Pompeu Fabra University

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    Defendiendo el 'suave yugo' de 'la mal llamada esclavitud': El Círculo Hispano Ultramarino de Barcelona (1871-1880)

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    Barcelona fue el lugar elegido por muchos indianos enriquecidos en Cuba y Puerto Rico al instalarse en Europa. Unos indianos que durante el Sexenio Democrático se organizaron en el Círculo Hispano-Ultramarino de dicha ciudad para presionar por el mantenimiento de la esclavitud en ambas Antillas, primero, y para desestabilizar a la I República, después. Aquella entidad fue capaz de implicar en sus campañas antiabolicionistas y proesclavistas a las principales organizaciones económicas catalanas, así como a amplios sectores de las élites de Cataluña, quienes asumieron públicamente sus argumentos participando en plataformas más amplias como la Liga Nacional o la Comisión Defensora de los Intereses de España en Cuba. Y aunque la presión proesclavista no pudo evitar la abolición de la esclavitud en Puerto Rico y en Cuba, sí consiguió alargar su vigencia durante unos años en la Gran Antilla mediante la institución del Patronato. El legado más destacable (y también el más perdurable) del Círculo Hispano-Ultramarino de Barcelona fue el Banco Hispano Colonial, una entidad financiera nacida en 1876 que acabaría transformándose en un verdadero banco de negocios y que gestionaría las aduanas cubanas hasta el final de la dominación española sobre la isla, en 1898.Este artículo forma parte del proyecto de investigación financiado por el Ministerio de Ciencia e Innovación PID2019-105204GB-I00

    A Multi-Organ and Multi-Modal Data-Driven Analysis of Metabolic Patterns in Type 2 Diabetes. Unravelling the Pathologic Mechanisms Between Organs: The Impact of Tissue-Specific Insulin Resistance.

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    La diabetis tipus 2 (T2D) és una malaltia crònica caracteritzada per insulino-resistència (IR) i inflamació, sovint associada a comorbiditats cardiovasculars, hepàtiques i cognitives – conegudes com l’eix fetge-cor-cervell. El seu diagnòstic, basat en índexs sistèmics, no reflecteix l’afectació específica dels teixits dificultant els diagnòstics i tractaments personalitzats. Els objectius d’aquesta tesi han estat caracteritzar trets específics dels teixits a partir d’escàners PET/CT i fenotipar pacients amb risc de comorbiditats multi-òrgan mitjançant intel·ligència artificial. Aquest és, segons el nostre coneixement, el primer estudi que aborda les mancances en la gestió de la T2D des d’una perspectiva biomèdica-tecnològica proposant nous fenotips de progressió de la T2D i eines d’avaluació de risc metabòlic específic. Presentem eines no-invasives i eficients per avaluar l’afectació específica dels teixits mitjançant algoritmes de segmentació, així com models de classificació basats en anàlisis de sang, que afavoreixen estratègies clíniques personalitzades en el marc de la T2D centrades en l’eix fetge-cor-cervell.La diabetes tipo 2 (T2D) es un trastorno metabólico crónico y de alto riesgo, caracterizado por resistencia a la insulina e inflamación, que comúnmente coexiste con comorbilidades cardiovasculares, hepáticas y cognitivas, también conocidas como el eje hígado-corazón-cerebro. Las limitaciones diagnósticas surgen del uso de índices sistémicos que pasan por alto disfunciones específicas en los tejidos, lo que conlleva el riesgo de diagnósticos erróneos y tratamientos no optimizados. Los objetivos de esta tesis han sido caracterizar las características específicas de los tejidos a partir de escáneres PET/CT y fenotipar a pacientes en riesgo de desarrollar comorbilidades multiorgánicas mediante herramientas basadas en inteligencia artificial. Este es, hasta donde sabemos, el primer estudio que aborda las lagunas en el manejo de la T2D desde una perspectiva biomédica-técnica, proponiendo nuevos fenotipos de progresión de la enfermedad y novedosas herramientas de evaluación del riesgo específicas por tejido. Presentamos herramientas no invasivas y computacionalmente eficientes para evaluar el deterioro metabólico específico de los tejidos mediante algoritmos de segmentación, junto con modelos de clasificación de fenotipos basados en análisis de sangre. Estos nuevos métodos respaldan estrategias personalizadas y clínicamente aplicables para un tratamiento optimizado de la T2D, enfocado en el eje hígado-corazón-cerebro.Type 2 diabetes (T2D) is a chronic, high-risk metabolic disorder characterized by insulin resistance (IR) and inflammation commonly co-occurring with cardiovascular, hepatic, and cognitive comorbidities – also known as the liver-heart-brain axis. Diagnostic limitations arise from using systemic indices that overlook tissue-specific dysfunction, thus risking misdiagnosis and unoptimized treatment. The aims of this thesis have been to characterize tissue-specific features from PET/CT scans, and to phenotype patients at risk of developing multi-organ comorbidities using artificial intelligence-based tools. This is, to our knowledge, the first study to fill in the gaps in T2D management using a biomedical-technical perspective by proposing new phenotypes of T2D progression and novel tissue-specific risk assessment tools. We present non-invasive, computationally efficient tools for assessing tissue-specific metabolic impairment via segmentation algorithms, alongside with blood test-based phenotype classification models. These new methods support personalized, clinically applicable strategies for optimized T2D treatment targeting the liver-heart-brain axis.Universitat Pompeu Fabra. Doctorat en Tecnologies de la Informació i les Comunicacion

