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Flipped learning (FL) has positive effects on the teaching-learning process. Nevertheless, and given that it is a relatively new methodology, it still raises some misgivings. This work aims to highlight the potential of FL by the analysis of academic results in a subject in higher engineering education and, thus, to contribute to overcome possible misgivings. Methods were based on statistical analysis, using Pearson's correlation coefficient (PCC), and comparative analysis using graphs. Data from eight academic years were analysed, three with traditional methodology and five with FL. Influence of specific factors, such as participation in FL activities, on students' performance over time has been identified. FL has a very positive impact on students' academic performance and the active participation of students' results in a significant increase in the pass rate as well as in the quality of learning. These improvements have increased over time despite challenges such as the COVID-19 pandemic.

The current university model in a market-driven and knowledge-based society entails a change in the teachers' roles. The prevailing narrative sustains a competence-based approach in higher education, considering that quality education implies that teachers in this context must have personal, research and pedagogical skills that enable them to perform their teaching function effectively. A systematic review of empirical articles published between 2009 and 2019 provides a comprehensive and updated analysis of the higher education teachers' pedagogical competences. A total of 51 texts that describe the teaching competence components (knowledge, skills, and attitudes) were reviewed and retrieved from seven international databases in three languages. Personal skills and qualities stand out as the features most valued by students, whereas teachers highlight curriculum and instructional competence as the most important. Cultural competence and specific competences to respond to diversity and promote inclusion in higher education classrooms are almost nonexistent. The study has implications for defining quality teaching practice transnationally and designing professional development programs focused on the competences and indicators most valued. The resulting framework is also helpful for individual teachers as a tool for reflecting on their teaching characteristics and for improving their practice. It also problematises the current dominant performance-based model of teaching competence in a context that does not recognise the importance of situational profiles that cater for diversity in academic settings.

Abstract Mural cells are central to vascular integrity and function. In this study, we demonstrate the innovative use of the transcription factor NKX3.1 to guide the differentiation of human induced pluripotent stem cells into mural progenitor cells (iMPCs). By transiently activating NKX3.1 in mesodermal intermediates, we developed a method that diverges from traditional growth factor-based differentiation techniques. This approach efficiently generates a robust iMPC population capable of maturing into diverse functional mural cell subtypes, including smooth muscle cells and pericytes. These iMPCs exhibit key mural cell functionalities such as contractility, deposition of extracellular matrix, and the ability to support endothelial cell-mediated vascular network formation in vivo. Our study not only underscores the fate-determining significance of NKX3.1 in mural cell differentiation but also highlights the therapeutic potential of these iMPCs. We envision these insights could pave the way for a broader use of iMPCs in vascular biology and regenerative medicine.

Resumen: Objetivos: La enfermedad de la válvula tricúspide ha ido en constante aumento generando preocupación la morbimortalidad asociada a la cirugía cuando se realiza a través de esternotomía convencional. En este contexto, se pretenden exponer las ventajas clínicas y estéticas de la cirugía tricuspídea aislada mediante minitoracotomía anterior derecha sin clampaje aórtico. Material y métodos: Analizamos de forma retrospectiva entre junio del 2014 y octubre del 2023 una serie de 29 pacientes de nuestro centro intervenidos de cirugía tricúspide aislada mínimamente invasiva. La intervención se realizó por minitoracotomía anterior derecha sin exclusión de cavas y sin clampaje aórtico a corazón latiendo asistida por videotoracoscopia 3D. Se administró levosimendán preoperatorio en pacientes con hipertensión pulmonar severa y/o disfunción ventricular derecha. Resultados: Se realizaron 28 sustituciones tricuspídeas y una reparación. La edad media de los pacientes fue de 63 años (DE: 8 años). Dieciocho pacientes (62%) tenían cirugía cardíaca previa. Veintidós pacientes (75,8%) tenían hipertensión pulmonar severa y 12 (41,3%) disfunción ventricular derecha. El Euroscore II medio fue de 4,10%. La mortalidad hospitalaria fue del 3,4% (un paciente). El tiempo medio de circulación extracorpórea fue de 109 min (DE: 41 min). Hubo una reoperación por sagrado y un implante de marcapasos definitivo (3,4%). La necesidad de terapia de depuración extrarrenal temporal fue del 21% (6 pacientes). La mediana de estancia hospitalaria fue de 7 días. Conclusiones: La cirugía tricúspide aislada mínimamente invasiva es una técnica segura como tratamiento definitivo de la valvulopatía tricúspide aislada con una baja tasa de morbimortalidad. Abstract: Background: Tricuspid valve disease has been steadily increasing, raising concerns about the morbidity and mortality associated with surgery when performed via conventional sternotomy. In this context, the clinical and aesthetic advantages of isolated tricuspid surgery by right anterior mini-thoracotomy without aortic clamping are presented. Material and methods: A case series of 29 patients who underwent minimally invasive isolated tricuspid valve surgery in our center, from 2014 to 2023, have been studied retrospectively. The operation was performed by right anterior mini-thoracotomy without caval exclusion and without aortic clamping to a beating heart assisted by 3 D videothoracoscopy. Preoperative levosimendan was administered in patients with severe pulmonary hypertension and/or right ventricular dysfunction. Results: Twenty-eight tricuspid valve replacement and one repair were performed. Average patients age was 63 years old (SD 8 years old). 18 patients (62%) had previous cardiac surgery. 22 patients (75,8%) had severe pulmonary hypertension and 12 (41,3%) had right ventricule disfunction. Average EuroSCORE II was 4,10%. In-hospital mortality was 3,4% (one patient). The average extracorporeal circulation was 109 (SD 41 minutes). There was a reoperation due bleeding and a permanent pacemaker implantation (3,4%). Temporary renal replacement therapy was required in 21% (6 patients). The median length of hospital stay was 7 days. Conclusions: Minimally invasive isolated tricuspid valve surgery is a safe technique as a definitive treatment of isolated tricuspid valve disease with a low mortality and morbidity.

