Repositorio Científico

New Dates for the Emergence of the Megalithic Phenomenon on the Iberian Plateau: The Funerary Practices of Valdelasilla, Toledo (Spain)

2026-05-12T12:45:58Z

[EN] This study presents an analysis of funerary practices at the site of Valdelasilla (Illescas, Toledo, Spain). The methodology integrates the morphological study of burial structures, anthropological analyses, a consideration of grave goods and the radiocarbon dating of human bone. The chronological data indicate funerary activity at the site from the Late Neolithic to the Chalcolithic period. Bayesian modelling confirms the establishment of a planned cemetery by the end of the fifth millennium cal. BC, featuring small burial chambers organized around a larger tomb enclosed by a ditch. The burial chambers, which were constructed from wood, clay and small stones, created distinct spaces for the deceased. This embryonic form of monumentalization, the funerary practices observed and the early chronology link Valdelasilla to other peninsular cemeteries associated with the emergence of megalithism, now identified for the first time on the plateau. The location of the necropolis offers new insights into the role of inland regions in the emergence of Iberian and European megalithism.

TRAIL receptor activation overcomes resistance to trastuzumab in HER2 positive breast cancer cells

2026-05-12T12:43:10Z

[EN]The appearance of resistance to the anti-HER2 targeted drug trastuzumab constitutes, nowadays, an important challenge in the oncology clinic. To fight such resistance, we searched for potential vulnerabilities in cells resistant to that drug. To that end, we used cell lines primary resistant to trastuzumab, as well as cells made secondarily resistant to the drug upon continuous exposure. Using genomic and proteomic approaches, a deregulation in cell death pathways was identified in trastuzumab-resistant cells. More precisely, an increased response to the death factor TRAIL, caused by an increase in the cellular receptors for this factor, was observed. In parallel, a decrease in inhibitory components of the pathway was detected. This combination produces a more efficient assembly of the functional complex in the trastuzumab-resistant cells that translates in the observed increased response to TRAIL. Analysis of HER2 positive patient samples confirmed deregulation of this pathway in trastuzumab-resistant patients. Taken together our data identify a vulnerability of trastuzumab-resistant cells that could be used to design new targeted therapies in that context.

Central role of cell cycle regulation in the antitumoral action of ocoxin

2026-05-12T12:27:50Z

[EN]Nutritional supplements which include natural antitumoral compounds could represent safe and efficient additives for cancer patients. One such nutritional supplement, Ocoxin Oral solution (OOS), is a composite formulation that contains several antioxidants and exhibits antitumoral properties in several in vitro and in vivo tumor conditions. Here, we performed a functional genomic analysis to uncover the mechanism of the antitumoral action of OOS. Using in vivo models of acute myelogenous leukemia (AML, HEL cells, representative of a liquid tumor) and small-cell lung cancer (GLC-8, representative of a solid tumor), we showed that OOS treatment altered the transcriptome of xenografted tumors created by subcutaneously implanting these cells. Functional transcriptomic studies pointed to a cell cycle deregulation after OOS treatment. The main pathway responsible for this deregulation was the E2F-TFDP route, which was affected at different points. The alterations ultimately led to a decrease in pathway activation. Moreover, when OOS-deregulated genes in the AML context were analyzed in patient samples, a clear correlation with their levels and prognosis was observed. Together, these data led us to suggest that the antitumoral effect of OOS is due to blockade of cell cycle progression mainly caused by the action of OOS on the E2F-TFDP pathway.

Qué escribir del viaje, qué escribir: estrategias de repetición en las poéticas contemporáneas del desplazamiento

2026-05-12T09:25:51Z

[ES] Frente la linealidad del relato clásico, las poéticas contemporáneas del desplazamiento instauran una nueva retórica del viaje en la que priman las figuras de repetición que relevan en importancia a los tropos de comparación que definían el paradigma tradicional. En el presente trabajo analizamos los procedimientos de repetición en los relatos de viaje actuales que, como el amigo que rememora sus aventuras pasadas contándolas y volviéndolas a contar, insisten en la reformulación y la versión. Para ello, nos detendremos en primer lugar en la narración de viajes iterativos; en segundo lugar, estudiaremos la renovación retórica del género y, finalmente, revisaremos las motivaciones que conducen a los autores a movilizar sus obras de viaje a través de sucesivos formatos o ediciones.