    Characterization of synthetic lethality between MYC activation and splicing inhibition in an immortalized cell line : roles of alternative splicing

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    Cancer cells exhibit a synthetic lethal (SL) phenotype when Myc upregulation is combined with antitumor drugs targeting the splicing factor SF3B1. However, the molecular events and mechanisms responsible for this vulnerability remain poorly understood. We used an immortalized cell line (h-TERT RPE MYC-ER p53KO) which allows inducible MYC activation, and the SF3B1-targeting drug Pladienolide B (PLAD B), to recreate the SL phenotype, scored in viability and clonogenic assays. Our data indicate that apoptosis is a key pathway involved in the SL phenotype. However, contrary to the proposed role of MCL1 alternative splicing as a major mediator of apoptotic effects induced by PLAD B treatment, upregulation of the pro-apoptotic mRNA isoform of MCL1 cannot explain the SL phenotype. We carried out RNA-seq analyses to identify and functionally characterize gene expression and alternative splicing changes potentially associated with the SL phenotype. Importantly, we identified a set of exons known to be essential for cancer cells that, when induced to be skipped using antisense oligonucleotides, are detrimental for cell viability and likely contribute to the SL phenotype.Las células cancerosas muestran un fenotipo de letalidad sintética (SL) cuando se combina la sobreexpresión de Myc con fármacos anticancerígenos dirigidos contra el factor de splicing SF3B1. Sin embargo, los eventos moleculares responsables de esta vulnerabilidad son poco comprendidos. Usamos una línea celular inmortalizada (h-TERT RPE MYC-ER p53KO) que permite la activación inducida de MYC, y el fármaco dirigido contra SF3B1 Pladienolide B (PLAD B), para recrear el fenotipo SL, medido en ensayos de clonogenicidad y viabilidad. Nuestros datos indican que la apoptosis es una ruta clave en el fenotipo SL. Sin embargo, al contrario del papel propuesto para el splicing alternativo de MCL1 como mediador de los efectos apoptóticos inducidos por tratamiento con PLAD B, el incremento de la isoforma proapoptótica de mRNA de MCL1 no puede explicar el fenotipo SL. No obstante, hemos confirmado que la apoptosis es una ruta clave para conseguir el fenotipo SL. Ejecutamos análisis de RNA-seq para identificar y caracterizar funcionalmente los cambios de expresión génica y splicing alternativo potencialmente asociados a SL. Destacablemente, identificamos un set de exones esenciales para células cancerosas que, al inducir su salto con oligonucleótidos antisentido, son perjudiciales para la viabilidad celular y probablemente contribuyen al fenotipo SL.Programa de Doctorat en Biomedicin

