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Comorbidity and temporal associations between mental disorders among college students in the world mental health international college student initiative
No full textBackground: Mental disorders are highly prevalent among students worldwide. This study aims to examine comorbidity and temporal associations between mental disorders among students. Methods: The study included 72,288 students from 18 countries as part of the World Mental Health International College Student (WMH-ICS) Initiative, with cross-sectional data collected between 2017 and 2023. Screening for common DSM-5 disorders was conducted using validated screening measures. Latent variables were examined using exploratory principal axis factor analysis on a correlation matrix among the lifetime mental disorders. Based on age-of-onset information, multivariable poisson regression models were used to examine associations of prior disorders with the first onset of other disorders. Results: 27.0 % of students screened positive for only one lifetime disorder, 17.1 % for two, 10.9 % for three, and 10.6 % for 4+ disorders. In the factor analysis, three latent variables were found, comprising: internalizing disorders (generalized anxiety disorder, major depressive episode, post-traumatic stress disorder, and panic disorder), substance use disorders (drug use disorder and alcohol use disorder), and externalizing disorders (attention deficit/hyperactivity disorder and mania/hypomania). Prior internalizing and externalizing disorders were associated with the subsequent first onset of all other disorders with risk ratios ranging from 1.5-7.5. Substance use disorders were less consistently associated with the subsequent first onset of other disorders, but alcohol use disorder was associated with the first onset of drug use disorder and vice versa. Conclusions: Mental disorder comorbidity is common among students, and students with disorders across the internalizing and externalizing spectrum have an increased risk of future mental disorder comorbidities
Beyond passive audiences: children’s agency in media literacy research
No full textOne of the most salient contemporary debates in media research concerns the role of child audiences. The enduring legacy of media-centric approaches has contributed to the construction of childhood as marginalized or invisible, frequently framing young audiences as passive recipients (mere vessels or sponges). This perspective has often eclipsed essential questions such as: What do children do with the media and information they consume? What meanings and interpretations do they construct from content that is frequently presumed to “affect” them? (Buckingham, 2013; Kellner & Share, 2007; Livingstone, 2004). This paper analyzes the opportunities and challenges of conducting fieldwork with children, framed by the principles of the sociology of childhood. The study highlights key indicators that underscore the relevance of this perspective in our research and critically reflect on the practical limitations encountered in studying young audiences
Integrative data science in drug safety research: experiences, challenges, and perspectives
No full textPharmaceutical research and development largely depend on the quantity and quality of data that are available to support projects. The secondary use of data by means of collaborative and integrative approaches is yielding promising results in drug safety research. However, there are challenges that must be overcome in these integrative approaches, such as interoperability issues, intellectual property protection, and, in the case of clinical information, personal data safeguards. The OMOP common data model and the EHDEN and DARWIN EU platforms constitute successful examples of data sharing initiatives in the clinical domain, while the eTOX, eTRANSAFE, and VICT3R international projects are examples of corporate data sharing in toxicology research. The VICT3R project is using these shared data for generating virtual control groups to be applied in nonclinical drug safety assessment. Drug-related knowledge bases that integrate information from different sources also constitute useful tools in the drug safety domain.The author is cofounder and one of the shareholders of MedBioinformatics Solutions SL; DISGENET is a product of this company. The VICT3R project receives funding from the Innovative Health Initiative Joint Undertaking (IHI JU) under grant 101172693. The IHI JU receives support from the European Union's Horizon Europe research and innovation program and COCIR, EFPIA, Europa Bío, MedTech Europe, and Vaccines Europe and contributing partners. Views and opinions expressed are, however, those of the author only and do not necessarily reflect those of the aforementioned parties. None of the aforementioned parties can be held responsible for them
