http://hdl.handle.net/10366/4512 2026-07-01T09:21:29Z http://hdl.handle.net/10366/172024 [EN]The Joint Heads of Medicines Agencies and European Medicines Agency's (HMA/EMA) big data initiative paves the way for better integration of real-world data, including data from patient registries, into regulatory decisions on medicines. This article focuses on the outcome of a two-day multistakeholder workshop organized by EMA in 2024, which explored ways to optimize the EMA qualification procedure for patient registries, and to establish the value and enable the use of these data across the full spectrum of research questions. Key recommendations include the need to clarify the aim, scope, and added value of the qualification of registries, coupled with a review of the procedural steps to ensure the process is fit-for-purpose to evaluate the use of registries in specific regulatory contexts. Further recommendations focused on strengthening interactions between stakeholders, as well as providing them with enhanced support by increasing awareness of publicly available tools that could leverage the potential of registry data, together with existing guidance. The European Medicines Regulatory Network is now working together with all relevant stakeholders, including the EMA scientific committees and working parties, the Joint HMA/EMA Network Data Steering Group and existing focus groups with external partners, to implement concrete actions that will address these recommendations. Among others, the update of existing guidance, the development of templates and Questions & Answers documents, and the design of appropriate communication and stakeholder engagement plans will aid in achieving the common goal of making optimal use of patient registry data to support public health in the European Union. 2025-09-01T00:00:00Z http://hdl.handle.net/10366/172022 [EN]The inclusion of nine myelodysplasia-related gene (MRG) mutations (ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, ZRSR2) as adverse risk factors in the ELN risk classification has reshaped classification in acute myeloid leukemia (AML). AML with FLT3-ITD mutations and co-occurring MRG alterations is now classified to the ELN adverse risk group although supporting evidence remains limited. Among 4,078 patients with AML with available molecular information included in the HARMONY platform, 862 harbored FLT3-ITD mutations and underwent intensive chemotherapy. Of these, 171 (20%) exhibited co-occurring MRG mutations at diagnosis. In this cohort, MRGs were not independently associated with relapse-free survival (RFS) or overall survival (OS). In the FLT3-ITD/NPM1 co-mutated subgroup, MRG mutations were rare (9%) and showed no prognostic impact. Conversely, in FLT3-ITD/NPM1 wildtype AML, MRG mutations were predictive of shorter RFS (HR 1.37, 95%CI 1.01 - 1.88, p = 0.046) and OS (HR 1.34, 95%CI 1.02-1.74, p = 0.032) in multivariable analysis with survival times comparable to the ELN adverse risk category. The allelic ratio of FLT3-ITD did not further stratify OS and RFS in this subgroup. These findings suggest that the prognostic relevance of MRG mutations in FLT3-ITD AML is modulated by NPM1 co-mutational status and mirror findings in AML lacking FLT3-ITD. 2026-03-01T00:00:00Z http://hdl.handle.net/10366/172020 [EN]NPM1-mutated (NPM1-mut) acute myeloid leukemia (AML) is generally associated with a more favorable outcome, although the presence of additional gene mutations can influence patient prognosis. We analyzed intensively-treated adult NPM1-mut AML patients included in the HARMONY Alliance database. A newly developed risk classification, which included combinations of co-mutations in FLT3-ITD, DNMT3A, IDH1/IDH2, and TET2 genes, was applied to a training cohort of NPM1-mut AML patients included in clinical trials (n = 1001), an internal validation cohort more representative of real-world settings (n = 762), and an external validation cohort enrolled in UK-NCRI trials (n = 585). The HARMONY classification considered 51.8% of the NPM1-mut AML training cohort patients as favorable, 24.8% as intermediate, and 23.4% as adverse risk, with median overall survival (OS) of 14.4, 2.2, and 0.9 years, respectively; p < 0.001), thereby reclassifying 42.7% of NPM1-mut patients into a different European LeukemiaNet (ELN) 2022 risk category. These results were confirmed both in an internal and external validation cohort. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1) showed the highest benefit in the NPM1-mut adverse-risk subgroup. The HARMONY classification provides the basis for a refined genetic risk stratification for adult NPM1-mut AML with potential clinical impact on allo-HSCT decision-making. 