    Patellofemoral arthroplasty provides similar long-term survival rate and complications with better clinical outcomes compared to facetectomy for the treatment of isolated patellofemoral osteoarthritis

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    Purpose: This study aimed to analyse the clinical outcomes and survival of patellofemoral arthroplasty (PFA) in treating isolated patellofemoral osteoarthritis (IPFOA) at our centre. The secondary objective was to compare these results with a historical cohort treated with partial lateral facetectomy plus Insall realignment (PLFIR). We hypothesised that clinical outcomes and survival with PFA are superior to PLFIR and comparable to the literature. Methods: A retrospective analysis of 120 patients with IPFOA was conducted. The PFA series included 33 patients treated between 2012 and 2019 with a minimum follow-up of 5 years (range 1.2-12.1 years). The PLFIR historical cohort treated between 1995 and 2002 (range 4.1-15.7 years) consisted of 87 patients. Preoperative and post-operative clinical outcomes were assessed using the Knee Society Score (KSS) and Kujala score, and survivorship was evaluated via Kaplan-Meier analysis. Cox regression analysis was used to identify factors influencing surgical failure. Results: The PFA group demonstrated a 75.8% survival rate at 10 years, with a 24.2% failure rate requiring conversion to total knee arthroplasty (TKA). In the PLFIR group, the 10-year survival rate was 79.3%, although 26.4% required TKA. Both groups exhibited significant improvements in KSS and Kujala score, with PFA showing superior Kujala score improvement (p = 0.012). No statistically significant difference in survival between the two groups was observed at 10 years (p = 0.056), but PFA showed better long-term clinical outcomes. Conclusions: PFA demonstrated comparable survival rates to PLFIR in the treatment of IPFOA. Despite a higher initial failure rate, PFA showed a potential for greater improvement in the long term, particularly in terms of anterior knee pain. Level of evidence: Level IV, retrospective case series analysis compared with a historical cohort

    Reshaping sports journalism through innovation: an analysis of L'Équipe explore's strategies, practices and output

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    Data de publicació electrònica: 23-10-2024Sports journalism practice faces important challenges deriving from the multiplication of platforms, the acceleration of workflows, the emergence of new entrants and the audiences' shifting consumption habits. In a bid to overcome those challenges and advance innovation across the board, the French newspaper L'Équipe established a specific unit for that purpose: Explore. By focusing on this case study, this research has examined the formats, output and practices deployed by Explore and evaluated its impact within L'Équipe's offer. The study is informed by content analysis performed on the projects (N=201) published by Explore over a 32-month timeframe (May 2021-December 2023), ethnographic work and eight semi-structured interviews with its employees. Findings reveal that Explore stands out as a leading "media lab" in sports journalism. Through a broad range of formats and a multifaceted agenda, Explore occupies a unique position in terms of delivering cultural capital. Explore embraces alternative production modes that invest in freedom and research while rejecting hyper-accelerated cycles and clickbait-oriented approaches. Such proposition has resonated with audiences and positioned Explore as a cornerstone of L'Équipe's commercial strategy. Solutions articulated by Explore contribute to the broader discussion of how sports journalism practice can be reshaped in the digital age

    Unmet questions about frailty in kidney transplant candidates

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    Frailty occurs frequently among patients with advanced chronic kidney disease, especially among women. Assessing frailty in kidney transplant (KT) candidates is crucial for informing them about associated risks. However, there is poor agreement between frailty scales and research on their correlation with transplant outcomes. Being prefrail significantly impacts both graft and patient survival, often beginning with just 1 Fried criterion. Rather than viewing frailty as a categorical state, it should be regarded as a spectrum ranging from 1 to 5 criteria, with the risk of adverse outcomes escalating as frailty worsens. Frailty status fluctuates during the waiting period for KT; hence, a 1-time frailty evaluation is insufficient to determine risks and implement strategies for improving functional status. Further research should investigate the components of frailty that most frequently change during this waiting period and establish strategies to prevent or reverse frailty. Although careful evaluation of frail KT candidates is necessary to prevent early complications and mortality, exclusion based solely on a frailty score is unwarranted. Instead, efforts should focus on timely interventions to enhance their condition before transplantation. Although evidence is limited, exercise programs appear feasible and yield positive results. A pretransplant clinical framework encompassing multimodal prehabilitation-comprising physical therapy, nutritional measures, and psychological support-during the waiting list period may help alleviate the effects of frailty and poor fitness after KT, ultimately improving key outcomes. Despite logistical challenges, there is a pressing need for interventional trials in this area

