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Abstract Despite their recognised role in HER2-positive (HER2+) breast cancer (BC), the composition, localisation and functional orientation of immune cells within tumour microenvironment, as well as its dynamics during anti-HER2 treatment, is largely unknown. We here investigate changes in tumour-immune contexture, as assessed by stromal tumour-infiltrating lymphocytes (sTILs) and by multiplexed spatial cellular phenotyping, during treatment with lapatinib-trastuzumab in HER2+ BC patients (PAMELA trial). Moreover, we evaluate the relationship of tumour-immune contexture with hormone receptor status, intrinsic subtype and immune-related gene expression. sTIL levels increase after 2 weeks of HER2 blockade in HR-negative disease and HER2-enriched subtype. This is linked to a concomitant increase in cell density of all four immune subpopulations (CD3+, CD4+, CD8+, Foxp3+). Moreover, immune contexture analysis showed that immune cells spatially interacting with tumour cells have the strongest association with response to anti-HER2 treatment. Subsequently, sTILs consistently decrease at the surgery in patients achieving pathologic complete response, whereas most residual tumours at surgery remain inflamed, possibly reflecting a progressive loss of function of T cells. Understanding the features of the resulting tumour immunosuppressive microenvironment has crucial implications for the design of new strategies to de-escalate or escalate systemic therapy in early-stage HER2+ BC.

During the warm months of the year in Catalonia, the marine air overcomes the coastal mountain range and reaches the eastern Ebro sub-basin. This phenomenon is called marinada and has recently been thoroughly characterized for the first time by Jiménez et al. (2023), based on surface climatological data. However, the main physical mechanisms involved in its arrival and propagation remain to be discovered. This study aims to understand how the marinada is formed and how it interacts with the already developed atmospheric boundary layer. Surface and atmospheric observations are used in combination with the coupled surface–atmosphere model Meso-NH to reveal the mechanisms at play. It is shown that the marinada is generated by the advection of a cool marine air mass over the Catalan Pre-coastal Range by the action of the sea breeze and the upslope wind. This marine air mass then flows into the Ebro basin, creating what is known as the marinada. The characteristics and dynamics of the marinada allow it to be classified as a fall wind. It is also shown that the arrival, propagation and decay of the marinada is strongly dependent on the larger-scale weather situation: westerlies or thermal low. The current study provides a consistent framework for understanding the marinada, paving the way for better modeling and prediction of the phenomenon.

Substantial evidence supports the idea that engaged workers reach high performance levels. Nevertheless, most research does not take into account that job performance is multidimensional. The current study aimed to investigate the relationship between work engagement and performance (task performance, contextual performance, counterproductive work behaviors, and adaptive performance) and determine whether work engagement provides incremental validity over the Big Five personality traits in the prediction of performance. A questionaire with the variables of interest was filled in by 365 workers. Regression analyses revealed that work engagement plays a role in all dimensions of job performance. Results also revealed the differential functioning of work engagement dimensions, with vigor as the main predictor of task performance and the second predictor of adaptive performance, even when considering personality. High absorption decreases task performance but increases contextual performance, while dedication mediates between personality (i.e., agreeableness and extraversion) and CWB.

Abstract In this study, we performed genomic analyses of cell cycle and tumor microenvironment changes during and after ribociclib and letrozole or chemotherapy in the CORALLEEN trial. 106 women with untreated PAM50-defined Luminal B early breast cancers were randomly assigned to receive neoadjuvant ribociclib and letrozole or standard-of-care chemotherapy. Ki67 immunohistochemistry, tumor-infiltrating lymphocytes quantification, and RNA sequencing were obtained from tissue biopsies pre-treatment, on day 14 of treatment, and tumor specimens from surgical resection. Results showed that at surgery, Ki67 and the PAM50 proliferation scores were lower after ribociclib compared to chemotherapy. However, consistent reactivation of tumor cell proliferation from day 14 to surgery was only observed in the ribociclib arm. In tumors with complete cell cycle arrest (CCCA) at surgery, PAM50 proliferation scores were lower in the ribociclib arm compared to chemotherapy (p

Introduction. Individuals with Parkinson’s disease (PD) exhibit general impairments, particularly non-motor symptoms that are related to language, communication, and cognition processes. People with this disease may undergo a surgical intervention for the placement of a deep brain stimulation device, which improves their motor symptoms. However, this type of intervention leads to a decline in their linguistic and cognitive abilities that becomes increasingly noticeable as the disease progresses. Objective. The objective of this research was to compare the performance and linguistic–cognitive profile of individuals with Parkinson’s disease who underwent deep brain stimulation treatment based on the stage of the disease. Method. A total of 60 participants who were diagnosed with PD by their reference hospital were selected. These participants were divided into three groups based on the stage of the disease that they were in, forming three groups: a Stage I group (n = 20), a Stage II group (n = 20), and a Stage III group (n = 20). The linguistic–cognitive profile was assessed using the MoCA, ACE-III, and MetAphas tests. The design of this study was established as a quasi-experimental, cross-sectional investigation, and statistical analysis was performed using MANOVA to compare the scores between the study groups. Results. The results indicate that individuals in Stage I exhibit better linguistic and cognitive performance compared to the other groups of participants in Stage II and Stage III, with statistically significant differences (p < 0.05). Conclusion. In conclusion, the progression of PD leads to significant linguistic and cognitive decline in individuals with this disease who have a deep brain stimulation device, greatly limiting the autonomy and quality of life for people with PD.

