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Abstract Rationale & objective End-stage kidney disease (ESKD) negatively affects patients’ physical, emotional, and social functioning. Furthermore, adjustment to dialysis require substantial lifestyle changes that may further impact on patients physical and emotional well-being. However, the relationship between Health-Related Quality of life impairment with future adverse outcomes in dialysis is not well characterized. Our study aims to investigate the relationship between Health-Related Quality of Life (HRQoL) and patients’ survival and hospitalization rates within a large European dialysis network. Methods A historical cohort study was conducted to evaluate association of HRQoL with hospitalization and mortality rates over a 12-month follow-up period. Patients responded to a self-administered survey as part of a Continuous Quality Improvement Program implemented in clinics affiliated with the Spanish FMC-Nephrocare organization. Health-Related Quality of Life (HRQoL) was measured with the KDQOL-36. Potential confounders included socio-demographic characteristics, comorbidities, biochemical parameters, dialysis treatment. We used Cox’s Proportional Hazard regression to assess the hazard of death and Logistic Regression to assess the likelihood of hospital admissions during 12-month follow-up period. Results A total of 2280 (51.5%) completed the self-administrated survey, and 1838 patients met the inclusion/exclusion criteria of the study. Higher HRQoL scores were associated with significantly lower mortality and hospitalization risk. Risk estimates were robust to adjustment for potential confounders. Conclusions Several dimensions of HRQoL are associated with patient-centered outcomes (i.e., mortality and hospitalizations at 1 year). Patient-Reported Outcomes contribute unique pieces of information characterizing patients’ health. Residual confounding cannot be fully ruled out; moreover, the high attrition rate could result in selection bias, which may limit the generalizability of the findings to a broader population.

Abstract Background In a case study in Spain, the unequal proportion of men and women in a research organization in the energy sector is severe, and long-established dynamics that might determine differences in access to leadership positions and inequalities in research careers are evident. The gender gap in historically masculinized fields, such as energy engineering reflects more than simply the differences in male and female values and personalities. This study seeks to explore the gender gap in energy research centres and to identify barriers that potentially hinder the research careers of women. It proposes the development of a diagnostic tool, based upon indicators, to monitor and evaluate gender roles and inequalities in the management of research centres for identifying and addressing the dynamics and obstacles that hinder women's progress in the energy sector and their potential contribution to the field. This participatory multicriteria-based tool prioritizes the proposed indicators by their influence and importance in the context of energy research and applies it to the monitoring of a specific Spanish energy research centre. Results The results are threefold: (i) the methodology is adaptable to different research centres; (ii) the analysis of indicators’ prioritization could lead to recommendations that should be addressed first; (iii) the diagnostic tool used in this in-depth case study of an energy research centre in Spain allowed results to be achieved in terms of gender dynamics. Two indicators stand out as the most relevant in our analysis: gender diversity in leadership positions and uncomplicated application of work–life balance measures. In this case study, the measurement of the first indicator has drawn unsatisfactory results, and the research of the latter is considered still insufficient. In conclusion, this difference becomes a vicious or negative circle for attracting and retaining more women to the research centre. Despite these results, no gender gap seems to be recognized and thus, no measures are being taken to improve the situation. Conclusions Comprehensive data and contextualized monitoring are necessary to effectively study and enhance the presence and participation of women in the energy science sector. This approach, combining quantitative and qualitative techniques, is suitable for any research centre that would like to monitor its gender gap, identify potential sources of inequity and address them.

