http://hdl.handle.net/10366/4512 2026-07-03T21:33:51Z http://hdl.handle.net/10366/172049 [EN]The seismicity in the SE Iberian Peninsula is distributed parallel to the coast in a well-developed strike-slip fracture system known as the Eastern Betic Shear Zone (EBSZ). This work focuses on the characterization of the shallow subsurface structure of the Algezares-Casas Nuevas Fault, within the Carrascoy Fault System of the EBSZ. The Carrascoy Fault borders the Guadalentín Depression to the south, which is a densely populated area with extensive agricultural activity. Therefore, this fault system represents a seismic hazard with significant social and economic implications. We have constructed two velocity-depth models based on P-wave tomography and Multichannel Analysis of Surface Waves (MASW) acquired from seismic reflection data. The resulting velocity models have allowed us to interpret the first ~250m depth and have revealed: i) the thickness of the critical zone; ii) the geometry of the Algezares-Casas Nuevas Fault; iii) the depth of the Messinian/Tortonian contact and iv) the presence of blind thrusts and damage zones under the Guadalentín Depression. Our results have also helped us to estimate an apparent vertical slip rate of 0.66±0.06m/ky for the Algezares-Casas Nuevas Fault since 209.1±6.2ka. Our results provide a methodological and backflow protocol to study the shallow subsurface of active faults, complementing previous geological models based on paleoseismological trenches, and can be used to improve the seismic hazard assessment of tectonically active regions around the world. 2022-09-08T00:00:00Z http://hdl.handle.net/10366/172048 [EN]Wide-angle seismic reflection/refraction (WA) surveys provide data that can be modeled to obtain lithospheric-scale P-wave velocity (VP) models. The interpretation of these datasets is often performed as a laborious and time-consuming trial-and-error procedure, in which the relevant model parameters (layer thickness and VP) are manually adjusted until the forward modeling matches the observed travel-times. In this work, we present a fully automatic iterative nonlinear approach to invert WA datasets based on the simulated annealing technique. We test our proposed approach with data from the MARCONI-3 WA profile (southern Bay of Biscay) and compare the outcome with an existing detailed interpretation, discussing the similarities between the two models and the agreement between our model and the observed travel-times. 2021-11-26T00:00:00Z http://hdl.handle.net/10366/172047 [EN]The critical zone (CZ) represents the most-shallow subsurface, where the bio-, hydro-, and geospheres interact with anthropogenic activity. To characterize the thickness and lateral variations of the CZ, here we focus on the Eastern Betic Shear Zone (EBSZ), one of the most tectonically active regions in the Iberian Peninsula. Within the EBSZ, the Guadalentín Depression is a highly populated area with intensive agricultural activity, where the characterization of the CZ would provide valuable assets for land use management and seismic hazard assessments. To achieve this, we have conducted an interdisciplinary geophysical study along the eastern border of the Guadalentín Depression to characterize the CZ and the architecture of the shallow subsurface. The datasets used include Electrical Resistivity Tomography (ERT), first-arrival travel time seismic tomography, and multichannel analysis of surface waves (MASW). The geophysical datasets combined help to constrain the high-resolution structure of the subsurface and image active fault systems along four transects. The resulting geophysical models have allowed us to interpret the first ~150 m of the subsurface and has revealed: (i) the variable thickness of the CZ; (ii) the CZ relationship between the fault zone and topographic slope; and (iii) the differences in CZ thickness associated with the geological units. Our results provide a method for studying the shallow subsurface of active faults, complementing previous geological models based on paleo-seismological trenches, and can be used to improve the CZ assessment of tectonically active regions 2022-03-27T00:00:00Z http://hdl.handle.net/10366/172046 [EN]The immense advances in computer power achieved in the last decades have had a significant impact in Earth science, providing valuable research outputs that allow the simulation of complex natural processes and systems, and generating improved forecasts. The development and implementation of innovative geoscientific software is currently evolving towards a sustainable and efficient development by integratingmodels of different aspects of the Earth system. This will set the foundation for a future digital twin of the Earth. The codification and update of this software require great effort from research groups and therefore, it needs to be preserved for its reuse by future generations of geoscientists. Here,we report onGeo-Soft-CoRe, a Geoscientific Software & Code Repository, hosted at the archive DIGITAL.CSIC. This is an open source, multidisciplinary and multiscale collection of software and code developed to analyze different aspects of the Earth system, encompassing tools to: 1) analyze climate variability; 2) assess hazards, and 3) characterize the structure and dynamics of the solid Earth. Due to the broad range of applications of these software packages, this collection is useful not only for basic research in Earth science, but also for applied research and educational purposes, reducing the gap between the geosciences and the society. By providing each software and code with a permanent identifier (DOI), we ensure its self-sustainability and accomplish the FAIR (Findable, Accessible, Interoperable and Reusable) principles. Therefore, we aim for a more transparent science, transferring knowledge in an easier way to the geoscience community, and encouraging an integrated use of computational infrastructure. 