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La adquisición de fijeza de los trabajadores temporales por no haber sido dados de alta en la Seguridad Social
No full textEl artículo 15.4 "in fine" del Estatuto de los Trabajadores contempla un mecanismo que permite a las personas trabajadoras con un contrato de trabajo temporal adquirir la condición de fijas en la empresa, si ésta no las hubiera dado de alta en la Seguridad Social una vez transcurrido un plazo igual al que legalmente se hubiera podido fijar para el período de prueba. Se trata ésta de una previsión normativa con una larga tradición histórica, pero de difíciles contornos y que funciona como un mecanismo disuasorio dirigido a exigir a la empresa el cumplimiento de sus obligaciones de afiliación y alta respecto de sus trabajadores. Tras analizar su régimen jurídico, se concluye que resulta criticable que la ley esté trasladando al contrato de trabajo las irregularidades cometidas en el ámbito del aseguramiento social ya que un contrato temporal no tiene por qué convertirse en indefinido ante el incumplimiento de una obligación de Seguridad Social, más allá de las responsabilidades administrativas y prestacionales que pudieran derivarse de dicha actuación.Article 15.4 of the Workers’ Statute law provides a mechanism that allows workers with a temporary employment contract to acquire permanent status if their employer has not registered them in Social Security after a period equal to that, which could legally be set for the trial period. This is a regulatory provision with a long historical tradition, but with difficult contours. It has a deterrent purpose and aims to ensure that the employer fulfils its obligations to affiliate and register its workers. After analysing its legal system, we conclude that it is questionable that the legislator is transferring irregularities committed in the area of social security to the employment contract because a temporary worker does not have to become permanent if the employer fails to fulfil a Social Security obligation. It is enough to demand the administrative and benefits responsibilities derived from this action
Urinary tract infection in adults: gaps in current guidelines - opinions from an international multidisciplinary panel and relevance to clinical practice
No full textPurpose: Although urinary tract infections (UTIs) are one of the most common infections encountered in clinical practice, many challenges remain with respect to classification and management. The purpose of this report is to discuss key issues in the management of UTIs and identify gaps in current knowledge and guidelines, as well as future research needs. Design: A multidisciplinary panel of 13 experts from 6 European countries and the United States met on April 27, 2024. They discussed predefined key clinical questions, including classification of UTIs, current management guidelines, management of UTIs in men, antimicrobial switching, and post-treatment asymptomatic bacteriuria. Results: The panel agreed that differentiation between complicated and uncomplicated UTIs is crucial to antimicrobial selection and can impact outcomes. In particular, definitions of complicated UTIs (cUTIs) vary widely between guidelines and in the literature. Patients with cUTIs are not a homogeneous group and differences in risk factors and prognosis should be considered. However, a balance must be sought between appropriate antimicrobial treatment and complexity of guidelines, which can hinder their implementation, especially in primary care. Guidelines published by the European Urology Association and the Infectious Diseases Society of America differ in their antimicrobial treatment recommendations for cUTIs, which is important at a time of increasing antimicrobial resistance. In men with UTIs, it has been established that a longer duration of antimicrobial therapy is needed in cases where fever is present. De-escalation from broad- to narrow-spectrum antimicrobials is recommended wherever possible, and is associated with similar outcomes in many patients relative to remaining on broad-spectrum treatment. Post-treatment asymptomatic bacteriuria should not be assessed, and treatment is not recommended. Non-specialist physician education is crucial to achieving better outcomes for patients with UTIs. Implications: Many challenges remain in the management of UTIs in adults, most notably making an accurate classification, which drives antimicrobial treatment selection. A balance between adequacy of management guidelines and their uptake in routine clinical practice is needed to improve outcomes
Web of Science Research Assistant: functional analysis and usage recommendations