Almadén era una mina poco importante hasta que a mediados del siglo XVI Bartolomé de Medina aplicó el proceso industrial de amalgamación con azogue, conocido como método de patio, en el yacimiento de plata de Pachuca (Nueva España). A partir de entonces, la producción de azogue de Almadén fue en aumento, si exceptuamos la segunda mitad de la centuria del XVII, cuando hubo una fuerte escasez de consignaciones económicas para el establecimiento minero. En la segunda mitad del siglo XVIII, Almadén se había transformado en un gran establecimiento minero, el más importante del territorio metropolitano, pues sin azogue no había plata y Nueva España iba en camino de convertirse en el primer productor mundial de este metal. Por ello, el superintendente Francisco Javier de Villegas comunicó en 1750 al marqués de la Ensenada que no disponía de verdaderos técnicos de minas. Ensenada se mostró de acuerdo con Villegas y ordenaron, tanto él como su sucesor Arriaga, la búsqueda de los hombres más capacitados para solventar la situación, que por entonces eran los ingenieros militares debido a sus conocimientos matemáticos y a su experiencia en túneles y explosivos. Este artículo analiza concretamente los trabajos llevados a cabo en Almadén por los ingenieros militares Francisco Nangle, Miguel Antonio de Escurrechea, Silvestre Abarca y Jorge Juan entre 1750 y 1765, y cómo su intervención contribuyó a hacer frente a la creciente demanda de mercurio de la minería argentífera del virreinato de Nueva España.

This research consists of a quantitative analysis of the perspective of a group of university professors from different areas of knowledge and from 19 different Latin American countries on the use of humor and memes in virtual learning environments (VLEs) in higher education. The data have been obtained from an own-design survey, and the answers have been analyzed in a descriptive and inferential way with the aim of knowing the opinion of the 401 participants (professors) about the didactic effectiveness of humor and the benefits and employability of memes in virtual classrooms. The analysis differentiates the sample by the professors' area of knowledge as the main variable, and by gender, age and teaching experience. As results, the participants give a high evaluation of humorous didactic resources, particularly memes, although the evaluation of their usability in the classroom is intermediate. In this sense, it is shown that the area of knowledge has a significant influence on opinions in this regard.

Summary: The blood enzyme glutamate-oxaloacetate transaminase (GOT) has been postulated as an effective therapeutic to protect the brain during stroke. To demonstrate its potential clinical utility, a new human recombinant form of GOT (rGOT) was produced for medical use.We tested the pharmacokinetics and evaluated the protective efficacy of rGOT in rodent and non-human primate models that reflected clinical stroke conditions.We found that continuous intravenous administration of rGOT within the first 8 h after ischemic onset significantly reduced the infarct size in both severe (30%) and mild lesions (48%). Cerebrospinal fluid and proteomics analysis, in combination with positron emission tomography imaging, indicated that rGOT can reach the brain and induce cytoprotective autophagy and induce local protection by alleviating neuronal apoptosis.Our results suggest that rGOT can be safely used immediately in patients suspected of having a stroke. This study requires further validation in clinical stroke populations.

Introduction A proportion of people develop Long Covid after acute COVID-19, but with most studies concentrated in high-income countries (HICs), the global burden is largely unknown. Our study aims to characterise long-term COVID-19 sequelae in populations globally and compare the prevalence of reported symptoms in HICs and low-income and middle-income countries (LMICs).Methods A prospective, observational study in 17 countries in Africa, Asia, Europe and South America, including adults with confirmed COVID-19 assessed at 2 to

IntroductionHistorically, Multiple Endocrine Neoplasia type 1 (MEN1)-related pituitary adenomas (PAs) were considered more aggressive and treatment-resistant than sporadic PAs. However, recent studies suggest similarities in their behavior. This study aimed to evaluate the long-term outcomes of MEN1 PAs and identify predictive factors.MethodsNationwide multicenter retrospective cohort study of MEN1-related PAs with a minimum 1-year follow-up, collecting patient demographics, germline MEN1 pathogenic variants (PV), PA size, secretory profile, radiological characteristics, treatments, and outcomes.ResultsWe analyzed 84 PAs, 69%in females and 31% in males (P