2022-04-26T00:00:00Z http://hdl.handle.net/10366/172045 [EN]Tectonic inversion of continental passive margins, orogens formation and deformation transfer to build intraplate ranges are processes that shape plate boundaries, define topography, and delineate continent/ocean transitions. However, the crustal deformation mechanisms that govern these processes vary depending on the tectonic setting and on the overlap of successive tectonic phases. The central and NW Iberian Peninsula comprises from north to south: (i) the North Iberian Margin (NIM), a partly inverted passive margin with limited oceanic subduction, (ii) the Cantabrian Mountains (CM), formed in the northern boundary of the Iberian microplate, and (iii) the Spanish-Portuguese Central System (SPCS), an intraplate mountain range. With the aim of unraveling the crustal-scale structure and the deformation mechanisms in these areas, we present a 650-km long cross-section from the NIM to the south of the Madrid Cenozoic basin based on new wide-angle seismic reflection/refraction data and on the reinterpretation of P-wave velocity (Vp) models. The hyperbolic moveout seismic data revealed an asymmetry of the PmP phases (Moho reflections) at both sides of the SPCS and deep subvertical reflectors to the south of the SPCS, that we interpreted as the image of south-vergent crustal-scale faults. In contrast, in the CM the Vp models presented show the northwards subduction of the Iberian lower crust. Therefore, the deformation mechanisms that govern the current crustal architecture in the central and NW Iberian Peninsula are a crustal-coupled deformation with significant vertical displacement in the SPCS and a crustal-decoupled deformation with mainly horizontal displacement in the CM. 2025-04-01T00:00:00Z http://hdl.handle.net/10366/172040 [EN]Chronic myelomonocytic leukemia (CMML) is frequently associated with mutations in the rat sarcoma gene (RAS), leading to worse prognosis. RAS mutations result in active RAS-GTP proteins, favoring myeloid cell proliferation and survival and inducing the NLRP3 inflammasome together with the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which promote caspase-1 activation and interleukin (IL)-1β release. Here, we report, in a cohort of CMML patients with mutations in KRAS, a constitutive activation of the NLRP3 inflammasome in monocytes, evidenced by ASC oligomerization and IL-1β release, as well as a specific inflammatory cytokine signature. Treatment of a CMML patient with a KRASG12D mutation using the IL-1 receptor blocker anakinra inhibits NLRP3 inflammasome activation, reduces monocyte count, and improves the patient's clinical status, enabling a stem cell transplant. This reveals a basal inflammasome activation in RAS-mutated CMML patients and suggests potential therapeutic applications of NLRP3 and IL-1 blockers. 2023-12-19T00:00:00Z http://hdl.handle.net/10366/172037 [EN]Real-world data (RWD) previously contributed to post-marketing regulatory decision-making, but are currently also considered as external controls to single-arm trials. The use of RWD control data may be compromised by methodological issues, urging validation of RWD control cohorts. Two external control cohorts of newly diagnosed acute myeloid leukaemia patients, one registered by the HARMONY Alliance (HA) and one by the Netherlands Cancer Registry (NCR), were compared to the control arm of the randomized HOVON-103 trial (H103 controls). All patients, aged >65 years with a WHO performance score of 0-2 (or missing), received standard induction chemotherapy. 1:1 propensity score calliper matching (PSM) was applied to improve comparability, and overall (OS) and relapse-free survival (RFS) were assessed. Fewer data elements were available in external cohorts compared to H103 controls, specifically in the NCR cohort. Baseline characteristics of the external cohorts differed from H103 controls; missing data were also more frequent and predominantly concerned WHO performance score. After PSM, HA patients demonstrated non-significantly different OS and RFS to H103 controls at 2 years (26 ± 4% vs. 31 ± 5%, p = 0.59; 24 ± 5% vs. 30 ± 6%, p = 0.52), while NCR patients had 12% lower OS (28 ± 4% vs. 40 ± 4%, p = 0.21). Validation of external control cohorts is needed before incorporating RWD control data into comparative analyses, as missing data, specifically comorbidities, and residual confounding may limit comparability. 2026-01-01T00:00:00Z http://hdl.handle.net/10366/172033 [EN]Aberrant active NOTCH1 signaling is a key pathogenic factor in chronic lymphocytic leukemia (CLL), detectable in half of patients and associated with disease progression. While some cases of active NOTCH1 signaling can be explained by mutations in NOTCH1 or its regulators, like FBXW7, alternative mechanisms remain elusive. Here, we identified the deubiquitinase USP28 as regulator of NOTCH1 signaling in CLL. Notably, USP28 is located within the frequently deleted chr11q23 region and is deleted in 90% of del(11q) patients, resulting in its decreased expression. USP28 interacts with the NOTCH1 intracellular domain (NICD) independently of FBXW7 and the NICD-PEST domain, stabilizing NICD and enhancing NOTCH1 signaling. Integrating RBPJ-occupied genes in HG3 cells, RNA-Seq of USP28WT/KO cells and gene expression from del(11q) CLL patients, we identified 15 NOTCH1 target genes specifically dysregulated by deletion of USP28 and del(11q) potentially influencing CLL pathogenesis. Pharmacological inhibition of USP28 with the small molecule AZ1 suppressed NOTCH1 activation in primary CLL cells. AZ1 combined with the BCL-2 inhibitor venetoclax reduced CLL cell viability, particularly in samples with high NOTCH1 activity. Our findings highlight USP28 as promising therapeutic target and provide a rationale for combined inhibition of USP28 and BCL-2 in CLL patients with active NOTCH1 signaling. 