No full textThis chapter provides a comprehensive functional analysis of the Web of Science Research Assistant, a generative AI tool integrated into Clarivate’s academic database. Designed to enhance research workflows, the tool supports tasks such as literature reviews, topic exploration, expert identification, and journal selection. Through a detailed examination of its interface and functionalities, including thematic summarization, co-citation mapping, and trend visualization, this chapter highlights the tool’s potential to streamline scientific discovery. Several practical use cases are presented, demonstrating its capabilities in optimizing searches, identifying seminal papers, and suggesting relevant publication venues. Despite its innovative features, the tool’s use must be guided by critical thinking, transparency, and ethical considerations. Researchers are encouraged to view the assistant not as a substitute, but as a complement to scholarly inquiry. The chapter concludes by emphasizing the value of reflective, layered interaction with AI to responsibly integrate these technologies into academic practice.This work is part of the Project “Parameters and strategies to increase the relevance of media and digital communication in society: curation, visualisation and visibility (CUVICOM)”. Grant PID2021-123579OB-I00 funded by MICIU/AEI/10.13039/501100011033 and by ERDF, EU
Decoding the immune evasive properties of cancer stem cells in breast cancer immunotherapy resistance
No full textCancer stem cells (CSCs) fuels tumours and are involved in therapy resistance, yet their contribution immunotherapy resistance and immunological properties are poorly understood. Herein, we show that within tumour phenotypic heterogeneity, CSCs shutdown the antigen processing and presentation machinery (APM) by downregulating LCOR, thus driving immune escape and immune checkpoint blockade (ICB) immunotherapy resistance. Mechanistically, we unveiled LCOR as master regulator of the conserved MHC cluster region in chromosome 6 through SWI/SNF interaction and binding to interferon (IFN)-stimulated response elements (ISREs) independently of IFN-signalling. Accordingly, LCOR upregulation differentiates CSCs, increase tumour immunogenicity and ICB responsiveness, thus showing prognostic value to ICB response in clinical samples of triple-negative breast cancer (TNBC). Importantly, Lcor-messenger RNA based therapy delivered in extracellular vesicles (EVs) in combination with anti-PD-L1 shows unprecedented results in metastatic TNBC models, overcoming resistance and leading to tumour eradication. Overall, this study demonstrates LCOR as a promising target for ICB response in TNBC through the regulation of the APM.Las células madre cancerosas (CMC) mantienen el crecimiento tumoral y están implicadas en la resistencia a terapias; aunque su rol durante la adquisición de resistencias a inmunoterapias aún no está bien demostrado. En este estudio mostramos que las CMC reducen la maquinaria de procesamiento y presentación antigénica (MPA) por el silenciamiento de LCOR, dando lugar a resistencias a la inmunoterapia basada en el bloqueo del punto de control inmune con anti-PD-L1. Además, demostramos como LCOR regula la región genómica del complejo mayor de histocompatibilidad en el cromosoma 6 juntamente con SWI/SNF, regulando la expresión de genes de la MPA de manera independiente de interferón. De acuerdo con ello, mostramos que LCOR incrementa la respuesta a anti-PD-L1 en ensayos preclínicos; así como su valor pronóstico de respuesta a inmunoterapia en diferentes ensayos clínicos. Finalmente, ensayos preclínicos usando una nueva terapia basada en ARN mensajero de LCOR encapsulada en vesículas extracelulares muestran una respuesta total en combinación con anti-PD-L1. Por todo ello, nuestro estudio sugiere que LCOR es nuevo factor a modular para incrementar la respuesta a anti-PD-L1.Programa de doctorat en Biomedicin
Enhanced television broadcast monitoring with source separation-assisted audio fingerprinting: a case study
No full textData de publicació electrònica 13-10-2025Music identification is crucial for distributing royalties in the music industry. This problem is solved using Audio fingerprinting (AFP) algorithms. However, these methods often struggle in real-world scenarios such as TV broadcasting, when music is in the background, masked by other sounds such as speech. While prior research has focused on improving AFP robustness to pitch and tempo variations, less attention has been
given to enhancing robustness for background music identification. In this work, we assess whether source separation systems improve background music identification by recovering the music signal in these recordings. We present the first extensive study comprising 13 source separation algorithms and five AFP models. We evaluate them on a public dataset of TV recordings, assessing both music identification performance and computational cost. Our results show that source separation substantially improves peakbased AFP identifications, particularly when music is in the background. Additionally, this finding extends to foreground music, making the approach versatile for various music identification tasks, such as query-by-example. Deep learning-based model NeuralFP* (tailored for background music identification) shows no substantial benefit from adding a separation model as preprocessing. This reproducible study provides a comprehensive evaluation framework, offering valuable insights into using source separation methods to improve music identification in real-world contexts.This research is part of NextCore – New generation of music monitoring technology (RTC2019-007248-7)
funded by the Spanish Ministerio de Ciencia e Innovación and the Agencia Estatal de Investigación; and