PURPOSE: Track structure Monte Carlo (MC) codes have achieved successful outcomes in the quantitative investigation of radiation-induced initial DNA damage. The aim of the present study is to extend a Geant4-DNA radiobiological application by incorporating a feature allowing for the prediction of DNA rejoining kinetics and corresponding cell surviving fraction along time after irradiation, for a Chinese hamster V79 cell line, which is one of the most popular and widely investigated cell lines in radiobiology. METHODS: We implemented the Two-Lesion Kinetics (TLK) model, originally proposed by Stewart, which allows for simulations to calculate residual DNA damage and surviving fraction along time via the number of initial DNA damage and its complexity as inputs. RESULTS: By optimizing the model parameters of the TLK model in accordance to the experimental data on V79, we were able to predict both DNA rejoining kinetics at low linear energy transfers (LET) and cell surviving fraction. CONCLUSION: This is the first study to demonstrate the implementation of both the cell surviving fraction and the DNA rejoining kinetics with the estimated initial DNA damage, in a realistic cell geometrical model simulated by full track structure MC simulations at DNA level and for various LET. These simulation and model make the link between mechanistic physical/chemical damage processes and these two specific biological endpoints.

Este artículo explora la expresión artística a través del juego en la exposición "NEGOCIO", realizada en el Centro Cultural Las Cigarreras, Alicante. Analiza el juego como medio artístico, considerando aspectos estéticos, simbólicos y narrativos. El método de análisis, combinando encuestas y observación, evalúa la percepción del público, mostrando cambios positivos hacia la interactividad y la consideración de los juegos como medio de expresión artística.

Changing economic landscapes have shifted from industrial innovation to entrepreneurial knowledge-based economies requiring educational experiences based on practice and real-world connections. Whereas much focus has centred on curricular activities to achieve this aim, in comparison there is scant attention paid to the important role that organised and spatially embedded out-of-curriculum activities can afford. We present an innovative and practical initiative that takes a systematic approach to effectively blend diverse elements from both the formal and informal curriculum, providing a holistic and immersive learning experience for aspiring entrepreneurs. By embracing a multifaceted method, the integrated model of entrepreneurship education that we detail aims to equip students with the knowledge, skills, and networks needed to navigate the complexities of entrepreneurship and excel in today's dynamic business landscape.

BackgroundPrior to the onset of dementia, individuals commonly undergo a phase marked by subtle cognitive changes, known as subtle cognitive decline. Recognizing these early cognitive alterations is crucial, as they can serve as indicators of an impending decline in cognitive function, warranting timely intervention and support.ObjectivesTo determine the incidence of subtle cognitive decline in a population of Spanish women and establish the relationship with possible protective and/or risk factors such as cognitive reserve, cardiovascular risk factors, medication consumption and psychosocial factors.Design and participantsThis is a cross-sectional observational study with women from the general population and a more homogeneous population composed of nuns from the Valencian region (Spain).MeasurementsA validated questionnaire was used including lifestyle variables, chronic illnesses, level of education and pharmacological treatments. Three validated subtle cognitive decline screening tests with varying levels of sensitivity and specificity were used: Memory Impairment Screening, Pfeiffer’s Short Portable Mental State Questionnaire, and Semantic Verbal Fluency.ResultsOur results suggest that nuns may have a significantly reduced risk of cognitive decline compared to the general population (20.67% in nuns vs. 36.63% in the general population). This lower risk for subtle cognitive decline in nuns may be partly attributed to their higher cognitive reserve and long-time engagement in intellectually stimulating activities. Additionally, nuns tend to adopt healthy lifestyles, they are not isolated because they live in community and obtained lower scores for risk factors such as depression, anticholinergic burden, and benzodiazepine consumption.ConclusionA healthy lifestyle combined with intellectually stimulating activities is related with preserved cognitive function.

Educational institutions have had the pending task of knowing what really happens in their classrooms, which professors make a real difference, which students would need help to improve their performance, and even more importantly, how to manage the enormous amount of information gathered each year. To address this problem, in this paper we propose the use of retrospective data from 210 undergraduate courses in Spain, which equals 1,320 European credits, 10,500 students, and four complete academic years (18/19, 19/20, 20/21, 21/22) to generate a monitoring tool or automatic dashboard with which to try to optimize the operation of such institutions and help them to make (even more) optimal decisions. To do this, all courses were grouped into ten typologies or categories: (1) if they were 'soft skills'/'hard skills' courses, (2) if they were taught in the 1st, 2nd, 3rd or 4th academic year, (3) if the professor was male or female, (4) whether the course was taught in English or not, (5) whether the professor was internal and permanent staff of the university or an associate professor with a temporary contractual relationship with the institution, (6) whether his/her main professional activity was teaching, therefore being more academic-oriented or this was rather a hobby and a complementary professional activity, therefore being more practical-oriented, (7) their age, (8) if several professors shared the course or only one taught it, (9) if it was a semester or annual course, (10) and if it was taught during the Covid-19 period or outside of it. Our results show that, despite the existence of numerous types of methodologies to achieve the desired student motivation, there would only be one category that would generate significant differences in the grades of the students: if they were ‘soft skills’/’hard skills’ courses. However, on the contrary, there would be much more types of courses (and professors) which would affect the preferences and valuation of the student to the teaching received (and effectively paid by him/her). That is, despite reaching the same academic results, students do value one type of professors better than others. Likewise, through this work it is intended to demonstrate the non-existence of the "false belief" that better evaluations received by professors are since they give higher grades to their students, regardless of its dispersion. In this way, it is intended to prevent possible atypical behaviors by professors. Thus, this paper gives light to (re)consider which variables should actually matter in educational institutions, analyzing its teaching-learning processes, management and even the retention of its key players.