Resumen: Antecedentes y objetivos: El desarrollo de lesión renal aguda (FRA) durante la hospitalización por SARS-Cov-2 se ha asociado a una elevada morbimortalidad. El Registro FRA-COVID SEN ha recogido datos de pacientes con este perfil durante los meses de la pandemia. El objetivo de este trabajo fue caracterizar la población española ingresada por COVID-19 que desarrolló FRA, con/sin necesidades de tratamiento renal sustitutivo (TRS), modalidades terapéuticas utilizadas y resultados en términos de mortalidad. Material y método: Estudio retrospectivo de datos procedentes de 30 hospitales españoles, recopilados en el Registro español FRA COVID desde mayo de 2020 hasta noviembre 2021. Se registraron variables clínicas y demográficas, datos relacionados con la gravedad de la COVID-19, con el FRA y de supervivencia. Mediante estudio de regresión multivariante se analizan los factores relacionados con la necesidad de TRS y con la mortalidad. Resultados: Se registraron datos de 730 pacientes. El 71,9% eran hombres, con edad media de 70 años (60-78). El 70,1% eran hipertensos, el 32,9% diabéticos, el 33,3% con enfermedad cardiovascular y el 23,9% presentaban algún grado de enfermedad renal crónica. Desarrollaron neumonía el 94,6%, con necesidad de soporte ventilatorio en el 54,2% e ingreso en UCI en un 44,1% de los casos.La mediana de tiempo desde el inicio de los síntomas de COVID hasta la aparición de FRA fue de 6 días (4-10). En cuanto a la gravedad: 37,1% KDIGO I, 18,3% KDIGO II y 44,6% KDIGO III; requirieron TRS 235 pacientes (33,9%). Las técnicas continuas (TCRR) fueron las más empleadas (155 pacientes), seguidas de hemodiálisis (HD) intermitente (89 pacientes), HD diaria (36 pacientes), hemodiafiltración (HDF) 17 pacientes y HD expandida (HDexp) en 24 casos. El hábito tabáquico (OR 3,41), la necesidad de soporte ventilatorio (OR 20,2), la cifra de creatinina máxima (OR 2,41) y el tiempo transcurrido desde el inicio de los síntomas hasta la aparición del FRA (OR 1,13) se identificaron como predictores de la necesidad de TRS en nuestra cohorte, mientras la edad se comporta como protector (OR: 0,95). El grupo que no requirió TRS se caracterizó por presentar mayor edad, menor gravedad de FRA y un tiempo de aparición y recuperación de la lesión renal más corto (p

Abstract The function of many bacterial processes depends on the formation of functional membrane microdomains (FMMs), which resemble the lipid rafts of eukaryotic cells. However, the mechanism and the biological function of these membrane microdomains remain unclear. Here, we show that FMMs in the pathogen methicillin-resistant Staphylococcus aureus (MRSA) are dedicated to confining and stabilizing proteins unfolded due to cellular stress. The FMM scaffold protein flotillin forms a clamp-shaped oligomer that holds unfolded proteins, stabilizing them and favoring their correct folding. This process does not impose a direct energy cost on the cell and is crucial to survival of ATP-depleted bacteria, and thus to pathogenesis. Consequently, FMM disassembling causes the accumulation of unfolded proteins, which compromise MRSA viability during infection and cause penicillin re-sensitization due to PBP2a unfolding. Thus, our results indicate that FMMs mediate ATP-independent stabilization of unfolded proteins, which is essential for bacterial viability during infection.

