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Loli Uribe Echevarría,1 Carolina Leimgruber,2 Jorge García González,1 Alberto Nevado,1 Ruth Álvarez,3 Luciana N García,2 Amado A Quintar,2 Cristina A Maldonado2 1Pneumonology Service, Sanatorio Allende (Nueva Córdoba), Córdoba, Argentina; 2Electronic Microscopy Center, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina; 3Smoking Cessation Cente, Nuevo Hospital San Roque of Córdoba, Córdoba, Argentina Abstract: In spite of the numerous studies on chronic obstructive pulmonary disease (COPD), the cellular and molecular basis of the disease’s development remain unclear. Neutrophils and eosinophils are known to be key players in COPD. Recently, neutrophil extracellular trap cell death (NETosis), a mechanism due to decondensation and extrusion of chromatin to form extracellular traps, has been demonstrated in COPD. However, there is limited knowledge about eosinophil extracellular trap cell death (EETosis) and its role in the pathogenesis of COPD. The aim of this study was to evaluate EETosis in stable COPD. Induced sputum obtained from healthy smokers and low exacerbation risk COPD A or B group patients or high exacerbation risk COPD C or D group patients were included. Samples were examined using electron microscopy and immunofluorescence. Healthy smokers (n=10) and COPD A (n=19) group exhibited neutrophilic or paucigranulocytic phenotypes, with NETosis being absent in these patients. In contrast, COPD B (n=29), with eosinophilic or mixed phenotypes, showed EETosis and incipient NETosis. COPD C (n=18) and COPD D groups (n=13) were differentiated from low exacerbation rate-COPD group by the abundant cellular debris, with COPD C group having an eosinophilic pattern and numerous cells undergoing EETosis. A hallmark of this group was the abundant released membranes that often appeared phagocytosed by neutrophils, which coincidentally exhibited early NETosis changes. The COPD D group included patients with a neutrophilic or mixed pattern, with abundant neutrophil extracellular trap-derived material. This study is the first to demonstrate EETosis at different stages of stable COPD. The results suggest a role for eosinophils in COPD pathophysiology, especially at the beginning and during the persistence of the disease, regardless of whether the patient quit smoking, with EETosis debris probably triggering uncontrolled NETosis. The main target of these findings should be young smokers with the potential to develop COPD. Keywords: COPD, eosinophils, neutrophils, NETosis, EETosis, induced sputum

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs.

COVID-19 caused by SARS-CoV-2 is an emerging respiratory disease that likely originated from wildlife in late 2019 (1). Although the main driver of SARS-CoV-2 spread is human-to-human transmission, several wild [...]

BackgroundDeep learning has shown potential in various scientific domains but faces challenges when applied to complex, high-dimensional multi-omics data. Alzheimer's Disease (AD) is a neurodegenerative disorder that lacks targeted therapeutic options. This study introduces the Circular-Sliding Window Association Test (c-SWAT) to improve the classification accuracy in predicting AD using serum-based metabolomics data, specifically lipidomics.MethodsThe c-SWAT methodology builds upon the existing Sliding Window Association Test (SWAT) and utilizes a three-step approach: feature correlation analysis, feature selection, and classification. Data from 997 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) served as the basis for model training and validation. Feature correlations were analyzed using Weighted Gene Co-expression Network Analysis (WGCNA), and Convolutional Neural Networks (CNN) were employed for feature selection. Random Forest was used for the final classification.FindingsThe application of c-SWAT resulted in a classification accuracy of up to 80.8% and an AUC of 0.808 for distinguishing AD from cognitively normal older adults. This marks a 9.4% improvement in accuracy and a 0.169 increase in AUC compared to methods without c-SWAT. These results were statistically significant, with a p-value of 1.04 × 10ˆ-4. The approach also identified key lipids associated with AD, such as Cer(d16:1/22:0) and PI(37:6).InterpretationOur results indicate that c-SWAT is effective in improving classification accuracy and in identifying potential lipid biomarkers for AD. These identified lipids offer new avenues for understanding AD and warrant further investigation.FundingThe specific funding of this article is provided in the acknowledgements section.

