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Characterization of iron deficiency in COPD patiens: implications in exercise tolerance and redox balance in muscle and systemic compartments
No full textChronic obstructive pulmonary disease (COPD) patients may present different types of systemic manifestations. Iron deficiency (ID) (Fe, an essential nutritional element) is common and can negatively affect exercise tolerance and, therefore, their quality of life. The objectives of this thesis were to study the effects of ID on exercise capacity and lung function in patients with severe COPD and muscle dysfunction. Forty COPD patients (n=20 without ID and n=20 with ID) were recruited, from whom blood and muscle specimens (vastus lateralis, VL) were obtained. Lung function, exercise capacity (6-minute walk test, 6MWT), and limb muscle strength were assessed in all patients. In addition, the levels of biomarkers of iron metabolism regulators, oxidative stress (blood and muscle) and muscle architecture was analyzed. Correlations between clinical and biological variables were performed. Besides, in the current thesis, another objective was to evaluate the effect of iron replacement on oxidative stress in ID COPD patients. For this study, 66 ID COPD patients were recruited (n=22 treated with placebo and n=44 treated with ferric carboxymaltose). Biomarkers of iron metabolism and oxidative stress were analyzed in the blood of these patients, before and after treatment. Among all COPD patients (with and without ID), serum ferritin levels correlated with FEV1. In ID COPD patients, their exercise capacity was reduced; likewise, the 6MWT distance was positively associated with iron metabolism regulators (ferritin, hepcidin, and muscle iron content). In the VL of ID patients, the percentage of type I fibers decreased, while the percentage of type II fibers increased. Moreover, in these patients the systemic and muscle levels of pro-oxidant markers were increased, meanwhile antioxidants were reduced. In ID COPD patients, after iron replacement therapy, systemic oxidative stress markers were attenuated. In conclusion, in COPD patients, exercise capacity and lung function are associated with the content of iron metabolism regulators. In addition, in these patients, oxidative stress levels seem to be related to iron availability, increasing in the case of iron deficiency and improving in the case of iron replacement treatment.Los pacientes con enfermedad pulmonar obstructiva crónica (EPOC) presentan manifestaciones sistémicas de diversa índole. El déficit de hierro (DH) (Fe, elemento nutricional esencial) es frecuente, y puede incidir negativamente en la tolerancia al ejercicio, y, por ende, en su calidad de vida. Los objetivos de esta tesis fueron estudiar los efectos de la depleción de hierro en la capacidad de ejercicio y función pulmonar en pacientes con EPOC grave y con disfunción muscular. Se reclutaron 40 pacientes EPOC (n=20 sin DH y n=20 con DH) de los que se obtuvieron muestras sanguíneas y musculares (vasto lateral, VL). Se evaluó la función pulmonar, la capacidad de ejercicio (prueba de marcha de 6 minutos, PM6M) y la fuerza muscular de las extremidades en todos los pacientes. Además, se analizaron los niveles de biomarcadores reguladores del metabolismo férrico, de estrés oxidativo (sangre y músculo) y la arquitectura del músculo. Se realizaron correlaciones entre variables clínicas y biológicas. Al mismo tiempo, en la presente tesis, se estableció como objetivo evaluar el efecto de la reposición de hierro en el estrés oxidativo en pacientes EPOC con DH. Para ello, se reclutaron 66 pacientes EPOC con DH (n=22 tratados con placebo y n=44 tratados con carboximaltosa férrica). En la sangre de estos pacientes se analizaron biomarcadores del metabolismo del hierro y de estrés oxidativo, antes y después del tratamiento. Entre todos los pacientes EPOC (con y sin DH), los niveles séricos de ferritina correlacionaron con su FEV1. En los pacientes EPOC con DH, su capacidad de ejercicio disminuyó; asimismo, la distancia recorrida en la PM6M se asoció positivamente con reguladores del metabolismo del hierro (ferritina, hepcidina y contenido muscular de hierro). En el VL de los pacientes con DH, el porcentaje de las fibras de tipo I disminuyó, mientras que el de las fibras de tipo II aumentó. Además, en estos pacientes los niveles sistémicos y musculares de marcadores prooxidantes aumentaron, mientras que los antioxidantes disminuyeron. En pacientes EPOC con DH, después de un tratamiento sustitutivo de hierro, los marcadores de estrés oxidativo sistémicos se atenuaron. En conclusión, en pacientes EPOC, la capacidad al ejercicio y la función pulmonar se asocian al contenido de reguladores del metabolismo del hierro. Además, en estos pacientes, los niveles de estrés oxidativo parecen estar relacionados con la disponibilidad del hierro, aumentando en caso de su déficit y mejorando en caso de tratamiento de reemplazo de hierro.Programa de doctorat en Biomedicin
Eficacia indirecta de los pactos parasociales a través del artículo 204.1 II LSC: estudio de su oponibilidad y eficacia
No full textTreball de Fi de Grau en Dret. Curs 2024-2025Tutor: Ignacio Farrando MiguelEl artículo 204.1 II de la actual Ley de Sociedades representa un avance significativo en la tutela jurídica de los socios minoritarios al introducir la causa autónoma de impugnación por abuso de mayoría, consolidando un mecanismo que trasciende la mera formalidad de los acuerdos sociales. En este marco, los pactos parasociales, instrumentos esenciales para la regulación privada y flexible de la convivencia societaria, enfrentan el obstáculo de su inoponibilidad frente a la sociedad, derivada del principio de relatividad contractual y la falta de publicidad registral. La problemática surge cuando los acuerdos sociales, formalmente adoptados, vulneran las expectativas legítimas surgidas de tales pactos, generando un conflicto entre la legalidad estatutaria y la realidad contractual entre socios.
