Core-Shell Palladium/MOF Platforms as Diffusion-Controlled Nanoreactors in Living Cells and Tissue Models

Translating the potential of transition metal catalysis to biological and living environments promises to have a profound impact in chemical biology and biomedicine. A major challenge in the field is the creation of metal-based catalysts that remain active over time. Here, we demonstrate that embedding a reactive metallic core within a microporous metal-organic framework-based cloak preserves the catalytic site from passivation and deactivation, while allowing a suitable diffusion of the reactants. Specifically, we report the fabrication of nanoreactors composed of a palladium nanocube core and a nanometric imidazolate framework, which behave as robust, long-lasting nanoreactors capable of removing propargylic groups from phenol-derived pro-fluorophores in biological milieu and inside living cells. These heterogeneous catalysts can be reused within the same cells, promoting the chemical transformation of recurrent batches of reactants. We also report the assembly of tissue-like 3D spheroids containing the nanoreactors and demonstrate that they can perform the reactions in a repeated mannerThe authors thank the financial support of the MINECO ( CTQ2017-89588-R , SAF2016-76689-R , CTQ2017-84767-P , RYC-2014-16962 , and RYC-2017-23457 ), the Xunta de Galicia ( ED431F 2017/02 , 2015-CP082 , ED431C 2017/19 , and Centro singular de investigación de Galicia accreditation 2019-2022, ED431G 2019/03 ), the European Union (European Regional Development Fund [ERDF]; H2020-MSCA-IF-2016 grant agreement no. 749667 ; and INTERREG V-A Spain-Portugal [POCTEP] 2014-2020, project 0624_2IQBIONEURO_6_E ), and the European Research Council (advanced grant no. 340055 ). Support of the orfeo-cinqa network ( CTQ2016-81797-REDC ) is also kindly acknowledgedS

Nomogram-based prediction of survival in patients with advanced oesophagogastric adenocarcinoma receiving first-line chemotherapy: a multicenter prospective study in the era of trastuzumab

Background: To develop and validate a nomogram and web-based calculator to predict overall survival (OS) in Caucasian-advanced oesophagogastric adenocarcinoma (AOA) patients undergoing first-line combination chemotherapy. Methods: Nine hundred twenty-four AOA patients treated at 28 Spanish teaching hospitals from January 2008 to September 2014 were used as derivation cohort. The result of an adjusted-Cox proportional hazards regression was represented as a nomogram and web-based calculator. The model was validated in 502 prospectively recruited patients treated between October 2014 and December 2016. Harrell's c-index was used to evaluate discrimination. Results: The nomogram includes seven predictors associated with OS: HER2-positive tumours treated with trastuzumab, Eastern Cooperative Oncology Group performance status, number of metastatic sites, bone metastases, ascites, histological grade, and neutrophil-to-lymphocyte ratio. Median OS was 5.8 (95% confidence interval (CI), 4.5–6.6), 9.4 (95% CI, 8.5–10.6), and 14 months (95% CI, 11.8–16) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the derivation set and 4.6 (95% CI, 3.3–8.1), 12.7 (95% CI, 11.3–14.3), and 18.3 months (95% CI, 14.6–24.2) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the validation set. The nomogram is well-calibrated and reveals acceptable discriminatory capacity, with optimism-corrected c-indices of 0.618 (95% CI, 0.591–0.631) and 0.673 (95% CI, 0.636–0.709) in derivation and validation groups, respectively. The AGAMENON nomogram outperformed the Royal Marsden Hospital (c-index=0.583; P=0.00046) and Japan Clinical Oncology Group prognostic indices (c-index=0.611; P=0.03351). Conclusions: We developed and validated a straightforward model to predict survival in Caucasian AOA patients initiating first-line polychemotherapy. This model can contribute to inform clinical decision-making and optimise clinical trial design

Jornada de Grandes infraestructuras europeas de Ciencias Sociales y Humanidades en el CSIC: DARIAH y CLARÍN en el horizonte (11 de mayo de 2023)

Peer reviewe

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Nanocomposites plasmónicos para manipulación de moléculas en célula viva