Introduction and Objectives: Different patterns of liver injury have been reported in association with the SARS-CoV-2 vaccines. The aim of this study was to describe a nationwide cohort of patients with SARS CoV-2 vaccine-induced liver injury, focusing on treatment and the evolution after further booster administration. Patients and Methods: multicentre, retrospective-prospective study, including subjects who developed abnormal liver tests within 90 days after administration of SARS-CoV-2 vaccination. Results: 47 cases were collected: 17 after prime dose and 30 after booster. Age was 57 years, 30 (63.8 %) were female, and 7 (14.9 %) had a history of prior autoimmune hepatitis (AIH). Most cases were non-severe, though 9 (19.1 %) developed acute liver injury or failure (ALF). Liver injury tended to be more severe in those presenting after a booster (p=0.084). Pattern of liver injury was hepatocellular (80.9 %), mixed (12.8 %) and 3 (6.4 %) cholestatic. Liver biopsy was performed on 33 patients; 29 showed findings of AIH. Forty-one (87.2 %) patients received immunosuppressants, mostly corticosteroids (35/41). One required liver transplantation and another died due to ALF. Immunosuppression was discontinued in 6/41 patients without later rebound. Twenty-five subjects received at least one booster and 7 (28.0 %) relapsed from the liver injury, but all were non-severe. Recurrence was less frequent among patients on immunosuppressants at booster administration (28.6 % vs. 88.9 %, p=0.007). Conclusions: SARS CoV-2 vaccine-induced liver injury is heterogeneous but mostly immune-mediated. Relapse of liver injury after re-exposure to vaccine is frequent (28.0 %) but mild. Immunosuppression at booster administration is associated with a lower risk of liver injury.

Abstract B and T cell responses were evaluated in patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) after 1 or 2 weeks of methotrexate (MTX) withdrawal following each COVID-19 vaccine dose and compared with those who maintained MTX. Adult RA and PsA patients treated with MTX were recruited and randomly assigned to 3 groups: MTX-maintenance (n = 72), MTX-withdrawal for 1 week (n = 71) or MTX-withdrawal for 2 weeks (n = 73). Specific antibodies to several SARS-CoV-2 antigens and interferon (IFN)-γ and interleukin (IL)-21 responses were assessed. MTX withdrawal in patients without previous COVID-19 was associated with higher levels of anti-RBD IgG and neutralising antibodies, especially in the 2-week withdrawal group and with higher IFN-γ secretion upon stimulation with pools of SARS-CoV-2 S peptides. No increment of RA/PsA relapses was detected across groups. Our data indicate that two-week MTX interruption following COVID-19 vaccination in patients with RA or PsA improves humoral and cellular immune responses.

The use of game-related assessments (GRAs) in personnel selection is increasing. However, the type of GRA under investigation should be considered. This study focuses on game-based assessments, which closely resemble leisure-oriented videogames. We specifically examined a serious game that assesses personality traits (assertiveness, sociability, tolerance, and rules). We analyzed its predictive validity, applicant reactions, and the impact of personal and job-related factors on scores. The study included 182 participants who played the GRA and completed a Big Five questionnaire. Findings revealed that the game predicts adaptive performance, offering incremental value over the Big Five (ΔR2 = .107). Additionally, candidates reacted more positively to the GRA in terms of comfort and fit, although the effect size was small (d = -0.1757 and -0.3119, respectively). Relating to personal and job-related characteristics, only job experience significantly affected the assertiveness score, albeit with a small effect size (d = -0.3870).

We analyzed immune response to SARS-CoV-2 vaccination by measuring specific IgG titers and T-cell reactivity to different SARS-CoV-2 peptides in multiple sclerosis patients taking different disease-modifying treatments. Of the 88 patients included, 72 developed any kind of immune response after vaccination. Although DMTs such as fingolimod and anti-CD20+ treatments prevented patients from developing a robust humoral response to the vaccine, most of them were still able to develop a cellular response, which could be crucial for long-term immunity. It is probably advisable that all MS patients take additional/booster doses to increase their humoral and/or cellular immune response to SARS-CoV-2.

Gendered barriers that have traditionally impeded entry into entrepreneurship are lessening. Nonetheless, there is still a clear need to further encourage female students into an entrepreneurial career pathway. To do so, traditional classroom discourse that promotes the masculinised concept of the 'heroic' entrepreneur who experiences overnight success needs to be challenged. By providing a case study of a young successful female entrepreneur we open a pathway beyond a narrow vision of the homogenous entrepreneur driven by purely profit-seeking motives. It is well recognised that the socialisation process differs between individuals, making it important to consider the lived experiences of a variety of entrepreneurs that can appeal to the idiosyncratic needs of our students. At the same time, to amplify the value of such narratives they need to be connected to what we already know. The overriding aim of this teaching case is to offer a narrative of a successful female entrepreneur that can be used as a tool to stimulate an entrepreneurial mindset in students.