resCUE – Smart system for automatic usage reporting of musical works in audiovisual productions (SAV20221147) funded by CDTI and the European Union - Next Generation EU, and supported by the Spanish Ministerio de Ciencia, Innovación y Universidades and the Ministerio para la Transformación Digital y de la Función Pública
Genetic adaptation in underrepresented populations: the cases of Peruvian and North African populations
No full textAs a result of local selective pressures, genetic adaptation leaves distinct recognisable marks in the genomes of human populations. Several cases of positive natural selection have been described in humans, but only in a narrow set of populations. In this thesis, we search for signatures of positive selection in two largely understudied populations. Specifically, we analyse the genomes of native populations from three differentiated ecological regions of Perú (the Andes, the desert Pacific coast, and the Amazon rainforest), identifying private selective sweeps in each ecoregion, but also common ones, as well as some candidate genes that are correlated with environmental variables. We also interrogated the genomes of North African individuals, finding candidate genes for selection that are exclusive to North Africans, and others that are shared with European and West and East African neighbouring populations. Moreover, we detected post-admixture selection in Western North Africans facilitated by a European-like ancestry component.Como resultado de presiones selectivas locales, la adaptación genética deja distintas marcas reconocibles en los genomas de las poblaciones humanas. Se han descrito múltiples casos de selección natural positiva en humanos, pero solo en un pequeño grupo de poblaciones. En esta tesis, buscamos señales de selección positiva en dos poblaciones poco estudiadas. Específicamente, analizamos los genomas de poblaciones nativas procedentes de tres regiones ecológicas diferenciadas en Perú (los Andes, la costa desértica del Pacífico y la selva Amazónica), identificando barridos selectivos tanto privados para cada ecorregión, como compartidos, y genes candidatos correlacionados con variables ambientales. Además, también interrogamos los genomas de individuos del Norte de África, identificando genes candidatos de selección exclusivos de norteafricanos, y otros compartidos con poblaciones vecinas europeas y del este y oeste de África. Asimismo, detectamos selección post-mestizaje en norteafricanos del oeste, facilitada por un componente ancestral parecido al encontrado en europeos.Programa de doctorat en Biomedicin
Resolving the continuous high-order organization of the exocyst during vesicle tethering
No full textConstitutive exocytosis is an essential and highly-conserved trafficking pathway for the delivering of cargo to the plasma membrane and the extracellular space. During this pathway, cargo-loaded vesicles are tethered to the plasma membrane by the exocyst, an heterodiramic complex, prior the vesicle fusion. Despite exocyst-mediated vesicle tethering represents a crucial stage, how multiple exocysts organize in space and time remains poorly understood. Here, we employed an integrative approach to unveil the dynamic architecture of exocyst-mediated vesicle tethering. To achieve this goal, we developed a computational workflow for the analysis of datasets from live-cell imaging, super-resolution microscopy and correlative cryo-electron tomography. We demonstrated that the exocyst high-order structure consists on seven exocyst, on average, assembled into in ring-like shapes. The radius of those rings expand from 18 to 38 nm following a saturated-exponential function defined by a characteristic time of 3.1 s.Universitat Pompeu Fabra. Doctorat en Biomedicin
StreamChol: a web-based application for predicting cholestasis
No full textThis article introduces StreamChol, a software for developing and applying mechanistic models to predict cholestasis. StreamChol is a Streamlit application, usable as a desktop application or web-accessible software when installed on a server using a docker container.StreamChol allows a seamless integration of pharmacokinetic analyses with Machine Learning models. This integration not only enables cholestasis prediction but also opens avenues for predicting other toxicological endpoints requiring similar integrations. StreamChol's Docker containerization also streamlines deployment across diverse environments, addressing potential compatibility issues. StreamChol is distributed as open-source under GNU GPL v3, reflecting our commitment to open science. Through StreamChol, researchers are offered a potent tool for predictive modelling in toxicology, harnessing its strengths within an intuitive and user-friendly interface, without the need for any programming knowledge.Scientific contribution This work offers a user-friendly web-based tool for cholestasis prediction and a complete workflow for creating web platforms that require the combination of both programming languages, R and Python.The authors received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement No. 964537 (RISK-HUNT3R), which is part of the ASPIS cluster
The political effects of communicative interventions during crises
