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Introducción. La innovación educativa contempla varias áreas constructivas: tecnología, didáctica, pedagogía, procesos y personas, integradas para transformar el proceso de enseñanza-aprendizaje, manteniendo la novedad de contextos sociales, conservando la memoria milenaria colectiva en la integración e inclusión de los diferentes actores educativos y recreativos en el ámbito nacional donde la Universidad Técnica de Babahoyo mediante su programa de proyectos de vinculación se forja socialmente para conducir y lograr la salvaguarda en la solución de problemas, la toma de decisiones, generando conocimientos sustanciosos en la pertinencia de las carreras universitarias incorpora experiencia en la teoría y práctica sustantiva, multidisciplinar, multiniveles, transformación contextual humana y profesional a través de los talleres participativos colaboran con el aprendizaje virtual sincrónico y asincrónico brindando información actualizada con múltiples beneficios directos para los proyectos de desarrollo comunitario. Objetivo. Innovar en una serie de talleres participativos turísticos gratuitos para apoyar la vinculación de la población hacia nuevas alternativas de empleabilidad local. Metodología. Esta investigación tuvo dos etapas una direccionada hacia la actualización de la línea base de la región conspirando con líneas de investigación institucionales y la segunda etapa incluye el diseño de la recolección de la información aplicando una encuesta digital a los participantes. Conclusiones. Los resultados de la encuesta realizada a 100 personas debelo que las necesidades de reactivación económica post pandemia recae en la seguridad de aplicarse la vacuna bajo todo riesgo nacional e internacional, buscar aliados estratégicos e inversionistas que propicien el financiamiento de nuevos bienes y servicios turísticos.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy and there is an unmet need for targeted therapies, especially for patients with relapsed disease. We have recently identified pre-T cell receptor (preTCR) and lymphocyte-specific protein tyrosine kinase (LCK) signaling as a common therapeutic vulnerability in T-ALL. LCK inhibitor dasatinib showed efficacy against T-ALL in preclinical studies and also in patients with T-ALL, however, this is transient in most cases. Leveraging the Proteolysis Targeting Chimera (PROTAC) approach, we developed a series of LCK degraders using dasatinib as an LCK ligand and phenyl-glutarimide as a cereblon-directing moiety. Our lead compound SJ11646 exhibited marked efficiency in cereblon-mediated LCK degradation in T-ALL cells. Relative to dasatinib, SJ11646 showed up to three orders of magnitude higher cytotoxicity in LCK-activated T-ALL cell lines and primary leukemia samples in vitro, with drastically prolonged suppression of LCK signaling. In vivo pharmacokinetic and pharmacodynamic profiling indicated a 630% increase in the duration of LCK suppression by SJ11646 over dasatinib in patient-derived xenograft models of T-ALL, which translated into its extended leukemia-free survival over dasatinib in vivo. Lastly, SJ11646 retained a high binding affinity to 51 human kinases, particularly ABL1, KIT, and DDR1, all of which are known drug targets in other cancers. Taken together, our dasatinib-based phenyl-glutarimide PROTACs are promising therapeutic agents in T-ALL and also valuable tools for developing degradation-based therapeutics for other cancers.

FLT3 is an attractive therapeutic target in acute lymphoblastic leukemia (ALL) but the mechanism for its activation in this cancer is incompletely understood. Profiling global gene expression in large ALL cohorts, we identify over-expression of FLT3 in ZNF384-rearranged ALL, consistently across cases harboring different fusion partners with ZNF384. Mechanistically, we discover an intergenic enhancer element at the FLT3 locus that is exclusively activated in ZNF384-rearranged ALL, with the enhancer-promoter looping directly mediated by the fusion protein. There is also a global enrichment of active enhancers within ZNF384 binding sites across the genome in ZNF384-rearranged ALL cells. Downregulation of ZNF384 blunts FLT3 activation and decreases ALL cell sensitivity to FLT3 inhibitor gilteritinib in vitro. In patient-derived xenograft models of ZNF384-rearranged ALL, gilteritinib exhibits significant anti-leukemia efficacy as a monotherapy in vivo. Collectively, our results provide insights into FLT3 regulation in ALL and point to potential genomics-guided targeted therapy for this patient population.

The nongenetic contributors to attention deficit/hyperactivity disorder (ADHD) remain to be identified. A previous study in eastern Wisconsin (prevalence 13.5%) suggested that male gender, white race, lower block group median household income and population density, and greater distance to the nearest park were factors predictive of ADHD diagnosis. We performed a similar study in Dane County, Wisconsin.Cross sectional study of children age 5-17, with and without ADHD diagnosis, who received well child care in Dane County UW Family Medicine clinics (N=7954) 2007-2008. Street addresses were geocoded to 2000 Census block group. Univariate analysis was done by chi-square test or Mann-Whitney U test, multivariate analysis by logistic regression.ADHD diagnosis was present in 309 (3.9%) children (74.1% male; P = 0.000, compared to females) and more frequently diagnosed in black children (6.8% of black children had ADHD diagnosis) than white (4%), Native American (2.7%), Hispanic (1.6%), or Asian (1.3%) children. In contrast to eastern Wisconsin and to Milwaukee County (a subset of the eastern Wisconsin study where black rates were identical to that of Dane County), black race rather than white race was predictive of ADHD in Dane County, while median household income, population density, and distance to nearest park were not associated. The range of ADHD within school district boundaries was 2.4%-7.1% (for N100/district). In the group of districts with4% ADHD diagnosis, the increased rates were largely among whites.ADHD diagnosis was much less common in this Dane County cohort than in eastern Wisconsin and was more common among blacks, but not predicted by other geo-demographic factors. Like eastern Wisconsin, ADHD diagnosis prevalence varied with apparent school district boundaries.