2026-01-01T00:00:00Z http://hdl.handle.net/10366/172018 [ES] La presente contribución lleva sobre el escriptovisual como práctica didáctica en la enseñanza– aprendizaje del español en Camerún. Pretende diseñar una práctica didáctica del escriptovisual en comprensión del texto para desarrollar las habilidades comunicativas socioculturales e interculturales en los alumnos del sexto curso de ELE. Es a partir del enfoque de la ingeniería didáctica de Artigue y del enfoque experimental con un plan de experiencia grupo testigogrupo experimental que ha sido posible de poner en evidencia el impacto positivo del escriptovisual sobre el desarrollo de las competencias. 2025-01-01T00:00:00Z http://hdl.handle.net/10366/172016 [ES] Este artículo propone, en primer lugar, un estudio del sermón Cunctorum (CPL 1185), compuesto para la festividad del famoso mártir hispano san Vicente de Zaragoza. Para ello, se analizan sus contenidos, sus fuentes, su posteridad literaria y su tradición manuscrita. Además, se ofrece la primera edición crítica de esta misma obra a partir del análisis de toda su tradición manuscrita conocida. Este trabajo viene a confirmar que este sermón, atribuido inicialmente tanto a Agustín de Hipona, como a León Magno, es, sin duda, una obra de origen hispano-visigodo. Además, el estudio de su tradición manuscrita lleva a concluir que el manuscrito Paris, BnF, lat. 13760, ejecutado en Saint Germain des Prés hacia el año 870, es, verosímilmente, el arquetipo conservado de toda la tradición. Finalmente, debido al estilo altamente retórico de este sermón, que no siempre favorece su comprensión, nos ha parecido conveniente incluir una traducción completa. 2025-01-01T00:00:00Z http://hdl.handle.net/10366/172010 [EN]Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) with heterogeneous clinical course. Allogeneic hematopoietic cell transplantation remains the only curative therapy, but its morbidity and mortality require careful candidate selection. Therefore, accurate disease risk prognostication is critical for treatment decision-making. We obtained registry data from patients diagnosed with MF in 60 Spanish institutions (N = 1386). These were randomly divided into a training set (80%) and a test set (20%). A machine learning (ML) technique (random forest) was used to model overall survival (OS) and leukemia-free survival (LFS) in the training set, and the results were validated in the test set. We derived the AIPSS-MF (Artificial Intelligence Prognostic Scoring System for Myelofibrosis) model, which was based on 8 clinical variables at diagnosis and achieved high accuracy in predicting OS (training set c-index, 0.750; test set c-index, 0.744) and LFS (training set c-index, 0.697; test set c-index, 0.703). No improvement was obtained with the inclusion of MPN driver mutations in the model. We were unable to adequately assess the potential benefit of including adverse cytogenetics or high-risk mutations due to the lack of these data in many patients. AIPSS-MF was superior to the IPSS regardless of MF subtype and age range and outperformed the MYSEC-PM in patients with secondary MF. In conclusion, we have developed a prediction model based exclusively on clinical variables that provides individualized prognostic estimates in patients with primary and secondary MF. The use of AIPSS-MF in combination with predictive models that incorporate genetic information may improve disease risk stratification. 2023-01-01T00:00:00Z http://hdl.handle.net/10366/172006 [EN]Hypereosinophilic syndrome (HES) is a rare condition characterized by elevated eosinophil levels and related symptoms of eosinophil-mediated organ damage. We reviewed the effectiveness and safety of mepolizumab for the treatment of HES. A scoping review was conducted following the PRISMA Scoping Reviews Checklist to identify real-world evidence of mepolizumab use in HES. In total, 36 references were identified as relevant and selected for review. Overall, 105 patients previously treated with glucocorticoids received mepolizumab at different dosages (range: 100-750 mg), routes of administration (subcutaneous/intravenous), and schedules (every 2-12 weeks). Remission rates were 57.1-76.0%. Most studies reported a range of 71.4-99.1% reduction in mean blood eosinophil counts with mepolizumab treatment. In addition, a glucocorticoid-sparing effect was observed; 85.7% of patients discontinued glucocorticoids after 12 months of mepolizumab administration. Mepolizumab was considered safe and well-tolerated and severe adverse events were rare. Mepolizumab provided clinically significant benefits in patients with HES in a real-world setting. 