Summary: Background: People with diabetes are at increased risk of hospitalisation, morbidity, and mortality following SARS-CoV-2 infection. Long-term outcomes for people with diabetes previously hospitalised with COVID-19 are, however, unknown. This study aimed to determine the longer-term physical and mental health effects of COVID-19 in people with and without diabetes. Methods: The PHOSP-COVID study is a multicentre, long-term follow-up study of adults discharged from hospital between 1 February 2020 and 31 March 2021 in the UK following COVID-19, involving detailed assessment at 5 and 12 months after discharge. The association between diabetes status and outcomes were explored using multivariable linear and logistic regressions. Findings: People with diabetes who survived hospital admission with COVID-19 display worse physical outcomes compared to those without diabetes at 5- and 12-month follow-up. People with diabetes displayed higher fatigue (only at 5 months), frailty, lower physical performance, and health-related quality of life and poorer cognitive function. Differences in outcomes between diabetes status groups were largely consistent from 5 to 12-months. In regression models, differences at 5 and 12 months were attenuated after adjustment for BMI and presence of other long-term conditions. Interpretation: People with diabetes reported worse physical outcomes up to 12 months after hospital discharge with COVID-19 compared to those without diabetes. These data support the need to reduce inequalities in long-term physical and mental health effects of SARS-CoV-2 infection in people with diabetes. Funding: UK Research and Innovation and National Institute for Health Research. The study was approved by the Leeds West Research Ethics Committee (20/YH/0225) and is registered on the ISRCTN Registry (ISRCTN10980107).

El infoshow es el macrogénero de mayor crecimiento a nivel global durante las últimas décadas. Esto se debe, en gran medida, a los procesos de desregulación de los mercados televisivos, que han fomentado que los contenidos se adapten cada vez más a los gustos y demandas de la audiencia. En España, el auge del infoshow comenzó en la década de los 2000, en un contexto de crisis económica y desafección política que propició un mayor interés del público general por temas económicos, sociales y políticos, todos ellos muy propicios a la crítica y la espectacularización. En este contexto, la sátira de actualidad se consolidó como un género destacado en la televisión española. Esta investigación se centra en El Intermedio, producido por Globomedia para La Sexta. Este programa formaba parte de los primeros contenidos con los que la cadena inició sus emisiones oficiales, en el año 2006, y sigue presente en su prime time dieciocho años después. Se trata, sin duda, del programa más longevo y, también, uno de los de mayor éxito de su parrilla. Aunque sigue la tradición de formatos previos, El Intermedio ofrece un enfoque innovador alejándose del ámbito puramente humorístico para ofrecer un acercamiento alternativo a las noticias de actualidad. Mediante el análisis de contenido de sus diez primeras temporadas se analiza el perfil de sus presentadores y colaboradores y su estructura de contenidos. Los resultados muestran un enfoque innovador en el tratamiento de las noticias y en el equilibrio entre la función informativa y el entretenimiento.

El presente artículo describe la intervención efectuada en el escenario del Teatro romano de Medellín (Badajoz, España) desde enero a abril de 2011. Este teatro, datado en los últimos años del siglo I a.C., fue abandonado, expoliado y ocupado por edificaciones diversas a lo largo de la Edad Media. Las excavaciones arqueológicas acometidas de 2007 a 2010 sacaron a la luz los restos del edificio. En el caso del escenario, los vestigios originales fueron la base sobre la que apuntalar su conservación, que combinó la lectura arqueológica, la anastilosis, la consolidación y la aportación de arquitectura. La intervención ha permitido: la conservación de los restos, la posibilidad de ahondar en su conocimiento, y la recuperación de los accesos y recorridos que hacen posible tanto su visita turística como su recuperación para uso teatral (fig. 1). Desde su apertura al público en 2013 ha recibido multitud de visitas, y en la actualidad es una de las sedes del Festival Internacional de Teatro Clásico de Mérida.

Introduction: This article analyses the impact of an intercultural learning intervention in a Spanish university post-European Higher Education Area implementation. Objective: Our research's main objective consisted of measuring the development of intercultural competence in the first cohort of a Translation and Intercultural Communication bachelor's degree in a Spanish university, before and after taking specific courses in intercultural studies and spending a study abroad semester. Methodology: A mixed methodology was implemented, in which the Intercultural Development Inventory (IDI) was used as a measuring instrument. Additionally, in-depth personal interviews were conducted to complement the data obtained. Results: The results of this study show that the programming and sequencing of specific courses, together with experiences abroad, contribute to the development of intercultural competence. Conclusions: More intercultural learning interventions are needed in higher education courses to develop and build an intercultural campus and educate global citizens. When applying intercultural learning interventions and intercultural methodologies, students develop their intercultural competence, a key competence for 21st-century graduates.

