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Abstract Particle-Based (PB) simulations, including Molecular Dynamics (MD), provide access to system observables that are not easily available experimentally. However, in most cases, PB data needs to be processed after a simulation to extract these observables. One of the main challenges in post-processing PB simulations is managing the large amounts of data typically generated without incurring memory or computational capacity limitations. In this work, we introduce the post-processing tool: MDSuite. This software, developed in Python, combines state-of-the-art computing technologies such as TensorFlow, with modern data management tools such as HDF5 and SQL for a fast, scalable, and accurate PB data processing engine. This package, built around the principles of FAIR data, provides a memory safe, parallelized, and GPU accelerated environment for the analysis of particle simulations. The software currently offers 17 calculators for the computation of properties including diffusion coefficients, thermal conductivity, viscosity, radial distribution functions, coordination numbers, and more. Further, the object-oriented framework allows for the rapid implementation of new calculators or file-readers for different simulation software. The Python front-end provides a familiar interface for many users in the scientific community and a mild learning curve for the inexperienced. Future developments will include the introduction of more analysis associated with ab-initio methods, colloidal/macroscopic particle methods, and extension to experimental data.

Abstract Background The real impact of the degree of association (DoA) between endpoint components of a composite endpoint (CE) on sample size requirement (SSR) has not been explored. We estimate the impact of the DoA between death and acute myocardial infarction (AMI) on SSR of trials using use the CE of major adverse cardiac events (MACE). Methods A systematic review and quantitative synthesis of trials that include MACE as the primary outcome through search strategies in MEDLINE and EMBASE electronic databases. We limited to articles published in journals indexed in the first quartile of the Cardiac & Cardiovascular Systems category (Journal Citation Reports, 2015–2020). The authors were contacted to estimate the DoA between death and AMI using joint probability and correlation. We analyzed the SSR variation using the DoA estimated from RCTs. Results Sixty-three of 134 publications that reported event rates and the therapy effect in all component endpoints were included in the quantitative synthesis. The most frequent combination was death, AMI, and revascularization (n = 20; 31.8%). The correlation between death and AMI, estimated from 5 trials¸ oscillated between − 0.02 and 0.31. SSR varied from 14,602 in the scenario with the strongest correlation to 12,259 in the scenario with the weakest correlation; the relative impact was 16%. Conclusions The DoA between death and AMI is highly variable and may lead to a considerable SSR variation in a trial including MACE.

During May-June 2022, after an alert notification initiated by the United Kingdom (1,2), >4,500 monkeypox cases had been confirmed worldwide, mainly in the European region (3-6). Chains of transmission without [...]

The purpose of this study was to analyse the perceived usefulness of a set of Information and Communication Technologies (ICT) applied in a virtual learning environment (VLE) in a distance education model. We analysed whether the numerical and technological preferences of the students could explain the perceived usefulness related to the ICT applied to teaching. We also tested whether the work experience of the students can modify the perceived usefulness. Diverse ICT were applied to the teaching of accounting in undergraduate courses, in a distance education model in the European Higher Education Area (EHEA). The research had an experimentation phase to implement the ICT teaching tools, one of data collection and another for the data analysis. The perceived usefulness of the ICT was measured through a questionnaire with evaluation using a Likert scale. The evaluations given by the students allowed modelling each ICT according to the variables of numerical and technological skills, including work experience as a dichotomous variable. The results of this research suggest that the perceived usefulness of the ICT is, in part, explained by numerical and technological skills. Furthermore, there are indications that work experience can diminish the perceived usefulness for a set of teaching ICT.