Introduction SUV measurements from static brain [18F]FDG PET acquisitions are a commonly used tool in preclinical research, providing a simple alternative for kinetic modelling, which requires complex and time-consuming dynamic acquisitions. However, SUV can be severely affected by the animal handling and preconditioning protocols, primarily by those that may induce changes in blood glucose levels (BGL). Here, we aimed at developing and investigating the feasibility of SUV-based approaches for a wide range of BGL far beyond normal values, and consequently, to develop and validate a new model to generate standardized and reproducible SUV measurements for any BGL.Material and methods We performed dynamic and static brain [18F]FDG PET acquisitions in 52 male Sprague-Dawley rats sorted into control (n = 10), non-fasting (n = 14), insulin-induced hypoglycemia (n = 12) and glucagon-induced hyperglycemia (n = 16) groups. Brain [18F]FDG PET images were cropped, aligned and co-registered to a standard template to calculate whole-brain and regional SUV. Cerebral Metabolic Rate of Glucose (CMRglc) was also estimated from 2-Tissue Compartment Model (2TCM) and Patlak plot for validation purposes.Results Our results showed that BGL=100±6 mg/dL can be considered a reproducible reference value for normoglycemia. Furthermore, we successfully established a 2nd-degree polynomial model (C1=0.66E-4, C2=-0.0408 and C3=7.298) relying exclusively on BGL measures at pre-[18F]FDG injection time, that characterizes more precisely the relationship between SUV and BGL for a wide range of BGL values (from 10 to 338 mg/dL). We confirmed the ability of this model to generate corrected SUV estimations that are highly correlated to CMRglc estimations (R2= 0.54 2TCM CMRgluc and R2= 0.49 Patlak CMRgluc). Besides, slight regional differences in SUV were found in animals from extreme BGL groups, showing that [18F]FDG uptake is mostly directed toward central regions of the brain when BGLs are significantly decreased.Conclusion Our study successfully established a non-linear model that relies exclusively on pre-scan BGL measurements to characterize the relationship between [18F]FDG SUV and BGL. The extensive validation confirmed its ability to generate SUV-based surrogates of CMRglu along a wide range of BGL and it holds the potential to be adopted as a standard protocol by the preclinical neuroimaging community using brain [18F]FDG PET imaging.

Background: Vascular malformations (VaMs) are caused by errors in vascular morphogenesis. Diagnosis and treatment can be complex. Few specialized centers care for these patients, and limited literature exists regarding their characteristics and clinical course. The vascular anomalies clinic (VAC) at the Instituto Nacional de Pediatría (National Institute for Pediatrics) is a multidisciplinary team and has been a reference center for patients with VaMs since 2012. We sought to describe the characteristics of patients cared for at the VAC, types of VaMs, treatments used, and clinical course. Methods: This was a descriptive, observational, retrospective, and cross-sectional study conducted from 2012 to 2022. Results: We included 435 patients with VaMs; the median age of presentation was 1 month. The most frequent signs and symptoms were increased volume (97.2%), superficial color change (65.5%), and pain (43.3%). The most common VaMs were lymphatic (36.7%) and venolymphatic (18.3%). Sclerotherapy was the most frequent treatment (73.4%), followed by medical treatment with sirolimus (18.5%); response to both was excellent/good in > 85% of cases. Conclusion: In this retrospective study of children with VaMs, we found that low-flow malformations were the most common, and sclerotherapy and sirolimus were the most frequently used treatments. The therapeutic response was excellent/good in most cases.

This article introduces Interactive Video Application (IVA), an open source, web-based framework for creating and deploying interactive videos in the cloud. IVA has been designed and developed with modularity and scalability in mind, using a state-of-the-art technological stack. A detailed description of the architecture that supports IVA is discussed to facilitate and promote its extension by other developers. The interactive components supported by IVA are easily specified in a YAML file format. IVA facilitates the integration of new interactive components and includes an analysis module that supports metrics related to performance, events, and how users interact with the video. Researchers from areas such as education, marketing or entertainment, among others, can benefit from the functional capabilities offered by IVA. The article also presents a case study on the creation of an interactive video.