There were 6,491,502 foreign residents living in Spain in January 2024, a number that indicates a significant increase since the beginning of the 21st century. Among this foreign population, the largest communities are Moroccans, Romanians and British, whose mother tongue is not Spanish. According to the results from several studies conducted over the last decades, when these allophone residents use the Spanish healthcare services, they frequently ask their children to help them communicate with healthcare providers through linguistic and cultural mediation, even when professional interpreting or mediation services are available. How did these children feel while mediating for their parents in this context? Did they have any negative experiences? We intend to provide answers to these questions through semi-structured individual interviews with adults who had mediated for their parents in healthcare settings in Spain when they were children or young adults. These answers contribute to a clear understanding of the consequences of language brokering, thus promoting the use of professional interpreting and mediation services in these settings.

El sistema educativo establece la importancia de conocer cuáles deben ser las características de los docentes que garanticen el éxito educativo, capaces de generar un aprendizaje significativo, mediante el desarrollo de una relación docente-discente recíproca, compasiva, donde se fomenten los valores democráticos. El engagement docente podría ser la respuesta a esta problemática, de modo que interesa analizar qué variables influyen y son determinantes para que exista compromiso en la educación. Variables como la autoeficacia, la inteligencia emocional y la felicidad son nucleares. Hallar un modelo que las relacione podría ofrecer nuevas perspectivas en la identidad profesional y formación del profesorado. En este estudio han participado 458 docentes de educación física, se ha llevado a cabo un análisis correlacional, una regresión lineal jerárquica y de mediación, obteniendo un modelo significativo donde el engagement se predice por la autoeficacia, seguido por la inteligencia emocional y la felicidad subjetiva. Por género, las mujeres presentan una mayor percepción en la autoeficacia. Por años de experiencia se hallan diferencias en el nivel de engagement. Las variables analizadas presentan una relación lógica en la interacción entre ellas, siendo diferente entre mujeres y varones. Estos resultados establecen la importancia e influencia de las variables personales sobre el engagement de los docentes de educación física, y, cómo éstas varían en función del género y los años de experiencia. Aspectos por evaluar para diseñar la identidad profesional y, como consecuencia, la formación inicial y continua del profesorado.

The genetic basis of severe COVID-19 has been thoroughly studied, and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we conducted a genome-wide association study (GWAS) for COVID-19 hospitalization in admixed Americans, comprising a total of 4702 hospitalized cases recruited by SCOURGE and seven other participating studies in the COVID-19 Host Genetic Initiative. We identified four genome-wide significant associations, two of which constitute novel loci and were first discovered in Latin American populations (BAZ2B and DDIAS). A trans-ethnic meta-analysis revealed another novel cross-population risk locus in CREBBP. Finally, we assessed the performance of a cross-ancestry polygenic risk score in the SCOURGE admixed American cohort. This study constitutes the largest GWAS for COVID-19 hospitalization in admixed Latin Americans conducted to date. This allowed to reveal novel risk loci and emphasize the need of considering the diversity of populations in genomic research.

BackgroundDNA polymerase theta (POLQ) is a translesion synthesis polymerase essential for the repair of double strand breaks by the error-prone TMEJ (Theta Mediated End Joining) pathway. Although POLQ participates in maintaining genome stability, several studies have shown that its overexpression correlates with cancer progression and poor prognosis. Due to the fact that its role as a biomarker in pancreatic cancer remains unexplored, we aimed to study the usefulness of POLQ H-score as a prognostic factor in a pancreatic cancer patient cohort.MethodsWe evaluated POLQ gene expression using a web-based tool to deliver gene expression profiling and interactive analyses based on TCGA and GTEx (GEPIA) and we examined the POLQ immunostaining in 152 biliopancreatic cancer surgical specimens using tissue microarrays. Association with survival was evaluated by Kaplan Meier curves and uni-multivariate Cox regression.ResultsGEPIA analysis showed statistical differences according to POLQ mRNA levels in Disease Free Survival (DFS) (log rank 0.023, HR 2.8, p=0.029) and Overall Survival (OS) (log rank 0.011, HR 3.1, p=0.016). For immunohistochemistry (IHC) evaluation, POLQ H-score was calculated, and showed statistical differences for OS in Kaplan Meier curves (log rank 0.001) and uni-multivariate analysis (HR 2.27; 95% CI 1.24-4.15, p=0.008).ConclusionsOur results indicate that POLQ is an independent prognostic factor in pancreatic cancer when analyzed by immunostaining, which is in agreement with the results shown by the POLQ gene expression analysis (GEPIA).

