La Infraestructura de Datos Espaciales como recurso educativo para el profesorado de la Educación Secundaria Obligatoria. Una propuesta innovativa de formación e-learning.

Los avances en las nuevas Tecnologías de la Información y las Comunicaciones (TIC), evidentes en materias técnicas y científicas, repercuten directamente en el ámbito educativo. Preparar a los alumnos en el campo de las TIC tiene su base en la formación del profesorado para que utilicen recursos educativos, herramientas metodológicas y soportes tecnológicos en el aula ofreciendo al alumno la posibilidad de informarse, aprender y comunicarse utilizando las TIC. En este contexto, se propone la utilización de las Infraestructuras de Datos Espaciales (IDE) como un recurso educativo en aquellas materias de la Educación Secundaria Obligatoria que abordan contenidos vinculados a la información geográfica y las TIC, lo que implica brindar al profesorado formación en materia de IDE que le permita tener una visión de las posibilidades que ofrecen las mismas como recurso educativo. Con el fin de dar respuesta a la formación del profesorado en materia de IDE y contribuyendo a su difusión en el ámbito educativo se esta desarrollando el proyecto: “Formación e-learning para el profesorado de la Educación Secundaria Obligatoria para utilizar las IDE como recurso educativo”, a través de un convenio de colaboración entre el Instituto Geográfico Nacional de España y la Universidad Politécnica de Madrid

Cytochrome P450 Epoxygenase-Derived Epoxyeicosatrienoic Acids Contribute to Insulin Sensitivity in Mice and in Humans

Aims/hypothesis: Insulin resistance is frequently associated with hypertension and type 2 diabetes. The P450 arachidonic acid epoxygenases (CYP2C, CYP2J) and their epoxyeicosatrienoic acid (EET) products lower blood pressure and may also improve glucose homeostasis. However, the direct contribution of endogenous EET production on insulin sensitivity has not been previously investigated. In this study we tested the hypothesis that endogenous CYP2C-derived EETs alter insulin sensitivity by analyzing mice lacking Cyp2c44, amajor EET producing enzyme, and by testing the association of plasma EETs with insulin sensitivity in humans.Methods: We assessed insulin sensitivity in wild-type (WT) and Cyp2c44(-/-) mice using hyperinsulinaemic-euglycaemic clamps and isolated skeletal muscles. Insulin secretory function was assessed using hyperglycaemic clamps and isolated islets. Vascular function was tested in isolated-perfused mesenteric vessels. Insulin sensitivity and secretion were assessed in humans using frequently sampled intravenous glucose tolerance tests and plasma EETs were measured by mass spectrometry.Results: Cyp2c44(-/-) mice showed decreased insulin sensitivity compared to WT controls. Although glucose uptake was diminished in Cyp2c44(-/-) mice in vivo, insulin-stimulated glucose uptake was unchanged ex vivo in isolated skeletal muscle. Capillary density was similar but vascular KATP-induced relaxation was impaired in isolated Cyp2c44(-/-) vessels, suggesting that impaired vascular reactivity produces impaired insulin sensitivity in vivo. Similarly, plasma EETs positively correlated with insulin sensitivity in human subjects. Conclusions/Interpretation: CYP2C-derived EETs contribute to insulin sensitivity in mice and in humans. Interventions to increase circulating EETs in humans could provide a novel approach to improve insulin sensitivity and treat hypertension

PPARα Ligands as Antitumorigenic and Antiangiogenic Agents

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor family of ligand-activated transcription factors. This subfamily is composed of three members—PPARα, PPARδ, and PPARγ—that differ in their cell and tissue distribution as well as in their target genes. PPARα is abundantly expressed in liver, brown adipose tissue, kidney, intestine, heart, and skeletal muscle; and its ligands have been used to treat diseases such as obesity and diabetes. The recent finding that members of the PPAR family, including the PPARα, are expressed by tumor and endothelial cells together with the observation that PPAR ligands regulate cell growth, survival, migration, and invasion, suggested that PPARs also play a role in cancer. In this review, we focus on the contribution of PPARα to tumor and endothelial cell functions and provide compelling evidence that PPARα can be viewed as a new class of ligand activated tumor “suppressor” gene with antiangiogenic and antitumorigenic activities. Given that PPAR ligands are currently used in medicine as hypolipidemic drugs with excellent tolerance and limited toxicity, PPARα activation might offer a novel and potentially low-toxic approach for the treatment of tumor-associated angiogenesis and cancer

Formación E-learning para el profesorado de la Educación Secundaria Obligatoria de España para utilizar las Infraestructura de Datos Espaciales como un recurso educativo TIC.