O presente artigo tem por objetivo narrar experiências vivenciadas enquanto professora de Química na rede pública de educação do Amazonas, durante a pandemia de Covid-19. Neste trabalho, adotamos a Filosofia da Diferença como abordagem teórico-metodológica, utilizando especialmente as ferramentas conceituais oriundas das contribuições de Michel Foucault (1987); (1992); (2006); (2008). As narrativas compõem uma dissertação de mestrado, impulsionada pela necessidade de compreender o ocorrido. Optamos por organizá-las em “eras”, um conceito inspirado na poesia de Manoel de Barros (2010), que simboliza diferentes fases da vida. Cada “era” aqui representa um período distinto, visando destacar registros pontuais de cada ano vivenciado, enquanto buscamos um lugar de novos olhares, correr riscos, reinventar, experimentar e transformar o sujeito lesionado em um sujeito cicatricial. Por meio dessas narrativas, fomos levados a refletir sobre os desafios enfrentados durante a pandemia, revelando possíveis clarões para os pensamentos inflamados ao longo desta jornada desafiadora.

ABSTRACT The high quality of soybean seeds is essential for the success of the crop, as it determines the field performance of seedlings. Seed physiological attributes are associated with genotype stability; thus, the maintenance of genome integrity is crucial to ensure seed quality. To evaluate the quality of soybean seed lots at physiological and molecular levels, a completely randomized design was carried out in four replications, with 12 soybean seed lots (cv. BMX Potência RR). Seeds were evaluated through standard germination and vigor tests. Genomic DNA was extracted from the root meristem of seeds from different lots with the Kasvi Spin 50 ® extraction kit. The analysis was performed through electrophoresis and visualized under ultraviolet (UV) light. The Comet assay was also applied to investigate DNA damage. Soybean seed lots exhibited differences in germination and vigor, as determined by the tests of accelerated aging, field emergence, emergence speed index, shoot length, root length, shoot fresh weight, root fresh mass, and shoot dry mass. In seeds with low germination and vigor, DNA damage and genotoxicity were observed. DNA from samples with high germination and vigor observed by the field emergence and accelerated aging tests was more preserved than DNA extracted from seeds with low physiological quality.

Background Immunodeficient mice engrafted with peripheral blood mononuclear cells (PBMCs) are models to study new cancer immunotherapy agents. However, this approach is associated with xenograft-versus-host disease (xGVHD), which starts early after PBMC transfer and limits the duration and interpretation of experiments. Here, we explore different approaches to overcome xGVHD and better support the development of cancer immunotherapies.Methods Immunodeficient NOD-scid IL2Rgnull (NSG) mice were intravenously transferred with human PBMCs and subcutaneously co-engrafted with HT29 human colon carcinoma cells. Diverse strategies to reduce xGVHD while preserving the antitumor activity of human immune cells were evaluated: (1) ex vivo immune graft modification by depleting CD4+ T cells pre-transfer using magnetic beads, (2) post-transplantation cyclophosphamide administration to eliminate proliferating xenoreactive T-cell clones and (3) using major histocompatibility complex (MHC) class I and II-deficient NSG mice: (Kb Db)null (IA)null (MHC-dKO NSG). Body weight and plasma murine alanine aminotransferase levels were measured as indicators of xGVHD and tumor size was measured every 2–3 days to monitor antitumor activity. The antitumor effects and pharmacodynamics of nivolumab plus ipilimumab and an anti-epithelial cell adhesion molecule (EpCAM)/CD3 T-cell engager (αEpCAM/CD3 bispecific antibody (BsAb)) were evaluated in the model.Results CD4+ T-cell depletion attenuates xGVHD but also abrogates the antitumor activity. Cyclophosphamide limits the antitumor response and does not substantially prevent xGVHD. In contrast, xGVHD was significantly attenuated in MHC-dKO NSG recipients, while the antitumor effect of human PBMCs was preserved. Furthermore, the administration of nivolumab plus ipilimumab caused exacerbated xGVHD in conventional NSG mice, thereby precluding the observation of their antitumor effects. Severe xGVHD did not occur in MHC-dKO NSG mice thus enabling the study of complete and durable tumor rejections. Similarly, NSG mice treated with an αEpCAM/CD3 BsAb showed complete tumor regressions, but died due to xGVHD. In contrast, MHC-dKO NSG mice on treatment with the αEpCAM/CD3 BsAb achieved complete tumor responses without severe xGVHD. A significant proportion of mice rendered tumor-free showed tumor rejection on rechallenge with HT29 cells without further treatment. Finally, tumor-infiltrating CD8+ T-cell number increase, activation and CD137 upregulation were observed on αEpCAM/CD3 BsAb treatment.Conclusion Humanized MHC-dKO immunodeficient mice allow and refine the preclinical testing of immunotherapy agents for which experimentation is precluded in conventional immunodeficient mice due to severe xGVHD.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). The current solutions for its management, such as oral rehydration salts (ORS), inhibitors of gut motility, antibiotics, and living probiotics, only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. The potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signalling assays, the gut barrier formation assay, and the rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