De novo basecalling of RNA modifications at single molecule and nucleotide resolution
No full textRNA modifications influence RNA function and fate, but detecting them in individual molecules remains challenging for most modifications. Here we present a novel methodology to generate training sets and build modification-aware basecalling models. Using this approach, we develop the m6ABasecaller, a basecalling model that predicts m6A modifications from raw nanopore signals. We validate its accuracy in vitro and in vivo, revealing stable m6A modification stoichiometry across isoforms, m6A co-occurrence within RNA molecules, and m6A-dependent effects on poly(A) tails. Finally, we demonstrate that our method generalizes to other RNA and DNA modifications, paving the path towards future efforts detecting other modifications.SC was supported by “la Caixa” InPhINIT PhD fellowship (LCF/BQ/DI19/11730036). EMBO YIP Bridging Funds, and is currently supported by Centro de Excelencia Severo Ochoa funding. AD-T was supported by an FPI Severo-Ochoa fellowship by the Spanish Ministry of Economy, Industry and Competitiveness (MEIC). LPP was supported by funding from the European Union’s H2020 research and innovation programme under Marie Sklodowska-Curie grant agreement No. 754422. This work was supported by the Spanish Ministry of Science, Innovation and Universities (MCIN/AEI/10.13039/501100011033/ FEDER, UEMEIC) (PID2021-128193NB-100 to EMN), the European Research Council (ERC-StG-2021 No 101042103 to EMN) and the Australian Research Council (DP180103571 to EMN). We acknowledge support of the Spanish Ministry of Science and Innovation through the Centro de Excelencia Severo Ochoa (CEX2020-001049-S, MCIN/AEI /10.13039/501100011033), the Generalitat de Catalunya through the CERCA programme and to the EMBL partnership. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union. Neither the European Union nor the granting authority can be held responsible for them
The spatial landscape of cancer hallmarks reveals patterns of tumor ecological dynamics and drug sensitivity
No full textTumors are complex ecosystems of interacting cell types. The concept of cancer hallmarks distills this complexity into underlying principles that govern tumor growth. Here, we explore the spatial distribution of cancer hallmarks across 63 primary untreated tumors from 10 cancer types using spatial transcriptomics. We show that hallmark activity is spatially organized, with the cancer compartment contributing to the activity of seven out of 13 hallmarks, while the tumor microenvironment (TME) contributes to the activity of the rest. Additionally, we discover that genomic distance between tumor subclones correlates with differences in hallmark activity, even leading to clone-hallmark specialization. Finally, we demonstrate interdependent relationships between hallmarks at the junctions of TME and cancer compartments and how they relate to sensitivity to different neoadjuvant treatments in 33 bladder cancer patients from the DUTRENEO trial. In conclusion, our findings may improve our understanding of tumor ecology and help identify new drug biomarkers.This research was funded by MCIN/AEI/10.13039/501100011033 and the ERDF through PID2021-125282OB-I00, Generalitat de Catalunya (2021 SGR 01494) and the Sarah Jennifer Knott Foundation. The authors would like to thank Abel Gonzalez-Perez, Nuria Lopez-Bigas, and Eliezer Van Allen for their valuable feedback and the kind and generous patients who donated the samples that made this study possible. This work has been done as part of the PhD Programme in "Biochemistry, molecular biology and biomedicine" from Universitat Autonoma de Barcelona
Unravelling new targets for pancreatic cancer: Galectin-1 and Parp-2
No full textPancreatic ductal adenocarcinoma (PDAC) is an unmet medical need characterized by a poor prognosis and high mortality. Until now, no effective therapies have been discovered to achieve disease control. Thus, there is an urgent need for finding new therapeutic strategies for pancreatic cancer patients. In this project, we focused on two new putative therapeutic targets for PDAC: Galectin-1 (Gal1) and poly(ADP-ribose) polymerase 2 (Parp-2).