Summary: Background: Early-stage triple-negative breast cancer (TNBC) displays clinical and biological diversity. From a biological standpoint, immune infiltration plays a crucial role in TNBC prognosis. Currently, there is a lack of genomic tools aiding in treatment decisions for TNBC. This study aims to assess the effectiveness of a B-cell/immunoglobulin signature (IGG) alone, or in combination with tumor burden, in predicting prognosis and treatment response in patients with TNBC. Methods: Genomic and clinical data were retrieved from 7 cohorts: SCAN-B (N = 874), BrighTNess (n = 482), CALGB-40603 (n = 389), METABRIC (n = 267), TCGA (n = 118), GSE58812 (n = 107), GSE21653 (n = 67). IGG and a risk score integrating IGG with tumor/nodal staging (IGG-Clin) were assessed for event-free survival (EFS) and overall survival (OS) in each cohort. Random effects model was used to derive pooled effect sizes. Association of IGG with pathological complete response (pCR) was assessed in CALGB-40603 and BrighTNess. Immune significance of IGG was estimated through CIBERSORTx and EcoTyper. Findings: IGG was associated with improved EFS (pooled HR = 0.77, [95% CI = 0.70–0.85], I2 = 18%) and OS (pooled HR = 0.79, [0.73–0.85], I2 = 0%) across cohorts, and was predictive of pCR in CALGB-40603 (OR 1.25, [1.10–1.50]) and BrighTNess (OR 1.57 [1.25–1.98]). IGG-Clin was predictive of recurrence (pooled HR = 2.11, [1.75–2.55], I2 = 0%) and death (pooled HR = 1.99, 95% [0.84–4.73], I2 = 79%) across cohorts. IGG was associated with adaptive immune response at CIBERSORTx and EcoTyper analysis. Interpretation: IGG is linked to improved prognosis and pCR in early-stage TNBC. The integration of IGG alongside tumor and nodal staging holds promise as an approach to identify patients benefitting from intensified or de-intensified treatments. Funding: This study received funding from: Associació Beca Marta Santamaria, European Union’s Horizon 2020 research and innovation and Marie Skłodowska–Curie Actions programs, Fundación FERO, Fundación CRIS contra el cáncer, Agència de Gestó d'Ajuts Universitaris i de Recerca, Instituto de Salud Carlos III, Fundación Contigo, Asociación Cáncer de Mama Metastásico IV, Breast Cancer Research Foundation, RESCUER, Fundación científica AECC and FSEOM.

Autism Spectrum Disorder (ASD) and epilepsy are increasingly prevalent comorbidities in our society. These two disorders are often accompanied by other comorbidities, such as sleep disorders, significantly impacting the quality of life of individuals with ASD and epilepsy. To date, clinical approaches have primarily been descriptive in nature. Therefore, this study aimed to analyze the relationship between ASD, epilepsy, and sleep disorders, exploring neurobiological dysfunctions and cognitive alterations. A total of 22 scientific articles were selected using a systematic literature review following the criteria established using the PRISMA model. The selected articles were gathered from major databases: Medline, PubMed, PsycINFO, Google Scholar, and Web of Science. Inclusion criteria specified that study participants had an official diagnosis of ASD, the article precisely described the evaluation parameters used in the study participants, and individual characteristics of the sleep disorders of the study participants were specified. The results indicate, firstly, that the primary cause of sleep disorders in this population is directly linked to abnormal serotonin behaviors. Secondly, significant alterations in memory, attention, and hyperactivity were observed. In conclusion, sleep disorders negatively impact the quality of life and neurocognitive development of the pediatric population with ASD and epilepsy.

Los canales de denuncia se han extendido considerablemente entre organizaciones públicas y privadas, y, con la transposición operada en España de la Directiva 1937/2019, mediante la Ley estatal 2/2023, se consolida y generaliza esta tendencia, con la imposición de obligaciones al respecto. Surge, pues, la necesidad de establecer qué son los buzones o canales de denuncias, qué tipos hay, si existe una obligación de disponer de ellos, qué requisitos deben observar y cómo pueden contribuir a la facilidad de denunciar y a la protección de las personas denunciantes. Los canales de denuncia, entendidos como el cauce para la formulación de comunicaciones referidas a incumplimientos normativos u otras malas prácticas, deben observar ciertos requisitos que faciliten la denuncia, como ser accesibles, proteger la identidad de la persona denunciante e incluso permitir el anonimato.

