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ObjectivesTo investigate factors associated with severe COVID-19 in people with idiopathic inflammatory myopathy (IIM).MethodsDemographic data, clinical characteristics and COVID-19 outcome severity of adults with IIM were obtained from the COVID-19 Global Rheumatology Alliance physician-reported registry. A 3-point ordinal COVID-19 severity scale was defined: (1) no hospitalisation, (2) hospitalisation (and no death) and (3) death. ORs were estimated using multivariable ordinal logistic regression. Sensitivity analyses were performed using a 4-point ordinal scale: (1) no hospitalisation, (2) hospitalisation with no oxygen (and no death), (3) hospitalisation with oxygen/ventilation (and no death) and 4) death.ResultsOf 348 patients, 48% were not hospitalised, 39% were hospitalised (and did not die) and 13% died. Older age (OR=1.59/decade, 95% CI 1.31 to 1.91), high disease activity (OR=3.50, 95% CI 1.25 to 9.83; vs remission), ≥2 comorbidities (OR=2.63, 95% CI 1.39 to 4.98; vs none), prednisolone-equivalent dose >7.5 mg/day (OR=2.40, 95% CI 1.09 to 5.28; vs no intake) and exposure to rituximab (OR=2.71, 95% CI 1.28 to 5.72; vs conventional synthetic disease-modifying antirheumatic drugs only) were independently associated with severe COVID-19. In addition to these variables, in the sensitivity analyses, male sex (OR range: 1.65-1.83; vs female) was also significantly associated with severe outcomes, while COVID-19 diagnosis after 1 October 2020 (OR range: 0.51-0.59; vs on/before 15 June 2020) was significantly associated with less severe outcomes, but these associations were not significant in the main model (OR=1.57, 95% CI 0.95 to 2.59; and OR=0.61, 95% CI 0.37 to 1.00; respectively).ConclusionsThis is the first large registry data on outcomes of COVID-19 in people with IIM. Older age, male sex, higher comorbidity burden, high disease activity, prednisolone-equivalent dose >7.5 mg/day and rituximab exposure were associated with severe COVID-19. These findings will enable risk stratification and inform management decisions for patients with IIM.

BackgroundDifferences in the distribution of individual-level clinical risk factors across regions do not fully explain the observed global disparities in COVID-19 outcomes. We aimed to investigate the associations between environmental and societal factors and country-level variations in mortality attributed to COVID-19 among people with rheumatic disease globally.MethodsIn this observational study, we derived individual-level data on adults (aged 18-99 years) with rheumatic disease and a confirmed status of their highest COVID-19 severity level from the COVID-19 Global Rheumatology Alliance (GRA) registry, collected between March 12, 2020, and Aug 27, 2021. Environmental and societal factors were obtained from publicly available sources. The primary endpoint was mortality attributed to COVID-19. We used a multivariable logistic regression to evaluate independent associations between environmental and societal factors and death, after controlling for individual-level risk factors. We used a series of nested mixed-effects models to establish whether environmental and societal factors sufficiently explained country-level variations in death.Findings14 044 patients from 23 countries were included in the analyses. 10 178 (72·5%) individuals were female and 3866 (27·5%) were male, with a mean age of 54·4 years (SD 15·6). Air pollution (odds ratio 1·10 per 10 μg/m3 [95% CI 1·01-1·17]; p=0·0105), proportion of the population aged 65 years or older (1·19 per 1% increase [1·10-1·30]; p

Robot-mediated physical interaction between humans, or physical Human-Robot-Human Interaction (pHRHI for short) can transcend the physical constraints associated with direct human-human interaction such as constant interaction medium and the need for proximity. Control for pHRHI is related to bilateral teleoperation, but pHRHI must necessarily focus on human safety features on both sides of the interaction in a general setting. This paper presents a safety-aware framework for a robot mediated bilateral physical interaction between two humans in general setting while handling safety constraints with different priorities on two sides. The proposed framework also allows a user to haptically feel any number of constraints that are active on the other side, enabling a safe and intuitive interaction. Additionally, this approach is not dependent on the robot model and allows generalization across robots. We have formulated the safety-aware pHRHI problem as a hierarchical optimization framework with higher-priority safety tasks and lower-priority bilateral interaction and constraint communication tasks. We validated this framework by assessing the bilateral interaction, hierarchical constraint handling, and constraint communication performances on a dual human-robot setup. We also compared the performance with current approaches based on constrained optimization without any hierarchy or constraint communication feature. Results show that the proposed framework can handle prioritized physical/safety constraints, enabling bilateral interaction and providing a physical feeling of the other robot’s constraints.