Gal1 is a small lectin that has been strongly implicated in tumour-stroma crosstalk in PDAC, since its genetic depletion impairs tumour growth, angiogenesis and enhances the anti-tumour immune response. Here, the pharmacological inhibition of Gal1 was characterized as a novel therapeutic strategy for PDAC. On the other hand, current pan-Parp inhibitors have not shown positive results in PDAC clinical trials. Moreover, preclinical data in several tumours have shown that single Parp-2 blockade can hamper cancer progression. Parp-2 is an enzyme implicated in DNA damage response and repair, controlling replication stress, a hallmark of PDAC. In this work, the specific role of Parp-2 in PDAC in a c-myc driven mouse model was studied, showing impaired tumour progression after selective genetic Parp-2 depletion. Finally, the underlying mechanisms of this effect on tumour progression were further deciphered using transcriptomic analysis. Our data unveil Gal1 and Parp-2 as novel putative therapeutic targets for pancreatic cancer.El adenocarcinoma de páncreas es una urgencia médica debido a su mal pronóstico y alta mortalidad. Hasta ahora, no se han encontrado nuevas dianas terapéuticas que permitan controlar la enfermedad, por lo que hay una urgente necesidad de encontrar nuevas estrategias para los pacientes con cáncer de páncreas. Este proyecto, se ha centrado en dos posibles dianas terapéuticas: Galectina-1 (Gal1) y Poli(ADP-ribosa) polimerasa 2 (Parp-2).
Gal1 es una pequeña lectina que está estrechamente implicada en la interacción entre el tumor y el estroma del adenocarcinoma de páncreas, ya que la depleción genética de ésta dificulta el crecimiento tumoral y la angiogénesis, además de mejorar la respuesta inmune anti-tumoral. En este trabajo, se ha caracterizado la inhibición farmacológica de Gal1 como nueva estrategia terapéutica para el adenocarcinoma de páncreas. Por otro lado, la inhibición inespecífica de Parp no ha mostrado resultados positivos en ensayos clínicos y, además, datos preclínicos han demostrado que la inhibición selectiva de Parp-2 puede retrasar la progresión tumoral en varios tumores. Parp-2 es una enzima implicada en la respuesta al daño en el ADN, que controla el estrés replicativo, el cual es una característica frecuente en el adenocarcinoma de páncreas. En este trabajo, hemos estudiado el papel de Parp-2 en el adenocarcinoma de páncreas en el modelo murino Ela-myc, mostrando un retraso en la progresión tumoral tras la inhibición genética y selectiva de Parp-2. Finalmente, también se ha estudiado en más profundidad los mecanismos responsables de este efecto. Por lo tanto, nuestros datos identifican Gal1 y Parp-2 como dos nuevas dianas terapéuticas para el cáncer de páncreas.Programa de Doctorat en Biomedicin
Welfare policy and immigration attitudes in Western Europe
No full textData de publicació electrònica: 09-03-2025How do welfare systems affect natives' attitudes to immigration? The impact of immigration on public support for welfare and redistribution has received considerable scholarly attention, but we know much less about how welfare policies shape citizens' views about immigration. We focus on two mechanisms: an instrumental channel and a values-based approach. Our empirical strategy is two-pronged. Hierarchical models leveraging variation in immigration attitudes and welfare generosity both between countries and over time (2002-2019) suggest that more comprehensive welfare regimes are associated with more positive views of immigrants. Furthermore, a regression discontinuity design drawing on a natural experiment in Denmark reveals that hostility towards immigrants increased following the announcement of a welfare retrenchment reform. Together, these analyses shed light on how the welfare state influences immigration attitudes
Social media feedback and extreme opinion expression
