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Abstract Introduction Birth weight is described as one of the main determinants of newborns’ chances of survival. Among the associated causes, or risk factors, the mother’s nutritional status strongly influences fetal growth and birth weight outcomes of the concept. This study evaluates the association between food deserts, small for gestational age (SGA), large for gestational age (LGA) and low birth weight (LBW) newborns. Design This is a cross-sectional population study, resulting from individual data from the Live Birth Information System (SINASC), and commune data from mapping food deserts (CAISAN) in Brazil. The newborn’s size was defined as follows: appropriate for gestational age (between 10 and 90th percentile), SGA ( 90th percentile), and low birth weight

Abstract Background Antibiotics are synthetic or natural substances used to treat bacterial infectious diseases. When used incorrectly, they can be a factor in the development of antimicrobial resistance, increased treatment time, costs, and mortality. The present study aimed to assess the pattern of inappropriate use of antibiotics and their predictors in pediatric patients admitted to the Central Hospital in Nampula, Mozambique. Methods A cross-sectional, retrospective study with a quantitative approach was conducted between January and July 2019. The population consisted of children ages 0–10 years hospitalized in the pediatric ward I. Binary logistic regression was used to determine risk factors for the inappropriate use of antibiotics with 95% confidence interval. Results The prevalence of antibiotic use among pediatric patients was 97.5%. Of the 464 antibiotics prescribed, 39.9% were for patients suffering from gastroenteritis, 21.8% and 9.1% for those affected with pneumonia and malaria, respectively. Most antibiotics were for parenteral use (95.9%, 445/464). Many (36.5%) of the prescriptions had errors, primarily in the duration of treatment (74.0%) or dosage (24.4%). Binary logistic regression analysis revealed that patients prescribed ≥ 3 antibiotics (OR = 2.83, 95% CI 1.245–6.462, p-value = 0.013) or hospitalized for a short time (OR = 1.88, 95% CI 1.133–2.3140, p-value = 0.015) were more likely to experience inappropriate use of antibiotics. Conclusion The study showed both a high prevalence of antibiotic use and a high error rate in prescriptions, especially among patients prescribed ≥ 3 antibiotics or hospitalized for a short time. These results are concerning, since inappropriate and excessive use of antibiotics is a major factor in the development of antibiotic-resistant microorganisms. Therefore, policies to reduce the inappropriate and excessive use of antibiotics are necessary.

Communication through social media is a phenomenon whose relevance has involved the consideration of online discourse in the language teaching context. This article explores the functionality of Twitter (now called "X") for science dissemination within the teaching and learning of English as a foreign language. To do this, 100 tweets from the accounts @WWF and @Greenpeace were gathered and analysed from the perspective of digital discourse analysis and communicative language teaching. I argue that using these tweets encourages the development of key competencies, provides room for the practice of integrated skills, and enhances the application of 21st-century skills. Conclusively, science dissemination tweets may be considered adequate for teaching and learning English.

Mª del Carmen Álamo,1 Sebastian Ochenduszko,2 Guillermo Crespo,3 Mónica Corral,4 Juana Oramas,5 Pilar Sancho,6 Javier Medina,7 Fernando Garicano,8 Pedro López,9 Begoña Campos Balea,10 Analia Rodríguez Garzotto,11 Eva Muñoz-Couselo12,13 1Oncology Department, Hospital Universitario Virgen Macarena, Sevilla, Spain; 2Oncology Department, Hospital Universitario Dr. Peset, Valencia, Spain; 3Oncology Department, Hospital Universitario de Burgos, Burgos, Spain; 4Oncology Department, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain; 5Oncology Department, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain; 6Oncology Department, Hospital Universitario Virgen del Rocío, Sevilla, Spain; 7Oncology Department, Hospital Universitario Virgen de la Salud, Toledo, Spain; 8Oncology Department, Hospital de Galdakao, Bizkaia, Spain; 9Oncology Department, Complejo Hospitalario General de Jaén, Jaén, Spain; 10Oncology Department, Hospital Lucus Augusti, Lugo, Spain; 11Medical Department and Strategy, Roche S.A, Madrid, Spain; 12Oncology Department, Hospital Universitario Vall d´Hebron, Barcelona, Spain; 13VHIO Vall d’Hebron Institute on Oncology, Barcelona, SpainCorrespondence: Eva Muñoz-CouseloOncology Department, Hospital Universitario Vall d´Hebron, Passeig de la Vall d’Hebron, 119, Barcelona, 08035, SpainEmail emunoz@vhio.netBackground: The combination of BRAF and MEK inhibitors delays the onset of resistance and provides more sustained and dramatic responses in comparison with a BRAF inhibitor in monotherapy. The objective of the study was to evaluate the effectiveness of the combination therapy with vemurafenib/cobimetinib in terms of durability, and to describe differential characteristics in patients associated to durable responses in real-world settings.Patients and Methods: Retrospective, observational, cross-sectional, multicenter study involving 41 patients with advanced melanoma harboring a BRAFV600 mutation who initiated a combination therapy with vemurafenib/cobimetinib between May 2018 and March 2019. Participants were differentiated regarding the durability of the response: durable (complete response, CR, or a partial response, PR, for at least 12 months) and non-durable (stable disease, SD, progressive disease, PD, or CR/PR < 12 months). Secondary endpoints included treatment adherence, labor productivity, anxiety/depression, and safety profile.Results: During the combination therapy, 12 patients (29.3%) had a CR, 19 a PR (46.3%), 5 showed SD (12.2%), and 5 had PD. A total of 12 patients (29.3%) were considered as achieving a durable response and 29 (70.7%) as a non-durable one. Practically all sociodemographic and clinical characteristics were similar between patients. Body mass index was the only differential factor (with higher body mass index achieving a non-durable response). The treatment adherence was 100% in patients with durable response and 66.7% in those with non-durable.Conclusion: The combination treatment with vemurafenib/cobimetinib results in an important impact on long-term survival, leading to a steady CR in one-third of the patients.Keywords: vemurafenib, cobimetinib, BRAF, metastatic melanoma, durable response, clinical practice