Protein structure determination has made progress with the aid of deep learning models, enabling the prediction of protein folding from protein sequences. However, obtaining accurate predictions becomes essential in certain cases where the protein structure remains undescribed. This is particularly challenging when dealing with rare, diverse structures and complex sample preparation. Different metrics assess prediction reliability and offer insights into result strength, providing a comprehensive understanding of protein structure by combining different models. In a previous study, two proteins named ARM58 and ARM56 were investigated. These proteins contain four domains of unknown function and are present in Leishmania spp. ARM refers to an antimony resistance marker. The study’s main objective is to assess the accuracy of the model’s predictions, thereby providing insights into the complexities and supporting metrics underlying these findings. The analysis also extends to the comparison of predictions obtained from other species and organisms. Notably, one of these proteins shares an ortholog with Trypanosoma cruzi and Trypanosoma brucei, leading further significance to our analysis. This attempt underscored the importance of evaluating the diverse outputs from deep learning models, facilitating comparisons across different organisms and proteins. This becomes particularly pertinent in cases where no previous structural information is available.

Resumen: Antecedentes: En España, aunque el Ministerio de Sanidad elabora el informe de posicionamiento terapéutico (IPT) y las condiciones de reembolso de los fármacos, las Comunidades Autónomas (CC. AA.) gestionan los servicios de salud y deciden sobre las condiciones de prescripción en su ámbito territorial. El objetivo del estudio EQUIDAD fue describir los condicionantes para la prescripción de los nuevos fármacos en Dermatología en las CC. AA. y sus posibles diferencias. Material y métodos: Estudio transversal realizado en abril-mayo del 2023. Dos dermatólogos con responsabilidades directivas de cada Comunidad Autónoma (C. A.) informaron sobre los condicionantes autonómicos y locales en la prescripción de los fármacos cuyo IPT para el tratamiento de enfermedades dermatológicas fue publicado en los años 2016-2022. Los datos fueron recogidos mediante un cuestionario online. Resultados: Un total de 33 investigadores de 17 CC. AA. participaron en el estudio. Se observaron inequidades entre CC. AA. para el acceso a los nuevos fármacos. Existieron condicionantes autonómicos adicionales al IPT en psoriasis en el 64,7% de las CC. AA., siendo este porcentaje menor en dermatitis atópica (35,3%) o melanoma (11,8%). El más frecuente fue el requisito de un orden de prescripción previo para el uso del fármaco. En algunas CC. AA. se detectaron además variaciones y condicionantes locales (diferencias entre centros de una misma C. A.). Conclusiones: Existe una multiplicidad de criterios tanto a nivel autonómico como local que añade restricciones adicionales a las establecidas por los IPT y que plantean una situación de inequidad entre los pacientes y los profesionales de las diferentes CC. AA. en el acceso a los nuevos fármacos. Abstract: Background: Although the Spanish Ministry of Health prepares national therapeutic positioning reports (TPRs) and drug reimbursement policies, each of the country's 17 autonomous communities (ACs) is responsible for health care services and prescription requirements in its territory. The aim of the EQUIDAD study was to describe and explore potential differences in prescription requirements for new dermatology drugs across the autonomous communities. Material and methods: Cross-sectional study conducted in April and May, 2023. Two dermatologists with management responsibilities from each autonomous community reported on territorial and more local prescription requirements for drugs covered by national TPRs issued between 2016 and 2022. Results: Thirty-three researchers from 17 autonomous communities participated. The data submitted revealed between-community inequities in access to new drugs. Overall, 64.7% of the regions imposed additional prescription requirements to those mentioned in the TPRs for psoriasis. This percentage was lower for atopic dermatitis (35.3%) and melanoma (11.8%). The most common requirement for accessing a new drug was a previous prescription for another drug. Differences and additional requirements were also detected atthe local level (i.e., differences between hospitals within the same autonomous community). Conclusions: Spain's autonomous communities have multiple regional and local prescription requirements that are not aligned with national TPR recommendations. These differences result in inequitable access to new drugs for both patients and practitioners across Spain.

