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Cellular senescence is a stress response characterised by a permanent cell cycle arrest and a proinflammatory secretome. In addition to its tumour suppressor role, senescence is involved in ageing and promotes many disease processes such as cancer, type 2 diabetes, osteoarthritis, and SARS-CoV-2 infection. There is a growing interest in therapies based on targeted elimination of senescent cells, yet so far only a few such senolytics are known, partly due to the poor grasp of the molecular mechanisms that control the senescence survival programme. Here we report a highly effective machine learning pipeline for the discovery of senolytic compounds. Using solely published data, we trained machine learning algorithms to classify compounds according to their senolytic action. Models were trained on as few as 58 known senolytics against a background of FDA-approved compounds or in late-stage clinical development (2,523 in total). We computationally screened various chemical libraries and singled out top candidates for validation in human lung fibroblasts (IMR90) and lung adenocarcinoma (A549) cell lines. This led to the discovery of three novel senolytics: ginkgetin, oleandrin and periplocin, with potency comparable to current senolytics and a several hundred-fold reduction in experimental screening costs. Our work demonstrates that machine learning can take maximum advantage of existing drug screening data, paving the way for new open science approaches to drug discovery for senescence-associated diseases.

Introduction: The best therapeutic alternative for patients affected by end-stage chronic kidney disease is kidney transplantation. General objective: To characterize the long-term survival of patients with kidney transplants belonging to the Central Hospital of the Social Welfare Institute. Specific objectives: Describe the factors associated with kidney graft failure. Evaluate the causes of kidney graft failure. List the complications related to the transplant Patients and methods: Retrospective, descriptive, cross-sectional study, 173 medical records of people over 18 years of age under regular follow-up by the Transplant Service of the Central Hospital “Dr. Emilio Cubas” from the Social Welfare Institute. Conclusion: The long-term survival of renal transplantation represents 99% at one year, 91% at three years, and 81% at five years., Introducción: La mejor alternativa terapeutica para los pacientes con afectación de enfermedad renal cronica terminal es el trasplante renal. Objetivo general: Caracterizar la sobrevida a largo plazo de los pacientes con trasplante renal de los pacientes pertenecientes al Hospital Central del Instituto de Prevision Social. Objetivos específicos: Describir los factores asociados al fracaso del injerto renal. Evaluar las causas del fracaso del injerto renal. Enumerar las complicaciones relacionadas al trasplante Pacientes y métodos: Estudio retrospectivo, descriptivo de corte transversal, se revisaron 173 historias clinicas de mayores de 18 anos en seguimiento regular por el Servicio de Trasplante del Hospital Central “Dr. Emilio Cubas” del Instituto de Prevision Social. Conclusión: La sobrevida a largo plazo del trasplante renal representa al ano 99%, a los tres anos 91%, a los cinco anos 81%.

Este trabajo de investigación, busca establecer que a pesar de que el elemento culpabilidad es un límite al ius punendi en el ordenamiento jurídico colombiano, existen estados alterados de conciencia, que disminuyen la capacidad de culpabilidad o la imputabilidad del individuo y las mismas están en una laguna normativa, ésta situación no es completamente ajena a nuestro marco legal, ya que existe el estado de ira e intenso dolor, y dicho estado es un atenuante de la responsabilidad penal, éste no es más que uno de esos estados de culpabilidad disminuida donde se ve afectada la capacidad de entendimiento del individuo y le genera una atenuación de la conducta cometida. Por lo tanto, si se analiza el origen dogmático de esta atenuante, nos encontraremos con que tiene su génesis en el reconocimiento de la nivelación de las emociones o el escalonamiento de las mismas, determinando que con el acompañamiento adecuado por parte de un perito, se puede determinar que si bien el sujeto no era inimputable, tampoco era imputable completamente., This research work, seeks to establish that despite the fact that the guilt element is a limit to the ius punendi in the Colombian legal system, there are altered states of consciousness, which decrease the capacity for guilt or the accountability of the individual and they are in a regulatory gap, this situation is not completely foreign to our legal framework, since there is a state of anger and intense pain, Therefore, if we analyze the dogmatic origin of this mitigating factor, we will find that it has its genesis in the recognition of the leveling of emotions or the staggering of them, determining that with the appropriate accompaniment by an expert, it can be determined that although the subject was not accountable, he was not fully attributable either.

