An extensive search algorithm to find feasible healthy menus for humans.

Promoting healthy lifestyles is nowadays a public priority among most public entities. The ability to design an array of nutritious and appealing diets is very valuable. Menu Planning still presents a challenge which complexity derives from the problems’ many dimensions and the idiosyncrasies of human behavior towards eating. Among the difculties encountered by researchers when facing the Menu Planning Problem, being able of fnding a rich feasible region stands out. We consider it as a system of inequalities to which we try to fnd solutions. We have developed and implemented a two-phase algorithm -that mainly stems from the Randomized Search and the Genetic- that is capable of rapidly fnding an pool of solutions to the system with the aim of properly identifying the feasible region of the underlying problem and proceed to its densifcation. It consists of a hybrid algorithm inspired on a GRASP metaheuristic and a later recombination. First, it generates initial seeds, identifying best candidates and guiding the search to create solutions to the system, thus attempting to verify every inequality. Afterwards, the recombination of diferent promising candidates helps in the densifcation of the feasible region with new solutions. This methodology is an adaptation of other previously used in literature, and that we apply to the MPP. For this, we generated a database of a 227 recipes and 272 ingredients. Applying this methodology to the database, we are able to obtain a pool of feasible (healthy and nutritious) complete menus for a given D number of days.Open Access granted by Universidad de Málaga / CBUA. This work has been partially supported by the Spanish *Ministerio de Ciencia, Innovación y Universidades *(MCIU/AEI/FEDER, UE) with grant ref PID2019-104263RBC42; and Junta de Andalucía with grant refs. P18-RT-1566, (contract ref CI-21-228) UMA18-FEDERJA- 065. Funding for open access charge: Universidad de Málaga / CBU

CSA06 Computing, Software and Analysis challenge at the Spanish Tier-1 and Tier-2 sites

This note describes the participation of the Spanish centres PIC, CIEMAT and IFCA as Tier-1 and Tier-2 sites in the CMS CSA06 Computing, Software and Analysis challenge. A number of the facilities, services and workflows have been demonstrated at the 2008 25% scale. Very valuable experience has been gained running the complex computing system under realistic conditions at a significant scale. The focus of this note is on presenting achieved results, operational experience and lessons learnt during the challenge

Highly Regio- and Stereoselective Diels-Alder Cycloadditions via Two-Step and Multicomponent Reactions Promoted by Infrared Irradiation under Solvent-Free Conditions

Infrared irradiation promoted the Diels-Alder cycloadditions of exo-2-oxazolidinone dienes 1–3 with the Knoevenagel adducts 4–6, as dienophiles, leading to the synthesis of new 3,5-diphenyltetrahydrobenzo[d]oxazol-2-one derivatives (7, 9, 11 and 13–17), under solvent-free conditions. These cycloadditions were performed with good regio- and stereoselectivity, favoring the para-endo cycloadducts. We also evaluated the one-pot three-component reaction of active methylene compounds 20, benzaldehydes 21 and exo-2-oxazolidinone diene 2 under the same reaction conditions. A cascade Knoevenagel condensation/Diels-Alder cycloaddition reaction was observed, resulting in the final adducts 13–16 in similar yields. These procedures are environmentally benign, because no solvent and no catalyst were employed in these processes. The regioselectivity of these reactions was rationalized by Frontier Molecular Orbital (FMO) calculations