Abstract Cibisatamab is a bispecific antibody-based construct targeting carcinoembryonic antigen (CEA) on tumour cells and CD3 epsilon chain as a T-cell engager. Here we evaluated cibisatamab for advanced CEA-positive solid tumours in two open-label Phase 1 dose-escalation and -expansion studies: as a single agent with or without obinutuzumab in S1 (NCT02324257) and with atezolizumab in S2 (NCT02650713). Primary endpoints were safety, dose finding, and pharmacokinetics in S1; safety and dose finding in S2. Secondary endpoints were anti-tumour activity (including overall response rate, ORR) and pharmacodynamics in S1; anti-tumour activity, pharmacodynamics and pharmacokinetics in S2. S1 and S2 enrolled a total of 149 and 228 patients, respectively. Grade ≥3 cibisatamab-related adverse events occurred in 36% of S1 and 49% of S2 patients. The ORR was 4% in S1 and 7% in S2. In S2, patients with microsatellite stable colorectal carcinoma (MSS-CRC) given flat doses of cibisatamab and atezolizumab demonstrated an ORR of 14%. In S1 and S2, 40% and 52% of patients, respectively, developed persistent anti-drug antibodies (ADAs). ADA appearance could be mitigated by obinutuzumab-pretreatment, with 8% of patients having persistent ADAs. Overall, cibisatamab warrants further exploration in immunotherapy combination strategies for MSS-CRC.

Resumen: Introducción Las infecciones asociadas con instrumentación de columna (IAIC) son una de las principales causas de complicación posquirúrgica y comorbilidad. Nuestro objetivo fue describir las características clínicas, microbiológicas, tratamiento y pronóstico de estas infecciones. Material y métodos: Realizamos un estudio retrospectivo en nuestro hospital (2011-2018) e incluímos a pacientes adultos con cirugía instrumentada de columna, que cumplieran los criterios diagnósticos de infección confirmada. Se procesaron muestras de herida quirúrgica superficial y muestras intraoperatorias profundas para cultivo microbiológico. El equipo médico y traumatológico fue siempre el mismo. Resultados: Se diagnosticaron 41 casos, de los que 39 pacientes (95,1%) presentaron infección precoz ( 3 meses tras cirugía). El tratamiento de elección en las infecciones precoces fue la estrategia Debridement, Antibiotics and Implant Retention (DAIR) sin retirada del injerto óseo, que demostró la curación en el 84,2% de los pacientes. La principal etiología fueron los grampositivos (S. aureus: 31,7%), seguido por los gramnegativos y la flora polimicrobiana. Los antibióticos fueron optimizados según los cultivos con una duración media de 12 semanas. Conclusiones: En las infecciones precoces, el diagnóstico precoz y la estrategia DAIR (con retención del injerto óseo) demostró una tasa de curación superior al 80%. Abstract: Introduction: Spinal instrumentation-related infections (SIRI) are one of the main causes of post-surgical complication and comorbidity. Our objective was to describe the clinical and microbiological characteristics, treatment and prognosis of these infections. Material and methods: We conducted a retrospective study in our institution (2011-2018) including adult patients undergoing spinal instrumentation who met the diagnostic criteria for confirmed infection. Superficial surgical wound and deep intraoperative samples were processed for microbiological culture. The medical and orthopaedic team was always the same. Results: Forty-one cases were diagnosed of which 39 patients (95.1%) presented early infection (3 months after surgery). The treatment of choice in early infections was the Debridement, Antibiotics and Implant Retention (DAIR) strategy without removal of the bone graft, which successfully resolved 84.2% of the infections. The main etiology was gram-positive (Staphylococcus aureus: 31.7%), followed by gram-negative and polymicrobial flora. Antibiotics were optimized according to cultures with a mean duration of 12 weeks. Conclusions: In early infections, early diagnosis and DAIR strategy (with bone graft retention) demonstrated a healing rate higher than 80%.

