http://hdl.handle.net/10366/3823 Investigación científica producida o editada por los departamentos y centros de la Universidad de Salamanca 2026-05-11T20:19:07Z http://hdl.handle.net/10366/171351 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. 2026-04-29T00:00:00Z http://hdl.handle.net/10366/171350 [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. 2022-10-10T00:00:00Z http://hdl.handle.net/10366/171347 [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. 2022-06-07T00:00:00Z http://hdl.handle.net/10366/171346 [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. 2017-01-01T00:00:00Z http://hdl.handle.net/10366/171344 [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. 2022-07-01T00:00:00Z http://hdl.handle.net/10366/171341 [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. 2017-01-01T00:00:00Z http://hdl.handle.net/10366/171340 [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. 2021-05-10T00:00:00Z http://hdl.handle.net/10366/171332 [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. 2001-03-01T00:00:00Z http://hdl.handle.net/10366/171330 [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. 2021-04-08T00:00:00Z http://hdl.handle.net/10366/171329 [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. 2018-07-01T00:00:00Z http://hdl.handle.net/10366/171327 [EN] In the present paper we systematically evaluate the radiometric database underlying the Middle to Upper Palaeolithc transition in southwestern Europe.The different models which attempt to explain the demographical processes underlying this transition rely to a large degree on radiocarbon chronology. We observe that: 1) with increasing age, dates on bone samples show large offsets against those on charcoal, often underestimating these for several thousand years BP and; 2) there is no proof for a persistence of Middle Palaeolithic industries into the time of the earliest Aurignacian in SW Europe. These data contradict the “Ebro- Frontier” model that distinguishes Late Middle Palaeolithic industries in the SW of the Iberian Peninsula from early Aurignacian ones in the NE. On the contrary, our data 3) imply a model of interregional shifts of populations contracting during severe cold and arid phases and expanding under warmer, interstadial conditions, raising ideas on a regional in situ development of the SW European Aurignacian out of Latest Middle Palaeolithic industries made by Neanderthals some 40.0 kyr cal BC. 2023-01-01T00:00:00Z http://hdl.handle.net/10366/171326 [ES] Estudio de las conchas marinas de la especie Columbella rustica en los sitios mesolíticos europeos 2003-01-01T00:00:00Z http://hdl.handle.net/10366/171325 [EN] A spatula recovered from the Late Palaeolithic site of Boppard is manufactured on a fragment of the plantar face of a metatarsal bone of red deer (Cervus elaphus). Along its narrow side, the tool exhibits numerous parallel notches at right angles to the longitudinal axis of the bone. These are arranged in groups separated by notch-free areas of bone. Comparable bone tools are described, mainly from Cantabrian Spain, but also from France, Italy, Germany, the Czech Republik and Sweden. The best paralells for the Boppard specimen are, insofar as they are dated, known from the Later Upper Palaeolithic. 2014-01-01T00:00:00Z http://hdl.handle.net/10366/171324 Introducción: La negativa a la fístula arteriovenosa es un reto en hemodiálisis. La intervención enfermera es determinante en la toma de decisiones compartidas. Objetivo: Evaluar el impacto de una intervención multidisciplinar estructurada para abordar la negativa de pacientes con enfermedad renal crónica a la creación de una fístula arteriovenosa. Material y Método: Estudio piloto prospectivo y multicéntrico dividido en cuatro grupos según su situación respecto al acceso vascular. La intervención incluyó educación visual, formación del equipo en habilidades comunicativas y ecografía. Se analizaron variables demográficas, clínicas y de intervención. El estudio contó con aprobación ética y consentimiento informado. Análisis mediante pruebas paramétricas (t-Student, ANOVA) y no paramétricas (U de Mann-Whitney, Kruskal-Wallis). Resultados: Se incluyeron 51 pacientes con una edad media de 67,4±13,4 años (68,6% hombres). Tras la intervención, el 68,6% optó por fístula arteriovenosa. Enfermería lideró el 100% de las primeras consultas (media 30±12,7 minutos). La aceptación fue total en el grupo ERCA (100%) y alta en incidentes (78%), frente al 35% en prevalentes con CVC>6 meses (p<0,001). Las consultas sucesivas multidisciplinares aumentaron significativamente la aceptación frente a consultas solo de enfermería (p<0,05). Las principales barreras fueron miedo a la cirugía (54%) y comodidad del catéter (46%). Quienes aceptaron la fístula fueron más jóvenes (p<0,05). Conclusiones: La enfermería lidera positivamente la toma de decisiones mediante un enfoque estructurado y empático. La consulta ERCA es clave para la planificación anticipada, mientras que en portadores de catéter de larga duración se requieren intervenciones más tempranas. 2026-03-30T00:00:00Z http://hdl.handle.net/10366/171323 A acessibilidade dos dicionários digitais é um fator fundamental para a inclusão educativa e profissional das pessoas cegas. Esta investigação centra-se na interação entre utilizadores de linhas Braille e diversos tipos de dicionários digitais, abordando as complexidades do acesso tátil e contrastando-o com as modalidades visual e auditiva. Enquanto a leitura visual permite uma exploração global e não linear, a linha Braille oferece uma perceção tátil sequencial e plana, construindo o contexto palavra por palavra. Alguns estudos sugerem que a ausência de acesso ao Braille pode contribuir para formas de iliteracia funcional, tornando crucial a correta estruturação da informação. Este estudo realiza uma avaliação formal de dicionários instaláveis (OUP-MacOS e Larousse-MacOS), online (Infopédia, DLE) e adaptados (Wikcionário-Brailliant e Wikcionário-SeeingHands), utilizando três conceitos-chave: sequência, planos de interação e condensação. Os resultados demonstram que existem falhas na navegação por tabelas, excesso de descondensação e problemas de foco técnico, propondo-se novos princípios de design lexicográfico para a leitura tátil. Accessibility in digital dictionaries is fundamental for the educational and professional inclusion of blind people. This research focuses on the interaction between refreshable Braille display users and various types of digital dictionaries, addressing the complexities of tactile access and contrasting it with visual and auditory modalities. While visual reading allows for global, non-linear exploration, refreshable Braille displays offer a sequential and flat tactile perception, building context word by word. Some studies suggest that the lack of access to Braille can contribute to forms of functional illiteracy, making the correct structuring of information crucial. This study conducts a formal evaluation of installable dictionaries (OUP-macOS and Larousse-macOS), online dictionaries (Infopédia, DLE), and Braille-adapted versions (Wiktionary-Brailliant and Wiktionary-SeeingHands), using three key concepts: sequence, interaction planes, and condensation. The results demonstrate flaws in table navigation, excessive decondensation, and technical focus issues. New lexicographic design principles specifically for tactile reading are proposed. 2026-01-01T00:00:00Z http://hdl.handle.net/10366/171313 [ES]El Manual de prevención y tratamiento del tabaquismo ofrece una síntesis sistemática de los conocimientos científicos y clínicos sobre el consumo de tabaco, sus consecuencias para la salud y las estrategias de intervención disponibles. 2003-01-01T00:00:00Z