La tesis defendida sostiene que el abuso de mayoría previsto en el artículo 204.1 II LSC puede interpretarse como un cauce para conferir eficacia indirecta a los pactos parasociales, al permitir la impugnación de aquellos acuerdos sociales que, sin contravenir normas explícitas, frustran de manera arbitraria y desproporcionada las previsiones asumidas por los socios. Esta interpretación, fundamentada en el espíritu y la finalidad protectora de la norma, contribuye a una comprensión dinámica y coherente del Derecho societario, promoviendo la equidad interna y evitando prácticas abusivas que comprometan el equilibrio corporativo. Así, se articula una respuesta jurídica que reconoce la complejidad contemporánea del gobierno societario, integrando la eficacia funcional de los pactos parasociales en la salvaguarda de los derechos minoritarios
Contested collective memories of migrations in Catalonia
No full textThis prospective study examines the role of the M-Factor (Migration Factor) in the formation of a country’s collective memory. Despite the seminal contributions of memory studies to the field of identity formation, the M-Factor in nations’ historical heritage is particularly under-researched. The relationship between national identity and the collective memory of migration, and vice versa, represents a fertile area of enquiry into the formation of contested collective memories. By framing the analysis on the case study of Catalonia, a territorial community in Spain with national claims, which lacks a structured state apparatus and where 73% of the population is result of migrations in the 20th and 21st centuries, this paper provides an illustrative case study of a contested collective memories. In Catalonia there is a discrepancy between the historical reality of migration and its social and political acknowledgment. This apparent paradox presents a compelling opportunity for research that seeks to bridge the fields of collective memory studies and migration studies. The data was collected from existing documents and a sample of 18 semi-structured interviews with a variety of profiles at the meso level, allowing us to saturate the information. The subsequent analysis traversed two domains: diagnosis (the contested collective memories of migration) and normative considerations regarding the potential of a future memory politics. This research provides a basis for a future political theory that addresses intergenerational relations and shared intercultural experiences to ground an inclusive collective memory of migrations
Mortality in patients with giant cell arteritis in Spain: results from the ARTESER registry
No full textObjectives: To compare mortality rates between GCA patients and the general population in Spain, and to identify associated factors influencing mortality. Methods: ARTESER, a multicenter registry by the Spanish Society of Rheumatology, includes GCA patients from June 2013 to March 2019. Demographic, clinical, imaging, histological and mortality data were collected retrospectively. Only patients with at least one year of follow-up were included for analysis. The mortality rates were expressed as the number of deaths per 1000 person-years, with 95% confidence interval (CI) by sex and age group. Kaplan-Meier method was performed for survival analysis. The factors influencing mortality were analyzed using Cox regression model. Results: A total of 1200 patients with GCA were analyzed, with a mean (SD) follow-up of 2.18 (1.53) years. The overall five-year cumulative mortality rate (95%CI) was 37.86 (31.75-43.96) per 1000 patients/year. The cumulative mortality rate was significantly higher in males than females (59.04vs29.06; p<0.001). The age- and sex-adjusted cumulative mortality rate was similar to the Spanish general population (19.75vs20.72;p=0.559). In the multivariate analysis, older age (HR 1.11, 95%CI 1.073-1.142) and male sex (HR 1.775, 95%CI 1.214-2.594) were associated with increased mortality. Headache (HR 0.55, 95%CI 0.362-0.843) and high hemoglobin levels (HR 0.85, 95%CI 0.744-0.970) were protective factors against death. Conclusions: The overall five-year age- and sex-adjusted cumulative mortality rate in GCA is similar compared to the general population. Older age and male sex appear to be associated with an increased risk of mortality, whereas headache and high hemoglobin levels might serve as protective factors against death