Los avances en las nuevas Tecnologías de la Información y las Comunicaciones (TIC), evidentes en materias técnicas y científicas, influyen directa o indirectamente en el ámbito educativo. Sin embargo, contribuir desde los distintos niveles educativos a que los alumnos adquieran una preparación en el campo de las TIC requiere una formación previa del profesorado. Tanto desde el punto de vista teórico como práctico, el profesor tiene que conocer los nuevos recursos educativos TIC y las posibilidades de aplicación en aula a través de propuestas didácticas concretas y viables. En este contexto, se propone la utilización de las Infraestructuras de Datos Espaciales (IDE) como un recurso educativo TIC en aquellas materias de la Educación Secundaria Obligatoria que abordan contenidos directa o indirectamente relacionados con la Información Geográfica y las TIC. Para dar respuesta a la formación del profesorado en materia de IDE, tanto desde el punto de vista teórico como práctico, se ha desarrollado el proyecto basado en el Modelo de Diseño Instruccional ADDIE: “Formación e-learning para el profesorado de la Educación Secundaria Obligatoria para utilizar las IDE como recurso educativo”, a través de un Convenio de Colaboración entre el Instituto Geográfico Nacional de España y la Universidad Politécnica de Madrid

Desarrollo, implementación y utilización de modelos para el procesamiento automático de textos

El libro recoge ponencias y talleres seleccionados de JALIMI 2005 (Jornadas Argentinas de Lingüística Informática: Modelización e Ingeniería), y está organizado en nueve capítulos y un apéndice. Si bien hay sustantivas diferencias en los enfoques, las metodologías, las propiedades específicas estudiadas y las aplicaciones propuestas o proyectadas, todos los capítulos comunican resultados de investigaciones que pretenden contribuir a alcanzar el objetivo a largo plazo de la Lingüística Informática, a saber: emular en términos cibernéticos la extraordinaria capacidad humana de producir y comprender textos en lengua natural

What is the status of immunotherapy in thyroid neoplasms?

Immunotherapy; Thyroid neoplasms; Tumor mutational burdenInmunoterapia; Neoplasias de la tiroides; Carga mutacional tumoralImmunoteràpia; Neoplàsies de les tiroides; Càrrega mutacional tumoralImmunotherapy has changed the treatment of patients with advanced cancer, with different phase III trials showing durable responses across different histologies. This review focuses on the preclinical and clinical evidence of potential predictive biomarkers of response and efficacy of immunotherapy in thyroid neoplasms. Programmed death-ligand 1 (PD-L1) staining by immunohistochemistry has shown higher expression in anaplastic thyroid cancer (ATC) compared to other subtypes. The tumor mutational burden in thyroid neoplasms is low but seems to be higher in ATC. Immune infiltrates in the tumor microenvironment (TME) differ between the different thyroid neoplasm subtypes. In general, differentiated thyroid cancer (DTC) has a higher number of tumor-associated lymphocytes and regulatory T cells (Tregs), while ATC and medullary thyroid cancer (MTC) display a high density of tumor-associated macrophages (TAMs). Nevertheless, results from clinical trials with immunotherapy as monotherapy or combinations have shown limited efficacy. Further investigation into new strategies aside from anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4)/programmed death 1 (PD-1)/PD-L1 antibodies, validation of predictive biomarkers, and better population selection for clinical trials in thyroid neoplasms is more than needed in the near future

Increased Progression-Free Survival with Cabozantinib Versus Placebo in Patients with Radioiodine-Refractory Differentiated Thyroid Cancer Irrespective of Prior Vascular Endothelial Growth Factor Receptor-Targeted Therapy and Tumor Histology: A Subgroup Analysis of the COSMIC-311 Study