The chemical stage of the Monte Carlo track-structure (MCTS) code Geant4-DNA was extended for its use in DNA strand break (SB) simulations and compared against published experimental data. Geant4-DNA simulations were performed using pUC19 plasmids (2686 base pairs) in a buffered solution of DMSO irradiated by60Co or137Csγ-rays. A comprehensive evaluation of SSB yields was performed considering DMSO, DNA concentration, dose and plasmid supercoiling. The latter was measured using the super helix density value used in a Brownian dynamics plasmid generation algorithm. The Geant4-DNA implementation of the independent reaction times method (IRT), developed to simulate the reaction kinetics of radiochemical species, allowed to score the fraction of supercoiled, relaxed and linearized plasmid fractions as a function of the absorbed dose. The percentage of the number of SB after •OH + DNA and H• + DNA reactions, referred as SSB efficiency, obtained using MCTS were 13.77% and 0.74% respectively. This is in reasonable agreement with published values of 12% and 0.8%. The SSB yields as a function of DMSO concentration, DNA concentration and super helix density recreated the expected published experimental behaviors within 5%, one standard deviation. The dose response of SSB and DSB yields agreed with published measurements within 5%, one standard deviation. We demonstrated that the developed extension of IRT in Geant4-DNA, facilitated the reproduction of experimental conditions. Furthermore, its calculations were strongly in agreement with experimental data. These two facts will facilitate the use of this extension in future radiobiological applications, aiding the study of DNA damage mechanisms with a high level of detail.

The chemical stage of the Monte Carlo track-structure simulation code Geant4-DNA has been revised and validated. The root-mean-square (RMS) empirical parameter that dictates the displacement of water molecules after an ionization and excitation event in Geant4-DNA has been shortened to better fit experimental data. The pre-defined dissociation channels and branching ratios were not modified, but the reaction rate coefficients for simulating the chemical stage of water radiolysis were updated. The evaluation of Geant4-DNA was accomplished with TOPAS-nBio. For that, we compared predicted time-dependentGvalues in pure liquid water for·OH, e-aq, and H2with published experimental data. For H2O2and H·, simulation of added scavengers at different concentrations resulted in better agreement with measurements. In addition, DNA geometry information was integrated with chemistry simulation in TOPAS-nBio to realize reactions between radiolytic chemical species and DNA. This was used in the estimation of the yield of single-strand breaks (SSB) induced by137Csγ-ray radiolysis of supercoiled pUC18 plasmids dissolved in aerated solutions containing DMSO. The efficiency of SSB induction by reaction between radiolytic species and DNA used in the simulation was chosen to provide the best agreement with published measurements. An RMS displacement of 1.24 nm provided agreement with measured data within experimental uncertainties for time-dependentGvalues and under the presence of scavengers. SSB efficiencies of 24% and 0.5% for·OH and H·, respectively, led to an overall agreement of TOPAS-nBio results within experimental uncertainties. The efficiencies obtained agreed with values obtained with published non-homogeneous kinetic model and step-by-step Monte Carlo simulations but disagreed by 12% with published direct measurements. Improvement of the spatial resolution of the DNA damage model might mitigate such disagreement. In conclusion, with these improvements, Geant4-DNA/TOPAS-nBio provides a fast, accurate, and user-friendly tool for simulating DNA damage under low linear energy transfer irradiation.

This paper demonstrates the impact of the pre-chemical stage, especially the dissociation scheme and the associated probabilities, on water radiolysis simulation using the Geant4-DNA Monte Carlo track structure simulation toolkit. The models and parameters provided by TRACs have been collected and implemented into Geant4-DNA. In order to evaluate their influence on water radiolysis simulation, the radiochemical yields (G-values) are evaluated as a function of time and LET using the chem6 Geant4-DNA example, and they are compared with published experimental and calculated data. The new pre-chemical models lead to a better agreement with literature data than the default pre-chemical models of Geant4-DNA, especially for OH radicals and H2O2. The revised chemistry constructor G4EmDNAChemistry_option3 is available in Geant4-DNA version 10.7.

Resumen Objetivos: Conocer la calidad de vida, la capacidad funcional, psicológica y cognitiva de las personas mayores de 60 años con insuficiencia renal crónica según el tipo de tratamiento utilizado. Metodología: Se realizó una búsqueda sistemática de la literatura desde el 1 de enero de 2014 hasta el 29 de abril de 2020 utilizando las bases de datos PubMed, ProQuest, ScienceDirect y Scopus, y siguiendo la metodología propuesta en Preferred Items for Systematic Reviews and Meta-Analyses (PRISMA). Resultados: La calidad de vida abarca múltiples dimensiones y, aunque hay variedad de instrumentos para medirla, se obtienen resultados similares pero dispares, lo que no facilita la obtención de resultados universales de impacto. Las mujeres en hemodiálisis tienen peores resultados en el dominio físico y psicológico. No hay datos concluyentes en lo que se refiere a la mejora o empeoramiento de la calidad de vida con el paso de los años. El tratamiento conservador parece ser una alternativa que arroja mejores resultados en la calidad de vida frente a terapias como la diálisis, pero no en lo que se refiere a la tasa de supervivencia en edades comprendidas entre 70 y 80 años. Conclusiones: Sería adecuado medir la calidad de vida de forma estandarizada, al inicio del tratamiento, del mismo modo que otras variables biológicas, y así poder diseñar estrategias y/o intervenciones que puedan evitar complicaciones.