This study delves into the Smart Readiness Indicator (SRI), an innovative measure designed to assess and enhance the smart capabilities of buildings across Europe. Addressing the critical question, ‘How can the SRI be effectively documented, made more accessible to European citizens, continuously monitored, and financially supported to enhance its adoption and under-standing?’ This research aims to bridge the gap between the conceptual framework of SRI and its practical implementation for the benefit of European citizens. The study introduces the SRI FAQ Initiative, a pivotal effort aimed at demystifying the SRI through the compilation and dissemination of essential questions and answers. The establishment of the SRI Observatory is another significant outcome, documenting the ongoing development of SRI and providing annual out-looks for future advancements. The research employs a multifaceted methodology, incorporating field research, extensive literature reviews, stakeholder interviews, and both digital and roundtable discussions.

Human CD200R1 (hCD200R1), an immune inhibitory receptor expressed predominantly on T cells and myeloid cells, was identified as a promising immuno-oncology target by the 23andMe database. Blockade of CD200R1-dependent signaling enhances T cell-mediated antitumor activity in vitro and in vivo. 23ME–00610 is a potential first-in-class, humanized IgG1 investigational antibody that binds hCD200R1 with high affinity. We have previously shown that 23ME–00610 inhibits the hCD200R1 immune checkpoint function. Herein, we dissect the molecular mechanism of 23ME–00610 blockade of hCD200R1 by solving the crystal structure of 23ME–00610 Fab in complex with hCD200R1 and performing mutational studies, which show 23ME–00610 blocks the interaction between hCD200 and hCD200R1 through steric hindrance. However, 23ME–00610 does not bind CD200R1 of preclinical species such as cynomolgus monkey MfCD200R1. To enable preclinical toxicology studies of CD200R1 blockade in a pharmacologically relevant non-clinical species, we engineered a surrogate antibody with high affinity toward MfCD200R1. We used phage display libraries of 23ME–00610 variants with individual CDR residues randomized to all 20 amino acids, from which we identified mutations that switched on MfCD200R1 binding. Structural analysis suggests how the surrogate, named 23ME–00611, acquires the ortholog binding ability at the equivalent epitope of 23ME–00610. This engineering approach does not require a priori knowledge of structural and functional mapping of antibody–antigen interaction and thus is generally applicable for therapeutic antibody development when desired ortholog binding is lacking. These findings provide foundational insights as 23ME–00610 advances in clinical studies to gain understanding of the hCD200R1 immune checkpoint as a target in immuno-oncology.

The Hodgkin and Reed – Sternberg (HRS) cells in classical Hodgkin Lymphoma (cHL) actively modify the immune tumor microenvironment (TME) attracting immunosuppressive cells and expressing inhibitory molecules. A high frequency of myeloid cells in the TME is correlated with an unfavorable prognosis, but more specific and rare cell populations lack precise markers. Myeloid-derived suppressor cells (MDSCs) have been identified in the peripheral blood of cHL patients, where they appear to be correlated with disease aggressiveness. TNFRSF9 (CD137) is a T cell co-stimulator expressed by monocytic and dendritic cells. Its expression has also been described in HRS cells, where it is thought to play a role in reducing antitumor responses. Here, we perform qualitative and quantitative analyses of lymphocytic and MDSC subtypes and determine the CD137 cell distribution in cHL primary tumors using multiplex immunofluorescence and automated multispectral imaging. The results were correlated with patients’ clinical features. Cells were stained with specific panels of immune checkpoint markers (PD-1, PD-L1, CD137), tumor-infiltrating T lymphocytes (CD3, PD-1), and monocytic cells/MDSCs (CD68, CD14, CD33, Arg-1, CD11b). This approach allowed us to identify distinct phenotypes and to analyze spatial interactions between immune subpopulations and tumor cells. The results confirm CD137 expression by T, monocytic and HRS cells. In addition, the expression of CD137, T exhausted cells, and monocytic MDSCs (m-MDSCs) in the vicinity of malignant HRS cells were associated with a worse prognosis. Our findings reveal new elements of the TME that mediate immune escape, and confirm CD137 as a candidate target for immunotherapy in cHL.