2025-01-01T00:00:00Z http://hdl.handle.net/10366/172032 [ES] Este artículo analiza la titularidad femenina de iglesias y monasterios locales en el Reino de León entre los siglos X y XII, con el objetivo de comprender el papel de las mujeres de las comunidades y élites locales en la gestión de estos espacios clave en la articulación de las micropolíticas. A partir del análisis documental cualitativo, se estudian los mecanismos a través de los cuales las mujeres accedieron al control de estos centros como parte de las parentelas y de los grupos locales. Se concluye que, lejos de ser figuras pasivas, las mujeres ejercieron agencia propia y utilizaron estos espacios como plataformas de poder y de mediación social dentro de las comunidades y en relación con poderes supralocales. 2026-01-01T00:00:00Z http://hdl.handle.net/10366/172031 [EN] Quantifying marine reservoir effects (MREs) across time and space is crucial for establishing accurate archaeological chronologies, including the activities of past hominines. Although the northern Iberian Peninsula shows a high density of Upper Paleolithic sites and marine shells are frequently found in these assemblages, quantification of MREs in this coastal region remains limited. We performed Bayesian modeling of radiocarbon measurements from both terrestrial (Capra pyrenaica, Cervus elaphus and other herbivores unidentified at species level) and marine (Littorina littorea Linnaeus, 1758 and Patella vulgata Linnaeus, 1758 taxa) archaeological samples recovered from the Tito Bustillo cave (Asturias, Spain) in order to determine the ΔR values for northern Iberia during the Lower Magdalenian period (ca. 20–17 ka cal BP). For the time span between 18.6 and 18.2 ka cal BP we estimated ΔR values of –298±44 14C yr and –495±122 14C yr for the periwinkle L. littorea and the common limpet P. vulgata, respectively. This finding has significant implications for future archaeological research in the northern Iberian Peninsula, as researchers must apply distinct ΔR values depending on the mollusk species selected for radiocarbon dating. Furthermore, the consistency between our calculated ΔR value for P. vulgata and previously recorded data for the same taxon from a neighboring coastal region (Cantabria, Spain) suggests remarkable stability in the marine environment of this area during the Lower Magdalenian period. 2026-01-01T00:00:00Z http://hdl.handle.net/10366/172030 [EN]Intraplate ranges are topographic features that can occur far from plate boundaries, the expected position of orogens as described in the plate tectonics theory. To understand the lithospheric structure of intraplate ranges, we focused on the Spanish-Portuguese Central System (SPCS), the most outstanding topographic feature in the central Iberian Peninsula. The SPCS is an Alpine range that exhumes Precambrian-Paleozoic rocks and is located at >200 km from the northern border of the Iberian microplate. Here, we provide a P-wave velocity model based on wide-angle seismic reflection/refraction data of the central SPCS (Gredos sector). Our results show: (a) a layered lithosphere characterized by three major interfaces: Conrad, Mohorovicic, and Hales discontinuities, (b) an asymmetry of the crust-mantle boundary under the SPCS, (c) the extent of the Variscan batholith forming the main outcrops of Gredos, and (d) the thinning of the lower crust toward the south. This model suggests that the exhumation of the SPCS basement was driven by a south-vergent thick-skinned thrust system, developed in the southern part of the SPCS and that promoted crustal imbrication and a Mohorovicic discontinuity's offset under the SPCS. Thus, the deformation mechanisms of the crust seem to be controlled by the presence of the late- to post-Variscan granitoids that assimilated the Variscan mid-crustal detachment creating a new rheological boundary. This tectonic structure allowed the formation of Alpine crustal-scale thrust systems that eased coupled deformation of the upper and lower crust, leading to limited underthrusting of both crustal layers. 2022-07-02T00:00:00Z http://hdl.handle.net/10366/172026 [EN]This paper is focused on discussing the case of Las Loras UNESCO Global Geopark, in Spain, as an example to show the contribution of Geoparks to the dissemination of science and the relevance of preserving geoheritage by implementing simple measures based on communication and prevention. Natural and anthropic hazards derived from climate change are endangering heritage and the wellness of the society. Geoheritage is vulnerable. Nowadays we are witnessing the destruction of monuments with high emotional significance due to wars, but climate change is also contributing to the loss of the same cultural heritage. Prevention is often the best way to protect geoheritage from disappearing and society is the best agent to implement preventive measures. Citizens are often unaware of the important treasures they have around them. Geoparks have been a great tool to bring awareness in society, since by involving the public in the whole process of recognition and promotion, they protect the space and the cultural and economic values associated with them. It is important to communicate the initiatives taking place in the Geoparks to explain the importance of geology and the risk of losing the geoheritage if natural hazards increase. Las Loras study is a good practice to implement in other Geoparks. 2025-03-01T00:00:00Z 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