Specific Glutamylation Patterns of the Cytoskeleton Confer Neuroresistance to Lobe X of the Cerebellum in a Model of Childhood-Onset Neurodegeneration with Cerebellar Atrophy

2026-05-12T08:14:29Z

[EN]The cytoskeleton relies heavily on the dynamic nature of microtubules, regulated by posttranslational modifications such as polyglutamylation and deglutamylation. Disruption of its internal balance, particularly through the absence of cytosolic carboxypeptidase 1 (CCP1), leads to cytoskeletal collapse and cell death. An example of this occurrence exists in the Purkinje Cell Degeneration (PCD) mouse, a direct animal model for childhood-onset neurodegeneration with cerebellar atrophy (CONDCA) human disease. Both CONDCA patients and PCD mice suffer a dramatic degeneration of Purkinje cells. Intriguingly, lobe X appears less vulnerable to this insult. This study revealed in wild-type mice that lobe X expresses less Ccp1 compared to other lobes, correlating with its delayed degeneration in PCD mice. Further expression analysis of other deglutamylating enzymes (CCP4 and CCP6) and glutamylating enzymes (TTLL1) revealed distinctive patterns: Ccp4 showed minimal relevance in cerebellum, while Ccp6 displayed a compensatory increase during critical stages. Meanwhile, Ttll1 expression remained consistent across lobes, suggesting that the resistance of lobe X may be related to a more dynamic, hyperglutamylated cytoskeleton. Unraveling the neuroresistance mechanisms of Purkinje cells may help mitigate neuronal loss in CONDCA patients and may offer a glimmer of hope for alleviating the symptoms of other neurodegenerative diseases.

Factores asociados a la eficacia y el rendimiento académico escolar: un estudio basado en la aplicación de modelos estadísticos de regresión multinivel con penalización en el informe PISA 2022

2026-05-12T07:30:39Z

[ES]Esta investigación pretende hallar un modelo de regresión multinivel más fiable y ajustado a la realidad que los modelos estadísticos de regresión lineal por mínimos cuadrados ordinales comúnmente utilizados en las Ciencias de la Educación. Para alcanzar dicho propósito, el objetivo principal de este trabajo de investigación consiste en obtener un modelo estadístico eficiente e innovador que identifique los factores y variables que tienen una mayor incidencia en el rendimiento académico, independientemente del factor socioeconómico. De esta forma, se pretende conocer cuáles son las metodologías, contenidos o actividades que son más efectivas de cara a mejorar la formación y calidad educativa, mediante un análisis estadístico exhaustivo de los informes PISA 2022.

Socially responsible investors and corporate resistance to climate disruptions: agents of change or passive participants?

2026-05-12T00:01:23Z

Climate change is a global challenge with far-reaching implications for firms and capital markets. This study examines whether ownership by socially responsible investors (SRIs) enhances firms' resilience to climate shocks. Focusing on transition and physical climate risks, we analyse whether SRI ownership reduces firms' stock return sensitivity to climate events. Using a panel of listed European firms (2018–2022), we find that SRI ownership is associated with greater corporate capacity to manage climate disruptions. Further analyses show that SRIs are linked to firms' adoption of science-based climate targets, higher green revenue shares, and lower carbon emissions intensity. However, these effects are conditional. SRI stewardship is stronger when investors are domiciled in countries with stringent climate regulations, maintain longer investment horizons, and invest in firms with high climate change exposure and located in jurisdictions with strong climate performance. These findings highlight the role of SRIs as catalysts for corporate climate adaptation while emphasizing boundary conditions that shape their active ownership.