Smart Grid integration plays a crucial role in transitioning towards a climate-neutral future by enabling advanced monitoring, management, and control of renewable energy sources, energy systems, and networks. However, several barriers related to technological, economic, regulatory, and social aspects hinder the integration of these innovative resources and strategies into current power systems due to the inherent complexity of heterogeneous technologies, entities, and actors. For example, interoperability issues, cybersecurity concerns and data management are relevant to the integration and digitalization of smart grids. To address these challenges, this paper proposes a hybrid multi-model co-simulation infrastructure to simulate innovative Smart Grid scenarios. The infrastructure enables the interconnection of heterogeneous software simulators with real-time hardware simulators within a shared and distributed co-simulation environment, facilitating Hardware-In-the-Loop (HIL) applications through a semi-automated scenario configuration procedure. The proposed infrastructure’s capabilities and performance are assessed through a smart grid scenario, focusing on implementing a distribution voltage regulation service provided by distributed resources installed on a building premise. Specifically, the scenario includes a physical smart meter device interconnected in HIL with the simulated building energy management system to test the integrated functionality and interoperability for the ancillary service. The scenario results demonstrate the facilitated scenario design process, and the promising performance and low co-simulation latencies of the co-simulation infrastructure when coupling software and hardware simulators with HIL applications. Overall, the infrastructure has the potential to assist researchers, system operators, and energy stakeholders in evaluating Smart Grid scenarios and designing, developing, and testing new systems, technologies, and business models.

Educational institutions have been adopting business simulation games as a resource for developing skills and competencies. However, the real-time study of aspects related to learning during their use still needs to further investigation. This work aims to present contributions of a new methodology that considers the analysis of the player’s experience from the physiological, behavioural, and psychological perspectives, supported by biometric devices. Its validation was based on data collection conducted at a university in Brazil, with ten participants during a game monitored by Electroencephalogram and Eye Tracking technologies, relating the behaviour of the cerebral cortex with areas of greater interest and gaze fixation of the players. Additionally, pre-and post-test questionnaires highlighted personal behaviours and collective patterns influenced by aspects such as tutorial and game design elements, prior knowledge, ergonomic issues, cognitive strategy definition, organization of executive functions, and memory formation. The results show that the proposed model can be beneficial in assessing the potential of this type of organizational environment simulation, both for those who use it in the teaching process and for serious game developers.

In the context of neurorehabilitation, there have been rapid and continuous improvements in sensors-based clinical tools to quantify limb performance. As a result of the increasing integration of technologies in the assessment procedure, the need to integrate evidence-based medicine with benchmarking has emerged in the scientific community. In this work, we present the experimental validation of our previously proposed benchmarking scheme for upper limb capabilities in terms of repeatability, reproducibility, and clinical meaningfulness. We performed a prospective multicenter study on neurologically intact young and elderly subjects and post-stroke patients while recording kinematics and electromyography. 60 subjects (30 young healthy, 15 elderly healthy, and 15 post-stroke) completed the benchmarking protocol. The framework was repeatable among different assessors and instrumentation. Age did not significantly impact the performance indicators of the scheme for healthy subjects. In post-stroke subjects, the movements presented decreased smoothness and speed, the movement amplitude was reduced, and the muscular activation showed lower power and lower intra-limb coordination. We revised the original framework reducing it to three motor skills, and we extracted 14 significant performance indicators with a good correlation with the ARAT clinical scale. The applicability of the scheme is wide, and it may be considered a valuable tool for upper limb functional evaluation in the clinical routine.