Biomarkers for cancer immunotherapy are an unmet medical need. The group of Daniela Thommen at the NKI recently reported on novel methodologies based on short-term cultures of patient-derived tumor fragments whose cytokine concentrations in the supernatants and activation markers on infiltrating T cells were associated with clinical response to PD-1 blockade. We set up a similar culture technology with tumor-derived fragments using mouse tumors transplanted into syngeneic immunocompetent mice to test an agonist anti-CD137 mAb and its combinations with anti-PD-1 and/or anti-TGF-β. Increases in IFNγ concentrations in the tissue culture supernatants were detected upon in-culture activation with the anti-CD137 and anti-PD-1 mAb combinations or concanavalin A as a positive control. No other cytokine from a wide array was informative of stimulation with these mAbs. Interestingly, increases in Ki67 and other activation markers were substantiated in lymphocytes from cell suspensions gathered at the end of 72 h cultures. In mice bearing bilateral tumors in which one was excised prior to in vivo anti-CD137 + anti-PD-1 treatment to perform the fragment culture evaluation, no association was found between IFNγ production from the fragments and the in vivo therapeutic outcome in the non-resected contralateral tumors. The experimental system permitted freezing and thawing of the fragments with similar functional outcomes. Using a series of patient-derived tumor fragments from excised solid malignancies, we showed IFNγ production in a fraction of the studied cases, that was conserved in frozen/thawed fragments. The small tumor fragment culture technique seems suitable to preclinically explore immunotherapy combinations.

Adoptive T-cell therapies (ACTs) including tumor-infiltrating lymphocytes and engineered T cells (transgenic T-cell receptor and chimeric antigen receptor T cells), have made an important impact in the field of cancer treatment over the past years. Most of these therapies are typically administered systemically in approaches that facilitate the elimination of hematologic malignancies. Therapeutical efficacy against solid tumors, however, with the exception of tumor-infiltrating lymphocytes against melanoma, remains limited due to several barriers preventing lymphocyte access to the tumor bed. Building upon the experience of regional administration in other immunotherapies, the regional administration of adoptive cell therapies is being assessed to overcome this challenge, granting a first round of access of the transferred T cells to the tumor niche and thereby ensuring their activation and expansion. Intralesional and intracavitary routes of delivery have been tested with promising antitumor objective responses in preclinical and clinical studies. Additionally, several strategies are being developed to further improve T-cell activity after reinfusing them back to the patient such as combinations with other immunotherapy agents or direct engineering of the transferred T cells, achieving long-term immune memory. Clinical trials testing different regional adoptive T-cell therapies are ongoing but some issues related to methodology of administration and correct selection of the target antigen to avoid on-target/off-tumor side-effects need to be further evaluated and improved. Herein, we discuss the current preclinical and clinical landscape of intratumoral and locoregional delivery of adoptive T-cell therapies.

Cemented carbide alloys are well known powder metallurgically processed materials used for a wide range of tooling and components that require a good balance of hardness and fracture toughness, together with wear resistance. After 100 years of the first patent, research and development within this area continues to fulfil more demanding applications and adapt to new requirements. The last decade especially has witnessed important advances. In that sense, Co-free compositions are being studied due to the health issues that its use implies and its criticality in the supply chain. Secondly, the steps towards near-net-shape components by means of additive manufacturing technologies to avoid waste of powder and the technological advance of fast sintering processes are promising. Finally, new microstructural and mechanical characterization methods at micro and nanoscale provide helpful insights for a better understanding of these materials under performance.

