Expression of immune checkpoints genes in tumour samples from resectable NSCLC patients. Role as prognostic biomarkers

[EN] Lung cancer is the leading cause of cancer-related death worldwide, with a 5-year survival lower than 5% in advanced stages of the disease. Non-Small Cell Lung Cancer (NSCLC) represents approximately 80% of lung cancer cases. Despite the advances achieved in the last years, there is still an urgent need to develop new and more efficient therapeutic strategies in this type of cancer and a lack of knowledge concerning the tumour microenvironment. Although it is widely known that the immune system is capable of preventing cancer initiation and its progression, it is also known that one of the hallmarks of cancer is the evasion of the immune surveillance through different mechanisms, one of which is the inhibition of antitumour T cell response. This research focuses on the fact that cancer cells induce inhibitory signals to evade the immune response. The expression of 8 genes involved in immune-regulation (PD-L1, PD-L2, IDO-1, IDO-2, ICOS-LG, CD5, CD6 and CD200) was analysed by RTqPCR in 201 paired fresh frozen tumour and normal tissue samples of resected NSCLC. Relative expression was calculated by Pfaffl formulae using ACTB, CDKN1B and GUSB as endogenous controls. Non-parametric tests were used for correlations between clinico-pathological and analytical variables and survival was assessed by Cox regression analysis. For those statistically significant analysis, Kaplan-Meier curves (log-rank test), were represented, considering significant p<0.05. Patients with higher expression of CD5 and IDO-2 had a significant increase in overall survival (OS, 53.3 months vs NR, p=0.011 and 51.9 months vs NR; p=0.050, respectively). Regarding the analysis performed in the adenocarcinoma (ADC) subgroup, it was observed a tendency of longer OS and relapse-free survival (RFS) in those patients with high expression levels of PD-L1, IDO-1 and IDO-2. A score including three genes: PD-L1, IDO-1 and IDO-2 was generated (PDIDO score). Patients with high expression levels of the PDIDO score show better RFS (17.9 months vs NR; p=0.001) and OS (29.8 vs NR months; p=0.0002). Multivariate analysis established that PDIDO score was an independent prognostic factor for RFS [HR, 0.274; 95%CI, 0.126-0.593; p=0.001] and OS [HR=0,267; 95% CI, 0.113- 0.630; p=0.003]. Altogether, the study of the immune profile in resected NSCLC has allowed the establishment of PDIDO score as an independent biomarker for RFS and OS in the ADC group of patients. Moreover, CD5 would be a feasible prognostic biomarker for OS regardless of histology in resectable NSCLC.[ES] El cáncer de pulmón es la principal causa de muerte debida a cáncer a nivel mundial, con una supervivencia a los 5 años menor del 5% en estadios avanzados de la enfermedad. El cáncer de pulmón no microcítico representa aproximadamente un 80% de los casos de cáncer de pulmón. A pesar de los avances logrados en los últimos años, hay una gran necesidad de desarrollo de nuevas estrategias terapéuticas más eficientes contra este tipo de cáncer y una falta de comprensión del microambiente tumoral. Por un lado, se sabe que el sistema inmune es capaz de evitar el cáncer, así como su progresión, pero también se sabe que una de las características distintivas del cáncer es la capacidad de evadir la vigilancia inmunológica a través de distintos mecanismos, siendo uno de ellos la inhibición de la respuesta antitumoral mediada por las células T. Este trabajo se basa en el hecho de que las células tumorales inducen señales inhibitorias que les permiten evadir la respuesta inmune. Se analizó la expresión de 8 genes relacionados con la inmunoregulación (PD-L1, PD-L2, IDO-1, IDO-2, ICOS-LG, CD5, CD6 y CD200) mediante RTqPCR en 201 muestras pares de tejido tumoral fresco congelado y del correspondiente tejido normal. Se calculó la expresión génica relativa mediante la fórmula de Pfaffl utilizando ACTB, CDKN1B y GUSB como controles endógenos. Con el fin de establecer correlaciones entre las variables analíticas y clinicopatológicas, se realizaron tests no paramétricos. Se analizó la supervivencia por análisis de regresión de Cox, y se representaron las curvas Kaplan-Meier (test log-rank) de aquellos análisis estadísticamente significativos (p<0.05). Aquellos pacientes con altos niveles de CD5 e IDO-2 presentaron mayor supervivencia global (SG, 53.3 meses vs NA, p=0.011 y 51.9 meses vs NA; p=0.050, respectivamente). En cuanto al análisis realizado en el subgrupo de adenocarcinoma (ADC), se observó una tendencia de mayor supervivencia libre de recaída (SLR) y SG en aquellos pacientes con altos niveles de expresión de PDL1, IDO-1 e IDO-2. Se generó una firma génica (firma PDIDO) basada en la expresión de los genes PDL1, IDO-1 e IDO-2. Los pacientes con altos niveles de expresión de la firma tuvieron mayor SLR (17.867 vs NA meses; p=0.001) y SG (29.83 vs NA meses; p=0.0002). El análisis multivariante estableció la firma PDIDO como factor pronóstico independiente para SLR [HR, 0.274; 95%CI, 0.126- 0.593; p=0.001] y SG [HR, 0.267; 95% CI, 0.113-0.630; p=0.003]. Por tanto, el estudio del perfil inmunológico en muestras resecadas de CPNM ha permitido establecer la firma PDIDO como biomarcador independiente de SLR y SG en el grupo de pacientes con ADC. Además, CD5 podría establecerse como biomarcador pronóstico de SG independientemente del tipo histológico en estadios tempranos de CPNM.Moreno Manuel, A. (2017). Expression of immune checkpoints genes in tumour samples from resectable NSCLC patients. Role as prognostic biomarkers. http://hdl.handle.net/10251/86419TFG