Background & Aims: Schistosomiasis is one of the most prominent parasite-induced infectious diseases, affecting more than 250 million people. Schistosoma mansoni causes metabolic exhaustion and a strong redox imbalance in the liver, causing parenchymal damage, and may predispose for cancer. We investigated whether oxidative stress provokes hepatocellular proliferation upon S. mansoni infection. Methods: The cell cycle, replication stress response, and proliferation were analyzed on transcriptional and protein levels in the livers of S. mansoni–infected hamsters and by mechanistic gain- and loss-of-function experiments in human hepatoma cells. Major results were validated in human biopsy specimens of S. mansoni–infected patients. Results: S. mansoni infection induced licensing factors of DNA replication and cell-cycle checkpoint cyclins in parallel with a DNA damage response in hamster hepatocytes. Moreover, even unisexual infection without egg effects, as a reflection of a chronic inflammatory process, resulted in a moderate activation of several cell-cycle markers. S. mansoni soluble egg antigens induced proliferation of human hepatoma cells that could be abolished by reduced glutathione. Conclusions: Our data suggest that hepatocellular proliferation is triggered by S. mansoni egg-induced oxidative stress.

Abstract Background Neoantigens are patient- and tumor-specific peptides that arise from somatic mutations. They stand as promising targets for personalized therapeutic cancer vaccines. The identification process for neoantigens has evolved with the use of next-generation sequencing technologies and bioinformatic tools in tumor genomics. However, in-silico strategies for selecting immunogenic neoantigens still have very low accuracy rates, since they mainly focus on predicting peptide binding to Major Histocompatibility Complex (MHC) molecules, which is key but not the sole determinant for immunogenicity. Moreover, the therapeutic potential of neoantigen-based vaccines may be enhanced using an optimal delivery platform that elicits robust de novo immune responses. Methods We developed a novel neoantigen selection pipeline based on existing software combined with a novel prediction method, the Neoantigen Optimization Algorithm (NOAH), which takes into account structural features of the peptide/MHC-I interaction, as well as the interaction between the peptide/MHC-I complex and the TCR, in its prediction strategy. Moreover, to maximize neoantigens’ therapeutic potential, neoantigen-based vaccines should be manufactured in an optimal delivery platform that elicits robust de novo immune responses and bypasses central and peripheral tolerance. Results We generated a highly immunogenic vaccine platform based on engineered HIV-1 Gag-based Virus-Like Particles (VLPs) expressing a high copy number of each in silico selected neoantigen. We tested different neoantigen-loaded VLPs (neoVLPs) in a B16-F10 melanoma mouse model to evaluate their capability to generate new immunogenic specificities. NeoVLPs were used in in vivo immunogenicity and tumor challenge experiments. Conclusions Our results indicate the relevance of incorporating other immunogenic determinants beyond the binding of neoantigens to MHC-I. Thus, neoVLPs loaded with neoantigens enhancing the interaction with the TCR can promote the generation of de novo antitumor-specific immune responses, resulting in a delay in tumor growth. Vaccination with the neoVLP platform is a robust alternative to current therapeutic vaccine approaches and a promising candidate for future personalized immunotherapy.

In this contribution, the design and manufacturing of an all-metal coaxial-line X-band bandpass filter is discussed. The device is 3D-printed as a self-supported structure without any dielectric inside the coaxial. The mechanical support between the inner and outer coaxial-line conductors is provided by means of $\lambda /4$ short-circuited stubs, which are also used in the bandpass filter design. The real transmission zeros (TZs) produced by the short-circuited stubs are responsible for a high filter selectivity. In order to enhance the filter performance, a second stage consisting in a coaxial-line stepped-impedance low-pass filter is integrated in the design to provide the rejection level required for the out-of-band behaviour. Following our design method, the bandpass and low-pass filters are designed separately, and a final matching step is performed to connect both and to achieve the aimed frequency specifications. In this way, a monoblock coaxial filter with very good in-band and out-of-band performance can by obtained by using an additive manufacturing (AM) procedure. Only the input/output (I/O) coaxial connectors will need to be assembled to the filter to perform the frequency measurements. The filters in this work can be seen as a first proposal towards more complex multi-functional monoblock structures using additively-manufactured coaxial technology, for highly-integrated RF chains. Other expected benefits beyond the compactness or lightweight are an increased RF shielding, electrostatic discharge risk reduction, and Passive Intermodulation (PIM) protection. In the paper, a prototype with a passband between 8 and 12 GHz is designed and manufactured, using a bandpass filter with three stubs and an integrated 15th-order low-pass filter, providing rejection for spurious frequencies up to 30 GHz. The filter is manufactured using Selective Laser Melting (SLM) and measurements show an excellent agreement with the simulations.