Second revision of the international staging system (R2-ISS) for overall survival in multiple myeloma: a european myeloma network (EMN) report within the HARMONY project

2026-05-12T00:01:31Z

[EN]Patients with newly diagnosed multiple myeloma (NDMM) show heterogeneous outcomes, and approximately 60% of them are at intermediate-risk according to the Revised International Staging system (R-ISS), the standard-of-care risk stratification model. Moreover, chromosome 1q gain/amplification (1q+) recently proved to be a poor prognostic factor. In this study, we revised the R-ISS by analyzing the additive value of each single risk feature, including 1q+. The European Myeloma Network, within the HARMONY project, collected individual data from 10,843 patients with NDMM enrolled in 16 clinical trials. An additive scoring system on the basis of top features predicting progression-free survival (PFS) and overall survival (OS) was developed and validated. In the training set (N = 7,072), at a median follow-up of 75 months, ISS, del(17p), lactate dehydrogenase, t(4;14), and 1q+ had the highest impact on PFS and OS. These variables were all simultaneously present in 2,226 patients. A value was assigned to each risk feature according to their OS impact (ISS-III 1.5, ISS-II 1, del(17p) 1, high lactate dehydrogenase 1, and 1q+ 0.5 points). Patients were stratified into four risk groups according to the total additive score: low (Second Revision of the International Staging System [R2-ISS]-I, 19.2%, 0 points), low-intermediate (II, 30.8%, 0.5-1 points), intermediate-high (III, 41.2%, 1.5-2.5 points), high (IV, 8.8%, 3-5 points). Median OS was not reached versus 109.2 versus 68.5 versus 37.9 months, and median PFS was 68 versus 45.5 versus 30.2 versus 19.9 months, respectively. The score was validated in an independent validation set (N = 3,771, of whom 1,214 were with complete data to calculate R2-ISS) maintaining its prognostic value. The R2-ISS is a simple prognostic staging system allowing a better stratification of patients with intermediate-risk NDMM. The additive nature of this score fosters its future implementation with new prognostic variables.

CRISPR/Cas9-directed gene trap constitutes a selection system for corrected BCR/ABL leukemic Cells in CML

2026-05-12T00:01:30Z

[EN]Chronic myeloid leukaemia (CML) is a haematological neoplasm driven by the BCR/ABL fusion oncogene. The monogenic aspect of the disease and the feasibility of ex vivo therapies in haematological disorders make CML an excellent candidate for gene therapy strategies. The ability to abolish any coding sequence by CRISPR-Cas9 nucleases offers a powerful therapeutic opportunity to CML patients. However, a definitive cure can only be achieved when only CRISPR-edited cells are selected. A gene-trapping approach combined with CRISPR technology would be an ideal approach to ensure this. Here, we developed a CRISPR-Trap strategy that efficiently inserts a donor gene trap (SA-CMV-Venus) cassette into the BCR/ABL-specific fusion point in the CML K562 human cell line. The trapping cassette interrupts the oncogene coding sequence and expresses a reporter gene that enables the selection of edited cells. Quantitative mRNA expression analyses showed significantly higher level of expression of the BCR/Venus allele coupled with a drastically lower level of BCR/ABL expression in Venus+ cell fractions. Functional in vitro experiments showed cell proliferation arrest and apoptosis in selected Venus+ cells. Finally, xenograft experiments with the selected Venus+ cells showed a large reduction in tumour growth, thereby demonstrating a therapeutic benefit in vivo. This study represents proof of concept for the therapeutic potential of a CRISPR-Trap system as a novel strategy for gene elimination in haematological neoplasms.

Varón de 49 años con fiebre, malestar general y nódulos pulmonares

2026-05-12T00:01:53Z

[ES]Caso clínico: Un varón de 49 años consultó por fiebre y síntomas respiratorios de 5 días de evolución. Era exfumador desde hacía 8 años (30 paquetes/año); no consumía alcohol, ni refería alergias o exposición a tóxicos inhalados. Trabajaba como vendedor de automóviles. Como antecedentes personales refería una reconstrucción facial tras un accidente de tráfico. No cumplía criterios de bronquitis crónica ni refería historia de tuberculosis o contacto con pacientes que la padecieran.