    CSDE1 isoforms in cancer progression and suppression

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    The RNA-binding protein CSDE1 is a key regulator of mRNA stability and translation, involved in a wide range of biological processes. Alterations of CSDE1 expression and/or genetic mutations have been found in neurodevelopmental disorders and in several human tumors, where CSDE1 displays context-specific roles. We have previously shown that CSDE1 functions as an oncoprotein in melanoma, where it promotes invasion and metastasis, whereas it behaves as a tumour suppressor in squamous cell carcinoma by promoting oncogene-induced senescence (1, 2). The reasons underlying these context-specific behaviours are so far unknown. To unveil whether different CSDE1 “proteoforms”, are a possible explanation for this context-specificity, we have combined Nanopore sequencing with one and two-dimensional gel analysis to characterize CSDE1 in melanoma cells and in keratinocytes. We have defined tissue-specific proteins, including one major isoform expressed in melanoma patient samples regardless of tumor stage, whose levels increase dramatically upon cell transformation. Notably, we have also detected differential CSDE1 PTMs and subcellular localization correlating with cell malignancy. Our data is consistent with a model where PTMs of CSDE1 are central to direct its function to shape the malignant phenotypes. (1) Wurth et al., Cancer Cell (2016). PMID: 27908735 (2) Avolio et al., Cell Reports (2022). PMID: 35021076La proteína de unión a ARN CSDE1 es un regulador clave de la estabilidad y traducción del ARNm, implicado en una amplia gama de procesos biológicos. Se han encontrado alteraciones de la expresión y/o mutaciones genéticas de CSDE1 en trastornos del neurodesarrollo y en varios tumores humanos, en los que CSDE1 desempeña funciones específicas según el contexto. Anteriormente, hemos demostrado que CSDE1 funciona como una oncoproteína en melanoma, donde promueve la invasión y la metástasis, mientras que se comporta como un supresor tumoral en el carcinoma de células escamosas mediante la promoción de la senescencia inducida por oncogenes (1, 2). Hasta ahora se desconocen las razones que subyacen a estos comportamientos en contextos específicos. Para desvelar si las diferentes "proteoformas" de CSDE1 son una posible explicación de esta especificidad de contexto, hemos combinado la secuenciación Nanopore con el análisis de gel unidimensional y bidimensional para caracterizar CSDE1 en células de melanoma y en queratinocitos. Hemos definido proteínas específicas de cada tejido, incluida una isoforma principal expresada en muestras de pacientes con melanoma, independientemente del estadio del tumor, cuyos niveles aumentan drásticamente tras la transformación celular. En particular, también hemos detectado modificaciones postraduccionales diferenciales de CSDE1 y una localización subcelular correlacionada con la malignidad celular. Nuestros datos concuerdan con un modelo en el que las modificaciones de CSDE1 son fundamentales para dirigir su función y dar forma a los fenotipos malignos. (1) Wurth et al., Cancer Cell (2016). PMID: 27908735 (2) Avolio et al., Cell Reports (2022). PMID: 35021076Programa de Doctorat en Biomedicin

    Mediterranean diet and mental health in children and adolescents: A systematic review