No full textCan communicative interventions by the government influence political trust and increase public compliance during crises? This study examines the impact of a televised speech by German Chancellor Angela Merkel at the onset of the COVID-19 pandemic. Using an unexpected-events-during-survey-design, we find that the speech led to a 7-percentage point increase in trust in the federal government and up to a 25-percentage point decrease in citizens' mobility. We also observe demographic variation in susceptibility to speech. We explore the underlying mechanisms by comparing Merkel's speech with similar televised addresses by Mark Rutte and Boris Johnson, where we observe no comparable effects on attitudes. We suggest that specific content, such as an emphasis on solidarity and positive sentiment, may have played a role in mobilizing public support. Our findings indicate that effective leader communication can be a powerful tool for sustaining public support and ensuring compliance with crisis measures
Unveiling a Novel Molecular Biotype of Depression - Effects of Dysregulated microRNA Biogenesis in Treatment Resistance Depression
No full textEl Trastorno Depresivo Mayor (TDM) es uno de los trastornos psiquiátricos más frecuentes e invalidantes, con más de 300 millones de personas afectadas en todo el mundo. Las estrategias de tratamiento actuales se basan en tratamientos de "ensayo y error", siguiendo directrices universales con diferentes grupos de medicamentos que actúan sobre los pocos mecanismos patogénicos conocidos. En consecuencia, más de dos tercios de los pacientes diagnosticados con TDM no responden a la primera línea de tratamiento, y más de un tercio pasará a ser considerado con un TDM "resistente al tratamiento". En este proyecto, investigamos la hipótesis de que existen mecanismos etiopatogénicos de este trastorno aún inexplorados, y que, sobre todo, van más allá del clásico enfoque en neurotransmisión, estrés o inflamación, dictados por la visión reduccionista actual. Además, creemos que lo que comúnmente llamamos "depresión resistente al tratamiento" (DRT) se trate de un distinto biotipo molecular de depresión, que comparte elementos de la sintomatología clínica, a pesar de tener otro origen etiopatológico. Para comprobar esta teoría, comparamos pacientes con DRT y no-DRT a través de un método multiómico, con el objetivo de investigar a un nivel de regulación molecular inexplorado en psiquiatría: los microRNAs (miRNAs). De hecho, se sabe que los miRNAs juegan un papel crucial en la regulación del sistema nervioso central, y se han observado cambios en sus concentraciones en diferentes trastornos psiquiátricos, especialmente según la respuesta al tratamiento. Nuestros resultados demuestran que la DRT se asocia a marcas de miRNA específicas y a una desregulación de la maquinaria de biogénesis de los miRNAs. Creemos que este fenómeno desencadene alteraciones funcionales en varios procesos biológicos, ayudando al desarrollo de fenotipo depresivo, o incluso de DRT. Además, validamos un subgrupo de candidatos de miRNAs en un modelo murino a través de una inyección intraventricular de antagomires, obteniendo fenotipos compatibles con depresión. Nuestros descubrimientos abren la puerta al uso de los miRNAs como biomarcadores predictivos para una identificación precoz de DRT y para el desarrollo de nuevas estrategias terapéuticas enfocadas en restablecer la maquinaria de los miRNAs.Major Depressive Disorder (MDD) is one of the most prevalent and invalidating psychiatric disorders, affecting more than 300 million people worldwide. Current therapeutic strategies rely on a trial-and-error approach, based on one-size-fits-all guidelines describing an ordered list of drugs targeting the recognized pathogenic pathways of MDD. However, more than two-thirds of MDD patients do not respond to first-line treatments, while over one-third are eventually deemed as “treatment-resistant”. In this project, we investigated our hypothesis that these oversimplistic views of depression, which focus on neurotransmission, stress and inflammation, disregard pivotal unexplored molecular etiologies of the disorder. Moreover, we believe that what we commonly refer to as "treatment resistant depression” (TRD) is a different molecular biotype of depression, with shared clinical symptomatology but an alternative etiopathogenic origin. To test this hypothesis, we compared TRD and non-TRD patients using a multi-omics approach to investigate an unexplored molecular regulatory layer in psychiatry, microRNAs (miRNAs). In fact, miRNAs are known to play a pivotal role in the central nervous system and changes in their levels have been observed in several psychiatric disorders, especially in response to treatment. Our results showed that TRD is associated with specific miRNA signatures and the dysregulation of the miRNA biogenesis machinery. We believe that this alteration might lead to changes in several biological processes, and in turn, to the depressive/TRD phenotype. We validated in mice a subset of those miRNAs by intracerebroventricular injection of antagomirs and recapitulated depressive-like phenotypes. Our findings pave the way for the use of miRNAs as predictive biomarkers for the early identification of TRD and for the development of novel therapeutic strategies targeting the miRNA machinery.Universitat Pompeu Fabra. Doctorat en Biomedicin