Análisis de la diversidad genética del búfalo en Colombia

ABSTRACT: Estimates of genetic diversity provide useful information on the genetic structure of animal populations, useful for the design of improvement strategies to impact traits of economic interest. They can also be used for implementing conservation and restoration policies regarding the sustainable use of genetic resources. The aim of this study was to characterize the genetic structure of buffalo population (Bubalus bubalis) in the most representative Colombian provinces by using 10 microsatellite markers. A total of 588 individuals were sampled from 12 buffalo herds. The MGTG7 and ETH225 microsatellites were monomorphic. Eighty seven alleles were observed for all the loci. The average number of alleles was 10.9 ± 3.6 and the effective average number of alleles was 3.9 ± 1.4. The PIC values ranged between 0.5 and 0.8, and the probability of exclusion over all loci was over 99.99%. The highest value for the Ho population was 0.68, and the lowest was 0.60. The GST value for the total loci was 0.062, indicating a very low level of genetic structure among subpopulations. Values for genetic distance between populations and racial groups were very low, suggesting there is still a genetic mix within buffalo herds in the analyzed population.RESUMEN: Las estimaciones de diversidad genética del búfalo en Colombia proveen información útil para conocer su estructura genética, diseñar programas de cría y mejoramiento genético para características de interés económico, e implementar políticas de conservación para la utilización sostenible y restauración de los recursos genéticos. El objetivo de este estudio fue caracterizar y determinar la estructura genética de la población bufalina (Bubalus bubalis) en las provincias (Departamentos) Colombianos más representativos, por medio de 10 marcadores microsatélites. Se muestrearon 588 individuos de 12 hatos bufalinos de Colombia. Los microsatélites ETH225 y MGTG7 fueron monomórficos. Se observó un total de 87 alelos para el total de los loci, el número de alelos observados promedio fue de 10.9 ± 3.6 y el número efectivo de alelos promedio fue de 3.9 ± 1.4. Los valores de PIC variaron entre 0.5 y 0.8, y la probabilidad de exclusión sobre todos los loci fue superior al 99.99%. El valor más alto de Ho por población fue de 0.68 y el más bajo 0.60. El valor promedio de GST para el total de los loci en la población total de búfalos fue de 0.062, indicando un grado muy bajo de estructura genética entre las subpoblaciones. Los valores de distancia genética fueron muy bajos entre poblaciones y entre grupos raciales, lo cual indica que aún existe una alta mezcla genética en los hatos bufalinos en Colombia

De cómo los lugares con contextos dominados por la desigualdad vuelven ineficaces las labores de las instituciones del Estado