ABSTRACT The scale-up of hepatitis C virus (HCV) diagnosis and treatment requires affordable and simple tools to improve access to care, especially in low- and middle-income settings with limited infrastructure or high-risk populations. Dried blood and plasma samples (DBS and DPS) are useful alternative for hepatitis C detection in settings lacking adequate infrastructure. We evaluated the performance of DBS and DPS vs plasma in a point-of-care HCV RNA quantitative assay (Xpert HCV Viral Load-Cepheid), and compared HCV core antigen (HCVcAg) detection by the Architect HCV core antigen assay (Abbott) in DBS vs serum. The dried samples were stored at room temperature for different storage times to reproduce the time from sampling to testing in settings with centralized diagnosis or when testing mobile populations. HCV RNA quantification in DBS and DPS presented 100% sensitivity and specificity and a high correlation for up to 3 months of storage. HCV viremia showed a mean decrease of 0.5 log10 IU/mL (DBS) and 0.3 log10 IU/mL (DPS) for storage times up to 1 month. Architect HCVcAg detection presented high sensitivity/specificity (96%/100%) in DBS tested immediately after sampling, decreasing to 86% sensitivity after 7 days of storage. However, sensitivity increased when an optimized cut-off was applied for each storage time. We conclude that DBS and DPS are suitable samples for HCV RNA detection and quantification, being DPS more reliable for shorter storage times. DBS can be also used for HCVcAg qualitative detection and the sensitivity can be increased when adjusting the cut-off values. IMPORTANCE Hepatitis C infection remains a global burden despite the effectiveness of antivirals. In the WHO roadmap to accomplish HCV elimination by 2030, HCV diagnosis is one of the main targets. However, identifying patients in resource-limited settings and high-risk populations with limited access to healthcare remains a challenge and requires innovative approaches that allow decentralized testing. The significance of our research is in verifying the good performance of dried samples for HCV diagnosis using two different diagnostics assays and considering the effect of room temperature storage in this sample format. We confirmed dried samples are an interesting alternative for HCV screening and reflex testing in resource-limited settings or high-risk populations.

Vietnam’s economy will be the fastest-growing in 2023 and 2024 compared to ASEAN-5 countries. Since the country is following a development pathway, it is in a position to bet on a Circular Economy (CE), which is a widespread phenomenon for Sustainable Development. This study identifies major environmental challenges and remarks on the evolution of regulations and notable actions in the CE direction. For instance, emphasizes the approximately 4,000 Recycling Craft Villages that poorly implement a CE, focusing on Da Hoi. Finally, this article aims to identify challenges and opportunities, provide recommendations, and portray the future of circularity. Both desk and field research was conducted, including interviews and event attendance. Three principal conclusions are depicted; the limitations in the waste value chain of Recycling Craft Villages, the necessity to minimize air pollution through circularity, and budgetary restrictions are noted as continual hurdles to moving toward circularity. This article will interest policymakers, Vietnamese and international businesses, and academics.

Gait impairments have been found in women with fibromyalgia, reducing the physical activity possibilities in this population and leading to a negative correlation with fibromyalgia impact. The aim of this study was to analyze the individual and independent associations of moderate-to-vigorous physical activity (MVPA), sedentary time, fat percentage, and physical fitness with gait parameters in women with fibromyalgia. A total of 84 women with fibromyalgia were included. MVPA and sedentary time were assessed with accelerometry, fat percentage with bioimpedance analysis, and physical fitness with field-based fitness tests. Gait was assessed during a “6 min walk test” and categorized in velocity, cadence, step length, step cycle duration, unipedal stance phase, and bipedal stance phase. Individual relationships were analyzed by partial correlations and independent relationships by linear regressions, adjusting by age and height. MVPA, sedentary time, fat percentage, and physical fitness were correlated with most gait parameters (rpartial between |0.842| and |0.219|; p ≤ 0.05). Physical fitness was independently associated with all gait parameters (β between |0.346| and |0.761|; p ≤ 0.002). In addition, MVPA was independently associated with velocity and step length (β = 0.241 and 0.292; both p = 0.004), and fat percentage was associated with bipedal stance phase (β = 0.242; p = 0.049). Good levels of MVPA, physical fitness, and adequate weight balance are associated with improved gait parameters in women with fibromyalgia.

