed to explain EDS in DM1, including dysregulation of the sleep-wake circadian rhythm through nocturnal actigraphy analysis. The central origin of EDS is increasingly delineated supported by serotonin and orexin pathways dysfunction, and recent neuroradiological findings showing that in DM1 hippocampus volume was positively correlated with self-reported fatigue and somnolence. Sleep-disordered breathing and respiratory dysfunctions are prevalent in DM, their direct correlation with EDS remains complex and inconclusive, but respiratory evaluation should be recommended if obstructive sleep apneas or respiratory muscle dysfunctions are suspected. Drug interventions, such as modafinil and mexiletine, have shown promise in managing excessive daytime sleepiness and reducing myotonia without significant cardiac conduction effects. Enhancing EDS management in myotonic dystrophy is key to improving overall patient well-being.

Background: Exercise is recommended for patients with chronic heart failure (CHF) and its intensity is usually set as a percentage of the maximal work rate (MWR) during cardiopulmonary exercise testing (CPX) or a symptom-limited incremental test (SLIT). As these tests are not always available in cardiac rehabilitation due to logistic/cost constraints, we aimed to develop a predictive model to estimate MWR at CPX (estMWR@CPX) in CHF patients using anthropometric and clinical measures and the 6-min walk test (6 MWT), the most widely used exercise field test. Methods: This is a multicentre cross-sectional retrospective study in a cardiac rehabilitation setting. Six hundred patients with HF in New York Heart Association (NYHA) functional class I-III underwent both CPX and 6 MWT and, through multivariable linear regression analysis, we defined several predictive models to define estMWR@CPX. Results: The best model included 6 MWT, sex, age, weight, NYHA class, left ventricular ejection fraction (LVEF), smoking status and chronic obstructive pulmonary disease COPD (adjusted R2 = 0.55; 95% LoA −39 to 33 W). When LVEF was excluded as a predictor, the resulting model performed only slightly worse (adjusted R2 = 0.54; 95% LoA −42 to 34 W). Only in 34% of cases was the percentage difference between estMWR@CPX and real MWR@CPX

Regulation coefficients assessment in a particle accelerator power conversion system depends on the topology, the magnet and the desired transient response. The series/parallel combination of a generic power converter (a brick) to develop a larger one (e.g., the SIRIUS power converter family developed at CERN) allows to feed several magnets with different parameters. Then, such standardization allows to develop a control platform and associated regulation system that is common to all the possible configurations. Regardless of the clear flexibility, the commissioning of these converters faces some drawbacks, like the large amount of coefficient sets and the tuning performed for different workers: this leads to certain inconsistency and spread in the transient responses obtained, which is coherent with the inherent subjectivity of the adopted approach. In this work, a methodology for automatic identification of regulator coefficients is developed. From the definition of a desired time transient response, the method uses the response to a step voltage test to evaluate some figures of merit and the particle swarm technique to change the coefficients accordingly to the error obtained. A MATLAB-based app to implement the method in a user-friendly environment is developed. Experimental results based on a $400\operatorname{kW}$ prototype validate the proposal.

Introduction. In the last decade, the significant expenditure and consumption increase of vitamin D in Italy led some regions to adopt strategies to improve prescribing appropriateness and contain expenditure. Materials and methods. Using the statistical analysis method of interrupted time series for consumption and expenditure of cholecalciferol, different types of interventions adopted in four Italian regions and their efficacy were evaluated. Results. Molise achieved the best results by adopting a health professionals’ education program in addition to a prescriber-sanction system. Emilia-Romagna also opted for a medical education strategy, but the results were less relevant due to the lack of penalties. Lazio obtained a slowdown in consumption growth by targeting on the utilization of lower-cost per defined daily dose (DDD) packs and adopting a therapeutic plan. Sardinia showed a decrease in expenditure by adopting a target threshold of lower-cost formulation. Conclusion. The reimbursement of the lowest-cost packs within the National Health Service (NHS) undoubtedly influences spending trend, but it does not solve prescriptive inappropriateness.

Background: Skin and soft-tissue infections (SSTIs) are common infectious syndromes in children. Overusing broad-spectrum antibiotics has contributed to rising antibiotic resistance, complicating treatment outcomes. To address this issue, antimicrobial stewardship programs (ASPs) have been implemented to optimize antibiotic use. This study evaluated the impact of a multifaceted ASP on antibiotic prescribing practices for SSTIs in a pediatric acute care setting over eight years. Methods: We conducted a quasi-experimental study at the Pediatric Acute Care Unit of the Padua University Hospital, including children admitted with SSTIs from October 2014 to September 2022, to evaluate the impact of a multifaceted ASP implemented in October 2015. The study was divided into three periods: pre-implementation (October 2014–September 2015), post-implementation (October 2015–March 2020), and COVID-19 (April 2020–August 2022). Data on antibiotic prescriptions and microbiological results were collected and analyzed. Results: The implementation of the ASP led to a significant reduction in the use of broad-spectrum antibiotics, particularly third-generation cephalosporins (from 40.4% to 9.8%) and glycopeptides (from 21.1% to 1.6%). There was a notable increase in the prescription of Access antibiotics, from 30% in the pre-implementation to over 60% in the post-implementation and 80% during COVID-19. No increase in the hospital length of stay was observed. Microbiological results showed no significant changes in bacterial profiles over time. Conclusions: The use of the ASP effectively improved antibiotic prescribing practices, reducing reliance on broad-spectrum antibiotics even during the COVID-19 pandemic. These findings highlight the value of ongoing stewardship efforts and suggest the need for similar programs in ambulatory settings to further address antibiotic resistance.