An SRRM3-regulated neural alternative splicing program is subverted to promote tumor progression in pancreatic neuroendocrine cells
No full textPancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of neoplasms arising in pancreatic islets and altering the hormone-secreting function of neuroendocrine cells. Genome-wide approaches have revealed the genomic landscape of PanNETs but have not explained their problematic hormone secretion. We show here that alternative splicing (AS) deregulation is responsible for changes in the secretory ability of PanNET cells. We reveal that the RNA-binding protein SRRM3 is upregulated in PanNETs and favors the inclusion of a group of alternative microexons in certain mRNAs. These microexons are part of a larger neural program regulated by SRRM3, and their inclusion results in protein isoforms that change stimulus-induced insulin trafficking and secretion. By downregulating SRRM3 or inhibiting its binding to three of the microexon-bearing pre-mRNAs in animal and cellular PanNET models, we prove the necessity of SRRM3 for hormone secretion, PanNET progression, and enhancement of the neural component of PanNET tumors.This study was supported by a Neuroendocrine Tumor Research Foundation (NETRF) Pilot Award (ID: 57222). M.P. was supported by the Hellenic Foundation for Research and Innovation (HFRI) (Fellowship: 11141). M.A. was supported by InfrafrontierGR/Phenotypos, NSRF 2014–2020, and MIS 5002135. M.E.R. and J.J.-M. were supported by ERC AdvG 670146. M.S. was supported by an RRF Action 16624 from the National Recovery and Resilience Plan “Greece 2.0” (Next Generation EU Grant ID: 5173820). V.K. was supported by a Fondation Santé Biomedical Research grant
MTHFD2 in healthy and cancer cells: Canonical and non-canonical functions
No full textMethylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a mitochondrial enzyme of the folate-mediated one-carbon metabolism pathway. MTHFD2 has become a highly attractive therapeutic target due to its consistent upregulation in cancer tissues and its major contribution to tumor progression, although it also performs vital functions in proliferating healthy cells. Here, we review the diversity of canonical and non-canonical functions of this key metabolic enzyme under physiological conditions and in carcinogenesis. We provide an overview of its therapeutic potential and describe its regulatory mechanisms. In addition, we discuss the recently described non-canonical functions of MTHFD2 and the mechanistic basis of its oncogenic function. Finally, we speculate on novel therapeutic approaches that take into account subcellular compartmentalization and outline new research directions that would contribute to a better understanding of the fundamental roles of this metabolic enzyme in health and disease
Multimodal hierarchical masked autoencoders tailored to ECG time series for atrial fibrillation risk stratification
No full textTreball fi de màster de: Erasmus Mundus joint Master in Artificial Intelligence (EMAI)Supervisors: Prof. Dr. Julia E. Vogt (ETH Zurich) Samuel Ruipérez-Campillo (ETH Zurich)
Co-supervisors: Prof. Vicenç Gómez Cerdà (Universitat Pompeu Fabra) Dr. Sven Knecht (University Hospital Basel)Background: Atrial fibrillation affects 26% of Europeans over 40, with catheter ablation being a primary treatment. Low voltage areas significantly influence ablation success, but their identification currently requires invasive electroanatomical mapping during the procedure.
Objective: We developed a deep learning framework to predict finegrained, region-specific low voltage areas from electrocardiograms and clinical data, enabling pre-procedural risk stratification.
Methods: We collected data from 138 atrial fibrillation patients undergoing catheter ablation at University Hospital Basel, with external validation cohorts from Lausanne (n=20) and Bern (n=9). Our multimodal architecture processes ECG signals through pretrained backbones (ST-MEM, CRNN, DenseNet) and clinical features through separate branches, fusing them for hierarchical multilabel classification across 8 atrial regions, 2 area thresholds, and 4 voltage thresholds (64 targets total). Key innovations include: (1) adaptation of max constraint loss to logit space for numerical stability, (2) parallel multi-lead QRS detection for robust heartbeat segmentation, and (3) region-specific adaptive learning rate scheduling.