Cabozantinib; Follicular; Thyroid cancerCabozantinib; Fol·licular; Càncer de tiroidesCabozantinib; Folicular; Cáncer de tiroidesBackground: Lenvatinib and sorafenib are standard of care first-line treatments for advanced, radioiodine-refractory (RAIR) differentiated thyroid cancer (DTC). However, most patients eventually become treatment-resistant and require additional therapies. The phase 3 COSMIC-311 study investigated cabozantinib in patients with RAIR DTC who progressed on lenvatinib, sorafenib, or both and showed that cabozantinib provided substantial clinical benefit. Presented in this study is an analysis of COSMIC-311 based on prior therapy and histology. Methods: Patients were randomized 2:1 (stratification: prior lenvatinib [yes/no]; age [≤65, >65 years]) to oral cabozantinib (60 mg tablet/day) or matched placebo. Eligible patients received 1–2 prior vascular endothelial growth factor receptor-targeting tyrosine kinase inhibitors for DTC (lenvatinib or sorafenib required), had a confirmed DTC diagnosis, and were refractory to or ineligible for radioiodine therapy. For this analysis, progression-free survival (PFS) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 by a blinded independent radiology committee were evaluated by prior therapy (lenvatinib only, sorafenib only, both) and histology (papillary, follicular, oncocytic, poorly differentiated). Results: Two hundred fifty-eight patients were randomized (170 cabozantinib/88 placebo) who previously received sorafenib only (n = 96), lenvatinib only (n = 102), or both (n = 60). The median follow-up was 10.1 months. The median PFS (months) with cabozantinib/placebo was 16.6/3.2 (sorafenib only: hazard ratio [HR] 0.13 [95% confidence interval, CI, 0.06–0.26]), 5.8/1.9 (lenvatinib only: HR 0.28 [95% CI 0.16–0.48]), and 7.6/1.9 (both: HR 0.27 [95% CI 0.13–0.54]). The ORR with cabozantinib/placebo was 21%/0% (sorafenib only), 4%/0% (lenvatinib only), and 8%/0% (both). Disease histology consisted of 150 papillary and 113 follicular, including 43 oncocytic and 36 poorly differentiated. The median PFS (months) with cabozantinib/placebo was 9.2/1.9 (papillary: HR 0.27 [95% CI 0.17–0.43]), 11.2/2.5 (follicular: HR 0.18 [95% CI 0.10–0.31]), 11.2/2.5 (oncocytic: HR 0.06 [95% CI 0.02–0.21]), and 7.4/1.8 (poorly differentiated: HR 0.18 [95% CI 0.08–0.43]). The ORR with cabozantinib/placebo was 15%/0% (papillary), 8%/0% (follicular), 11%/0% (oncocytic), and 9%/0% (poorly differentiated). Safety outcomes evaluated were consistent with those previously observed for the overall population. Conclusions: Results indicate that cabozantinib benefits patients with RAIR DTC, regardless of prior lenvatinib or sorafenib treatments or histology. Clinical Trial Registration Number: NCT03690388.This work was supported by Exelixis, Inc., Alameda, CA (no grant number). Exelixis was involved in the study design, the collection, analysis, and interpretation of data, the writing of the report, and the decision to submit for publication

Randomized phase II trial of FOLFIRI-panitumumab compared with FOLFIRI alone in patients with RAS wild-type circulating tumor DNA metastatic colorectal cancer beyond progression to first-line FOLFOX-panitumumab: the BEYOND study (GEMCAD 17-01)

Colorectal cancer; Metastatic disease; Liquid biopsyCáncer colorrectal; Enfermedad metastásica; Biopsia líquidaCàncer colorectal; Malaltia metastàtica; Biòpsia líquidaPurpose Panitumumab plus FOLFOX (P-FOLFOX) is standard first-line treatment for RAS wild-type (WT) metastatic colorectal cancer. The value of panitumumab rechallenge is currently unknown. We assessed addition of panitumumab to FOLFIRI (P-FOLFIRI) beyond progression to P-FOLFOX in patients with no RAS mutations in liquid biopsy (LB). Methods In this randomized phase II trial, patients were assigned (3:2 ratio) to second-line P-FOLFIRI (arm A) or FOLFIRI alone (arm B). LB for circulating tumor DNA analysis was collected at study entry and at disease progression. Primary endpoint was 6-month progression-free survival. Two-stage Simon design required 85 patients to be included (EudraCT 2017-004519-38). Results Between February 2019 and November 2020, 49 patients were screened (16 RAS mutations in LB detected) and 31 included (18 assigned to arm A and 13 to arm B). The study was prematurely closed due to inadequate recruitment. Serious adverse events were more frequent in arm A (44% vs. 23%). Overall response rate was 33% (arm A) vs. 7.7% (arm B). Six-month progression-free survival rate was 66.7% (arm A) and 38.5% (arm B). Median progression-free survival was 11.0 months (arm A) and 4.0 months (arm B) (hazard ratio, 0.58). At disease progression, RAS or BRAF mutations in LB were found in 4/11 patients (36%) in arm A and 2/10 (20%) in arm B. Conclusions The BEYOND study suggests a meaningful benefit of P-FOLFIRI beyond progression to P-FOLFOX in metastatic colorectal cancer patients with WT RAS status selected by LB. This strategy deserves further investigation.This work was supported by AMGEN S.A