La enseñanza del metabolismo: retos y oportunidades

En el marco del Proyecto de Innovación Educativa de la Universidad de Málaga PIE15-163, cuya descripción y resultados incluimos, decidimos que esta era una excelente oportunidad para reflexionar acerca de la enseñanza del metabolismo y de poner por escrito dichas reflexiones en un libro. Quisimos y pudimos contar con la colaboración de buena parte de los compañeros del Departamento de Biología Molecular y Bioquímica que apoyaron con su firma el proyecto PIE15-163 y extendimos nuestra invitaciones a otros compañeros de dentro y fuera de la Universidad de Málaga. Del Departamento de Biología Molecular y Bioquímica de la Universidad de Málaga hemos recibido aportaciones de los catedráticos Victoriano Valpuesta Fernández, Ana Rodríguez Quesada y Antonio Heredia Bayona, los profesores titulares María Josefa Pérez Rodríguez, José Luis Urdiales Ruiz e Ignacio Fajardo Paredes y la investigadora postdoctoral y profesora sustituta interina Beatriz Martínez Poveda. De otros departamentos de la Universidad de Málaga hemos contado con las aportaciones de la catedrática del Departamento de Especialidades Quirúrgicas, Bioquímica e Inmunología Pilar Morata Losa, del catedrático del Departamento de Lenguajes y Ciencias de la Computación José Francisco Aldana Montes y los componentes de su grupo de investigación Khaos Ismael Navas Delgado, María Jesús García Godoy, Esteban López Camacho y Maciej Rybinski, del catedrático Ángel Blanco López, del Área de Conocimiento de Didáctica de las Ciencias Experimentales y del Doctor en Ciencias Químicas y actual doctorando del Programa de Doctorado "Educación y Comunicación Social" Ángel Luis García Ponce. De fuera de la Universidad de Málaga, hemos contado con las aportaciones del catedrático de la Universidad de La Laguna Néstor V. Torres Darias, de la catedrática de la Universitat de les Illes Balears Pilar Roca Salom y de sus compañeros los profesores Jorge Sastre Serra y Jordi Oliver, de los catedráticos de la Universidad de Granada Rafael Salto González y María Dolores Girón González y su colaborador el Dr. José Dámaso Vílchez Rienda, del profesor titular de la Universidad de Alcalá Ángel Herráez, del investigador postdoctoral de la Universidad de Erlangen (Alemania) Guido Santos y del investigador postdoctoral de la empresa Brain Dynamics Carlos Rodríguez Caso.Hemos estructurado los contenidos del libro en diversas secciones. La primera presenta el Proyecto en cuyo marco se ha gestado la iniciativa que ha conducido a la edición del presente libro. La segunda sección la hemos titulado "¿Qué metabolismo?" e incluye diversas aportaciones personales que reflexionan acerca de qué metabolismo debe conocer un graduado en Bioquímica, en Biología, en Química, en Farmacia o en Medicina, así como una aportación acerca de qué bioquímica estructural y enzimología son útiles y necesarias para un estudiante que vaya a afrontar el estudio del metabolismo. La tercera sección, "Bases conceptuales", analiza las aportaciones del aprendizaje colaborativo, el contrato de aprendizaje y el aprendizaje basado en la resolución de casos prácticos a la mejora del proceso enseñanza-aprendizaje dentro del campo de la Bioquímica y Biología Molecular, más concretamente en el estudio del metabolismo. La cuarta sección se titula "Herramientas", es la más extensa e incluye las diversas aportaciones centradas en propuestas concretas de aplicación relevantes y útiles para la mejora de la docencia-aprendizaje del metabolismo. Sigue una sección dedicada a presentar de forma resumida los "Resultados" del proyecto PIE15-163. El libro concluye con una "coda final" en la que se reflexiona acerca del aprendizaje de la Química a la luz de la investigación didáctica.Patrocinado por el Proyecto de Innovación Educativa de la Universidad de Málaga PIE15-16

Safety and efficacy of ribociclib plus letrozole in patients with HR+, HER2– advanced breast cancer: Results from the Spanish sub-population of the phase 3b CompLEEment-1 trial

Background: Breast cancer is the most common malignancy and the second leading cause of cancer-related mortality in Spanish women. Ribociclib in combination with endocrine therapy (ET) has shown superiority in prolonging survival in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) vs. ET alone.Methods: CompLEEment-1 is a single-arm, open-label phase 3b trial evaluating ribociclib plus letrozole in a broad population of patients with HR+, HER2- ABC. The primary endpoints were safety and tolerability. Here we report data for Spanish patients enrolled in CompLEEment-1.Results: A total of 526 patients were evaluated (median follow-up: 26.97 months). Baseline characteristics showed a diverse population with a median age of 54 years. At study entry, 56.5% of patients had visceral metastases and 8.7% had received prior chemotherapy for advanced disease. Rates of all-grade and Grade >= 3 adverse events (AEs) were 99.0% and 76.2%, respectively; 21.3% of patients experienced a serious AE, and 15.8% of AEs led to treatment discontinuation. AEs of special interest of neutropenia, increased alanine aminotransferase, increased aspartate aminotransferase and QTcF prolongation occurred in 77.8%, 14.8%, 11.4% and 4.0% of patients, respectively. Patients aged >70 years experienced increased rates of all-grade and Grade >= 3 neutropenia and anemia. Efficacy results were consistent with the global study.Conclusions: Results from Spanish patients enrolled in CompLEEment-1 are consistent with global data showing efficacy and a manageable safety profile for ribociclib plus letrozole treatment in patients with HR+, HER2-ABC, including populations of interest (NCT02941926).Trial registration: ClinicalTrials.gov NCT0294192