Según algunos indicadores de gobernanza mundial, Colombia está clasificada por debajo de países no solo de Norteamérica, sino también de América Latina. El presente artículo estudia las instituciones gubernamentales, específicamente en relación con la desigualdad. Su objetivo principal es determinar la correspondencia entre la eficacia de las instituciones —entendida como el cumplimiento de los mínimos de actividades que debe efectuar un Estado, entre ellas la distribución de la riqueza y la orientación hacia la distribución de las capacidades (igualdad)— y las zonas más desiguales —que en este marco de análisis se definen como los territorios con mayores discrepancias económicas, sociales y culturales entre las personas—. La investigación se articula en tres etapas, a lo largo de las cuales se evidencia que en algunos municipios de Colombia existe una relación, no precisamente inversa, entre los territorios que tienen presencia de instituciones estatales y aquellos con mayores desigualdades. Se utilizaron indicadores de instituciones nacionales e internacionales, como la tasa de eficacia de la justicia, la razón entre la presencia de jueces y el territorio, el índice de desempeño fiscal, el índice de vulnerabilidad por presencia institucional, la tasa de informalidad en la tenencia de la tierra, el índice multidimensional de pobreza y el índice de Necesidades Básicas Insatisfechas (NBI). Los resultados indican que las instituciones en Colombia tienen poco o ningún efecto en la distribución de la riqueza. Dados los índices anteriormente mencionados, se seleccionaron siete regiones para el desarrollo del estudio: 1) los municipios de Santander, 2) los municipios de frontera entre Arauca y Casanare, 3) los municipios localizados entre Cundinamarca y Huila, 4) los municipios del departamento del Cesar, 5) los municipios situados entre Norte de Santander y Boyacá, 6) los municipios del Caquetá y 7) aquellos que están ubicados en el occidente del Casanare.According to some worldwide government indicators, Colombia is classified as being below countries not only in North America but also in Latin America. The current article studies government institutions, specifically in terms of inequality. Its main objectiveis to determine the relationship between the efficacy of institutions—understood as complying with the minimum number of activities that should effect a State, among those the distribution of wealth and the orientation toward the distribution of capabilities (equality)—and the most unequal zones—which in this framework of analysis are defined as the territories with the most economic, social, and cultural discrepancies among their inhabitants. The research is divided into three phases, through which is evidenced that in some Colombian villages a relationship exists, not precisely inverse, between the territories that experience the presence of State institutions and those with the most inequalities. Indicators from national and international institutions were used such as therate of efficiency of justice, the reasoning behind the presence of judges and the territory, the index of fiscal performance, the index of vulnerability due to institutional presence, the rate of informality in property holdings, the multidimensional index of poverty andthe index of Unfulfilled Basic Necessities (NBI). The results indicate that the institutions in Colombia have little or no effect on the distribution of wealth. Taking into account the aforementioned indexes, seven regions were selected for the development of the study: 1) the villages of Santander, 2) the border towns between Arauca and Casanare, 3) the towns located between Cundinamarca and Huila, 4) the towns of the department of Cesar, 5) the towns located between North Santander and Boyacá, 6) the towns of Caquetá, and 7) those located in the west of Casanare.Segundo alguns indicadores de governança mundial, a Colômbia está classificada abaixo de países não somente da América do Norte, como também da América Latina. Este artigo estuda as instituições governamentais, especificamente a respeito da desigualdade. Seu objetivo principal é determinar a correspondência entre a eficácia das instituições —entendida como o cumprimento dos mínimos de atividades que um Estado deve efetuar, entre elas a distribuição da riqueza e da orientação à distribuição das capacidades (igualdade)— e as áreas desiguais —que, nesse âmbito de análise, são definidas como os territórios com maiores discrepâncias econômicas, sociais e culturais entre as pessoas—.Esta pesquisa se articula em três etapas, ao longo das quais se evidencia que, em alguns municípios da Colômbia, existe uma relação, não precisamente inversa, entre os territórios que têm presença de instituições estatais e aqueles com maiores desigualdades. Utilizaramse indicadores de instituições nacionais e internacionais, como a taxa de eficácia da justiça, a razão entre a presença de juízes e o território, o índice de desempenho fiscal, o índice de vulnerabilidade por presença institucional, a taxa de informalidade na posse da terra, o índice multidimensional de pobreza e o índice de Necessidades Básicas Insatisfeitas.Os resultados indicam que as instituições na Colômbia têm pouco ou nenhum efeito na distribuição da riqueza. Tendo em vista esses índices, selecionaram-se sete regiões para o desenvolvimento do estudo: 1) os municípios de Santander, 2) os municípios da fronteira entre Arauca e Casanare, 3) os municípios localizados entre Cundinamarca e Huila, 4) os municípios do estado do Cesar, 5) os municípios localizados entre o Norte de Santander eBoyacá, 6) os municípios de Caquetá e 7) aqueles que estão no oeste do Casanare

Results of the JET real-time disruption predictor in the ITER-like wall campaigns

The impact of disruptions in JET became even more important with the replacement of the previous Carbon Fiber Composite (CFC) wall with a more fragile full metal ITER-like wall (ILW). The development of robust disruption mitigation systems is crucial for JET (and also for ITER). Moreover, a reliable real-time (RT) disruption predictor is a pre-requisite to any mitigation method. The Advance Predictor Of DISruptions (APODIS) has been installed in the JET Real-Time Data Network (RTDN) for the RT recognition of disruptions. The predictor operates with the new ILW but it has been trained only with discharges belonging to campaigns with the CFC wall. 7 realtime signals are used to characterize the plasma status (disruptive or non-disruptive) at regular intervals of 1 ms. After the first 3 JET ILW campaigns (991 discharges), the success rate of the predictor is 98.36% (alarms are triggered in average 426 ms before the disruptions). The false alarm and missed alarm rates are 0.92% and 1.64%