This study investigates the reasons behind the decision to send children aged under three to ECEC (Early Childhood Education and Care) and the causes that may explain why some families send their child to ECEC once they reach the age of two while others decide to do so at an earlier age. To answer the first question posed a probit model is used, while to answer the second query a Heckprobit model is estimated to take into account possible selection bias. The data for this study was taken from an unpublished database compiled by the Spanish National Institute for Educational Evaluation, which gathers information from 1,166 children schooled in the Infant Education stage. The results of our estimations show that the decision to enroll children under three in ECEC services depends fundamentally on the sociodemographic characteristics of the mother (educational level, employment situation and age), on household size (if it is a large family) and on the availability of ECEC services in the area in which the child lives. Our study has also shown that the only variable regarding factors that explain the differences in the age of access to ECEC services, two or under two, is the importance that parents place on their children developing empathy towards others. On the basis of our results, the study offers recommendations aimed at the progressive universalization of this initial educational stage.

In this paper, a quantitative, descriptive, and correlational research is carried out on the perceptions of the digital competence of Latin American engineering professors, their assessment of the didactic use of Information and Communication Technologies (ICT) in different didactic areas (interaction, communication, distribution, and administration and evaluation), and on the growth or decrease in the frequency of their use after the COVID-19 pandemic. In particular, the Latin American engineering professors' perceptions of digital competence is studied. Also, the existence of gender gaps (both in general and differentiating between private and public universities, and between professors with a more or less teaching experience) has been explored in the assessment of the perceptions of digital competence and the didactic use of ICT by engineering professors, as well as in the influence that the pandemic has had on the habits of ICT use. The results reveal that the use of ICT by engineering professors has achieved increases of over 40% in some educational activities due to the pandemic, and it has had a homogenizing effect on the frequency of use of ICT tools in the different activities. Female engineering professors have increased their use of ICT more than males, and engineering professors in private universities more than those in public universities. Consequently, it is suggested to the universities to reinforce the continuous training of engineering professors, considering the pedagogical specificities of engineering education and the necessary integration of ICT in the teaching activity of female engineering professors.

High dropout rates constitute a major concern for higher education institutions, due to their economic and academic impact. The problem is particularly relevant for institutions offering online courses, where withdrawal ratios are reported to be higher. Both the impact and these high rates motivate the implementation of interventions oriented to reduce course withdrawal and overall institutional dropout. In this paper, we address the identification of populations of learners at risk of withdrawing from higher education online courses. This identification is oriented to design interventions and is carried out using survival analysis. We demonstrate that the method's longitudinal approach is particularly suited for this purpose and provides a clear view of risk differences among learner populations. Additionally, the method quantifies the impact of underlying factors, either alone or in combination. Our practical implementation used an open dataset provided by The Open University. It includes data from more than 30,000 students enrolled in different courses. We conclude that low-income students and those who report a disability comprise risk groups and are thus feasible intervention targets. The survival curves also reveal differences among courses and show the detrimental effect of early dropout on low-income students, worsened throughout the course for disabled students. Intervention strategies are proposed as a result of these findings. Extending the entire refund period and giving greater academic support to students who report disability are two proposed strategies for reducing course withdrawal.