Antecedentes: El reconocimiento de la figura de la enfermera de práctica avanzada varía según los países. Las enfermedades respiratorias suponen una carga significativa en los sistemas sanitarios. Objetivos: Valorar la efectividad de la implementación de la enfermera de práctica avanzada en el cuidado del paciente respiratorio, describir su estado actual e identificar sus líneas de investigación. Material y métodos: Revisión sistemática por medio de búsqueda de artículos originales en inglés y/o español, publicados en los últimos 10 años y realizados por trabajadores de la salud en PubMed, CINAHL y Web of Science, evaluando la calidad metodológica según STROBE, COREQ y CONSORT. Resultados: De las 235 publicaciones, se incluyeron 10 documentos para revisión (60% observacionales, 20% cualitativos, 10% estudios mixtos y 10% ensayos clínicos aleatorizados). Se detectó una beneficiosa reducción del gasto sanitario, un aumento de la satisfacción de los pacientes atendidos y menores tiempos de espera. Las enfermeras de práctica avanzada respiratoria actúan de forma multidisciplinaria y multitarea, sin una regulación específica. Conclusiones: Se llega a la conclusión de que es necesario realizar más investigaciones que aborden la enfermería de práctica avanzada en pacientes respiratorios. Se cree que esto aumentará y mantendrá los beneficios de su implementación.

Tomando como referencia el concepto de metáfora bélica propuesto por Lakoff y Johnson (2003), esta investigación tiene como objetivo analizar cómo la prensa representa el feminismo a través de las metáforas bélicas y qué términos bélicos se emplean con más frecuencia en los textos. Para ello, se ha formado un corpus de 800 columnas escritas entre 2004 y 2023 y se han aplicado dos métodos de estudio: por un lado, se ha empleado la herramienta Sketch Engine para identificar los términos bélicos más frecuentes en los textos; y, por otra parte, se ha analizado cualitativamente los contextos en los que se utilizan dichas palabras bélicas.

Neste artigo são analisadas as repercussões das reformas educacionais paulistas na organização da escola e na autonomia docente. Considerando o sistema de avaliação como elemento persistentemente presente nas reformas e sua articulação com a dimensão curricular, buscou-se verificar de que forma alteraram o âmbito da escola. Considera-se na análise a política educacional paulista no período de 1995-2018, expressa em diferentes programas e projetos. Para tanto, apresentam-se alguns elementos documentais em diálogo com a produção bibliográfica. O artigo decorre de pesquisa mais ampla que investigou diversas dimensões da política educacional paulista no referido período. Neste estudo, buscou-se compreender como os pressupostos da Nova Gestão Pública se manifestam nas políticas educacionais, estabelecendo maior controle sobre as escolas e produzindo uma precariedade subjetiva nas condições de trabalho do magistério, especialmente na autonomia docente, com perda do controle sobre os meios e os fins do processo de ensino. Observou-se que a implementação do sistema de avaliação, instrumento central das reformas educacionais que permaneceu ao longo dos anos, associado à exigência de um currículo oficial, trouxe uma nova lógica nas escolas e refletiu-se na redução significativa da autonomia didática pedagógica dos professores e em maior controle do trabalho e das organizações escolares.

¿La cobertura que realizan los medios de comunicación en campaña electoral puede considerarse polarizante? ¿Son los contenidos mediáticos que consumimos, sobre todo en periodos de mayor actividad política, neutrales o alientan la división social en dos polos ideológicos enfrentados? Para tratar de responder a estas cuestiones se analiza la cobertura de los medios de comunicación y los contenidos polarizantes, durante el periodo de campaña electoral autonómica de 2023 en la Región de Murcia, concretamente la televisión (La 7 y La 1 de TVE en su emisión territorial) y la prensa regional (La Verdad y La Opinión). A partir del análisis de contenido como técnica metodológica, los resultados apuntan a que la información transmitida por los medios no parece presentar una polarización destacable en la Región de Murcia durante la campaña electoral del 28M.

In this work, we have investigated the role of pre-existing nano-scale cavities and irradiation sequence in helium clustering, and in the evolution of the cavity population in tungsten at 800 °C, by performing in-situ Transmission Electron Microscopy (TEM) characterizations under dual-beam W2+(600 keV)/He+(10 keV) irradiation to a total dose of 0.351 dpa, and supported by atomistic simulations. Pre-existing cavities, induced by single W2+ irradiation to 0.256 dpa, were seen to attract induced defects from subsequent irradiations, resulting in enhanced cavity size and a reduced number density in sequential irradiation when compared to concurrent irradiation. Such cavities developed faceted geometries and saturated in number density at an additional 0.051 dpa induced by He+ exposure in the sequential irradiation. In contrast, concurrent irradiations generate a denser cavity distribution that showed no sign of saturation or faceting up to the total irradiation damage of 0.351 dpa. In addition, Molecular Dynamics and Statics simulations were performed using LAMMPS software. These showed the pre-existing cavities to be trapping sites for helium atoms. Despite the large binding energy of ∼6 eV of those cavities, He-He interactions still occurred beyond the effective radius of such sinks, leading to additional He-He clustering not seeded by neighbouring cavities. These results point to the importance of selecting the irradiation conditions to simulate synergistic ion effects on cavity formation and evolution in plasma-facing tungsten-base materials.

