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Exhaled breath tests (BTs) are the main diagnostic method for fructose and lactose malabsorption/intolerance (FI and LI, respectively) and for detecting small intestine bacterial or methanogen overgrowth (SIBO/IMO). Although FI/LI-BTs may provide evidence of the presence of SIBO/IMO, there is limited literature evaluating their reliability for this purpose. The objective of this study was to assess the sensitivity and specificity of FI/LI-BTs in detecting SIBO and their concordance with SIBO-BTs in the identification of IMO.

The way we learn is changing, and this requires seeking learner-centred pedagogical strategies. Based on this idea, this paper is about the process of construction and validation of a pedagogical model approach based on the perspectives of co-design, learning pathways and self-regulated learning. Through a process of Design Based Research, different techniques and instruments have been applied to collect information aimed at the creation and validation of a co-design model in the construction of personal learning pathways. Among them is the validation of the results through an expert judgment carried out in a future workshop. These results and the methodology of how they were validated is the part that is presented in this work. The data show the dimensions of the model and its representation from two perspectives, teacher, and student. Both points of view have the objective that the students reach new knowledge and improve self-regulated learning, being the protagonists of the whole process. In addition, the work is a proposal for a strategy to be implemented in hybrid, online or mixed contexts where the students become the protagonists of their learning.

The development of mathematical skills for future engineers is essential. Game-based learning (GBL) and gamification have been widely used in elementary education, but less applied in higher education. The objective of this article was to evaluate the effect of didactic strategies mediated by games in the teaching of mathematics in first-year engineering students. A qualitative study was carried out. Five (5) teaching units were designed. Seven (7) focus groups were developed with 81 participants from the differential calculus course. The keyword in context-KWIC technique was used for the focus group analysis. The categories attention, relevance, confidence, and satisfaction (Keller's motivational model) were evaluated. An important contribution of the pedagogical strategy to student motivation, teamwork, commitment, and argumentation was verified. In conclusion, game-based learning makes it possible to strengthen the motivation of students in the educational processes of mathematics in engineering.

Abstract SDS22 forms an inactive complex with nascent protein phosphatase PP1 and Inhibitor-3. SDS22:PP1:Inhibitor-3 is a substrate for the ATPase p97/VCP, which liberates PP1 for binding to canonical regulatory subunits. The exact role of SDS22 in PP1-holoenzyme assembly remains elusive. Here, we show that SDS22 stabilizes nascent PP1. In the absence of SDS22, PP1 is gradually lost, resulting in substrate hyperphosphorylation and a proliferation arrest. Similarly, we identify a female individual with a severe neurodevelopmental disorder bearing an unstable SDS22 mutant, associated with decreased PP1 levels. We furthermore find that SDS22 directly binds to Inhibitor-3 and that this is essential for the stable assembly of SDS22:PP1: Inhibitor-3, the recruitment of p97/VCP, and the extraction of SDS22 during holoenzyme assembly. SDS22 with a disabled Inhibitor-3 binding site co-transfers with PP1 to canonical regulatory subunits, thereby forming non-functional holoenzymes. Our data show that SDS22, through simultaneous interaction with PP1 and Inhibitor-3, integrates the major steps of PP1 holoenzyme assembly.

Abstract Objective Duchenne and Becker muscular dystrophies (DMD and BMD) are dystrophinopathies caused by variants in DMD gene, resulting in reduced or absent dystrophin. These conditions, characterized by muscle weakness, also manifest central nervous system (CNS) comorbidities due to dystrophin expression in the CNS. Prior studies have indicated a higher prevalence of epilepsy in individuals with dystrophinopathy compared to the general population. Our research aimed to investigate epilepsy prevalence in dystrophinopathies and characterize associated electroencephalograms (EEGs) and seizures. Methods We reviewed 416 individuals with dystrophinopathy, followed up at three centers between 2010 and 2023, to investigate the lifetime epilepsy prevalence and characterize EEGs and seizures in those individuals diagnosed with epilepsy. Associations between epilepsy and type of dystrophinopathy, genotype, and cognitive involvement were studied. Results Our study revealed a higher epilepsy prevalence than the general population (1.4%; 95% confidence interval: 0.7–3.2%), but notably lower than previously reported in smaller dystrophinopathy cohorts. No significant differences were found in epilepsy prevalence between DMD and BMD or based on underlying genotypes. Cognitive impairment was not found to be linked to higher epilepsy rates. The most prevalent epilepsy types in dystrophinopathies resembled those observed in the broader pediatric population, with most individuals effectively controlled through monotherapy. Interpretation The actual epilepsy prevalence in dystrophinopathies may be markedly lower than previously estimated, possibly half or even less. Our study provides valuable insights into the epilepsy landscape in individuals with dystrophinopathy, impacting medical care, especially for those with concurrent epilepsy.