Results: Our model achieved an AUROC of 0.782 for general low voltage area prediction, outperforming models trained on 10 times more data from previous studies. A single model is enough to predict 64 classes of low voltage areas, which is a significant improvement over previous studies.
Conclusions: Non-invasive low voltage area prediction from routine ECGs is feasible and clinically relevant. The hierarchical multilabel framework provides detailed spatial information about atrial substrate, potentially enabling better patient selection and procedural planning for atrial fibrillation ablation
The psychological benefits of open-water (wild) swimming: Exploring a self-determination approach using a 19-country sample
No full textA growing body of qualitative and quantitative research has explored the potential benefits to mental health and well-being of open-water or “wild” swimming. To date, most studies have used small samples in specific locations, limiting generalisability, and have not distinguished open-water swimming from other forms of outdoor swimming, such as in open-air pools, raising questions about any additional benefits of wild swimming over and above swimming outside per se. Using survey data from n = 1200 recently recalled outdoor swimming visits across 19 different countries, we compared self-reported well-being outcomes for swims in either open-water (wild) locations or open-air pools. Additionally, we explored the degree to which satisfaction of the motivations identified by self-determination theory (i.e. autonomy, relatedness, and competence) may explain any differences. Swimming visits in both locations were associated with high levels of positive, and low levels of negative, well-being, as well as high levels of autonomy, relatedness and competence. Open-water swimming was, nonetheless, associated with significantly higher positive well-being than open-air pool swims, with mediation analysis indicating that feelings of greater autonomy and competence (but not relatedness) primarily accounted for the difference. Results for anxiety were more nuanced, perhaps because more competent swimmers were more likely to swim in less safe, more anxiety inducing, places. Results re-iterate, help explain, and support the generalisation of previous research reporting potential benefits of open-water swimming for mental health and well-being, and highlight the need to support further safe access to high quality open-water locations.This project received funding from the European Union's Horizon 2020 research and innovation programme under Grant Agreement No. 666773. Data collection in California was supported by the Center for Conservation Biology, Stanford University. Data collection in Canada was supported by the Faculty of Forestry, University of British Columbia. Data collection in Finland was supported by the Natural Resources Institute Finland (Luke). Data collection in Australia was supported by Griffith University and the University of the Sunshine Coast. Data collection in Portugal was supported by ISCTE—University Institute of Lisbon. Data collection in Ireland was supported by the Environmental Protection Agency, Ireland. Data collection in Hong Kong was supported by an internal University of Exeter—Chinese University of Hong Kong international collaboration fund. For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission
La Metodología Participativa Audiovisual como recurso para habitar espacios comunes
No full textAquesta tesi doctoral té com a objectiu explorar el potencial de la Metodologia Participativa Audiovisual (MPA) per fomentar els comuns educatius, així com analitzar el rol de les persones educadores en la seva implementació. La recerca s’emmarca en un estudi de cas del projecte H2020 SMOOTH, en el qual es va treballar amb joves del barri del Raval a través de tallers, complementats amb treball etnogràfic i implementats en dues fases (2022 i 2023). Es tracta d’una tesi per compendi, composta per cinc publicacions que mostren com la MPA va permetre als i les joves identificar situacions personals com a part de problemàtiques estructurals més àmplies. A més, va enfortir el seu sentiment de pertinença comunitària, promovent la cooperació i l’autoregulació entre iguals, entenent la producció audiovisual com una eina de construcció compartida. D’altra banda, l’estudi també identifica tensions derivades de les limitacions i la perspectiva adultocèntrica del sistema. La tesi conclou assenyalant la necessitat de generar espais que fomentin el diàleg, la confrontació d’idees i l’autoorganització, a partir dels interessos dels i les joves. En aquest sentit, la MPA es revela com un recurs valuós per resignificar l’audiovisual com a eina convivencial i motor d’una pedagogia dels comuns.Esta tesis doctoral tiene como objetivo explorar el potencial de la Metodología Participativa Audiovisual (MPA) para fomentar los comunes educativos, así como analizar el rol de las personas educadoras en su implementación. La investigación se enmarca en un caso de estudio del proyecto H2020 SMOOTH en el que se trabajó con jóvenes del barrio del Raval a través de talleres, complementados