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Metabolic mechanisms of immunotherapy resistance
Full text linkPublisher Copyright: © The Author(s) 2025.Immunotherapy has revolutionized cancer treatment, yet its efficacy is frequently compromised by metabolic mechanisms that drive resistance. Understanding how tumor metabolism shapes the immune microenvironment is essential for developing effective therapeutic strategies. This review examines key metabolic pathways influencing immunotherapy resistance, including glucose, lipid, and amino acid metabolism. We discuss their impact on immune cell function and tumor progression, highlighting emerging therapeutic strategies to counteract these effects. Tumor cells undergo metabolic reprogramming to sustain proliferation, altering the availability of essential nutrients and generating toxic byproducts that impair cytotoxic T lymphocytes (CTLs) and natural killer (NK) cell activity. The accumulation of lactate, deregulated lipid metabolism, and amino acid depletion contribute to an immunosuppressive tumor microenvironment (TME). Targeting metabolic pathways, such as inhibiting glycolysis, modulating lipid metabolism, and restoring amino acid balance, has shown promise in enhancing immunotherapy response. Addressing metabolic barriers is crucial to overcoming immunotherapy resistance. Integrating metabolic-targeted therapies with immune checkpoint inhibitors may improve clinical outcomes. Future research should focus on personalized strategies to optimize metabolic interventions and enhance antitumor immunity.Peer reviewe
Adjuvant hyperthermic intraperitoneal chemotherapy in patients with colon cancer at high risk of peritoneal metastases : Individual patient data meta-analysis
No full textPublisher Copyright: © 2025 The Author(s).Background: About a quarter of patients with locally advanced colon cancer (pT4) develop locoregional recurrence, including peritoneal metastases. The aim of this individual patient data meta-analysis (IPDMA) was to evaluate the efficacy of adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) with regard to reducing the locoregional recurrence rate in the overall population and high-risk subgroups of patients with locally advanced colon cancer. Methods: A systematic literature search was conducted in July 2024 to identify RCTs on adjuvant HIPEC in addition to routine adjuvant systemic chemotherapy in locally advanced colon carcinoma. An IPDMA was performed, with the locoregional recurrence rate as the primary endpoint and disease-free survival (DFS) and overall survival (OS) as secondary endpoints. Results: The search identified two trials (COLOPEC and HIPECT4). Individual patient data were pooled for 386 patients, of whom 189 patients received adjuvant HIPEC and 197 patients constituted the control group. The median follow-up was 36 (interquartile range 32-60) months. A modified intention-to-treat analysis showed a 36-month locoregional recurrence rate of 16.0% for HIPEC patients and 21.2% for control patients (P = 0.295). Predefined subgroup analyses revealed a significant reduction in locoregional recurrence after HIPEC in patients with right-sided tumours (HR 0.56 (95% c.i. 0.48 to 0.67)) (P < 0.001). No significant differences in survival were found for the overall study population; low event rates in subgroups did not allow for survival analyses. Conclusion: Adjuvant HIPEC significantly reduced the locoregional recurrence rate in right-sided locally advanced colon cancer, but not in the overall study population. Definitive conclusions on DFS and OS require longer follow-up.Peer reviewe
Analysis of Acoustic Emission Waveforms by Wavelet Packet Transform for the Detection of Crack Initiation Due to Fretting Fatigue in Solid Railway Axles
Full text linkPublisher Copyright: © 2025 by the authors.Railway axles are among the most safety-critical components in rolling stock, as their failure can lead to catastrophic consequences. One of the most subtle damage mechanisms affecting these components is fretting fatigue, which is a particularly challenging damage mechanism in these components, as it can initiate cracks under real service conditions and is difficult to detect in its early stages, which is vital to ensure operational safety and to optimize maintenance strategies. This paper focuses on the development of fretting fatigue damage in solid railway axles under realistic service-like conditions. Full-scale axle specimens with artificially induced notches were subjected to loading conditions that promote fretting fatigue crack initiation and growth. Acoustic emission techniques were used to monitor the damage progression, and post-processing of the emitted signals, by using wavelet-based tools, was conducted to identify early indicators of crack formation. The experimental findings demonstrate that the proposed approach allows for reliable identification of fretting-induced crack initiation, contributing valuable insights into the in-service behavior of railway axles under this damage mechanism.Peer reviewe
Dehydroisohispanolone alleviates NLRP3-driven inflammation in gout arthritis