Los test de aliento espirado (TAE) son la principal herramienta diagnóstica en la evaluación de la malabsorción/intolerancia a fructosa (IF) y lactosa (IL) y para la detección del sobrecrecimiento bacteriano o metanógenico intestinal (SCBI/SCMI). En ocasiones, los TAE-IF/IL muestran hallazgos sugerentes de la presencia de SCBI o SCMI, pero los estudios que evalúan la fiabilidad de éstos son escasos. Nuestro objetivo es analizar la sensibilidad y especificidad de los TAE-IF/IL en la detección de SCBI y la concordancia en la identificación de SCMI.

Summary: CombiVacS study has demonstrated a strong immune response of the heterologous ChAdOx1-S/BNT162b2 vaccine combination. The primary outcomes of the study were to assess the humoral immune response against SARS-CoV-2, 28 days after a third dose of a mRNA vaccine, in subjects that received a previous prime-boost scheme with ChAdOx1-S/BNT162b2. Secondary outcomes extended the study to 3 and 6 months. The third vaccine dose of mRNA-1273 in naive participants previously vaccinated with ChAdOx1-S/BNT162b2 regimen reached higher neutralizing antibodies titers against the variants of concern Delta and BA.1 lineage of Omicron compared with those receiving a third dose of BNT162b2 at day 28. These differences between BNT162b2 and mRNA-1273 arms were observed against the ancestral variant G614 at day 90. Suboptimal neutralizing response was observed against BQ.1.1, XBB.1.5/XBB.1.9, and JN.1 in a relevant proportion of individuals 180 days after the third dose, even after asymptomatic Omicron breakthrough infections. EudraCT (2021-001978-37); ClinicalTrials.gov (NCT04860739).

Present-day society calls for new student-centred didactic methodologies that make the student an active participant in their learning process. Strategies aimed at training citizens and professionals must adapt and respond to a society that is constantly changing. In this context, self-regulated learning and educational co-design emerge as key concepts in the development of new educational approaches. The present study seeks to identify the elements shared by models of self-regulation and educational co-design in technology-enhanced learning environments. To this end, a systematic review of the scientific literature during the period 2014-2019 has been conducted. The search was carried out using five databases: (1) Ebsco Host; (2) Web of Science; (3) Scopus; (4) ERIC; (5) Dialnet. A total of 830 references and 21 papers meeting the criteria for inclusion were identified. An analysis of the studies selected enabled us to identify the self-regulation models associated with co-design learning processes, as well as the elements they have in common. These include planning, motivation, cognition, task management, collaboration, and degree of success. The results provide the first steps for the construction of a co-design model, which includes guidelines for the creation of personalised learning pathways in technology-enhanced environments.

En un contexto político y mediático marcado por la posverdad y la desinformación, el paltering emerge como un uso particularmente sofisticado del engaño. Escasamente estudiado en la literatura, el paltering consiste en inducir una idea engañosa a partir de un enunciado verdadero, lo que lo convierte en una técnica propagandística ventajosa, dado que en ocasiones resulta más sencillo construir la propaganda sobre una verdad. Este artículo estudia la representación mediática de dos casos de la política española relacionados con el paltering. Se realiza un análisis de contenido de la cobertura periodística de ambos casos de paltering en los cuatro diarios españoles con mayor audiencia. Los resultados indican que el paltering está presente en los medios (fundamentalmente en el género noticioso), que es reproducido sin cuestionar su veracidad, y que su repercusión mediática se exacerba en contexto electoral.