No full textOn popular social media platforms such as Twitter, Facebook, Instagram, or Tiktok, the quantitative feedback received by content producers is asymmetric: counts of positive reactions such as 'likes,' or 'retweets,' are easily observed but similar counts of negative reactions are not directly available. We study how this design feature of social media platforms affects the expression of extreme opinions. Using simulations of a learning model, we compare two feedback environments that differ in terms of the availability of negative reaction counts. We find that expressed opinions are generally more extreme when negative reaction counts are not available than when they are. We rely on analyses of Twitter data and several online experiments to provide empirical support for key model assumptions and test model predictions. Our findings suggest that a simple design change might limit, under certain conditions, the expression of extreme opinions on social media.G. Le Mens benefited from financial support from ERC Consolidator Grant \#772268 from the European Commission, an ICREA Academia grant, the Fundación BBVA Grant G999088Q, and the Agencia Estatal de Investigación (AEI), through grant PID2019-105249GB-I00/AEI/10.13039/501100011033. G. Le Mens also acknowledge financial support from the Severo Ochoa Programme for Centres of Excellence in R\&D (Barcelona School of Economics CEX2019-000915-S), funded by MCIN/AEI/10.13039/501100011033
Melanoma acral en población caucásica: estudio de cohorte sobre factores epidemiológicos, clinicopatológicos y pronósticos
No full textArticle disponible en anglès: http://hdl.handle.net/10230/71242Introducción: El melanoma acral está asociado con un pronóstico desfavorable. El estudio sobre las características y el pronóstico en los pacientes caucásicos puede ser crucial para comprender las características distintivas de este tumor. Objetivos: Analizar las características epidemiológicas, clinicopatológicas y pronósticas del melanoma acral en los pacientes caucásicos. Material y métodos: Estudio de cohorte retrospectivo de melanoma acral a partir de una base de datos multiinstitucional en 20 hospitales españoles, entre enero de 2000 y diciembre de 2019. Resultados: Se identificaron un total de 733 melanomas acrales (edad media: 67,5 años, el 95,2% caucásicos y el 77,5% en los pies). En general, el 77,5% de los casos fueron invasivos. Los melanomas localizados en los pies tuvieron una mayor proporción de casos invasivos (80,8 vs. 69,8%; p=0,003), estadios III y IV al diagnóstico (24,8 vs. 11,7%; p<0,001), valores de Breslow más altos (2,8 vs. 2,0mm; p=0,021) y una mayor tasa de positividad de biopsia selectiva del ganglio centinela (30,7 vs. 15,7%; p=0,012). Un mayor índice de Breslow y una edad de aparición más tardía fueron factores de riesgo para menor supervivencia específica por melanoma. Un mayor índice de Breslow y la ulceración fueron factores pronósticos independientes para menor supervivencia libre de recaída. La localización del melanoma y el subtipo histopatológico no se asociaron con un peor pronóstico. Las recurrencias fueron frecuentes (27,7%), y las metástasis a distancia aparecieron antes que las recurrencias locorregionales (1,32 años [RIC: 1,12-1,87] vs. 2,14 años [RIC: 1,68-2,70]; p=0,015). Conclusión: Este estudio, el mayor en una población predominantemente caucásica, subraya los resultados desfavorables del melanoma acral. Los melanomas en los pies mostraron una detección tardía, mayor proporción de melanomas invasivos, valores de Breslow más altos, mayor positividad o afectación de biopsia selectiva del ganglio centinela y estadios AJCC más avanzados. La alta tasa de recurrencia y las metástasis a distancia tempranas enfatizan el papel crítico del seguimiento intensivo y las pruebas de imagen rutinarias para detectar recaídas asintomáticas.La investigación sobre melanoma en el Hospital Universitari Arnau de Vilanova de Lleida fue financiada mediante subvenciones del ISCIII/FEDER «Una manera de hacer Europa» (PI18/00573 y PI21/00294 a R.M. Marti), CIBERONC-CB16/12/00231 y la Generalitat de Catalunya (2021/SGR0093). La investigación del Grupo de Melanoma en el Hospital Clínic de Barcelona recibe apoyo del CIBER de Enfermedades Raras del Instituto de Salud Carlos III, España, AGAUR 2017_SGR_1134 y el Programa CERCA de la Generalitat de Catalunya, España; una beca de investigación de la Fundación Científica de la Asociación Española Contra el Cáncer (GCB15152978SOEN, España); y la Comisión Europea bajo los siguientes programas: Sexto Programa Marco (Contrato No. LSHC-CT-2006-018702, GenoMEL), Séptimo Programa Marco (Diagnoptics), Programa HORIZON2020 (iTobos y Qualitop), Programa Horizon Europe (HORIZON-MISS-2021-CANCER-02, MELCAYA, referencia 101096667). Esta investigación también fue financiada parcialmente por subvenciones del Fondo de Investigaciones Sanitarias (P.I. 18/00419 y 22/01467, España). Parte del trabajo se llevó a cabo en el Centro Esther Koplowitz, Barcelona. J. Angel-Baldo contó con una beca predoctoral del IRBLleida/Diputació de Lleida