Full text linkPublisher Copyright: © 2025 The Author(s)Natural products constitute an important resource for drug discovery with hispanolone derivatives recognized as bioactive diterpenes due to their broad therapeutic potential. Dehydroisohispanolone (DIH) is an anti-inflammatory labdane diterpene, that acts as a multi-target agent through various inflammation pathways. Aberrant activation of the Nod-like receptor protein 3 (NLRP3) inflammasome is involved in several inflammatory diseases, including gout. This study explores the mechanisms underlying the effects of DIH on the NLRP3 inflammasome and pyroptosis in vitro and evaluates its therapeutic effects on gouty arthritis in mice. DIH suppresses interleukin (IL)-1β secretion and pyroptosis in lipopolysaccharide (LPS)-primed bone-marrow-derived macrophages (BMDMs) elicited by broad stimuli. DIH exerts its action by disrupting adaptor apoptosis-associated speck-like protein (ASC) oligomerization, thereby inhibiting the assembly of inflammasome complex. Notably, DIH specifically inhibits NLRP3 inflammasome activation in murine BMDMs without affecting the absent in melanoma-2 (AIM2) or NOD-like receptor family CARD domain containing 4 (NLRC4) inflammasomes. In animal models, DIH significantly mitigated monosodium urate (MSU)-induced joint inflammation, reducing cytokine levels and myeloperoxidase (MPO) secretion. Overall, this study identified DIH as a specific inhibitor of the NLRP3 inflammasome, providing new insights into its potential as a therapeutic agent for NLRP3-mediated inflammatory diseases.Peer reviewe
Effectiveness of an intervention program for the reduction of hostile and benevolent sexism in male juvenile offenders
Full text linkPublisher Copyright: Copyright © 2015 SIPS.Sexist attitudes have traditionally been identified as a risk factor associated with violence against women, with male young offenders being a target population for prevention efforts. The main objective of this study was to evaluate the effectiveness of the “Intervention Program to Promote Egalitarian Relationships” aimed at reducing sexist attitudes in male adolescent offenders. A pre-experimental study was conducted involving 104 male adolescents aged between 14 and 21 years (M=17.35; ± 0.16) who were under judicial custody. Data on sexist attitudes were collected before and after participation in the intervention program using the Adolescent Sexism Detection Scale (DSA). The results revealed a significant reduction in both hostile and benevolent sexist attitudes, but only among those participants who displayed high levels of sexism at baseline. Conversely, participants with low levels of sexism prior to the intervention experienced a slight increase in hostile sexist attitudes. These findings demonstrated the usefulness of implementing programs targeted at reducing sexist attitudes in adolescent offenders, emphasizing the need to tailor interventions to the level of risk presented in order to maximize their effectiveness.Peer reviewe
Defining Excellence : The First Core Set of Quality Indicators for the European Paediatric Surgical Audit on Hirschsprung's Disease Care
No full textPublisher Copyright: © 2025 The Author(s). Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.Aim: This study aimed to develop a universally applicable core set of quality indicators for Hirschsprung's disease care through a consensus-driven process, to standardise and improve care quality across Europe. Methods: A modified Delphi method was used to achieve consensus among healthcare professionals (HPs) and patient representatives (PRs) across Europe. Participants completed three rounds of anonymous surveys, rating quality indicators for Hirschsprung's disease care. A systematic literature review informed the initial item list. Results were analysed using predefined criteria, and a final consensus meeting established the core set of indicators. Results: An international panel of 8 PRs and 96 multidisciplinary health care professionals representing 59 European hospitals completed all questionnaires, eventually including 12 baseline characteristics and 39 indicators. Six of the top 10 indicators were commonly prioritised by both groups. The remaining items were refined through debate and finalised during a consensus meeting. Conclusion: This study established a core set of 12 baseline characteristics and 14 quality indicators for evaluating Hirschsprung's disease care. These indicators will support benchmarking and continuous quality improvement within the European Paediatric Surgical Audit framework, ultimately enhancing outcomes and care for children with Hirschsprung's disease.Peer reviewe
Alberto Methol Ferré, between theology, history and geopolitics
No full textPublisher Copyright: © 2025 The Author(s).Desde su muerte, en 2009, no cesan de crecer los estudios sobre el pensador uruguayo Alberto Methol Ferré: más allá de la diversidad de enfoques, alcances y juicios, hay una coincidencia amplia sobre su originalidad. En el presente artículo nos proponemos un análisis de los principales contenidos y rasgos de su pensamiento geopolítico, como camino para precisar en qué consistió su originalidad en el campo específico de la geopolítica.Since his death in 2009, studies on the Uruguayan thinker Alberto Methol Ferré have not ceased to grow: beyond the diversity of approaches, scopes and judgments, there is a broad agreement on his originality. In this article we propose an analysis of the main contents and features of his geopolitical thought, to specify what his originality consisted of in the specific field of geopolitics.Peer reviewe
Análisis de softwares de inteligencia artificial generativa de voz aplicados al podcasting.