TRAF3 alterations are frequent in del-3'IGH chronic lymphocytic leukemia patients and define a specific subgroup with adverse clinical features

2026-05-12T00:01:27Z

[EN]Interstitial 14q32 deletions involving IGH gene are infrequent events in chronic lymphocytic leukemia (CLL), affecting less than 5% of patients. To date, little is known about their clinical impact and molecular underpinnings, and its mutational landscape is currently unknown. In this work, a total of 871 CLLs were tested for the IGH break-apart probe, and 54 (6.2%) had a 300 kb deletion of 3'IGH (del-3'IGH CLLs), which contributed to a shorter time to first treatment (TFT). The mutational analysis by next-generation sequencing of 317 untreated CLLs (54 del-3'IGH and 263 as the control group) showed high mutational frequencies of NOTCH1 (30%), ATM (20%), genes involved in the RAS signaling pathway (BRAF, KRAS, NRAS, and MAP2K1) (15%), and TRAF3 (13%) within del-3'IGH CLLs. Notably, the incidence of TRAF3 mutations was significantly higher in del-3'IGH CLLs than in the control group (p < .001). Copy number analysis also revealed that TRAF3 loss was highly enriched in CLLs with 14q deletion (p < .001), indicating a complete biallelic inactivation of this gene through deletion and mutation. Interestingly, the presence of mutations in the aforementioned genes negatively refined the prognosis of del-3'IGH CLLs in terms of overall survival (NOTCH1, ATM, and RAS signaling pathway genes) and TFT (TRAF3). Furthermore, TRAF3 biallelic inactivation constituted an independent risk factor for TFT in the entire CLL cohort. Altogether, our work demonstrates the distinct genetic landscape of del-3'IGH CLL with multiple molecular pathways affected, characterized by a TRAF3 biallelic inactivation that contributes to a marked poor outcome in this subgroup of patients.

Tabaco y diabetes: relevancia clínica y abordaje de la deshabituación tabáquica en pacientes con diabetes

2026-05-12T00:01:47Z

[ES]El tabaquismo es, junto con la diabetes mellitus, uno de los principales factores de riesgo cardiovascular. Los pacientes diabéticos presentan peculiaridades y características, algunas no bien conocidas, que hacen que el tabaquismo agrave los efectos de la diabetes y que el proceso de la deshabituación tabáquica en estos pacientes presente dificultades añadidas y que, por tanto, requiera un abordaje específico, más intensivo y con controles más rigurosos. En esta revisión se desgranan todos los aspectos conocidos que influyen en la interacción entre el tabaquismo y la diabetes, tanto en lo referente al incremento del riesgo de las complicaciones macrovasculares y microvasculares de la diabetes como a los factores que influyen en los resultados de los programas de deshabituación tabáquica. Así mismo se exponen las pautas de tratamiento de estos fumadores, incluyendo los algoritmos y pautas de tratamiento farmacológico que, basándose en evidencia científica, se han mostrado más eficaces.; [EN]Smoking is, together with diabetes mellitus, one of the main risk factors for cardiovascular disease. Diabetic patients have unique features and characteristics, some of which are not well known, that cause smoking to aggravate the effects of diabetes and impose difficulties in the smoking cessation process, for which a specificand more intensive approach with stricter controls is required. This review details all aspects with a known influence on the interaction between smoking and diabetes, both as regards the increased risk of macrovascular and microvascular complications of diabetes and the factors with an impact on the results of smoking cessation programs. The treatment guidelines for these smokers, including the algorithms and drug treatment patterns which have proved most useful based on scientific evidence, are also discussed.