Este trabajo pretende adentrarse en el modo en que la naturaleza, en distintas formas, está incorporada a nuestro imaginario compartido sobre la brujería. La propuesta se inscribe en la línea de una investigación más amplia, que explora las imbricaciones entre el imaginario de la caza de brujas y los discursos feministas contemporáneos. Desde este punto de partida, nos interesa explorar qué géneros textuales se activan en las narrativas de la brujería, concretamente los que tratan del aquelarre como acontecimiento que encumbra el poder de la bruja, y qué cabida tiene lo fantástico en una pugna discursiva que interroga lo verosímil, lo mágico y, en definitiva, los límites de lo real. En nuestro estudio, partiremos de la historiografía tradicional sobre la caza de brujas para llegar a la crítica feminista, para desde ella ahondar en sus implicaciones sociales y políticas, para pensar en la bruja como construcción discursiva vinculada fuertemente a la naturaleza en diversas formas.

Abstract The most prevalent genetic form of inherited arrhythmogenic cardiomyopathy (ACM) is caused by mutations in desmosomal plakophilin-2 (PKP2). By studying pathogenic deletion mutations in the desmosomal protein PKP2, here we identify a general mechanism by which PKP2 delocalization restricts actomyosin network organization and cardiac sarcomeric contraction in this untreatable disease. Computational modeling of PKP2 variants reveals that the carboxy-terminal (CT) domain is required for N-terminal domain stabilization, which determines PKP2 cortical localization and function. In mutant PKP2 cells the expression of the interacting protein MYH10 rescues actomyosin disorganization. Conversely, dominant-negative MYH10 mutant expression mimics the pathogenic CT–deletion PKP2 mutant causing actin network abnormalities and right ventricle systolic dysfunction. A chemical activator of non-muscle myosins, 4-hydroxyacetophenone (4-HAP), also restores normal contractility. Our findings demonstrate that activation of MYH10 corrects the deleterious effect of PKP2 mutant over systolic cardiac contraction, with potential implications for ACM therapy.

Background/Objectives: To analyze the best noninvasive tests prognosis marker in patients with diabetic foot ulcer (DFU) who underwent endovascular revascularization based on clinical outcomes, such as healing rate, time to heal, and free amputation survival after at least a six-month follow-up. Methods: A multicentric prospective observational study was performed with 28 participants with ischemic or neuroischemic DFU who came to the participant centers and underwent endovascular revascularization between January 2022 and March 2023. Toe systolic pressure (TP), ankle systolic pressure (AP), the ankle brachial pressure index (ABPI), the toe brachial pressure index (TBPI), transcutaneous pressure of oxygen (TcPO2), and skin perfusion pressure (SPP) were evaluated using PeriFlux 6000 System, Perimed, Sweden, before (Visit 0) and four weeks after revascularization (Visit 1). The primary clinical outcome was an evaluation of the clinical evolution of noninvasive tests comparing Visit 0 and Visit 1, estimating the sensitivity for predicting wound healing of noninvasive tests at six months following initial recruitment. Results: After six months, 71.43% (n = 20) of DFU healed, four patients (14.3%) received major amputations, and one (3.5%) died. The two tests that best predicted wound healing after revascularization according to the ROC curve were TcPO2 and TP with sensitivities of 0.89 and 0.70 for the cut-off points of 24 mmHg and 46 mmHg, respectively. Conclusions: TcPO2 and TP were the two tests that best predicted wound healing in patients who underwent endovascular revascularization. Clinicians should consider the importance of the evaluation of microcirculation in the healing prognosis of patients with diabetic foot ulcers.

This paper deals with the implementation of personal learning pathways in a technology-enriched environment to enhance learning experiences in initial teacher training. The study uses mixed-methods within a design-based research approach. In a first phase of the approach, the characteristics that personalised learning pathways should meet were identified. In the next stage, the learning sequences' structure for the pathways was designed, considering context, teaching-learning approach, tasks and assessment. The main result is an interchangeable learning sequence structure prototype that enables the configuration of personalised learning pathways by the students themselves, and the exchange and co-design of learning pathways between different teachers. The students select the sequences from a catalogue, organising their own learning pathways from the combination of different types of sequences offered. This strategy promotes students' autonomy and self-direction in the learning process, as well as their development of personal information management and collaborative work skills. The conclusion is that the proposed personalized pathways present an adequate balance between the structure, result of the learning design and / or co-design, and the necessary autonomy for the self-direction of their own learning process, whether in individual learning or in the collaborative construction of knowledge.