This article analyzes the self-concept about digital competence in university professors of Sciences, Health Sciences and Engineering and the impact that the COVID-19 pandemic has had on the Information and Communication Technologies (ICT) use habits of professors in these areas. For this purpose, a survey designed by the authors was completed by 340 university professors in the aforementioned areas. Based on the answers obtained from this survey, a descriptive quantitative analysis of the assessments of the self-concept of digital competence and training of the participants, of the didactic use of ICT and the frequency of their use before and after the pandemic has been carried out. The results showed that the digital competence of the professors is intermediate, but their training is valued as low, especially in Sciences and Health Sciences. The assessment of ICT is very good. The pandemic has caused a generalized increase in the use of ICT, mainly in Health Sciences, which is the area in which university students were most reluctant to use them. In addition, a gender gap which did not exist before the pandemic has been generated favoring females in the use of ICT in Science and Engineering. An age-based digital gap that existed before the pandemic has also been corrected in Health Sciences.

Bullying is a relevant concept in education, composed by different dimensions and it is significantly associated to other variables. Therefore, there is a need for an instrument which can analyze the level of bullying as a single dimension, as the Cisneros Self-test on Bullying (Oñate & Piñuel, 2005). This instrument analyzes the intensity of bullying and to value its relevance on the different variables mentioned above. Our main goal was to validate this instrument in 531 Dominican secondary students. To validate it, we utilized two instruments: the Emotional Instability Scale (Caprara & Pastorelli, 1993) and the Prosocial Conduct Questionnaire (Caprara & Pastorelli, 1993). Several competitive structural models were estimated, and results supported the reliability and validity of this instrument. Therefore, we can conclude that the Cisneros's scale is a good instrument to measure global bullying. We highlight its influence on future interventions considering the relevance that bullying has on many other variables as aggressiveness, prosocial behavior or suicide ideation.

Objectives: Analysis of the player profiles of professors is a fruitful line of research because player profiles may influence the design of gamified situations. We studied a sample of 243 university professors in Mexico to analyze the player profiles with which they identify and those they consider most effective didactically in gamified situations. Method: Descriptive quantitative research was used to analyze the distributions of the responses to a questionnaire given to a group of 243 professors from different Mexican universities. These responses have been statistically analyzed by computing the proportions of player profile choices and applying Pearson's chisquare test of independence to identify significant differences in these choices. Results: 42.4% of the participants identify as Explorers, the most frequent player profile among the participants. However, about 15.6% of them consider that their player profile is not the most suitable for learning. Player profiles chosen by the Mexican professors diverge from the player profiles of the students described in previous studies. Significant differences by gender, area of knowledge, and previous training in gamification are also identified. Conclusion: There is a strong gap between the player profiles of the participating professors and the profile that, in their opinion, is most suitable for learning. In addition, it has been identified that gender, area of knowledge, and previous experience in the use of gamification are influential factors in the player profiles of the professors. Implication for Practice: The training of professors in gamification should be adapted to the specificities of each area of knowledge. This will allow professors to develop pedagogical skills in gamification that will help them adapt gamified didactic situations to the needs of students.

Academic institutions dedicate a substantial effort to ensure the academic success of their students. At the course level, teachers recommend learning paths (RLPs) for students to guarantee the achievement of their learning outcomes. In terms of performance, these kinds of approaches are deemed more effective than others based uniquely on performing a collection of independent activities. However, there is neither systematic means to validate if following the learning path (LP) is effective, nor to assess whether and to what extent students adhere to these recommendations. This article introduces a novel technique for modeling recommended LPs, including not only an evaluation of path utility, but also a quantitative measure of student adherence thereto using process mining, and more precisely, log skeletons. Following an event abstraction process regarding real student-recorded activity, a scoping process is employed to retain the trajectories that adhere to the prescribed LP. The method based on process mining is translated into practice by considering an online university mathematics course. Results confirm the applicability of the method and, in this case, reveal that adhering to the suggested path correlates positively with final grades. Few students strictly follow the prescribed LP, although the vast majority support it. The method can be easily applied to overcome several challenges associated with enhancing academic performance from the learning analytics perspective.