The evolving landscape of chronic lymphocytic leukemia on diagnosis, prognosis and treatment

2026-05-12T00:01:19Z

[EN]The knowledge of chronic lymphocytic leukemia (CLL) has progressively deepened during the last forty years. Research activities and clinical studies have been remarkably fruitful in novel findings elucidating multiple aspects of the pathogenesis of the disease, improving CLL diagnosis, prognosis and treatment. Whereas the diagnostic criteria for CLL have not substantially changed over time, prognostication has experienced an expansion with the identification of new biological and genetic biomarkers. Thanks to next-generation sequencing (NGS), an unprecedented number of gene mutations were identified with potential prognostic and predictive value in the 2010s, although significant work on their validation is still required before they can be used in a routine clinical setting. In terms of treatment, there has been an impressive explosion of new approaches based on targeted therapies for CLL patients during the last decade. In this current chemotherapy-free era, BCR and BCL2 inhibitors have changed the management of CLL patients and clearly improved their prognosis and quality of life. In this review, we provide an overview of these novel advances, as well as point out questions that should be further addressed to continue improving the outcomes of patients.

Comparison of survival between stages IV-A and IV-B of head and neck cancer

2026-05-12T00:00:41Z

[SPA]Analiza la supervivencia comparada entre los estadios IV-A y IV-B del cáncer de cabeza y cuello. Los resultados muestran una mejor supervivencia a 24 meses en los pacientes clasificados en estadio IV-A frente a los de estadio IV-B, con diferencias estadísticamente significativas. La conclusión principal sostiene que los pacientes en estadio IV-B presentan peor pronóstico, y que los hallazgos respaldan las recomendaciones de la actualización de la clasificación TNM.

Chemotherapy or allogeneic transplantation in high-risk Philadelphia chromosome-negative adult lymphoblastic leukemia

2026-05-12T00:01:15Z

[EN]The need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) with high-risk (HR) features and adequate measurable residual disease (MRD) clearance remains unclear. The aim of the ALL-HR-11 trial was to evaluate the outcomes of HR Ph- adult ALL patients following chemotherapy or allo-HSCT administered based on end-induction and consolidation MRD levels. Patients aged 15 to 60 years with HR-ALL in complete response (CR) and MRD levels (centrally assessed by 8-color flow cytometry) <0.1% after induction and <0.01% after early consolidation were assigned to receive delayed consolidation and maintenance therapy up to 2 years in CR. The remaining patients were allocated to allo-HSCT. CR was attained in 315/348 patients (91%), with MRD <0.1% after induction in 220/289 patients (76%). By intention-to-treat, 218 patients were assigned to chemotherapy and 106 to allo-HSCT. The 5-year (±95% confidence interval) cumulative incidence of relapse (CIR), overall survival (OS), and event-free survival probabilities for the whole series were 43% ± 7%, 49% ± 7%, and 40% ± 6%, respectively, with CIR and OS rates of 45% ± 8% and 59% ± 9% for patients assigned to chemotherapy and of 40% ± 12% and 38% ± 11% for those assigned to allo-HSCT, respectively. Our results show that avoiding allo-HSCT does not hamper the outcomes of HR Ph- adult ALL patients up to 60 years with adequate MRD response after induction and consolidation. Better postremission alternative therapies are especially needed for patients with poor MRD clearance. This trial was registered at www.clinicaltrials.gov as # NCT01540812.

Antitumoral effect of Ocoxin, a natural compound-containing nutritional supplement, in small cell lung cancer

2026-05-12T00:01:25Z

[EN]Lung cancer is the most frequently diagnosed neoplasia and represents the leading cause of cancer-related deaths worldwide. Due to this fact, efforts to improve patient survival through the introduction of novel therapies, as well as preventive actions, are urgently required. Considering this scenario, the antitumoral action of the composite formulation Ocoxin® oral solution (OOS), that contains several antitumoral compounds including antioxidants, was tested in small cell lung cancer (SCLC) in vitro and in vivo preclinical models. OOS exhibited anti-SCLC action that was both time and dose dependent. In vivo OOS decreased the growth of tumors implanted in mice without showing signs of toxicity. The antitumoral effect was due to inhibition of cell proliferation and increased cell death. Genomic and biochemical analyses indicated that OOS augmented p27 and decreased the functioning of several routes involved in cell proliferation. In addition, OOS caused cell death by activation of caspases. Importantly, OOS favored the action of several standard of care drugs used in the SCLC clinic. Our results suggest that OOS has antitumoral action on SCLC, and could be used to supplement the action of drugs commonly used to treat this type of tumor.