The early identification of performance in the five-repetition sit-to-stand test (5-STS) at discharge in stroke patients could be of interest because it can determine independence for community-based activities. This study aimed to determine whether the initial measurement of the 5-STS test can be a determinant of the performance level prediction and amount of change in the 5-STS test at discharge in stroke patients. A prospective cohort study was conducted with a sample of 56 patients aged ≤60 d post-stroke. The 5-STS test results, as well as changes in patient condition, were measured at admission (T0) to an outpatient rehabilitation program, after the first month (T1), and at discharge (T2). The mean age was 62.7 (SD = 13.0), 58.9% of the subjects were male, and 75% had suffered an ischemic stroke. A multivariate linear regression model using the 5-STS test at T0 explained 57.7% of the variance in the performance at discharge. Using the 5-STS at T1 increased the variance to 75.5% (p < 0.001). Only the time from stroke onset at T0 significantly contributed to the two models. The measurement of the 5-STS at T0 and the amount of change in its performance at T2 explained 60.2% (p < 0.001) of the variance, while reassessment at T1 explained only 19.3% (p < 0.001). The level of patient performance on the 5-STS test at discharge, as well as any potential change, can be predicted by the admission measure of 5-STS in stroke patients.

The outcomes of metastatic and nonresponder pediatric osteosarcoma patients are very poor and have not improved in the last 30 years. These tumors harbor a highly immunosuppressive environment, making existing immunotherapies ineffective. Here, we evaluated the use of Semliki Forest virus (SFV) vectors expressing galectin-3 (Gal3) inhibitors as therapeutic tools, since both the inhibition of Gal3, which is involved in immunosuppression and metastasis, and virotherapy based on SFV have been demonstrated to reduce tumor progression in different tumor models. In vitro, inhibitors based on the Gal3 amino-terminal domain alone (Gal3-N) or fused to a Gal3 peptide inhibitor (Gal3-N-C12) were able to block the binding of Gal3 to the surface of activated T cells. In vivo, SFV expressing Gal3-N-C12 induced strong antitumor responses in orthotopic K7M2 and MOS-J osteosarcoma tumors, leading to complete regressions in 47% and 30% of mice, respectively. Pulmonary metastases were also reduced in K7M2 tumor-bearing mice after treatment with SFV-Gal3-N-C12. Both the antitumor and antimetastatic responses were dependent on modulation of the immune system, primarily including an increase in tumor-infiltrating lymphocytes and a reduction in the immunosuppressive environment inside tumors. Our results demonstrated that SFV-Gal3-N-C12 could constitute a potential therapeutic agent for osteosarcoma patients expressing Gal3.

During June 2022, Spain was one of the countries most affected worldwide by a multicountry monkeypox outbreak with chains of transmission without identified links to disease-endemic countries. We provide epidemiologic features of cases reported in Spain and the coordinated measures taken to respond to this outbreak.

Introduction/objective: West Nile virus (WNV) is one of the most widely distributed flaviviruses worldwide. It is considered an endemic and emerging pathogen in different areas of the Europe and Mediterranean countries (MR). Mosquitoes of the genus Culex spp. are the main vectors, and birds its main vertebrate hosts. It can occasionally infect mammals, including humans. Different environmental factors can influence its distribution and transmission through its effects on vector or host populations. Our objective was to determine environmental factors associated with changes in vector distribution and WNV transmission in Europe and MR. Material & methods: Systematic peer review of articles published between 2000 and 2020. We selected studies on WNV, and its vectors carried out in Europe and MR. The search included terms referring to climatic and environmental factors. Results: We included 65 studies, of which 21 (32%) were conducted in Italy. Culex spp. was studied in 26 papers (40%), humans in 19 papers (29%) and host animals (mainly horses) in 16 papers (25%), whereas bird reservoirs were addressed in 5 studies (8%). A significant positive relationship was observed between changes in temperature and precipitation patterns and the epidemiology of WNV, although contrasting results were found among studies. Other factors positively related to WNV dynamics were the normalized difference vegetation index (NDVI] and expansion of anthropized habitats. Conclusion: The epidemiology of WNV seems to be related to climatic factors that are changing globally due to ongoing climate change. Unfortunately, the complete zoonotic cycle was not analyzed in most papers, making it difficult to determine the independent impact of environment on the different components of the transmission cycle. Given the current expansion and endemicity of WNV in the area, it is important to adopt holistic approaches to understand WNV epidemiology and to improve WNV surveillance and control.