Cabozantinib plus Atezolizumab in Advanced, Progressive Endocrine Malignancies: A Multicohort, Basket, Phase II Trial (CABATEN/GETNE-T1914)

Cabozantinib; Atezolizumab; Advanced progressive endocrine malignanciesCabozantinib; Atezolizumab; Neoplasias endocrinas avanzadas y progresivasCabozantinib; Atezolizumab; Neoplàsies endocrines avançades i progressivesPurpose: Multikinase inhibitors have shown efficacy in endocrine neoplasms, and synergism with immune checkpoint inhibitors has been noted in other tumors. Patients and Methods: This is a prospective, multicenter, open-label, Simon two-stage optimal design, phase II study including patients with advanced and refractory endocrine and neuroendocrine neoplasms in six cohorts: lung well-differentiated neuroendocrine tumors, anaplastic thyroid cancer (ATC), adrenocortical carcinoma (ACC), pheochromocytoma/paraganglioma (PPGL), well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NET), and grade 3 extrapulmonary neuroendocrine neoplasms. Patients received atezolizumab 1,200 mg intravenously every 3 weeks plus cabozantinib 40 mg/day orally until disease progression or unacceptable toxicity. The primary objective was the overall response rate (ORR) by RECIST 1.1. Results: From October 2020 to December 2022, 93 patients were included. The ORR was 14.3% [95% confidence interval (CI), 1.8–42.8] in ATC (N = 14); 8.3% (95% CI, 1.0–27.0) in ACC (N = 24); 15.4% (95% CI, 1.9–45.5) in PPGL (N = 13), and 16.7% (95% CI, 4.7–37.4) in GEP-NET (N = 24). Lung well-differentiated neuroendocrine tumors and grade 3 extrapulmonary neuroendocrine neoplasms had no responses. The duration of response was 20.4 months in ATC, 13.1 months in ACC, 12.2 months in PPGL, and 15.8 months in GEP-NET. Survival rates at 12 months in ATC and ACC were 47.6% and 47.6%, respectively. No unexpected toxicity was observed. Conclusions: Cabozantinib and atezolizumab were safely administered and showed promising ORR, and preliminary long-term survival rates were observed in aggressive and pretreated ACC and ATC, which warrants further investigation.This work was supported by the Grupo Español de Tumores Neuroendocrinos y Endocrinos. Roche provided atezolizumab, whereas Ipsen supplied cabozantinib and awarded a grant to Grupo Español de Tumores Neuroendocrinos y Endocrinos to cover the costs of the study. The funders have no role in the design, conduct, or analysis of the study. The authors thank all patients and families, investigators, and study staff involved in the CABATEN trial; special thanks to the MFAR Clinical Research team for their support in regulatory, monitoring, and quality assurance activities; Pau Doñate, Ph.D., and Fanny Rubio, Ph.D., for their assistance with manuscript and language editing; and Oriol Prat M.S. for his statistical support

Las familias de SANAA. O cómo Kazuyo Sejima y Ryue Nishizawa responden a sus intereses arquitectónicos mediante secuencias de proyectos

Tras el estudio de la producción arquitectónica de Kazuyo Sejima y Ryue Nishizawa se puede detectar la existencia de diversas temáticas recurrentes en su trabajo, algo que se evidencia en las secuencias de proyectos que comparten características que se definen como “relaciones de parentesco”. Este artículo muestra las relaciones existentes entre diversos proyectos que integran la producción arquitectónica de estos arquitectos japoneses, en base a esta serie de temáticas recurrentes: modos de agrupación y de compartimentación no jerárquicos, neutralización de la estructura, transformaciones geométricas-equivalencias topológicas y parques. Se emplean para ello técnicas de visualización gráfica que dan como resultado la construcción de un árbol taxonómico. Este método de representación muestra 43 de sus proyectos estudiados, las relaciones existentes entre los mismos y las temáticas recurrentes abordadas.After the analysis of the architectonic production of Kazuyo Sejima and Ryue Nishizawa some recurrent themes can be detected, and an evidence of that can be found in sequences of projects that share some characteristics that are defined as “family relationships”. On the basis of a series of categories: non-hierarchical forms of grouping and compartimentalisation, neutralization of the structure, geometric transformations-topological equivalences and parks, this paper shows the existing relations in between a selection of projects by these Japanese architects. Some graphic visualization techniques are employed concluding in a taxonomic tree. This graphic representation method shows 43 of their analyzed projects, the existing relations in between them and the different recurrent themes discussed