2025-01-01T00:00:00Z http://hdl.handle.net/10366/172005 [EN]The potential prognostic value of conventional karyotyping in adult T-cell acute lymphoblastic leukemia (T-ALL) remains an open question. We hypothesized that a modified cytogenetic classification, based on the number and type of cytogenetic abnormalities, would allow the identification of high-risk adult T-ALL patients. Complex karyotype defined by the presence of ≥3 cytogenetic alterations identified T-ALL patients with poor prognosis in this study. Karyotypes with ≥3 abnormalities accounted for 16 % (22/139) of all evaluable karyotypes, corresponding to the largest poor prognosis cytogenetic subgroup of T-ALL identified so far. Patients carrying karyotypes with ≥3 cytogenetic alterations showed a significantly inferior response to therapy, and a poor outcome in terms of event-free survival (EFS), overall survival (OS) and cumulative incidence of relapse (CIR), independently of other baseline characteristics and the end-induction minimal residual disease (MRD) level. Additional molecular analyses of patients carrying ≥3 cytogenetic alterations showed a unique molecular profile that could contribute to understand the underlying molecular mechanisms of resistance and to evaluate novel targeted therapies (e.g. IL7R directed) with potential impact on outcome of adult T-ALL patients. 2021-10-01T00:00:00Z http://hdl.handle.net/10366/172002 [EN]Traditional risk stratification in multiple myeloma (MM) relies on clinical and cytogenetic parameters but has limited predictive accuracy. Machine learning (ML) offers a novel approach by leveraging large datasets and complex variable interactions. This study aimed to develop and validate novel ML-driven prognostic scores for newly diagnosed MM (NDMM), with the goal of improving upon existing ones. To this end, we analyzed data from the EMN-HARMONY MM cohort, comprising 14,345 patients, including 10,843 NDMM patients enrolled across 16 clinical trials. Three ML models were developed: (1) a comprehensive model incorporating 20 variables, (2) a reduced model including six key variables (age, hemoglobin, β2-microglobulin, albumin, 1q gain, and 17p deletion), and (3) a cytogenetics-free model. All models were internally validated using out-of-bag cross-validation and externally validated with data from the Myeloma XI trial. Model performance was evaluated using the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (ROC-AUC). The comprehensive model achieved C-index values of 0.666 (training) and 0.667 (test) for overall survival (OS) and 0.620/0.627 for progression-free survival (PFS). The reduced model maintained accuracy (OS: 0.658/0.657; PFS: 0.608/0.614). The cytogenetics-free model showed C-index values of 0.636/0.643 for OS and 0.600/0.610 for PFS. Incorporating treatment type and best response to first-line treatment further improved performance. The new prognostic models improved over the International Staging System (ISS), Revised International Staging System (R-ISS), and Second Revision of the International Staging System (R2-ISS) and were reproducible in real-world and relapsed/refractory MM, including daratumumab-treated patients. This ML-based risk stratification strategy provides individualized risk predictions, surpassing traditional group-based methods and demonstrating broad applicability across patient subgroups. An online calculator is available at https://taxonomy.harmony-platform.eu/riskcalculator/. 2025-10-01T00:00:00Z http://hdl.handle.net/10366/171994 [ES]El presente libro tiene como objetivo analizar diversas formas de repetición, retorno o versión en el arte y la cultura contemporáneos. Para ello, a lo largo de sus capítulos se abordan temas como las copias, los anacronismos, los homenajes, las simulaciones o las retromanías que recorren una parte importante de las prácticas artísticas y culturales de nuestro tiempo. En este sentido, estrategias como las de la ironía y sus distintas versiones actuales, las obsesiones por el pasado y la memoria, o trabajos sobre las tendencias y patrones de reconocimiento, son analizados desde una perspectiva filosófica y estética que se ejemplifica mediante constantes casos ficcionales, tanto artísticos como literarios. 