Abstract Background Buruli ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans that affects skin, soft tissues, and bones, causing long-term morbidity, stigma, and disability. The recommended treatment for BU requires 8 weeks of daily rifampicin and clarithromycin together with wound care, physiotherapy, and sometimes tissue grafting and surgery. Recovery can take up to 1 year, and it may pose an unbearable financial burden to the household. Recent in vitro studies demonstrated that beta-lactams combined with rifampicin and clarithromycin are synergistic against M. ulcerans. Consequently, inclusion of amoxicillin/clavulanate in a triple oral therapy may potentially improve and shorten the healing process. The BLMs4BU trial aims to assess whether co-administration of amoxicillin/clavulanate with rifampicin and clarithromycin could reduce BU treatment from 8 to 4 weeks. Methods We propose a randomized, controlled, open-label, parallel-group, non-inferiority phase II, multi-centre trial in Benin with participants stratified according to BU category lesions and randomized to two oral regimens: (i) Standard: rifampicin plus clarithromycin therapy for 8 weeks; and (ii) Investigational: standard plus amoxicillin/clavulanate for 4 weeks. The primary efficacy outcome will be lesion healing without recurrence and without excision surgery 12 months after start of treatment (i.e. cure rate). Seventy clinically diagnosed BU patients will be recruited per arm. Patients will be followed up over 12 months and managed according to standard clinical care procedures. Decision for excision surgery will be delayed to 14 weeks after start of treatment. Two sub-studies will also be performed: a pharmacokinetic and a microbiology study. Discussion If successful, this study will create a new paradigm for BU treatment, which could inform World Health Organization policy and practice. A shortened, highly effective, all-oral regimen will improve care of BU patients and will lead to a decrease in hospitalization-related expenses and indirect and social costs and improve treatment adherence. This trial may also provide information on treatment shortening strategies for other mycobacterial infections (tuberculosis, leprosy, or non-tuberculous mycobacteria infections). Trial registration ClinicalTrials.gov NCT05169554 . Registered on 27 December 2021.

Objectives: We analysed hepatitis A (HepA) notifications and hospitalisations in Italy, the Netherlands, Norway, Spain, and Sweden for available periods between 1995 and 2014. We aimed to investigate whether decreasing HepA incidence is associated with increasing age at infection and worsening HepA presentation and to identify groups at risk of severe disease. Methods: We performed a retrospective cohort study including 36 734 notified and 36 849 hospitalised patients. We used negative binomial regressions to identify over time: i) trends in hospitalisation and notification rates; ii) proportion of hospitalised and notified patients aged ≥40 years; iii) proportion of “severe hospitalisations”; and iv) risk factors for severe hospitalisation. Results: During the study period both HepA notifications and hospitalisations decreased, with notification rates decreasing faster, patients aged ≥40 years increased, however, the proportion of severe HepA hospitalisations remained stable. Older patients and patients with comorbidities, particularly liver diseases, were more likely to experience severe disease. Conclusions: We used digitalised health information to confirm decreasing trends in HepA hospitalisations and notifications, and the increasing age of patients with HepA in Europe. We did not identify an increase in the severity of the clinical presentation of patients with HepA. Older patients with liver diseases are at increased risk of severe disease and should be prioritised for vaccination.