In this paper, Virtual Reality Shopping Insights (VRSI) is presented, a framework that aids the development of Virtual Reality (VR) shopping applications as well as collecting data and analysing it. VRSI aims to help software developers and researchers by abstracting the layers needed to setup VR technology on applications developed with Unity. Moreover, it provides data registration tools that monitors user activity from non invasive data sources. This data can be useful for marketing analysts to understand user behaviour inside V-commerce applications, helping them to improve the setup and layout of such environments with data-driven decisions. Furthermore, we present an example of VR shopping application developed with VRSI.

Accurately modeling tumor biology and testing novel therapies on patient-derived cells is critically important to developing therapeutic regimens personalized to a patient's specific disease. The vascularized microtumor (VMT), or "tumor-on-a-chip," is a physiologic preclinical cancer model that incorporates key features of the native human tumor microenvironment within a transparent microfluidic platform, allowing rapid drug screening in vitro. Herein we optimize methods for generating patient-derived VMT (pVMT) using fresh colorectal cancer (CRC) biopsies and surgical resections to test drug sensitivities at the individual patient level. In response to standard chemotherapy and TGF-βR1 inhibition, we observe heterogeneous responses between pVMT derived from 6 patient biopsies, with the pVMT recapitulating tumor growth, histological features, metabolic heterogeneity, and drug responses of actual CRC tumors. Our results suggest that a translational infrastructure providing rapid information from patient-derived tumor cells in the pVMT, as established in this study, will support efforts to improve patient outcomes.

Digital technologies have brought changes to the nature and scope of education and led education systems worldwide to adopt strategies and policies for ICT integration. The latter brought about issues regarding the quality of teaching and learning with ICTs, especially concerning the understanding, adaptation, and design of the education systems in accordance with current technological trends. These issues were emphasized during the recent COVID-19 pandemic that accelerated the use of digital technologies in education, generating questions regarding digitalization in schools. Specifically, many schools demonstrated a lack of experience and low digital capacity, which resulted in widening gaps, inequalities, and learning losses. Such results have engendered the need for schools to learn and build upon the experience to enhance their digital capacity and preparedness, increase their digitalization levels, and achieve a successful digital transformation. Given that the integration of digital technologies is a complex and continuous process that impacts different actors within the school ecosystem, there is a need to show how these impacts are interconnected and identify the factors that can encourage an effective and efficient change in the school environments. For this purpose, we conducted a non-systematic literature review. The results of the literature review were organized thematically based on the evidence presented about the impact of digital technology on education and the factors that affect the schools' digital capacity and digital transformation. The findings suggest that ICT integration in schools impacts more than just students' performance; it affects several other school-related aspects and stakeholders, too. Furthermore, various factors affect the impact of digital technologies on education. These factors are interconnected and play a vital role in the digital transformation process. The study results shed light on how ICTs can positively contribute to the digital transformation of schools and which factors should be considered for schools to achieve effective and efficient change.

Abstract The E3 SUMO ligase PIAS2 is expressed at high levels in differentiated papillary thyroid carcinomas but at low levels in anaplastic thyroid carcinomas (ATC), an undifferentiated cancer with high mortality. We show here that depletion of the PIAS2 beta isoform with a transcribed double-stranded RNA–directed RNA interference (PIAS2b-dsRNAi) specifically inhibits growth of ATC cell lines and patient primary cultures in vitro and of orthotopic patient-derived xenografts (oPDX) in vivo. Critically, PIAS2b-dsRNAi does not affect growth of normal or non-anaplastic thyroid tumor cultures (differentiated carcinoma, benign lesions) or cell lines. PIAS2b-dsRNAi also has an anti-cancer effect on other anaplastic human cancers (pancreas, lung, and gastric). Mechanistically, PIAS2b is required for proper mitotic spindle and centrosome assembly, and it is a dosage-sensitive protein in ATC. PIAS2b depletion promotes mitotic catastrophe at prophase. High-throughput proteomics reveals the proteasome (PSMC5) and spindle cytoskeleton (TUBB3) to be direct targets of PIAS2b SUMOylation at mitotic initiation. These results identify PIAS2b-dsRNAi as a promising therapy for ATC and other aggressive anaplastic carcinomas.