Glial Innate Immunity Generated by Non-Aggregated Alpha-Synuclein in Mouse: Differences between Wild-type and Parkinson's Disease-Linked Mutants

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized pathologically by the presence in the brain of intracellular protein inclusions highly enriched in aggregated alpha-synuclein (alpha-Syn). Although it has been established that progression of the disease is accompanied by sustained activation of microglia, the underlying molecules and factors involved in these immune-triggered mechanisms remain largely unexplored. Lately, accumulating evidence has shown the presence of extracellular alpha-Syn both in its aggregated and monomeric forms in cerebrospinal fluid and blood plasma. However, the effect of extracellular alpha-Syn on cellular activation and immune mediators, as well as the impact of familial PD-linked alpha-Syn mutants on this stimulation, are still largely unknown.Methods and Findings: In this work, we have compared the activation profiles of non-aggregated, extracellular wild-type and PD-linked mutant alpha-Syn variants on primary glial and microglial cell cultures. After stimulation of cells with alpha-Syn, we measured the release of Th1- and Th2-type cytokines as well as IP-10/CXCL10, RANTES/CCL5, MCP-1/CCL2 and MIP-1 alpha/CCL3 chemokines. Contrary to what had been observed using cell lines or for the case of aggregated alpha-Syn, we found strong differences in the immune response generated by wild-type alpha-Syn and the familial PD mutants (A30P, E46K and A53T).Conclusions: These findings might contribute to explain the differences in the onset and progression of this highly debilitating disease, which could be of value in the development of rational approaches towards effective control of immune responses that are associated with PD

SARS-CoV-2 Breakthrough Infections: Incidence and Risk Factors in a Large European Multicentric Cohort of Health Workers

The research aimed to investigate the incidence of SARS-CoV-2 breakthrough infections and their determinants in a large European cohort of more than 60,000 health workers

Management and outcomes of patients with left atrial appendage thrombus prior to percutaneous closure.

Left atrial appendage (LAA) thrombus has heretofore been considered a contraindication to percutaneous LAA closure (LAAC). Data regarding its management are very limited. The aim of this study was to analyse the medical and invasive treatment of patients referred for LAAC in the presence of LAA thrombus. This multicentre observational registry included 126 consecutive patients referred for LAAC with LAA thrombus on preprocedural imaging. Treatment strategies included intensification of antithrombotic therapy (IAT) or direct LAAC. The primary and secondary endpoints were a composite of bleeding, stroke and death at 18 months, and procedural success, respectively. IAT was the preferred strategy in 57.9% of patients, with total thrombus resolution observed in 60.3% and 75.3% after initial and subsequent IAT, respectively. Bleeding complications and stroke during IAT occurred in 9.6% and 2.9%, respectively, compared with 3.8% bleeding and no embolic events in the direct LAAC group before the procedure. Procedural success was 90.5% (96.2% vs 86.3% in direct LAAC and IAT group, respectively, p=0.072), without cases of in-hospital thromboembolic complications. The primary endpoint occurred in 29.3% and device-related thrombosis was found in 12.8%, without significant difference according to treatment strategy. Bleeding complications at 18 months occurred in 22.5% vs 10.5% in the IAT and direct LAAC group, respectively (p=0.102). In the presence of LAA thrombus, IAT was the initial management strategy in half of our cohort, with initial thrombus resolution in 60% of these, but with a relatively high bleeding rate (~10%). Direct LAAC was feasible, with high procedural success and absence of periprocedural embolic complications. However, a high rate of device-related thrombosis was detected during follow-up