Introducción: la implementación del enfoque estratégico en la educación superior es una necesidad para enfrentar los desafíos que presentan estas instituciones en el ámbito internacional. Es por ello, que existe un marcado interés en el ámbito académico en generar aportes que sirvan de guía para la ejecución de efectiva del mismo. Objetivo: analizar las tendencias de la investigación sobre la aplicación del enfoque de dirección estratégica en las instituciones de educación superior. Método: mediante un estudio bibliométrico, se desarrolló un análisis de 351 artículos publicados en revistas indizadas en la base de datos Scopus durante el período 1990-2023. Resultados: se comprueba la existencia de un crecimiento sostenido en las publicaciones en el área, predominando los estudios con autoría individual. Reino Unido, España y Estados Unidos lideran la investigación en este campo, siendo los temas más tratados el de evaluación del desempeño con enfoque estratégico, el efecto social-económico de este enfoque y recientemente el uso de las tecnologías y la simulación de negocios. Conclusión: los resultados obtenidos demuestran la actualidad y vitalidad de la temática, la necesidad del desarrollo de redes de colaboración tanto a nivel de autores como de países, así como el nivel de impacto que han tenido los estudios a nivel internacional.

Abstract Novel perioperative strategies are needed to reduce recurrence rates in patients undergoing nephrectomy for high-risk, non-metastatic clear cell renal cell carcinoma (ccRCC). We conducted a prospective, phase I trial of neoadjuvant nivolumab prior to nephrectomy in 15 evaluable patients with non-metastatic ccRCC. We leveraged tissue from that cohort to elucidate the effects of PD-1 inhibition on immune cell populations in ccRCC and correlate the evolving immune milieu with anti-PD-1 response. We found that nivolumab durably induces a pro-inflammatory state within the primary tumor, and baseline immune infiltration within the primary tumor correlates with nivolumab responsiveness. Nivolumab increases CTLA-4 expression in the primary tumor, and subsequent nephrectomy increases circulating concentrations of sPD-L1, sPD-L3 (sB7-H3), and s4-1BB. These findings form the basis to consider neoadjuvant immune checkpoint inhibition (ICI) for high-risk ccRCC while the tumor remains in situ and provide the rationale for perioperative strategies of novel ICI combinations.

Objective: To assess the efficacy of virtual reality (VR) in reducing pain and anxiety associated with scheduled blood draws. Material and methods: We conducted multicentre randomized clinical trial in both primary care and hospital settings. The study included children aged 7–12 years undergoing blood extraction procedures between March and October 2022. The intervention group used headsets, and the control group received usual care. Pain was assessed using the visual analogue scale and anxiety using the Groningen Distress Scale. The anxiety of the nursing staff and family satisfaction were assessed with numerical scales ranging from 1 to 10. Results: The study included 83 patients: 40 in the control group and 43 in the VR group. The median age was 10 years (range, 7−12 years). In the VR group, 83.7% of the children reported mild pain, compared to 57.5% in the control group (P = .012). Also, 93% of children in the VR group showed calm or mild anxiety (score, 1−2), compared to 72% of the control group, a difference that was not statistically significant (P = .08). Family satisfaction was higher in the RV group (score ≥ 9/10: 93% of RV group vs 72.5% of control group; P = .026). The nursing staff anxiety score was less than 5 in more than 90% of cases, with no differences between groups (P = .13). Conclusion: The use of VR during venepuncture decreases the pain perceived by children and increases the satisfaction of their families. Resumen: Objetivo: Comprobar la eficacia de la realidad virtual (RV) en la disminución del dolor y ansiedad asociados a extracciones sanguíneas programadas. Material y Métodos: Ensayo clínico aleatorizado multicéntrico realizado en atención primaria y hospitalaria. Se incluyeron los pacientes de 7 a 12 años que acudieron entre marzo y octubre de 2022 a realizarse una extracción sanguínea programada.En el grupo intervención se utilizaron gafas de RV y en el grupo control cuidados habituales. Se evaluó el dolor mediante la Escala Visual Analógica y la ansiedad mediante la Groningen Distress Scale. Se evaluó la ansiedad de enfermería y la satisfacción de los familiares, mediante escala numérica del 1 al 10. Resultados: Se incluyeron 83 pacientes: 40 en el grupo control y 43 en el grupo RV. La mediana de edad fue de 10 años (rango de 7 a 12). El 83,7% de los niños en el grupo RV refirió dolor leve, frente al 57,5% del grupo control (p = 0,012). El 93% del grupo RV mostró calma o ansiedad leve (puntuación 1−2), frente al 72% del grupo control, aunque sin diferencias estadísticamente significativas (p = 0,08).La satisfacción de los familiares fue mayor en el grupo RV (≥9/10: 93% de RV vs 72,5% de controles, p = 0,026). La ansiedad de enfermería fue < 5 en más del 90% de los casos, sin diferencias entre grupos (p = 0,13). Conclusiones: El uso de RV durante la venopunción disminuye el dolor percibido por los niños y aumenta la satisfacción de sus familiares.