Personality questionnaires stand as crucial instruments in personnel selection but their limitations turn the interest towards alternatives like game-related assessments (GRAs). GRAs developed for goals other than fun are called serious games. Within them, gamified assessments are serious games that share similarities with traditional assessments (questionnaires, situational judgment tests, etc.) but they incorporate game elements like story, music, and game dynamics. This paper aims to contribute to the research on serious games as an alternative to traditional personality questionnaires by analyzing the characteristics of a gamified assessment called VASSIP. This gamified assessment, based on an existing measure of the Big Five personality traits, incorporates game elements such as storyfication, immersion, and non-evaluable gamified dynamics. The study performed included 98 university students (77.6% with job experience) as participants. They completed the original personality measure (BFI-2-S), the gamified evaluation of personality (VASSIP), a self-report measure of the main dimensions of job performance (task performance, contextual performance, and counterproductive work behaviors), and measures of applicant reactions to BFI-2-S and VASSIP. Results showed that the gamified assessment behaved similarly to the original personality measure in terms of reliability and participants' scores, although the scores in Conscientiousness were substantially higher in VASSIP. Focusing on self-reports of the three dimensions of job performance, regression models showed that the gamified assessment could explain all of them. Regarding applicant reactions, the gamified assessment obtained higher scores in perceptions of comfort, predictive validity, and attractiveness, although the effect size was small except for the latter. Finally, all applicant reactions except for attractiveness were related to age and personality traits. In conclusion, gamified assessments have the potential to be an alternative to traditional personality questionnaires but VASSIP needs more research before its application in actual selection processes.

IntroductionAutism Spectrum Disorder (ASD) and epilepsy pose significant challenges for early diagnosis during childhood. Current scientific literature does not reflect robust action protocols that allow for a detailed screening of difficulties in this population, especially in areas such as language, cognition, and sensory profile. Additionally, detecting epilepsy before the age of 4 is established as a major current public health challenge in our society.ObjectiveThe aim was to evaluate a patient exhibiting symptoms compatible with both ASD and epilepsy, determining the linguistic, cognitive, and sensory profile through a clinical assessment protocol. Furthermore, the objective included establishing a diagnosis of ASD.MethodThis single-case study (N = 1) presents the evaluation of a 7-year-old patient with suspected ASD, experiencing a decline in linguistic and cognitive competencies following a documented epileptic episode. Evaluation was conducted using instruments such as CELF-5, PROLEC-R, WISC-V, ENFEN, PS-2, ADI-R, and ADOS-2.ResultsFollowing assessment of language, cognition, sensory aspects, and behaviors associated with ASD, the diagnosis of ASD was confirmed in the patient, along with impairments in expressive and receptive language, executive functioning, and alterations in the sensory profile.ConclusionDiagnosing ASD and epilepsy, as well as their evaluation, is a complex process requiring interdisciplinary assessment involving a detailed exploration of all functional competencies in individuals with this comorbidity. Future studies should focus on creating and improving existing protocols to develop optimal and effective evaluation strategies for assessing this population during childhood.

PurposeSimulation of indirect damage originating from the attack of free radical species produced by ionizing radiation on biological molecules based on the independent pair approximation is investigated in this work. In addition, a new approach, relying on the independent pair approximation that is at the origin of the independent reaction time (IRT) method, is proposed in the chemical stage of Geant4-DNA.MethodsThis new approach has been designed to respect the current Geant4-DNA chemistry framework while proposing a variant IRT method. Based on the synchronous algorithm, this implementation allows us to access the information concerning the position of radicals and may make it more convenient for biological damage simulations. Estimates of the evolution of free species as well as biological hits in a segment of DNA chromatin fiber in Geant4-DNA were compared for the dynamic time step approach of the step-by-step (SBS) method, currently used in Geant4-DNA, and this newly implemented IRT.ResultsResults show a gain in computation time of a factor of 30 for high LET particle tracks with a better than 10% agreement on the number of DNA hits between the value obtained with the IRT method as implemented in this work and the SBS method currently available in Geant4-DNA.ConclusionOffering in Geant4-DNA more efficient methods for the chemical step based on the IRT method is a task in progress. For the calculation of biological damage, information on the position of chemical species is a crucial point. This can be achieved using the method presented in this paper.

Plasma ctDNA is a promising method to determine patient outcome in multiple cancer types. Here, the authors use shallow WGS to create machine learning signatures to identify tumor phenotypes and predict therapy response in patients with metastatic breast cancer.

PurposeThe simulation of individual particle tracks and the chemical stage following water radiolysis in biological tissue is an effective means of improving our knowledge of the physico-chemical contribution to the biological effect of ionizing radiation. However, the step-by-step simulation of the reaction kinetics of radiolytic species is the most time-consuming task in Monte Carlo track-structure simulations, with long simulation times that are an impediment to research. In this work, we present the implementation of the independent reaction times (IRT) method in Geant4-DNA Monte Carlo toolkit to improve the computational efficiency of calculating G-values, defined as the number of chemical species created or lost per 100 eV of deposited energy.MethodsThe computational efficiency of IRT, as implemented, is compared to that from available Geant4-DNA step-by-step simulations for electrons, protons and alpha particles covering a wide range of linear energy transfer (LET). The accuracy of both methods is verified using published measured data from fast electron irradiations for • OH and eaq- for time-dependent G-values. For IRT, simulations in the presence of scavengers irradiated by cobalt-60 γ-ray and 2 MeV protons are compared with measured data for different scavenging capacities. In addition, a qualitative assessment comparing measured LET-dependent G-values with Geant4-DNA calculations in pure liquid water is presented.ResultsThe IRT improved the computational efficiency by three orders of magnitude relative to the step-by-step method while differences in G-values by 3.9% at 1 μs were found. At 7 ps, • OH and eaq- yields calculated with IRT differed from recent published measured data by 5% ± 4% and 2% ± 4%, respectively. At 1 μs, differences were 9% ± 5% and 6% ± 7% for • OH and eaq- , respectively. Uncertainties are one standard deviation. Finally, G-values at different scavenging capacities and LET-dependent G-values reproduced the behavior of measurements for all radiation qualities.ConclusionThe comprehensive validation of the Geant4-DNA capabilities to accurately simulate the chemistry following water radiolysis is an ongoing work. The implementation presented in this work is a necessary step to facilitate performing such a task.