En esta tesis se investiga la síntesis, funcionalización y degradación de nanopartículas (NPs) plasmónicas con posibles aplicaciones en biomedicina. Se analiza su interacción con proteínas y su encapsulación en la Estructura Zeolítica de Imidazolato-8 (ZIF-8) para utilizarlas como sustratos en la Espectroscopía Raman Intensificada en Superficie. Además, se aborda la síntesis de NPs magnéticas, estudiando el impacto del dopaje con Co en sus propiedades magnéticas y la encapsulación de estas NPs magnéticas en ZIF-8, lo que da lugar a nanocompuestos que podrían servir como portadores de fármacos activados por campos magnéticos alternos. Por último, se investiga la influencia de la funcionalización de NPs de Pd, evaluando su eficacia catalítica en la reducción de azul de metileno y su posterior encapsulación en ZIF-8.2024-09-2

Alumnado con TEA : orientaciones para planificar la respuesta educativa. Propuestas inclusivas para intervenir en Infantil, Primaria y Secundaria

Dirigida al profesorado esta publicación plantea trabajar con el autismo no como un problema sino como un reto educativo. En ella se encuentran apartados teóricos, dentro del marco de referencia de la investigación científica (concepto, estilo perceptivo, estilo cognitivo…), pero también propuestas prácticas implementables en el aula; propuestas de carácter sencillo, planteamientos fácilmente aplicables y contextualizados en función del momento evolutivo y de la etapa educativa en que se encuentre el alumnado.ES

Convergencia de 4º hacia el TFG

Se trata de un proyecto piloto sobre el Trabajo Final de Grado. El alumno de Diseño ha utilizado en los tres primeros cursos una metodología de proyecto integrado, que hace converger el contenido de las diferentes materias hacia el proyecto propuesto por el profesor invitado. En esta primera edición del Trabajo Final de Grado, se ha planteado una innovación: el alumno elige voluntariamente el contenido del proyecto. El PID Convergencia4 ha hecho converger 11 asignaturas optativas y 2 obligatorias de 4º hacia los proyectos individuales de TFG. Es decir, no es una relación de cinco asignaturas con un proyecto como en cursos precedentes, sino de 13 asignaturas con 38 proyectos. Durante todo el curso, los alumnos han ido acumulando ideas, perspectivas y enfoques desde distintas asignaturas y han podido reflejarlos en sus TFG con naturalidad y acierto. De alguna manera, el TFG que supone 18 ECTS (30% de 4º curso), se ha visto ampliado con el enriquecimiento de los 30 ECTS optativos (50% del curso). Además, aunque inicialmente no habíamos previsto incluirlas en el PID, dos asignaturas obligatorias del segundo cuatrimestre (Estrategias de Comunicación y Web, y Business Management), también han influido directamente en los TFG, pues la mayoría de los alumnos ha incorporado estos contenidos a su TFG. De esta manera, el TFG de Diseño en la ETSAUN, se ha convertido en un trabajo casi anual, que sintetiza todo el aprendizaje adquirido por el alumno y sirve como carta de presentación para su trabajo profesional

On the Effect of Triplet or Doublet Chemotherapy in Advanced Gastric Cancer: Results From a National Cancer Registry

Background: There is currently no consensus regarding first-line chemotherapy for patients with advanced gastric cancer (AGC) who are ineligible to receive trastuzumab. The objective of this study was to evaluate the efficacy and tolerance of triplets versus doublets by analyzing a national gastric cancer registry. Patients and Method: Patients with AGC treated with polychemotherapy without associating trastuzumab were included from 2008 through 2016. The effect of triplets versus doublets was compared using 3 methods: Cox proportional hazards regression, propensity score matching (PSM), and coarsened exact matching (CEM). Results: A total of 970 patients were recruited (doublets: n=569; triplets: n=401). In the multivariate Cox model, the use of triplets was associated with better overall survival (OS), with a hazard ratio (HR) of 0.84 (95% CI, 0.72–0.98; P=.035). After PSM, the sample contained 340 pairs. A significant increase in OS, 11.14 months (95% CI, 9.60–12.68) versus 9.60 months (95% CI, 8.44–10.75), was seen in favor of triplets (HR, 0.77; 95% CI, 0.65–0.92; stratified log-rank test, P=.004). The effect appeared to be comparable for anthracycline-based (HR, 0.78; 95% CI, 0.64–0.94) or docetaxel-based triplets (HR, 0.78; 95% CI, 0.60–1.009). The trend was similar after applying the CEM algorithm, with an HR of 0.78 (95% CI, 0.63–0.97; P=.03). Triplet therapy was viable and relative dose intensities exceeded 85%, except for cisplatin in DCX (docetaxel, cisplatin, capecitabine). Triplets had more severe toxicity overall, especially hematologic, hepatic, and mucosal adverse events. Conclusions: With the limitations of a retrospective study that examines a heterogeneous set of chemotherapy regimens, we found that triplets are feasible in daily practice and are associated with a discreet benefit in efficacy at the expense of a moderate increase in toxicity