La formación ciudadana en las sociedades tecnocráticas: una perspectiva crítica desde el Geoforo Iberoamericano de Educación

En el año 2011 algunos países iberoamericanos asistieron a diversas movilizaciones contra los intentos de difuminar la presencia del Estado en la educación y privilegiar el papel regulador del mercado. Las competencias educativas se convirtieron en excusa para cambiar los planes educativos y la formación del profesorado parece quedar relegada al dominio de técnicas “neutras”.Dans le année 2011 certains pays ibéro-américains ont assisté à diverses mobilisations contre les tentatives de brouiller la présence du État dans l’éducation et privilégier le rôle régulateur du marché. Les compétences éducatives sont devenues excuse pour changer les plans d’enseignement et la formation des enseignants semble être reléguée au domaine de techniques “neutres”.In the year 2011 some ibero-american countries attended various mobilizations against attempts to blur the presence of the State in education and priori- ty access to regulatory role of the market. The educational competencies became an excuse to change the educational plans and the training of teachers appears to be relegated to the domain of techniques to “neutral”

The Influence of Technology on Mental Well-Being of STEM Teachers at University Level: COVID-19 as a Stressor

Stress can result in psychopathologies, such as anxiety or depression, when this risk factor continues in time. One major stressor was the COVID-19 pandemic, which triggered considerable emotional distress and mental health issues among different workers, including teachers, with another stressor: technology and online education. A mixed-method approach is presented in this research, combining a cross-sectional study of university teachers from Ecuador and Spain with a medium of twenty years of working experience (N = 55) and a bibliometric analysis carried out in three databases (161 documents). The levels of anxiety and depression, and therefore the risk of developing them as mental disorders, were high. The lack of training (p < 0.01), time (p < 0.05), or research regarding the use of technology in education (p < 0.01) and stress caused by COVID-19 (p < 0.001) were linked to frequency. The most relevant observational study obtained through the bibliometric analysis (138 citations and over 65% of methodological quality) indicated that previous training and behavioral factors are key in the stress related to technology. The combination of the results indicated that mental health in STEM teachers at university is related to diverse factors, from training to the family and working balance

Gamification as a Promoting Tool of Motivation for Creating Sustainable Higher Education Institutions

Higher Educational Institutions (HEIs) are responsible for creating healthy and sustainable environments for students and teachers through diverse educational paradigms such as gamification. In this sense, the Healthy People 2030 and the Sustainable Development Goals indicated the imperative to provide inclusive and equitable quality education to promote a healthy environment and life. The principal objective was to analyse the impact of gamification on health development in HEIs, highlighting their positive and negative effects. To achieve such an objective, a bibliometric analysis was carried out. The 257 documents showed no significant increasing trend in the last decade (p > 0.05) related to the pandemic. Most of the publications were conferences (45%), and the few published articles were the documents with more citations (p < 0.001). According to their index in Journal Citation Reports, there were significant differences between the citations of articles published in journals (p < 0.001). The analysis of journal co-citations showed that the leading journals (such as Computers in Human Behavior) had a significant part in the clusters formed (p < 0.001), conditioning also the keywords, especially the term “motivation”. These findings were discussed, concluding that the experimental studies focused on the teachers’ adverse effects are yet to come

The Higher Education Sustainability before and during the COVID-19 Pandemic: A Spanish and Ecuadorian Case

Information and communication technologies (ICTs) are key to create sustainable higher education institutions (HEIs). Most researchers focused on the students’ perspective, especially during the online teaching caused by COVID-19; however, university teachers are often forgotten, having their opinion missing. This study’s objective was to determine the factors that contribute to the inclusion of ICTs. The research based on a comparative study through an online qualitative survey focused on the inclusion and use of ICTs in two HEIs and two different moments (pre-and post-lockdowns). There were differences regarding country and working experience (p < 0.001), being linked to the ICTs use, evaluation of obstacles, and the role given to ICTs (p < 0.05). The COVID-19 caused modifications of the teachers’ perspectives, including an improvement of the opinion of older teachers regarding the essentialness of ICTs in the teaching process (p < 0.001) and worsening their perception about their ICTs skill (p < 0.05). Additionally, an initial model focused only on the university teachers and their use of ICTs has been proposed. In conclusion, the less experienced university teachers used more ICTs, identified more greatly the problematic factors, and considered more important the ICTs, with the perception of all teachers modified by COVID-19

Tiempo para el inicio de insulina y factores asociados al cambio de tratamiento en pacientes diabéticos tipo 2

Tiemp