Understanding the impact of early microexon misregulation on zebrafish sleep/wake behaviour
No full textThe developing nervous system requires a well-orchestrated and diverse set of proteins, setting the foundation of how an animal perceives the world. Disruptions may result in neurodevelopmental disorders, including autism spectrum disorders (ASD), with patients displaying altered sensitivity to their environment. A highly-conserved program of neuron-specific microexons (3-27 nucleotides) is frequently disrupted in ASD and known to shape protein-protein interactions during late neurogenesis, fine-tuning neuronal processes such as synapse formation. Little is known as to how misregulation of this program affects signalling cascades in the developing brain, shaping behaviour. Using zebrafish larvae, we set out to investigate this using a mutant of the microexon splicing master regulator srrm3. Performing single-cell and bulk RNA-sequencing experiments we found that microexon-harbouring genes are more frequently differentially expressed. Phenotypically, using zebrafish tracking and calcium imaging, we described ASD-like phenotypes including sensory hypersensitivity, hyperlocomotion and sleep loss accompanied by altered neuronal firing in srrm3 mutants. Coupling of behavioural and pharmacological assays allowed us to identify in mutants aberrant cAMP signalling, likely resulting in a downregulation of synaptic plasticity genes that could be rescued pharmacologically. Our research sheds new light onto the dynamics of the developing zebrafish nervous system in the context of microexon misregulation, with wider implications on the connection between brain state and behaviour.El sistema nervioso en desarrollo requiere un conjunto bien orquestado y diverso de proteínas, que sientan las bases de cómo un animal percibe el mundo. Las interrupciones en este proceso pueden resultar en trastornos del neurodesarrollo, incluyendo los trastornos del espectro autista (ASD, por sus siglas en inglés), cuyos pacientes muestran una sensibilidad alterada a su entorno. Un programa altamente conservado de microexones específicos de neuronas (3-27 nucleótidos) se ve frecuentemente alterado en ASD y se sabe que modula las interacciones proteína-proteína durante la neurogénesis tardía, afinando procesos neuronales como la formación de sinapsis. Se sabe poco acerca de cómo la desregulación de este programa afecta las cascadas de señalización en el cerebro en desarrollo, moldeando los comportamientos. Utilizando larvas de pez cebra, nos propusimos investigarlo usando un mutante del regulador maestro del splicing de microexones, srrm3. Realizando experimentos de secuenciación de ARN a nivel de célula única y en bulk, encontramos que los genes que contienen microexones están más frecuentemente expresados de manera diferencial. Fenotípicamente, utilizando seguimientos de pez cebra de alta duración y técnicas de visualización de calcio, describimos fenotipos similares a los del ASD, incluyendo hipersensibilidad sensorial, hiperlocomoción y pérdida de sueño acompañados de una activación neuronal alterada en las mutantes srrm3. Una combinación de ensayos comportamentales y farmacológicos nos permitió identificar en los mutantes una señalización aberrante de cAMP, que probablemente resulta en una regulación negativa de genes de plasticidad sináptica que podría ser rescatada farmacológicamente. Nuestra investigación arroja nueva luz sobre las dinámicas del sistema nervioso en desarrollo del pez cebra en el contexto de la desregulación de microexones, con implicaciones más amplias en la conexión entre el estado cerebral y el comportamiento.Programa de Doctorat en Biomedicin