Kysymme tutkimuksessamme, millaista matematiikkaa huonekalupuusepät työssään tarvitsevat ja käyttävät. Tutkimus asettuu teoreettisesti niin sanotun kansan matematiikan kehyksiin: tarkastelemme matemaattisen professionalismin ulkopuolella olevien ryhmien käyttämää matematiikkaa. Yleensä tutkimuksissa teoreettista tietoa käytetään ohjaamaan sitä, miten asiat pitäisi käytännössä tehdä. Me taas yritämme ymmärtää käytännön toimintaa, jotta teoreettista tietoa voitaisiin mukauttaa vastaamaan paremmin käytäntöjä. Tarkastelemme ensin sellaista arkipäivän työssä käytettävää matematiikkaa, jonka tutkittavat itse tunnistavat ja nimeävät matematiikaksi. Toiseksi tarkastelemme heidän työssään kohtaamiaan ongelmanratkaisua vaativia tilanteita. Keskeinen käsite tarkastelussamme on matemaattinen tieto, joka on osa numeerisia taitoja. Ongelmanratkaisutilanteet osana matematiikkaa voivat olla joko hyvin tai huonosti jäsenneltyjä. Edellisiin ratkaisut ovat täsmällisiä, usein yksiselitteisiä. Jälkimmäiset taas mahdollistavat monenlaiset ratkaisut. Tutkimustehtävään vastaamiseksi olemme käyttäneet kahdenlaista aineistoa: neljän huonekalupuusepän työpajoissa tuotettua etnografista haastattelu-, havainnointi- ja kuva-aineistoa sekä kolmen muun huonekalupuusepän haastatteluaineistoa. Analyysimme mukaan arjen rutiineissa huonekalupuusepät selviävät kontekstisidonnaisella matemaattisella tiedolla, josta osa on kehollistunutta. Ongelmanratkaisutilanteissa taas aktivoituu edellisten ohella myös käsitteellisempi matemaattinen tieto.

La red social TikTok se presenta como un formato de comunicación preponderantemente de entretenimiento no solo para las generaciones más jóvenes, sino para un público cada vez más seducido por los algoritmos de recomendación. En este contexto, los medios de información tradicionales plantean sus estrategias de desembarco en TikTok, conscientes de que en ella están ahora las audiencias futuras a las que poder fidelizar. Esta investigación tiene como principal objetivo revisar la actividad de los principales medios impresos de España. Se pretende analizar si el uso de TikTok de los medios impresos en España es o no significativo, si existe una profesionalización estratégica de la actividad editorial de estos medios y, finalmente, si esta actividad se realiza ad hoc, en función de las peculiaridades de la plataforma o si la dinámica es el reciclado de contenido del medio principal. Para ello, se revisarán los posts publicados en la red social por las principales cabeceras nacionales: El País, El Mundo, ABC, La Vanguardia y La Razón, en una secuencia temporal concreta que establece un análisis comparativo entre los principales hitos de interacción que proporciona dicha red social. Las principales conclusiones establecen cómo existe un intento mayor de lo esperado en la actividad que los medios impresos plantean en TikTok. Sin embargo, a pesar de ello, es una actividad poco profesionalizada y reflexionada, ya que no existe una pauta clara de publicación, continuidad o producción específica, sino más bien un contenedor más en el que volcar contenido ya producido.

This study aimed to analyse the influence of the match status on the conditional characteristics of tactical sprint actions among Spanish professional soccer players, considering playing positions. Thirty-two Spanish male professional soccer players from a LaLiga Spanish Second Division (LaLiga SmarthBank) team participated in this study. Actions above 85% of the players’ maximum velocity were analysed based on their tactical purpose. These findings provide valuable information regarding the tactical aspects of sprinting in soccer, emphasizing the influence of playing positions and match status on the distribution of tactical sprint actions. No effects of match status were observed for any game phase. However, when tactical actions were individually studied, it was observed that the maximum velocity in Chase actions was higher when the team was winning, while in Press actions, the maximum velocity was higher when the team was losing and in in Run in behind/Penetrate, the maximum velocity was higher in drawing situations compared to losing situations. No effects of match status on the distance covered during sprinting were observed, and regarding duration, significant differences were only observed in Recovery run actions. In addition, the influence of match status is higher when playing positions are considered, although the within playing positions analysis revealed significant differences only in CM players. These findings provide valuable information for the design of specific training drills considering playing positions, suggesting the need to analyse the previous match in order to structure the training load of the microcycle in a comprehensive manner.