Este estudio estima el efecto que tienen las características de las viviendas en los proyectos VIS, los subsidios entregados para la compra de viviendas a familias en los municipios a través de los años, el precio del metro cuadrado ofrecido por proyecto y el índice de pobreza multidimensional por manzana censal en el número de metros cuadrados ofrecidos por las compañías constructoras en proyectos de interés social ubicados en Medellín y su Área Metropolitana. Nosotros encontramos evidencias de la importancia de los subsidios para la compra de viviendas para las compañías constructoras y como la disponibilidad de tierras puede generar incentivos para la construcción de proyectos de interés social comparados con sitios con poca disponibilidad de las mismas. Los resultados muestran que para el total del Área Metropolitana del Valle de Aburrá la entrega de subsidios para la compra de vivienda tiene efectos positivos en la cantidad de metros cuadrados ofrecidos por las compañías constructoras hallando que un aumento de un 1% en los subsidios entregados para la compra de vivienda está relacionado a un aumento del 0.017% en los metros cuadrados ofrecidos, de la misma forma un aumento del 1% en el precio del metro está asociado 0.45% más metros cuadrados ofrecidos y por último se encuentra que el aumento de una alcoba está asociada a un aumento de 1.57% en los metros cuadrados ofrecidos, no obstante gracias a la estimación del polinomio cuadrado de las alcobas se observa que hay rendimientos marginales decrecientes encontrando una cantidad optima de entre 2 y 3 alcobas por unidad en los proyectos de interés social., This study estimates the effect of the subsidies given for the purchase of housing to families in the municipalities over the years, the characteristics of the public housing projects, the price per square meter offered per project and the multidimensional poverty index per block on the number of square meters offered by construction companies in public housing projects located in Medellín and its Metropolitan Area. We find evidence of the importance of housing subsidies for construction companies and how the availability of land can generate incentives for the construction of social interest projects compared to sites with low availability. The results show that for the total of the Metropolitan Area of the Aburrá Valley the delivery of subsidies for the purchase of housing has positive effects on the amount of square meters offered by construction companies, finding that a 1% increase in the subsidies delivered for the purchase of housing is related to a 0.017% increase in the square meters offered by construction companies. 017% in the square meters offered, likewise an increase of 1% in the price per meter is associated with 0.45% more square meters offered and finally it is found that the increase of one bedroom is associated with an increase of 1.57% in the square meters offered by construction companies, however, thanks to the estimation of the polynomial square of the bedrooms it is observed that there are decreasing marginal returns finding an optimal amount of between 2 and 3 bedrooms for units in the public housing projects.

This dissertation contains work from the author's papers [35] and [36] with coauthor Eyvindur Palsson. The classic Mattila-Sjolin theorem shows that if a compact subset of $mathbb{R}^d$ has Hausdorff dimension at least $frac{(d+1)}{2}$ then its set of distances has nonempty interior. In this dissertation, we present a similar result, namely that if a compact subset $E$ of $mathbb{R}^d$, with $d geq 3$, has a large enough Hausdorff dimension then the set of congruence classes of triangles formed by triples of points of $E$ has nonempty interior. These types of results on point configurations with nonempty interior can be categorized as extensions and refinements of the statement in the well known Falconer distance problem which establishes a positive Lebesgue measure for the distance set instead of it having nonempty interior