Background: It is widely recognised internationally that participation in higher education is likely to lead to increased opportunities and resources. However, only a minority of learners from Roma backgrounds continue into post-compulsory education. As important research into inclusion continues, more attention must be paid to the identification of practices that can help break down barriers and support the participation of Roma students in post-compulsory education. Purpose: The research sought to gain insight into particular factors influencing the decision-making processes of three students from Roma backgrounds who chose to pursue an academic pathway. Method: The setting for this qualitative study was a school in Spain located in a socioeconomically disadvantaged and predominantly Roma neighbourhood whose students had never previously participated in pre-university studies (courses preparing students for university entrance). In-depth interviews were conducted with three Roma students in their last year of compulsory education who were about to move on to pre-university studies, as well as with three significant adults: a Roma mother, a Roma role model working at the school, and the school principal. Findings: The analysis of participants' narratives suggested that, according to their views, the implementation of a set of successful educational actions involving high expectations, the involvement of Roma families, the influence of positive Roma role models and engagement with dialogic interactions contributed to the continuation of these three Roma students on a trajectory towards post-compulsory education. Conclusions: The study highlights some noteworthy factors that can be involved in transforming a context from one where access to university is not considered to be an option and towards a new one in which university becomes a real choice.

Virtual Reality (VR) is a computer-generated environment with noteworthy didactic applications in different educational levels and areas of knowledge. The study of the perceptions of the agents involved about the use of VR in lectures is a fruitful line of research because it has implications in terms of the measures to be taken to improve the training and competence of professors in its use. In this paper, a quantitative, descriptive, and correlational research is carried out on the assessments of a sample of 1638 Latin American university professors on both (i) the didactic use of VR and (ii) the influence of the professors' area of knowledge on these assessments. For this purpose, a validated questionnaire was used, the responses to which were subjected to statistical analysis. As a result, it was found that the ratings of VR are very high, but professors believe that their digital skills for its use are insufficient. In addition, the professors' area of knowledge significantly influences their ratings, being higher in the areas of knowledge in which professors have a better self-concept of their digital skills. Furthermore, gender gaps have also been identified in the answers given, which behave differently according to the area of knowledge. Finally, some conclusions, implications, and recommendations are drawn from the results obtained.

Practitioners of the statistics course embedded in a computer science programme at a fully online university were concerned with the high dropout rate. In the academic year 2018-19, they decided to carry out a two-phase project in order to address this issue. In the first phase, an early classifier to identify students at risk of dropping out of the 2018-19 statistics course was determined. The second phase was planned to design and implement an early intervention based on the results of the first phase. This article presents the analysis of this intervention. In the 2019-20 online statistics course, 35 students did not submit the first few quizzes before the respective deadlines. They were the target of this intervention, which gave them the chance to change their recent past by submitting the unsubmitted quizzes. Students were encouraged to change by means of an email message. The aim of the intervention was to reduce the dropout rate among the targeted students. Our analysis also includes the students' perception of the intervention collected via a set of interviews. The results show that the intervention clearly had a beneficial effect for some students.

Abstract Background Although insulin resistance (IR) is among the most frequent and pathogenically relevant complications accompanying childhood obesity, its role in modulating and exacerbating obesity pathophysiology has not yet been completely clarified. Methods To get deeper insights into the interplay between childhood obesity and IR, we leveraged a comprehensive experimental design based on a combination of observational data, in vivo challenge tests (i.e., oral glucose tolerance test), and ex vivo assays (i.e., incubation of erythrocytes with insulin) using a population comprising children with obesity and IR, children with obesity without IR, and healthy controls, from whom plasma and erythrocyte samples were collected for subsequent metabolomics analysis. Results Children with concomitant IR showed exacerbated metabolic disturbances in the crosstalk between endogenous, microbial, and environmental determinants, including failures in energy homeostasis, amino acid metabolism, oxidative stress, synthesis of steroid hormones and bile acids, membrane lipid composition, as well as differences in exposome-related metabolites associated with diet, exposure to endocrine disruptors, and gut microbiota. Furthermore, challenge tests and ex vivo assays revealed a deleterious impact of IR on individuals’ metabolic flexibility, as reflected in blunted capacity to regulate homeostasis in response to hyperinsulinemia, at both systemic and erythroid levels. Conclusions Thus, we have demonstrated for the first time that metabolite alterations in erythrocytes represent reliable and sensitive biomarkers to disentangle the metabolic complexity of IR and childhood obesity. This study emphasizes the crucial need of addressing inter-individual variability factors, such as the presence of comorbidities, to obtain a more accurate understanding of obesity-related molecular mechanisms.