Prognostic significance of performing universal HER2 testing in cases of advanced gastric cancer.

Trastuzumab significantly improves overall survival (OS) when added to cisplatin and fluoropyrimidine as a treatment for HER2-positive advanced gastric cancers (AGC). The aim of this study was to evaluate the impact of the gradual implementation of HER2 testing on patient prognosis in a national registry of AGC. This Spanish National Cancer Registry includes cases who were consecutively recruited at 28 centers from January 2008 to January 2016. The effect of missing HER2 status was assessed using stratified Cox proportional hazards (PH) regression. The rate of HER2 testing increased steadily over time, from 58.3 % in 2008 to 92.9 % in 2016. HER2 was positive in 194 tumors (21.3 %). In the stratified Cox PH regression, each 1 % increase in patients who were not tested for HER2 at the institutions was associated with an approximately 0.3 % increase in the risk of death: hazard ratio, 1.0035 (CI 95 %, 1.001-1.005), P = 0.0019. Median OS was significantly lower at institutions with the highest proportions of patients who were not tested for HER2. Patients treated at centers that took longer to implement HER2 testing exhibited worse clinical outcomes. The speed of implementation behaves as a quality-of-care indicator. Reviewed guidelines on HER2 testing should be used to achieve this goal in a timely manner

Nomogram-based prediction of survival in patients with advanced oesophagogastric adenocarcinoma receiving first-line chemotherapy: a multicenter prospective study in the era of trastuzumab

Background: To develop and validate a nomogram and web-based calculator to predict overall survival (OS) in Caucasian-advanced oesophagogastric adenocarcinoma (AOA) patients undergoing first-line combination chemotherapy. Methods: Nine hundred twenty-four AOA patients treated at 28 Spanish teaching hospitals from January 2008 to September 2014 were used as derivation cohort. The result of an adjusted-Cox proportional hazards regression was represented as a nomogram and web-based calculator. The model was validated in 502 prospectively recruited patients treated between October 2014 and December 2016. Harrell's c-index was used to evaluate discrimination. Results: The nomogram includes seven predictors associated with OS: HER2-positive tumours treated with trastuzumab, Eastern Cooperative Oncology Group performance status, number of metastatic sites, bone metastases, ascites, histological grade, and neutrophil-to-lymphocyte ratio. Median OS was 5.8 (95% confidence interval (CI), 4.5–6.6), 9.4 (95% CI, 8.5–10.6), and 14 months (95% CI, 11.8–16) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the derivation set and 4.6 (95% CI, 3.3–8.1), 12.7 (95% CI, 11.3–14.3), and 18.3 months (95% CI, 14.6–24.2) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the validation set. The nomogram is well-calibrated and reveals acceptable discriminatory capacity, with optimism-corrected c-indices of 0.618 (95% CI, 0.591–0.631) and 0.673 (95% CI, 0.636–0.709) in derivation and validation groups, respectively. The AGAMENON nomogram outperformed the Royal Marsden Hospital (c-index=0.583; P=0.00046) and Japan Clinical Oncology Group prognostic indices (c-index=0.611; P=0.03351). Conclusions: We developed and validated a straightforward model to predict survival in Caucasian AOA patients initiating first-line polychemotherapy. This model can contribute to inform clinical decision-making and optimise clinical trial design