The supply through commercial distribution allows people to have within their reach and acquire both products and services to meet their needs, in the last century these establishments have diversified into wholesalers and retailers, being these subs classified into modern and traditional that share similar markets. From which the literature has identified trends and debates that seem to oppose one over the other because of their differences mainly in large cities. The objective of this paper was to describe the main socioeconomic characteristics of retail trade, particularly those related to grocery stores and convenience stores in Zapopan, Jalisco, Mexico. Among the results, it stands out that grocery stores have decreased in percentage terms while convenience stores have increased in number, as well as the number of paid personnel in the municipality under study, which is why it was identified that they have decreased, but not disappeared as stated in the literature. It is concluded that in the traditional retail trade there are elements of a social nature on which economic aspects are sustained that have allowed them to remain in the market, so that it is invited to continue with approaches to these establishments from multidisciplinary perspectives in different time intervals., A oferta através da distribuição comercial permite que as pessoas tenham ao seu alcance e adquiram tanto produtos como serviços para satisfazer as suas necessidades, no século passado estes estabelecimentos diversificaram-se em grossistas e retalhistas, sendo estes subclassificados em modernos e tradicionais que partilham mercados semelhantes. A partir do qual a literatura identificou tendências e debates que parecem contrastar uns com os outros devido às suas diferenças principalmente nas grandes cidades. Este artigo teve como objetivo descrever as principais características socioeconómicas do comércio de varejo, particularmente em relação a mercearias e lojas de conveniência em Zapopan, Jalisco, México. Entre os resultados, destaca-se que os supermercados diminuíram em percentual enquanto os de conveniência aumentaram sua quantidade, assim como o pessoal remunerado no município de estudo, para o qual foi identificado que diminuíram, mas não desapareceram como propõe a literatura. Conclui-se que no retalho tradicional existem elementos de natureza social em que assentam aspetos económicos que lhes têm permitido permanecer no mercado, de tal forma que se convida a continuar com abordagens destes estabelecimentos a partir de perspetivas multidisciplinares em diferentes intervalos de tempo., El abasto por medio de la distribución comercial permite a las personas tener a su alcance y adquirir tanto productos como servicios para satisfacer sus necesidades, en el último siglo estos establecimientos se han diversificado en mayoristas y minoristas, siendo estos subclasificados en modernos y tradicionales que comparten mercados similares. A partir de lo cual la literatura ha identificado tendencias y debates que parecen contraponer uno sobre otro por sus diferencias principalmente en grandes ciudades. Este trabajo se planteó como objetivo describir las principales características socioeconómicas del comercio al por menor en particular lo referente a tiendas de abarrotes y tiendas de conveniencia en Zapopan, Jalisco, México. Entre los resultados resalta que las tiendas de abarrotes han disminuido porcentualmente mientras las tiendas de conveniencia han incrementado su cantidad, así como el personal remunerado en el municipio de estudio por lo cual se identificó que han decrecido, pero no desaparecido como lo plantea la literatura. Se concluye que en el comercio minorista tradicional existen elementos de índole social sobre los cuales se sustentan aspectos económicos que les han permitido mantenerse en el mercado, de tal manera que se invita a continuar con abordajes de estos establecimientos desde perspectivas multidisciplinares en distintos intervalos de tiempo.

Introduction: Nephrotoxicity is a common adverse effect that alters the clearance of lithium, which is eliminated predominantly by the kidneys.General Objective: Describe clinical cases related to Lithium poisoning.Materials and methods: Retrospective study of clinical cases related to Lithium poisoning.Results: 100% presented neurological disorders, requiring initiation of renal replacement therapy.Conclusion: The small gap between the therapeutic limit and the toxic limit can endanger patients who have a precise indication., Introducción: La nefrotoxicidad es un efecto adverso frecuente, que altera el aclaramiento del litio, que presenta eliminación predominantemente renal.Objetivo General: Describir los casos clínicos relacionados con la intoxicación por Litio.Materiales y métodos: Estudio retrospectivo de casos clínicos relacionados con intoxicación por Litio.Resultados: 100% presentó trastornos neurológicos, requiriendo inicio de terapia de sustitución renal.Conclusión: La escasa brecha entre el límite terapéutico y el tóxico, puede poner en peligro a los pacientes que cuentan con indicación precisa.&nbsp