Abstract The polarity of a surface can affect the electronic and structural properties of oxide thin films through electrostatic effects. Understanding the mechanism behind these effects requires knowledge of the atomic structure and electrostatic characteristics at the surface. In this study, we use annular bright-field imaging to investigate the surface structure of a Pr0.8Sr0.2NiO2+x (0 < x

La producción de asfaltos en las refinerías cubanas no satisface la demanda nacional de los proyectos viales. El propósito de este estudio fue delinear los posibles escenarios que pudieran tener lugar en la producción de asfaltos a partir de la refinación de crudos pesados en Cuba. Para ello se empleó una metodología que combinó el trabajo con expertos y la Prospectiva Estratégica de Godet. De la aplicación del método Matriz de Impactos Cruzados Multiplicación Aplicada a una Clasificación se obtuvieron tres variables (factores) claves que permitieron formular igual número de hipótesis y definir ocho posibles escenarios. Utilizando el método Sistema de Matrices de impactos Cruzados Probabilizados (Smic Prob-Expert) se precisaron los tres escenarios más probables: el más favorable, en el cual se cumplen las tres hipótesis; el menos favorable, en el que no se cumple ninguna de las tres, y un escenario en que se cumple solamente la primera hipótesis. Según estos resultados, el escenario más favorable sería aquel en el que se garanticen la materia prima para las refinerías, un procedimiento tecnológico que permita obtener más asfalto con menos costo y la disponibilidad técnica del equipamiento tecnológico.

Un corpus de traducción ofrece un marco de estudio comparativo inmejorable para la investigación diacrónica. A través del estudio de traducciones latín > romance se puede observar cómo las estructuras sintácticas latinas se continúan dentro de una misma tradición discursiva y perfil concepcional. En este estudio se analiza la convergencia y divergencia de la sintaxis de la traducción de la Heroida VII de Juan Gaytán (s. XVII) con respecto al original de Ovidio. Para ello se propone una serie de construcciones sintácticas latinas que se continúan en romance y se discute la procedencia y el estatus latinizante de cada una. En definitiva, este análisis trata de ilustrar cómo el latín, a través de la interferencia sintáctica, condiciona el perfil concepcional distante de la tradición discursiva de la Heroida y, en consecuencia, el estilo (hiper)latinizante de Juan Gaytán.

Background: The endothelium is the most posterior layer of the cornea and essential for maintaining corneal transparency. Due to variations in corneal endothelial parameters among different species, knowledge of the normal parameters for each species is crucial. Aim: To evaluate the corneal endothelium of bovines using contact specular microscopy. Methods: Twenty eyeballs from 10 male Brangus (Bos taurus) aged 24 months were evaluated. Contact specular microscopy was performed on the central corneal area. The analysed parameters were endothelial cell density (ECD) and endothelial cell morphology. Results: The ECD in the central area was 1277 cells/mm². Regarding the morphology, mainly cells with six (74.3%), five (14.7%) and seven sides (10%) were found. There were no significant differences in endothelial cell density and morphology between left and right eyes. Conclusion: Contact specular microscopy facilitated the analysis and measurement of corneal endothelial parameters in bovines. The data obtained will serve as a reference for the analysis of bovine corneal endothelium. [Open Vet J 2023; 13(12.000): 1554-1561]