Introduction: Tumor-induced osteomalacia (TIO), is a rare acquired paraneoplastic syndrome characterized by defective bone mineralization, caused by the overproduction of fibroblast growth factor 23 (FGF23) by a tumor. Material and methods: We conducted a systematic review to identify all case reports of TIO, focusing on those associated with mesenchymal tumors. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) consensus, and we included patients with a diagnosis of TIO and histological confirmation of phosphaturic mesenchymal tumors or resolution of the condition after treatment of the tumor. Bibliographical searches were carried out until December 2023 in the Cochrane Library, Medline and Embase, as well as congress abstracts online. Results: We identified 769 articles with 1979 cases reported. Most patients were adults, with a higher incidence on men. Disease duration before diagnosis is a mean of 4.8 years. Most tumors were histologically classified as PMT. Lower limbs were the predominant location. Hypophosphatemia was present in 99.8 % of patients. The FGF23 was elevated at diagnosis in 95.5 %. Resection of the tumor was the treatment of choice in most of patients. After resection, there was a clinical improvement in 97.6 % of cases, and serum phosphorus and FGF23 levels returned to normal ranges in 91.5 % and 81.4 % of the patients, respectively. Conclusion: TIO is usually misdiagnosed with rheumatological or musculoskeletal disorders. The diagnosis should be suspected in patients with hypophosphatemic osteomalacia, and the measurement of serum FGF23 can be useful for diagnosis and management.

The production of radioisotopes for nuclear medicine is boosted by different international agencies. IFMIF-DONES will be an infrastructure where neutrons will be generated by the impact of a high-power deuteron beam onto a lithium jet target. At present, IFMIF-DONES studies the possibility of deflecting 0.1% of its standard 125 mA current of 40 MeV deuteron beam for the complementary applications to be conducted inside a new experimental hall. Such deuteron beam is being considered to be used for radioisotope production for nuclear medicine. Here, we discuss the production of a potential Auger-electron emitter radioisotope for therapy 165Er with 125 μA deuterons on natHo. Due to the high-power delivered onto the sample, we study by means of SolidWorks simulations a realistic device as cooling system for the holmium sample. Our results show a significant 165Er production in comparison with other experimental routes available in the literature.

Spain is one of the countries that has been most severely affected by the COVID-19 pandemic. In times of uncertainty and stress, the media plays an important role in disseminating information. This study establishes which factors affected risk perception regarding the Coronavirus, which factors determined trust in the measures taken by the Government, and how the presentation of information influenced the spread of fake news. To answer these questions an online survey was created and was completed by 2,034 people from different autonomous communities in Spain, using two multiple linear regression models, as well as different bivariate techniques for parametric statistical analysis. The data shows increased risk perception among the sectors with greater exposure to news about the Coronavirus. A second conclusion refers to the role played by an individual's pre-existing political biases, such as ideology, and their effects on the trust placed in the measures adopted by the Government. In addition, the analysis conducted shows that sectors that follow the news more closely are not immune to the spread of fake news. This research highlights the importance of communication in risk perception and the need to conduct further research in this field, in terms of the psychological, social, and economic implications of this phenomenon.

Children's policies at the local level stimulate initiatives in the municipalities to encourage child participation. In this article, we focus on the local political sphere as a space for the promotion of child participation and citizenship through digital mediation. It is in this immediate environment where the rights of children and adolescents are exercised and promoted. The study aims to analyse the contributions perceived by municipal leaders (elected officials and technical figures) of the digital environment and the uses they make of it to promote children's participation in the municipality. This study is part of a national project that includes as collaborating entities the International Association of Educating Cities (IACE) and Child Friendly Cities (CAIUnicef). 279 subjects (191 technical figures and 88 elected officials) from 179 Spanish municipalities associated members of IACE and/or CAI. Data were collected in 2020. Two ad hoc designed questionnaires were applied. Two of the most significant results of the study are: (a) the finding of the variable that establishes differences between those technical figures that mediate children's participation with technological environments and those that do not; (b) the use made of the digital environment as an interactive space for informational purposes. It concludes on the need to rethink the digital environment as a participatory area and increasing the use of technology in support of children's citizenship.