Hungary has experienced a backslide in its rule of law ever since Viktor Orbán modified its constitution. Orbán, characterized by right-wing populism, has been questioned not only for the way in which he has seized power, but also for the way in which he has favored his close friends and family. Orbán portrays a constitutional vision that has been described as illiberal constitutionalism, which he complements with the idea of an illiberal democracy, where a vision against integration prevails and rather enhances the idea of a national identity opposed to the values of the European Union as an excuse to disregard EU law. The responses of theEuropean Union have varied, from political, judicial and economic sanctions, but seeing themselves trapped by the right to veto sanctions and the requirement of unanimity it would seem that there is no way out of the deterioration of the rule of law. Thus, the article analyzes different solutions, options, and possibilities in the face of the crisis of the rule of law and democracy in Hungary., Hungría ha experimentado un retroceso en su Estado de derecho desde que el partido de Viktor Orbán obtuvo una supermayoría y con ello modificó las normas constitucionales que regían al país. Orbán, caracterizado por un populismo de derecha, ha sido ampliamente cuestionado no solo por la manera en la que ha acaparado el poder, sino por la manera en la que ha favorecido desde el estado a sus amigos y familiares cercanos. El FIDESZ, partido político de Orbán, defiende una visión constitucional que se ha calificado como constitucionalismo iliberal, donde prima una visión opuesta al integracionismo y más bien realza la idea de una identidad nacional opuesta a los valores de la Unión Europea como excusa para incumplir las normas internacionales. Las respuestas de la Unión Europea han sido varias y de distinta índole, tanto política, judicial como económica, pero al verse entrampados por el derecho de vetar las sanciones y el requisito de unanimidad para poder sancionar a un país que no cumple con los valores de la Unión Europea, parecería que no hay salida al deterioro del Estado de derecho. Así, el artículo analiza distintas salidas, opciones y posibilidades frente a la crisis del Estado de derecho y la democracia en Hungría.

Cellular senescence is a stress response involved in ageing and diverse disease processes including cancer, type-2 diabetes, osteoarthritis and viral infection. Despite growing interest in targeted elimination of senescent cells, only few senolytics are known due to the lack of well-characterised molecular targets. Here, we report the discovery of three senolytics using cost-effective machine learning algorithms trained solely on published data. We computationally screened various chemical libraries and validated the senolytic action of ginkgetin, periplocin and oleandrin in human cell lines under various modalities of senescence. The compounds have potency comparable to known senolytics, and we show that oleandrin has improved potency over its target as compared to best-in-class alternatives. Our approach led to several hundred-fold reduction in drug screening costs and demonstrates that artificial intelligence can take maximum advantage of small and heterogeneous drug screening data, paving the way for new open science approaches to early-stage drug discovery.

MYC is an oncogenic transcription factor dysregulated in about half of total human tumors. While transcriptomic studies reveal more than 1000 genes regulated by MYC, a much smaller fraction of genes is directly transactivated by MYC. Virtually all Burkitt lymphoma (BL) carry chromosomal translocations involving MYC oncogene. Most endemic BL and a fraction of sporadic BL are associated with Epstein–Barr virus (EBV) infection. The currently accepted mechanism is that EBV is the BL-causing agent inducing MYC translocation. Herein we show that the EBV receptor, CR2 (also called CD21), is a direct MYC target gene. This is based on several pieces of evidence: MYC induces CR2 expression in both proliferating and arrested cells and in the absence of protein synthesis, binds the CR2 promoter and transactivates CR2 in an E-box-dependent manner. Moreover, using mice with conditional MYC ablation we show that MYC induces CR2 in primary B cells. Importantly, modulation of MYC levels directly correlates with EBV’s ability of infection in BL cells. Altogether, in contrast to the widely accepted hypothesis for the correlation between EBV and BL, we propose an alternative hypothesis in which MYC dysregulation could be the first event leading to the subsequent EBV infection.