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    Context: Childhood and adolescence are periods of critical importance in the development of mental health disorders. The Mediterranean diet (MD) has been linked to multiple positive health outcomes, including reduced incidence of mental health disorders and fewer psychiatric symptoms. Objective: This study aimed to investigate the association between adherence to an MD and mental health outcomes in children and adolescents. Methods: A systematic literature review was conducted of original research that explored the relationship between psychiatric symptoms or disorders and adherence to an MD. The literature search was conducted on PubMed, Scopus, Web of Science, MEDES, Dialnet, and Latindex from inception to November 2022, and the Newcastle-Ottawa Scale was used to evaluate the quality of studies. Results: A total of 13 studies (6 cross-sectional, 4 case-control, 2 randomized clinical trials, and 1 longitudinal cohort) out of 450 met the inclusion criteria. A total of 3058 children or adolescents with a mean age range from 8.6 to 16.2 years were included. Among the reviewed studies, 5 (71.42%) of those looking at attention-deficit/hyperactivity disorder, 4 (80%) examining depression, and 2 (50%) assessing anxiety found a significant protective association. Seven articles (53.84%) were found to be of high quality and 6 (46.15%) of moderate quality. Conclusion: Adherence to an MD could be a protective factor for mental health in child and adolescent populations. This suggests that promoting an MD could help prevent the onset of clinical psychiatric symptoms, reduce symptom severity, and improve prognosis in young patients. Systematic review registration: PROSPERO registration no. CRD42021276316

    Kill your darlings nostalgia autofágica en multiplicidades fílmicas y televisivas contemporáneas

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    Ningún retorno se define por la repetición prístina, la recuperación impoluta. En el encuentro entre pasado y presente existe una fricción ineludible, constructora de sentidos. Esta tesis buscará indagar cómo se articulan esas fricciones y qué sentidos emergen de ellas a través de la intersección entre las “multiplicidades”, modalidades de reescritura y repetición audiovisual, y la nostalgia, comprendida como un sentimiento temporalizante de continuidades y discontinuidades, un vínculo entre deseos, frustraciones y pérdidas. El concepto de autofagia propondrá identificar —a través de los flujos de repetición-diferencia y resonancias-distanciamientos que vehiculan estas multiplicidades— un proceso de regeneración dinámico que descarta y recupera elementos del pasado de los universos ficcionales en pos de mantener la vitalidad de su estructura narrativa, visual y afectiva. El tiempo, de esta forma, será considerado como una fuerza que atraviesa las películas y series analizadas, las cuales no solo reconocen su pasaje, sino que lo reabsorben para señalar su peso emotivo.No return can be defined by pristine repetition, by unpolluted recuperation. In the meeting between past and present there is an unavoidable friction, one able to generate new meanings. This dissertation will seek to inquire how those frictions are articulated and what meanings emerge from them through the intersection between “multiplicities” — modalities of audiovisual repetition—, and nostalgia —a temporalizing emotion of continuities and discontinuities, a linkage between desires, frustrations and losses—. The concept of autophagy —a lens for inspecting the fluxes of repetition-difference and resonances-discontinuities mobilized by these multiplicities— will define the dynamic regeneration process undertaken by these objects. A process that discards and recuperates elements from these universes’ fictional pasts in order to maintain the vitality behind their narrative, visual and affective structure. Time, in this sense, will be considered as a force that runs through the films and series, here analyzed as an element not only acknowledged by them, but also reabsorbed and assumed in its emotional weight.Programa de Doctorat en Comunicaci

    The meaning of 'literal meaning'

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    Although references to literal meaning are frequent in the legal field, it is not easy to determine what "literal meaning" means. In general, it seems to be considered as unproblematic not only by many legal scholars but also by lawyers and other participants in the legal practice. In this paper I will show that this position comes about because an intuitive view of language is assumed according to which words are related by competent speakers to descriptions that determine reference. However, this descriptivist approach is shown to be problematic in reconstructing our linguistic practices. In contrast, New Theories of Reference (NTR) provide a plausible account of our common and legal uses of words. In this paper I will present a version of NTR that avoids the criticisms that are normally addressed to them. I will also show that this version of NTR has advantages when compared to the traditional descriptivist model. In the legal field, this version of NTR allows us a better understanding of how legal interpretation works

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