2026-06-01T00:00:00Z http://hdl.handle.net/10366/171992 [ES] Arribes del Duero es una comarca con un largo pasado vitivinícola, donde los valores culturales asociados a esta actividad económica están fuertemente asentados en el ideario colectivo, creándose, así, un complejo patrimonial con un gran potencial turístico, pero con grandes problemas estructurales. Desde el año 2007, cuando se aprueba la declaración de la Denominación de Origen Arribes, se ha comenzado a vislumbrar un cierto proceso de desarrollo potenciado por la moviliza-ción del capital territorial (capital natural, capital social, capital productivo y capital intelectual), a lo que hay que sumarle las iniciativas que se están poniendo en marcha desde la Agrupación Europea de Cooperación Territorial Duero-Douro. 2025-01-01T00:00:00Z http://hdl.handle.net/10366/171991 [ES] En las últimas décadas las tecnologías industriales han registrado un gran avance impulsado por la digitalización. Este proceso no se deja sentir solamente en las manufacturas de mayor intensidad tecnológica (electrónica, farmacéutica, aeroespacial), sino que también ha comenzado a transformar la industria de la alimentación a lo largo de toda su cadena de valor, en este caso aplicando los avances de la biotecnología a la elaboración de alimentos. Esta transformación de la tecnología agroalimentaria puede servir como apoyo para afrontar los grandes retos que plantea la alimentación en un mundo globalizado donde la escasez, la contaminación y la desigualdad afectan a una gran parte de la población mundial. En este contexto incierto y cambiante, la denominada industria foodtech está adquiriendo mucha importancia, sobre todo a partir de la pandemia covid-19. El presente capítulo trata de hacer un análisis del marco legislativo que regula, según los ha definido el Reglamento (UE) 2015/2283 del Parlamento Europeo y del Consejo, los nuevos alimentos. En función de dicho Reglamento, y tras la valoración de la Autoridad Europea de Seguridad Alimentaria (EFSA, por sus siglas en inglés), se establecerá una lista de la Unión de nuevos alimentos autorizados. No obstante, el reflejo geográfico de la situación normativa en Europa es muy heterogéneo. Mientras países como Italia han prohibido la comercialización de estos nuevos productos, como la carne cultivada, España tiene una industria bastante dinámica, hasta el punto de que se están articulando iniciativas como Food & AgriTech Europe (FATE), Food (Tech)2 Challengers -ambos con la participación del Centro Nacional de Tecnología y Seguridad Alimentaria (CNTA)- que busca el impulso de las startups de este sector en el país. 2024-01-01T00:00:00Z http://hdl.handle.net/10366/171989 [EN] Sustainable food initiatives (SFIs) are organizational models of food production, distribution, and consumption whose principles and practices promote a food system respectful of nature and human health. These initiatives establish a more equitable distribution of economic value among the actors involved, minimize the number of intermediaries, operate preferably within geographically proximate areas, and are governed by inclusive and democratic decision-making mechanisms based on mutual trust among participants. This study examines a sample of SFIs located in the Spanish regions of Madrid and Castilla y León. It highlights the role of five dimensions of proximity —geographical, cognitive, organizational, social, and institutional— in enabling these initiatives to scale up and consolidate themselves as a reliable and viable alternative to the hegemony of large corporations. Based on an inventory of SFIs, projects across different stages of the food value chain were selected, and semi-structured interviews were conducted. The qualitative analysis of the interviews suggests that while geographical proximity between producers and consumers is important, it cannot support upscaling processes. Rather, it is necessary to develop the remaining dimensions of proximity to strengthen SFIs and fulfill the needs of producers and consumers. Public food policies at various geographic scales can play a significant role in supporting this process. 