Objectives: Advances in perioperative management for thoracic surgery have accelerated the postoperative recovery of patients by decreasing postoperative pain and the incidence of complications. We aimed to study whether it's safe to remove chest drains on table in selected cases. Methods: This was a 5-year retrospective analysis of protocolized chest-drain removal on the operating table. The chest drain was removed in patients undergoing sublobar/wedge lung resection and other minor thoracic procedure (pleural biopsy, mediastinal mass biopsy/resection) via a thoracoscopic approach (video-assisted thoracoscopic surgery). Chest drains were removed at the end of the operation if air leak as documented by the digital drain was less than 20 mL/min. Outcome data on postdrain removal pneumothorax, effusion, and need for further intervention were obtained by reviewing the postoperative chest films, all reported by a radiologist. Results: Between 2016 and 2021, 107 patients underwent drain removal in theater. Mean age (standard deviation) was 58 (17) years and 54 (50.5%) were male. Postdrain removal pneumothorax occurred in 22 patients (21%), pleural effusion in 6 (5.6%), and 21 of 22 postoperative pneumothoraces were managed conservatively without reinsertion of chest drain. As it is our standard policy to leave no pneumothorax in patients undergoing surgical management of primary spontaneous pneumothorax, only 1 such patient (0.9%) had a drain reinserted as a result. The median (interquartile) length of hospital stay was 1 day (1-2), and 14 patients (13%) were discharged on surgery day. Conclusions: Our results demonstrate that on table chest-drain removal in selected cases is safe and repeatable using a digital drain, challenging the practice of routine drain insertion after thoracic surgery.

Objective: Surgical mortality has traditionally been assessed at arbitrary intervals out to 1 year, without an agreed optimum time point. The aim of our study was to investigate the time-varying risk of death after lobectomy to determine the optimum period to evaluate surgical mortality rate after lobectomy for lung cancer. Methods: We performed a retrospective study of patients undergoing lobectomy for lung cancer at our institution from 2015 to 2022. Parametric survival models were assessed and compared with a nonparametric kernel estimate. The hazard function was plotted over time according to the best-fit statistical distribution. The time points at which instantaneous hazard rate peaked and stabilized in the 1-year period after surgery were then determined. Results: During the study period, 2284 patients underwent lobectomy for lung cancer. Cumulative mortality at 30, 90, and 180 days was 1.3%, 2.9%, and 4.9%, respectively. Log-logistic distribution showed the best fit compared with other statistical distribution, indicated by the lowest Akaike information criteria value. The instantaneous hazard rate was greatest during the immediate postoperative period (0.129; 95% confidence interval, 0.087-0.183) and diminishes rapidly within the first 30 days after surgery. Instantaneous hazard rate continued to decrease past 90 days and stabilized only at approximately 180 days. Conclusions: In-hospital mortality is the optimal follow-up period that captures the early-phase hazard during the immediate postoperative period after lobectomy. Thirty-day mortality is not synonymous to “early mortality,” as instantaneous hazard rate remains elevated well past the 90-day time point and only stabilizes at approximately 180 days after lobectomy.

La musealización de cementerios como estrategia de conservación de los mismos implica un análisis exhaustivo de la historia del recinto, revelando los valores y prácticas de las sociedades precedentes. Con un enfoque específico en el Cementerio Municipal de Alzira, se resalta el impacto de la revolución industrial y la burguesía en el estilo funerario, subrayando la necesidad de preservar las tradiciones pasadas como componente integral del patrimonio cultural. Esta propuesta de musealización integra un estudio histórico, sociológico y bibliográfico para su ejecución. Se reconoce la participación comunitaria como elemento esencial para enriquecer el proceso, fomentando una comprensión colectiva del patrimonio funerario destinada a las generaciones venideras

En este trabajo argumentamos la utilidad de integrar factores semánticos y pragmáticos en la descripción del perfecto compuesto y simple de las lenguas románicas, a fin de dar cuenta de su diversidad funcional intra e interlingüística. Partiendo de la tesis de la infradeterminación semántica (Sperber y Wilson, 1995) y de la idea de que el significado de los tiempos verbales tiene naturaleza procedimental (Moeschler, 1994, 1998; Nicolle, 1997, 1998; Saussure, 2003), desarrollamos una descripción de los perfectos basada en un conjunto limitado de combinaciones de rasgos semánticos. Algunos de estos rasgos son invariables y comunes a todas las lenguas románicas, mientras que otros presentan opciones paramétricas binarias, cuyo valor varía de una lengua a otra e incluso, dentro de una misma lengua, de una variedad geolectal a otra. Nuestra propuesta es compatible con la idea de una semántica procedimental rígida pero infraespecificada, susceptible de enriquecimiento contextual. El conjunto de rasgos y opciones paramétricas que proponemos explica los tipos de interpretaciones posibles en cada variedad. Además, los rasgos semánticos reciben sistemáticamente enriquecimiento contextual, y este desarrolla en direcciones diferentes las potencialidades de la forma verbal, semánticamente infraespecificadas. La competición entre expresiones lingüísticas semánticamente próximas es asimismo un factor importante en la distribución de las rutas interpretativas accesibles para cada una.