In recent years, there has been an increase in the prevalence of comorbidity between ASD and epilepsy in the pediatric population. Children with ASD and epilepsy often exhibit greater impairments in executive functions such as cognitive flexibility, planning, inhibition, and emotional control, as well as in language dimensions such as phonology, semantics, morphosyntax, and pragmatics. These impairments can significantly impact their maturation and development. The aim of this study was to assess and compare the executive functioning and language skills of 150 participants, divided into three groups: one with ASD only, another with epilepsy only, and the third group with both ASD and epilepsy. The study utilized the Behavior Rating Inventory of Executive Function (BRIEF-2) and Neuropsychological Evaluation of Executive Functions in Children (ENFEN) to assess executive functions, and Clinical Evaluation of Language Fundamentals 5 (CELF-5) to evaluate language skills. The results indicated that participants with this comorbidity had lower scores in both executive functioning and language skills compared to children with only ASD or epilepsy. The presence of epilepsy significantly limits the executive and linguistic performance of children with ASD, negatively affecting language acquisition, functionality, and the ability to carry out basic life activities independently.

Wireless chargers for electric vehicles are usually based on a magnetic field between two coils to transfer power without cables. Metallic objects in the volume comprised among these coils affect the magnetic field, reduce the power transferred to the load, and also result in hazards. Therefore, the implementation of techniques suitable to detect foreign objects is mandatory. The accurate modelling of the objects can help in the precision of the methods used for their detection. In this paper, we accurately identify the equivalent electrical model of a specific foreign object. The main advantage of using this model consists of the possibility of evaluating the performance of the whole charging system by performing time-domain simulations instead of complex finite element analysis. This is of interest for techniques using sensing coils and for self-sensing approaches. In particular, we have modelled a beverage can, which is an object expected in typical EV wireless chargers. The model is validated by comparing simulations based on this model and experimental results. From this analysis, some hot areas where the object causes a higher impact are identified. The procedure can be extended to other objects.

A key component of the magnetic resonant chargers is the coupler, which must be connected to the compensation networks to improve the power transfer. The design of both structures are tightly related since the configuration of one affects the other. Thus, the integration of both structures is convenient to ease the development of other systems of the wireless charger such as the power converters and control. This integration can be optimized if physical aspects are considered. In this paper, we propose a novel physical integration of circular pads and a LCC-LCC compensation. If both systems are connected without any specific consideration, the inclusion of the reactive components in this high-order compensation network derives in a more bulky-structure. Our proposal consists in implementing the inductors of the compensation networks in the same structure of the power coils, leading to a compact system. The position of the compensation coils must be carefully analysed in order to minimise undesired coupling effects. In the proposed integration approach, we have analysed the coupling coefficients between the magnetic components for several positions to identify the optimised configuration. The feasibility of this compact structure has been validated in a prototype, proving that the power transfer levels are suitable. These tests have been carried out for different misalignment conditions, which could model its performance for dynamic charging.

Entrepreneurship education represents a popular area of contemporary study. Nonetheless, topical interest is heavily biased towards final outcomes, such as entrepreneurial intentions or ending motives to become an entrepreneur. In this regard, further development is needed to unearth the pedagogical processes that allow these perceived beneficial outcomes to emerge. The aim of this paper is to approach a commonly studied outcome variable -- student motivation -- from a novel perspective. An attempt is made towards its reframing as a processual construct that energises and directs effective engagement in learning itself. Contributing to the sharing of innovative pedagogical best practice and the linking of outcomes to methods of teaching, a way through which students' motivation can be ignited and sustained is exposed. Specifically, an original approach towards increasing student autonomy is put forward and critiqued.