2026-01-01T00:00:00Z http://hdl.handle.net/10366/171988 [ES] Cuando los actores de una cadena alimentaria se sitúan próximos en un territorio, se pueden obtener sinergias y externalidades positivas (o reducir las negativas) mediante la acción colectiva, siempre que exista cooperación entre los actores e instituciones, lo que implica la existencia de proximidad organizativa (valores compartidos y redes comunes). Una cierta concentración de actividades agroecológicas o, en un sentido amplio, de actividades de producción, transformación y distribución de alimentos sostenibles, puede llegar a constituir una alternativa para superar tanto el aislamiento territorial como la fragmentación empresarial y social que suele darse en este tipo de experiencias, que generalmente presentan rasgos que permiten caracterizarlas como innovaciones sociales y organizativas. Con este fin, este trabajo desarrolla el nuevo concepto, propuesto por los autores, de los Sistemas Alimentarios Agroecológicos Locales (SIAAL): pueden definirse como una cierta concentración espacial de explotaciones agrícolas, agroindustrias artesanales, pequeños distribuidores, proveedores de insumos e instituciones locales, inspirados en la agroecología o en enfoques de alimentación sostenible, que conforma una red que muestra un grado significativo de relaciones de colaboración entre todos los agentes e instituciones 2023-01-01T00:00:00Z http://hdl.handle.net/10366/171987 [ES] El texto explora, a través de tres grandes bloques conceptuales, cómo los procesos de digitalización e hibridación teórica están reconfigurando la geografía económica actual y su contexto metodológico. En primer lugar, se analiza de qué manera la convergencia de datos y fuentes digitales desafía los paradigmas científicos tradicionales e impulsa metodologías transversales y la necesidad de infraestructuras de datos transparentes. En segundo lugar, propone redefinir las clasificaciones de las actividades económicas para responder a las complejidades contemporáneas, valorando sectores fundamentales que quedaron en evidencia tras crisis como la pandemia. Por último, debate la validez y persistencia de la escala regional y político-administrativa como un marco clave para comprender la división espacial del trabajo frente a las dinámicas del capitalismo global fluido. En síntesis, la obra constituye una rigurosa reflexión sobre los retos y herramientas metodológicas de la geografía ante los desafíos sociales, económicos y territoriales del siglo XXI. 2022-01-01T00:00:00Z http://hdl.handle.net/10366/171986 [ES]El sector de la ciencia, la tecnología, la ingeniería y las matemáticas (STEM) es un campo académico y profesional con altas cifras de disparidad de género a pesar de ser un campo con una baja tasa de desempleo. El "Cuestionario a Universitarios sobre Estudios STEM en Educación Superior" (QSTEMHE) fue diseñado para conocer la opinión de la población universitaria española en todas las ramas de conocimiento sobre los estereotipos de género en los estudios STEM. Este instrumento validado se aplicó a una muestra universitaria de 2101 personas de diferentes universidades españolas. Se utilizó una metodología cuantitativa y el método no experimental ex-post-facto, empleando una técnica de muestreo aleatorio simple. Este estudio pretende analizar la relación que se establece entre los modelos y referentes que han tenido los estudiantes universitarios y su manifestación de estereotipos de género sobre la capacidad de rendimiento en los estudios superiores STEM. Entre los principales resultados, persisten los estereotipos de género sobre las titulaciones STEM, considerándolas masculinizadas y orientadas a los hombres. Además, el estudio confirma que los modelos y referentes tenidos en cuenta a la hora de elegir estudios superiores influyen en la percepción de hombres y mujeres sobre los estereotipos en STEM.; [EN]The science, technology, engineering, and mathematics (STEM) sector is an academic and professional field with high gender disparity figures despite being a field with a low unemployment rate. The “Questionnaire with University Students on STEM Studies in Higher Education” (QSTEMHE) was designed to determine the opinion of the Spanish university population on all branches of knowledge about gender stereotypes in STEM studies. This validated instrument was applied to a university sample of 2101 people from different Spanish universities. A quantitative methodology and the non-experimental ex-post-facto method were used, employing a simple random sampling technique. This study aims to analyse the relationship established between the models and references that university students have had and their manifestation of gender stereotypes on the ability to perform in STEM higher education studies. Among the main results, gender stereotypes about STEM degrees persist, considering them masculinised and male-oriented. Furthermore, the study confirms that models and references taken into account when choosing higher education studies impact the perception of men and women regarding stereotypes in STEM. 2025-01-01T00:00:00Z