In recent years, the relation between Sound Event Detection (SED) and Source Separation (SSep) has received a growing interest, in particular, with the aim to enhance the performance of SED by leveraging the synergies between both tasks. In this paper, we present a detailed description of JSS (Joint Source Separation and Sound Event Detection), our joint-training scheme for SSep and SED, and we measure its performance in the DCASE Challenge for SED in domestic environments. Our experiments demonstrate that JSS can improve SED performance, in terms of Polyphonic Sound Detection Score (PSDS), even without additional training data. Additionally, we conduct a thorough analysis of JSS's effectiveness across different event classes and in scenarios with severe event overlap, where it is expected to yield further improvements. Furthermore, we introduce an objective measure to assess the diversity of event predictions across the estimated sources, shedding light on how different training strategies impact the separation of sound events. Finally, we provide graphical examples of the Source Separation and Sound Event Detection steps, aiming to facilitate the interpretation of the JSS methods.

Abstract Purpose To describe unusual clinical features and therapeutic management of a case of cytomegalovirus (CMV) ocular disease in a patient on immunomodulatory therapy. Setting/venue Moorfields Eye Hospital NHS Foundation Trust, London, UK. Methods Medical history, clinical findings, investigation results, and multimodal imaging were retrospectively collected. Results A 61-year-old, South-East Asian man, developed CMV-related endotheliitis and occlusive retinal vasculitis, diagnosed by wide-angle fluorescein angiography. No retinitis was present on the fundus examination. Suspicion of CMV etiology was based on anterior segment findings, especially the presence of coin-shaped endothelial lesions. The diagnosis was confirmed by aqueous polymerase chain reaction (PCR) analysis which was positive for CMV DNA. The combined use of topical and systemic valganciclovir resulted in significant improvement of the picture. Conclusions CMV can manifest in the eye as occlusive retinal vasculitis without the presence of typical retinitis.

Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative rare disease characterized by symptoms and signs in the upper and lower motor neurons, leading to progressive neuro-degeneration and muscle atrophy. Our objective was to analyse the quality of life (QoL) in patients with ALS and compare with general population and with patients with cancer. Prospective study from consecutive ALS patients in one center. In order to assess quality of life, during the first visit three questionnaires were administered: Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), Short Form-36 (SF-36) and EuroQoL 5D (EQ-5D). We compared SF-36 of ALS patients with a reference population (n = 9151), and we compared the EQ-5D index score of ALS patients versus patients with cancer in the same area and in the same period (2015–2018). Between June 2015 and September 2017, 23 were included. The mean age was 65.1 ± 12.6 years and 56.5% were women. Compared with the general population, patients with ALS showed lowest QoL (p

Pathogenic variants in LMNA have been associated with a wide spectrum of muscular conditions: the laminopathies. LMNA-related congenital muscular dystrophy is a laminopathy characterised by the early onset of symptoms and often leads to a fatal outcome at young ages. Children face a heightened risk of malignant arrhythmias. No established paediatric protocols for managing this condition are available. We review published cases and provide insights into disease progression in two twin sisters with LMNA-related muscular dystrophy. Our objective is to propose a cardiac surveillance and management plan tailored specifically for paediatric patients. We present a family of five members, including two twin sisters with LMNA-related muscular dystrophy. A comprehensive neuromuscular and cardiac work-up was performed in all family members. Genetic analysis using massive sequencing technology was performed in both twins. Clinical assessment showed that only the twins showed diagnoses of LMNA-related muscular dystrophy. Follow-up showed an early onset of symptoms and life-threatening arrhythmias, with differing disease progressions despite both twins passing away. Genetic analysis identified a de novo rare missense deleterious variant in the LMNA gene. Other additional rare variants were identified in genes associated with myasthenic syndrome. Early-onset neuromuscular symptoms could be related to a prognosis of worse life-threatening arrhythmias in LMNA related muscular dystrophy. Being a carrier of other rare variants may be a modifying factor in the progression of the phenotype, although further studies are needed. There is a pressing need for specific cardiac recommendations tailored to the paediatric population to mitigate the risk of malignant arrhythmias.