Objectives: This study aimed to test whether fibromyalgia-related characteristics differ by mode of commute and by age in women with fibromyalgia. Methods: A total of 450 women with fibromyalgia (aged 52.0 ± 8.0 years old) were included. Data on their body composition, socioeconomic factors, health-related quality of life (HRQoL), depressive symptoms, sleep quality, pain-related outcomes, fatigue, and mode of commute, as well as the impact of fibromyalgia on their lives, were obtained. We performed linear regression analyses to test the differences in fibromyalgia-related characteristics between the participants engaged in active/passive modes of commuting. To analyze in depth the differences, a one-way analysis of covariance with Bonferroni's correction for multiple comparisons was conducted. Results: In the younger group, active commuters presented differences in fibromyalgia-related characteristics (all, p < 0.01): they were less impacted by having fibromyalgia, had lower levels of fatigue, and had a higher HRQoL than passive commuters. We observed no differences in symptoms between active and passive commuters in the older group (all, p > 0.05). Conclusions: The possible positive effect of active commuting on fibromyalgia-related characteristics might be reduced by age and by a decrease in total physical activity. Physical activity programs for women with fibromyalgia focused on improving fibromyalgia-related characteristics should consider active commuting behaviors to increase their effectiveness. [ABSTRACT FROM AUTHOR]

This paper investigates Beam Loading in the positron source capture Linac of the Compact Linear Collider (CLIC). Beam Loading, caused by interactions between beam with accelerating cavities, leads to a reduction in the accelerating gradient, negatively affecting the Linac performance. Through simulations using the RF-Track code, we analyze Beam Loading effects and explore some optimization strategies. Key findings reveal significant transient Beam Loading effects and bunch-to-bunch variations.

Background: Active commuting to school may increase the total daily physical activity and achieve health benefits among preschool children. Rates of active commuting to school among Spanish children and adolescents have been widely analysed, while the rates of active commuting to school among Spanish preschool children are unknown. Aim: The main objective of this study was to examine the changes in the rates of active commuting to school in a sample of Spanish preschool children between 3 and 6 years old from 2013 to 2017. Methods: Data were found from five studies carried out across Spain. The study sample comprised 4787 preschool children (4.59 ± 0.77 years old; 51% males). The overall changes in active commuting to school were assessed using multilevel logistic regression analysis. Results: The rates of active commuting to school in Spanish preschool children are around 52%, and the active commuting to school rates have stayed stable throughout the period assessed (odds ratio from 0.40 to 0.58, all p > 0.05). Conclusion: In preschool children, the present study obtained a favourable result on active commuting to school, showing a pattern stability in the examined period similar to other ages. It will be of great importance to promote this behaviour to obtain high levels of active commuting to school.

Climate change will lead to higher temperatures, increased precipitation and runoff, as well as more intense and frequent extreme weather events in Norway. More extreme rainfall and increased runoff are historically associated with higher concentrations of indicator bacteria, colour and turbidity in raw water of Norwegian waterworks. Regional information about the risk for drinking water deterioration by the end of the century is essential for evaluating potential treatment capacity upgrades at the waterworks. We combined locally downscaled future climate scenarios with historical associations between weather/runoff and water quality from a wide spread of waterworks in Norway. With continued climate change, we estimate higher concentrations of water quality indicators of raw water by the end of the century. The water quality is estimated to deteriorate mainly due to the projected increase in rainfall, and mainly in the Western and Northern parts of Norway. While large waterworks seem to be able to adapt to future conditions, the degradation of raw water quality may cause future challenges for the treatment processes at smaller waterworks. Combining these results with further studies of treatment effects and microbial risk assessments is needed to ensure sufficient treatment capacities of the raw water in the future. HIGHLIGHTS Associations between weather/runoff and water at Norwegian waterworks were combined with local climate scenarios for the first time.; Higher concentrations of water quality indicators of raw water in Norway in the future.; The future increase in rainfall causes decreased raw water quality in the North and West of Norway.; Decreasing raw water quality may cause challenges for the treatment processes of small waterworks;