Abstract The diagnostic odysseys for rare disease patients are getting shorter as next-generation sequencing becomes more widespread. However, the complex genetic diversity and factors influencing expressivity continue to challenge accurate diagnosis, leaving more than 50% of genetic variants categorized as variants of uncertain significance. Genomic expression intricately hinges on localized interactions among its products. Conventional variant prioritization, biased towards known disease genes and the structure-function paradigm, overlooks the potential impact of variants shaping the composition, location, size, and properties of biomolecular condensates, genuine membraneless organelles swiftly sensing and responding to environmental changes, and modulating expressivity. To address this complexity, we propose to focus on the nexus of genetic variants within biomolecular condensates determinants. Scrutinizing variant effects in these membraneless organelles could refine prioritization, enhance diagnostics, and unveil the molecular underpinnings of rare diseases. Integrating comprehensive genome sequencing, transcriptomics, and computational models can unravel variant pathogenicity and disease mechanisms, enabling precision medicine. This paper presents the rationale driving our proposal and describes a protocol to implement this approach. By fusing state-of-the-art knowledge and methodologies into the clinical practice, we aim to redefine rare diseases diagnosis, leveraging the power of scientific advancement for more informed medical decisions.

Abstract Background Insulin resistance is a frequent precursor of typical obesity and metabolic syndrome complications. However, accurate diagnosis remains elusive because of its pathophysiological complexity and heterogeneity. Herein, we have explored the utility of insulin secretion dynamics in response to an oral glucose tolerance test as a surrogate marker to identify distinct metabotypes of disease severity. Methods The study population consisted of children with obesity and insulin resistance, stratified according to the post-challenge insulin peak timing (i.e., early, middle, and late peak), from whom fasting and postprandial plasma and erythrocytes were collected for metabolomics analysis. Results Children with late insulin peak manifested worse cardiometabolic health (i.e., higher blood pressure, glycemia, and HOMA-IR scores) than early responders. These subjects also showed more pronounced changes in metabolites mirroring failures in energy homeostasis, oxidative stress, metabolism of cholesterol and phospholipids, and adherence to unhealthy dietary habits. Furthermore, delayed insulin peak was associated with impaired metabolic flexibility, as reflected in compromised capacity to regulate mitochondrial energy pathways and the antioxidant defense in response to glucose overload. Conclusions Altogether, these findings suggest that insulin resistance could encompass several phenotypic subtypes characterized by graded disturbances in distinctive metabolic derangements occurring in childhood obesity, which serve as severity predictive markers.

Abstract The pathological role of interferon signaling is emerging in neuroinflammatory disorders, yet, the specific role of Interferon Regulatory Factor 3 (IRF3) in neuroinflammation remains poorly understood. Here, we show that global IRF3 deficiency delays TLR4-mediated signaling in microglia and attenuates the hallmark features of LPS-induced inflammation such as cytokine release, microglial reactivity, astrocyte activation, myeloid cell infiltration, and inflammasome activation. Moreover, expression of a constitutively active IRF3 (S388D/S390D: IRF3-2D) in microglia induces a transcriptional program reminiscent of the Activated Response Microglia and the expression of genes associated with Alzheimer’s disease, notably apolipoprotein-e. Using bulk-RNAseq of IRF3-2D brain myeloid cells, we identified Z-DNA binding protein-1 (ZBP1) as a target of IRF3 that is relevant across various neuroinflammatory disorders. Lastly, we show IRF3 phosphorylation and IRF3-dependent ZBP1 induction in response to Aβ in primary microglia cultures. Together, our results identify IRF3 as an important regulator of LPS and Aβ -mediated neuroinflammatory responses and highlight IRF3 as a central regulator of disease-specific gene activation in different neuroinflammatory diseases.

Abstract Background We have previously demonstrated the significant reliance of pancreatic Cancer Stem Cells (PaCSCs) on mitochondrial oxidative phosphorylation (OXPHOS), which enables versatile substrate utilization, including fatty acids (FAs). Notably, dysregulated lipid scavenging and aberrant FA metabolism are implicated in PDAC progression. Methods & results Our bioinformatics analyses revealed elevated expression of lipid metabolism-related genes in PDAC tissue samples compared to normal tissue samples, which correlated with a stemness signature. Additionally, PaCSCs exhibited heightened expression of diverse lipid metabolism genes and increased lipid droplet accumulation compared to differentiated progenies. Treatment with palmitic, oleic, and linolenic FAs notably augmented the self-renewal and chemotherapy resistance of CD133+ PaCSCs. Conversely, inhibitors of FA uptake, storage and metabolism reduced CSC populations both in vitro and in vivo. Mechanistically, inhibition of FA metabolism suppressed OXPHOS activity, inducing energy depletion and subsequent cell death in PaCSCs. Importantly, combining a FAO inhibitor and Gemcitabine treatment enhanced drug efficacy in vitro and in vivo, effectively diminishing the CSC content and functionality. Conclusion Targeting FAO inhibition represents a promising therapeutic strategy against this highly tumorigenic population.