Schistosomiasis affects over 250 million people worldwide, with the highest prevalence at the age of 10–14 years. The influence of the host’s age on the severity of liver damage is unclear. We infected male 8, 14, and 20-week-old mice with S. mansoni. Hepatic damage, inflammation, fibrosis, and metabolism were analyzed by RT-qPCR, Western blotting, ELISA, immunohistochemistry, and mechanistic transwell chamber experiments using S. mansoni eggs and human hepatic stellate cells (HSCs) or primary mouse hepatocytes. Major results were validated in human biopsies. We found that hepatosplenomegaly, granuloma size, egg load, inflammation, fibrosis, and glycogen stores all improved with the increasing age of the host. However, serum alanine transaminase (ALT) levels were lowest in young mice infected with S. mansoni. Hepatic carbohydrate exploitation was characterized by a shift towards Warburg-like glycolysis in S. mansoni-infected animals. Notably, S. mansoni eggs stimulated hepatic stellate cells to an alternatively activated phenotype (GFAP+/desmin+/αSMA−) that secretes IL-6 and MCP-1. The reduction of fibrosis in older age likely depends on the fine-tuning of regulatory and inflammatory cytokines, alternative HSC activation, and the age-dependent preservation of hepatic energy stores. The current results emphasize the significance of investigations on the clinical relevance of host age-dependent liver damage in patients with schistosomiasis.

Chemoresistance remains a major challenge in the treatment of breast and colorectal cancer. For this reason, finding reliable predictive biomarkers of response to chemotherapy has become a significant research focus in recent years. However, validating in vitro results may be problematic due to the outcome heterogeneity. In this study, we evaluate the use of tumorspheres as an in vitro model for validating biomarkers of chemoresistance in breast and colorectal cancer. Our investigation highlights the crucial role of inflammation-related pathways in modulating the response to chemotherapy. Using in silico approaches, we identified specific markers elevated in responders versus non-responders patients. These markers were consistently higher in three-dimensional (3D) tumorsphere models compared to traditional adherent cell culture models. Furthermore, the number of tumorspheres from breast and colorectal cancer cells increased in response to cisplatin and oxaliplatin treatment, respectively, whereas cell viability decreased in adherent cell culture. This differential response underscores the importance of the 3D tumorsphere model in mimicking the tumor microenvironment more accurately than adherent cell culture. The enhanced chemoresistance observed in the 3D tumorspheres model and their correlation of data with the in silico study suggest that 3D culture models are a better option to approach the in vivo model and also to validate in silico data. Our findings indicate that tumorspheres are an ideal model for validating chemoresistance biomarkers and exploring the interplay between inflammation and chemoresistance in breast and colon cancer.

Background: The objective of this study is to analyze the transplacental transmission of SARS-CoV-2 antibodies, their persistence in newborns, the factors that may influence this transmission, and the protection these antibodies confer over time. Methods: This prospective cohort was conducted in a tertiary pediatric hospital in the Barcelona Metropolitan Region, Spain. It included neonates born to mothers who had SARS-CoV-2 infection during pregnancy or delivery between August 2020 and January 2022. We followed the recruited children for at least six months, and blood tests were performed to determine the presence of SARS-CoV-2 antibodies. Results: A total of 101 children were recruited. Among the serologies performed on children under three months of age, 44/82 were positive (53.7%). Newborns whose mothers presented more severe disease exhibited higher seropositivity odds (coefficient 9.747; p = 0.002). There were increased preterm deliveries when maternal infection occurred closer to the time of delivery. No severe SARS-CoV-2 infections were detected in children during the follow-up. Conclusions: Slightly more than half of the SARS-CoV-2 serologies performed in the first three months were positive. This appears to confer protection during early childhood. The severity of maternal infection is the most significant factor influencing the transmission of antibodies in children born to unvaccinated mothers.