No full textLa IAG de voz es capaz de generar mensajes en lenguaje humano, mediante algoritmos de aprendizaje profundo, como las redes neuronales convolucionales o CNN, que aprenden a imitar los patrones vocales a partir de datos de habla. Ante este contexto, el principal objetivo es ofrecer una radiografía de la IAG de voz aplicada al podcasting para responder si la actual oferta tecnológica representa una amenaza para los empleos de los profesionales del audio, en particular para los/as locutores/as. Con este fin, se analizan los principales software que emplean los creadores de pódcast para la clonación de voz y se establece un marco comparativo. En segundo lugar, se recopilan las percepciones de los creadores acerca de los resultados obtenidos mediante el análisis de 10 títulos. Los principales software ofrecen herramientas específicas, que pueden mejorar el flujo de trabajo y optimizar los costes de producción. Gracias a los resultados sobre el estado actual de la IAG de voz aplicada al podcasting, hemos identificado tanto las oportunidades como las limitaciones que esta tecnología ofrece a los creadores.se observa que la industria de la IAG de voz está adaptándose a las necesidades del sector, ofreciendo múltiples herramientas a través de plataformas especializadas que permiten clonar la voz, editar grabaciones, publicar pódcast y distribuirlos en varios idiomas. Sin embargo, no se interpreta como una amenaza inmediata debido a la reproducción de una prosodia inexacta y la ausencia de elementos paralingüísticos.478 K
Avatares y replicantes en comunicación y humanidades.
No full textEl del film Blade Runner es uno de los ejemplos más notorios en los que en la ficción unos robots, con apariencia humana y construidos en laboratorios con parte de material genético, se postulan como un sustituto plausible de las personas. La comunicación en las pantallas desde los años 80 ha sufrido una aceleración masiva tanto con la irrupción de los móviles como por la popularización de internet y, finalmente, el uso extendido de la inteligencia artificial. La construcción de narraciones de ciencia ficción se asemejan cada vez más a la realidad comunicativa contemporánea. Cuáles son las causas que han suscitado el interés o la necesidad humana de sustituirse a sí mismo; qué evidencias podemos encontrar de esto en diferentes medios de comunicación y finalmente qué consecuencias podrían empezar a esbozarse. A través de diferentes aportaciones teóricas y ejemplos prácticos se concluye una progresiva presencia en crecimiento exponencial de la alienación humana a través de avatares, replicantes y sustitutos en las pantallas de los distintos medios de comunicación.244 K
Solid-liquid phase change materials for solar-driven interfacial evaporation: principles, design optimization, and emerging advances in sustainable seawater desalination.
No full textSolar-powered interfacial evaporation technology has emerged as a promising solution for sustainable seawater desalination, addressing freshwater scarcity while offering the advantages of low energy consumption and minimal environmental impact. However, the evaporation performance of solar evaporators is constrained by the intermittent and unstable nature of sunlight. Solid-liquid phase change materials (SLPCMs), with their high latent heat storage capacity and chemical stability, can efficiently store solar energy during periods of strong irradiation and release it when sunlight is insufficient. Integrating SLPCMs into solar-driven interfacial evaporation systems can enhance solar energy utilization efficiency and mitigate the impact of intermittent solar irradiation on evaporation performance. However, SLPCMs face challenges such as leakage during phase transitions and low thermal conductivity, limiting their direct application in evaporation systems. This review systematically analyzes these issues and explores optimization strategies, including porous material compositing and microencapsulation. The review also highlights recent advances in applying optimized SLPCMs to solar-driven interfacial evaporation while addressing remaining scientific and technical challenges. Finally, the review provides a forward-looking perspective on future developments in advanced interfacial evaporation systems to overcome intermittent solar irradiation constraints.57 p