Se presentan los resultados de una intervención educativa desarrollada en el ámbito universitario que pone en valor el potencial de los juegos de mesa en el aula y su repercusión en el aprendizaje dentro del contexto de las metodologías activas. Este serious game se crea principalmente desde un doble propósito, por un lado, como recurso para la mejora de habilidades y competencias expresivas en Educación Física y, por otro, como herramienta de transformación social que invita a profundizar en el conocimiento de los Objetivos de Desarrollo Sostenible (ODS), trabajando de manera transversal estas metas globales marcadas por la Organización de las Naciones Unidas (ONU) en la denominada Agenda 2030. El juego de mesa Dixit Mutatio, creado a partir de un juego comercial premiado internacionalmente, se ha adaptado a través del uso inspirador de la fotografía, las respuestas a partir del teatro imagen y las dinámicas de creación colectiva. A partir de las valoraciones que comparte el alumnado en un cuestionario y la observación directa realizada por el profesorado durante la experiencia, se evidencia la utilidad de este recurso didáctico y su puesta en práctica en el contexto universitario. Palabras clave: Juegos de mesa, juegos serios, Educación física, Expresión corporal, Objetivos de Desarrollo Sostenible. Abstract. We present the results of an educational intervention developed in the university environment that highlights the potential benefits of board games in the classroom and their impact on learning within the context of active methodologies. This serious game was created with a dual purpose: on the one hand, as a resource for improving expressive skills and competences in Physical Education and, on the other, as a tool for social transformation that invites us to deepen our knowledge of the Sustainable Development Goals (SDGs), working transversally on these global goals set by the United Nations (UN) in the so-called Agenda 2030. The board game Dixit Mutatio, created from an internationally awarded commercial game, has been adapted through the inspirational use of photography, responses based on image theatre and collective creation dynamics. The usefulness of this didactic resource and its implementation in the university context is demonstrated on the basis of evaluations shared in a questionnaire by the students and direct observation carried out by the teaching staff during the experience. Key Words: Board games; serious games; Physical education; Corporal expression; Sustainable Development Goals.

Bacterial secretion systems mediate the selective exchange of macromolecules between bacteria and their environment, playing a pivotal role in processes such as horizontal gene transfer or virulence. Among the different families of secretion systems, Type III, IV and VI (T3SS, T4SS and T6SS) share the ability to inject their substrates into human cells, opening up the possibility of using them as customized injectors. For this to happen, it is necessary to understand how substrates are recruited and to be able to engineer secretion signals, so that the transmembrane machineries can recognize and translocate the desired substrates in place of their own. Other factors, such as recruiting proteins, chaperones, and the degree of unfolding required to cross through the secretion channel, may also affect transport. Advances in the knowledge of the secretion mechanism have allowed heterologous substrate engineering to accomplish translocation by T3SS, and to a lesser extent, T4SS and T6SS into human cells. In the case of T4SS, transport of nucleoprotein complexes adds a bonus to its biotechnological potential. Here, we review the current knowledge on substrate recognition by these secretion systems, the many examples of heterologous substrate translocation by engineering of secretion signals, and the current and future biotechnological and biomedical applications derived from this approach.

Background: In chronic obstructive pulmonary disease (COPD), multiple recurrent severe exacerbations that require hospitalization can occur. These events are strongly associated with death and other clinical complications. Objectives: We aimed to develop a prognostic model that could identify patients with COPD that are at risk of multiple recurrent severe exacerbations within 3 years. Design: Prospective cohort. Methods: The derivation cohort comprised patients with stable, moderate-to-severe COPD. Multivariable logistic regression analyses were performed to develop the final model. Based on regression coefficients, a simplified index (ESEx) was established. Both, model and index, were assessed for predictive performance by measuring discrimination and calibration. Results: Over 3 years, 16.4% of patients with COPD experienced at least three severe recurrent exacerbations. The prognostic model showed good discrimination of high-risk patients, based on three characteristics: the number of severe exacerbations in the previous year, performance in the five-repetition sit-to-stand test, and in the 6-minute-walk test. The ESEx index provided good level of discrimination [areas under the receiver operating characteristic curve (AUCs): 0.913]. Conclusions: The ESEx index showed good internal validation for the identification of patients at risk of three recurrent severe COPD exacerbations within 3 years. These tools could be used to identify patients who require early interventions and motivate patients to improve physical performance to prevent recurrent exacerbations.