Summary: Background: The prevalence and impact of alcohol withdrawal syndrome (AWS) in patients with alcohol-associated hepatitis (AH) are unknown. In this study, we aimed to investigate the prevalence, predictors, management, and clinical impact of AWS in patients hospitalized with AH. Methods: A multinational, retrospective cohort study enrolling patients hospitalized with AH at 5 medical centres in Spain and in the USA was performed between January 1st, 2016 to January 31st, 2021. Data were retrospectively retrieved from electronic health records. Diagnosis of AWS was based on clinical criteria and use of sedatives to control AWS symptoms. The primary outcome was mortality. Multivariable models controlling for demographic variables and disease severity were performed to determine predictors of AWS (adjusted odds ratio [OR]) and the impact of AWS condition and management on clinical outcomes (adjusted hazard ratio [HR]). Findings: In total, 432 patients were included. The median MELD score at admission was 21.9 (18.3–27.3). The overall prevalence of AWS was 32%. Lower platelet levels (OR = 1.61, 95% CI 1.05–2.48) and previous history of AWS (OR = 2.09, 95% CI 1.31–3.33) were associated with a higher rate of incident AWS, whereas the use of prophylaxis decreased the risk (OR = 0.58, 95% CI 0.36–0.93). The use of intravenous benzodiazepines (HR = 2.18, 95% CI 1.02–4.64) and phenobarbital (HR = 2.99, 95% CI 1.07–8.37) for AWS treatment were independently associated with a higher mortality. The development of AWS increased the rate of infections (OR = 2.24, 95% CI 1.44–3.49), the need for mechanical ventilation (OR = 2.49, 95% CI 1.38–4.49), and ICU admission (OR = 1.96, 95% CI 1.19–3.23). Finally, AWS was associated with higher 28-day (HR = 2.31, 95% CI 1.40–3.82), 90-day (HR = 1.78, 95% CI 1.18–2.69), and 180-day mortality (HR = 1.54, 95% CI 1.06–2.24). Interpretation: AWS commonly occurs in patients hospitalized with AH and complicates the hospitalization course. Routine prophylaxis is associated with a lower prevalence of AWS. Prospective studies should determine diagnostic criteria and prophylaxis regimens for AWS management in patients with AH. Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

La región del sur de Aragón estuvo inmersa en una serie de flujos económicos, sociales y culturales a finales de la Edad Media. Así, las elites aldeanas desarrollaron hospitales a la vez que sus villas maduraron jurídicamente y obtuvieron privilegios de celebración de mercados y ferias. El objetivo de este artículo es comparar la financiación y los gastos de los hospitales de Rubielos de Mora y Puertomingalvo, dos instituciones en las que se aprecia una transición de una economía doméstica a una de mercado. Es posible observar cómo este último centro asistencial funcionó como una empresa de la caridad gracias a su política en el mercado de la deuda y la incorporación paulatina de documentación administrativa (libros de cuentas, albaranes, registros notariales, etc.).

IntroductionThe pediatric population with Autism Spectrum Disorder (ASD) and epilepsy presents behavioral and emotional alterations that hinder their correct developmental maturation as well as their integration in different contexts such as school, family or social. This population shows atypical behavioral and emotional patterns, with difficulties in emotional regulation, understanding of emotions, aggressiveness, or low frustration tolerance. They also present alterations in executive functions, which significantly influence the emotional and behavioral characteristics of this population. Research suggests that epilepsy worsens the emotional, behavioral, and executive functioning status.ObjectiveTo explore differences in behavioral, emotional, and executive functioning profile in individuals with a diagnosis of ASD, epilepsy, and ASD with epilepsy.MethodIn this quasi-experimental and cross-sectional study, a total of 170 participants were selected and distributed into three groups: a group of participants with ASD, a group with epilepsy, and a group of participants with ASD and epilepsy. The SENA, BASC-3, and ENFEN tests were administered to verify the behavioral, emotional, and executive functioning profile in the three groups.ResultsThe results indicate that individuals diagnosed with ASD and epilepsy present greater emotional, behavioral, and executive functioning alterations compared to those who only present ASD or epilepsy.ConclusionIndividuals with ASD and epilepsy present significant alterations in emotional, behavioral, and executive functioning processes, which hinder their adaptation to different contexts, as well as decreasing their quality of life and that of their family.

Juan Téllez Girón transformó urbanísticamente la villa de Osuna durante la primera mitad del siglo XVI. Incorporó en su programa constructivo y devocional el hospital de la Encarnación, demostrando un alto grado de implicación en la reforma de la caridad, lo que también se manifestó en otras poblaciones de su estado señorial como Peñafiel. Lo más destacable de la fundación ursaonense fue la utilización de distintos modelos hospitalarios peninsulares (Burgos, Toledo, Sevilla y Palma del Río) y extranjeros (Santo Espíritu de Roma) para formalizar la base jurídica de la nueva institución. Ordenanzas y privilegios fueron enviados desde diferentes localidades trazando con su movimiento una enmarañada madeja de relaciones y conexiones que pueden rastrearse gracias al archivo nobiliario y un análisis histórico y paleográfico de sus diplomas.

Blood testing has traditionally been the gold standard for the physiological analysis and monitoring of professional athletes. In recent years, blood testing has moved out of the laboratory thanks to portable handheld devices, such as lactate meters. However, despite its usefulness and widespread use, blood testing has several drawbacks and limitations, such as the need for the athlete to stop exercising for blood extraction and the inability to have data continuously collected. In this scenario, sweat has become an alternative to blood testing because of its rich content of electrolytes and metabolites, as well as small quantities of sugars, proteins, and ions. Nevertheless, there are few devices capable of analyzing this biofluid and providing useful information to users. In this paper, an electronic system designed for the autonomous analysis of sweat electrolytes and metabolites along with heart rate dynamics is presented. This system is part of a novel wearable device tailored for athletes that offers to the user a real-time assessment of their physiological status and performance.