por trabajo etnográfico e implementados dos fases (2022 y 2023). Al tratarse de una tesis por compendio, la investigación está compuesta por cinco publicaciones que muestran cómo la MPA permitió a las y los jóvenes identificar situaciones personales como parte de problemáticas estructurales más amplias. Además, fortaleció su sentido de pertenencia comunitaria, promoviendo la cooperación, la autorregulación entre pares; entendiendo la producción audiovisual como herramienta de construcción compartida. Por otra parte, el estudio también identifica tensiones derivadas de las limitaciones y perspectiva adultocéntrica del sistema. La tesis concluye señalando la necesidad de generar espacios que fomenten el diálogo, la confrontación de ideas y la autoorganización, a partir de los intereses de las y los jóvenes. En este sentido, la MPA se revela como un recurso valioso para resignificar el audiovisual como herramienta convivencial y motor de una pedagogía de los comunes.This doctoral thesis explores the potential of Participatory Audiovisual Methodology (PAM) to foster educational commons and analyzes the role of educators in its implementation. The research is framed within a case study developed as part of the H2020 SMOOTH project, involving young people from the Raval neighborhood (Barcelona) through participatory workshops complemented by ethnographic work. The fieldwork was conducted in two phases, in 2022 and 2023. As a thesis by compendium, the research comprises five publications that illustrate how PAM enabled young participants to identify personal situations as part of broader structural issues. It also strengthened their sense of community belonging, promoting cooperation, peer self-regulation, and a collective approach to audiovisual production. At the same time, the study identifies tensions stemming from adult-centric perspectives and systemic limitations. The thesis concludes by emphasizing the need to create spaces that foster dialogue, critical exchange, and self-organization, grounded in the interests of young people. In this context, PAM emerges as a valuable tool for reimagining audiovisual practices as convivial resources and as catalysts for a pedagogy of the commons.Universitat Pompeu Fabra. Doctorat en Comunicaci
Exploring RF-EMF levels in Swiss microenvironments: An evaluation of environmental and auto-induced downlink and uplink exposure in the era of 5G
No full textThe advancement of cellular networks requires updating measurement protocols to better study radiofrequency electromagnetic field (RF-EMF) exposure emitted from devices and base stations. This paper aims to present a novel activity-based microenvironmental survey protocol to measure environmental, auto-induced downlink (DL), and uplink (UL) RF-EMF exposure in the era of 5G. We present results when applying the protocol in Switzerland. Five study areas with different degrees of urbanization were selected, in which microenvironments were defined to assess RF-EMF exposure in the population. Three scenarios of data transmission were performed using a user equipment in flight mode (non-user), inducing DL traffic (max DL), or UL traffic (max UL). The exposimeter ExpoM-RF 4, continuously measuring 35 frequency bands ranging from broadcasting to Wi-Fi sources, was carried in a backpack and placed 30 cm apart from the user equipment. The highest median RF-EMF levels during the non-user scenario were measured in an urban business area (1.02 mW/m2). Here, DL and broadcasting bands contributed the most to total RF-EMF levels. Compared to the non-user scenario, exposure levels increased substantially during max DL due to the 5G band at 3.5 GHz with 50% of the median levels between 3.20 and 12.13 mW/m2, mostly in urban areas. Note that the time-division nature of this band prevents distinguishing between exposure contribution from DL beamforming or UL signals emitted at this frequency. The highest levels were measured during max UL, especially in rural microenvironments, with 50% of the median levels between 12.08 and 37.50 mW/m2. Mobile UL 2.1 GHz band was the primary contributor to exposure during this scenario. The protocol was successfully applied in Switzerland and used in nine additional countries. Inducing DL and UL traffic resulted in a substantial increase in exposure, whereas environmental exposure levels remained similar to previous studies. This data is important for epidemiological research and risk communication/management.This project has received funding from the European Union's Horizon Europe research and innovation programme under grant agreement No 101057262. Views and opinions expressed are however those of the authors only and do not necessarily reflect those of the European Union or the Health and Digital Executive Agency. Neither the European Union nor the granting authority can be held responsible for them. We acknowledge support from the grant CEX2023-0001290-S funded by MCIN/AEI/10.13039/501100011033, and support from the Generalitat de Catalunya through the CERCA Program. Mònica Guxens was funded by a Miguel Servet II fellowship (CPII18/00018) awarded by the Spanish Institute of Health Carlos III