Supervivencia global en pacientes con cáncer gástrico avanzado o metastásico en los últimos 10 años en el Centro Médico Nacional «20 de noviembre del ISSSTE»

ResumenAntecedentesLa introducción de nuevos fármacos para el tratamiento de los pacientes con cáncer gástrico irresecable, recurrente o metastásico ha reportado un modesto incremento en la supervivencia libre de progresión (SLP) y la supervivencia global (SG).ObjetivoDeterminar el impacto de la aplicación de los nuevos esquemas de quimioterapia paliativa en la SG de los pacientes con cáncer gástrico del Centro Médico Nacional 20 de noviembre, ISSSTE.Material y métodosEstudio retrospectivo, descriptivo. Analizamos expedientes de pacientes con cáncer gástrico irresecable o metastásico, tratados con quimioterapia paliativa de enero de 2002 a diciembre de 2012 en el Centro Médico Nacional 20 de noviembre, ISSSTE. Se evaluó la SG, SLP y los esquemas de quimioterapia más frecuentemente utilizados. Se asignaron los casos a 2 cohortes de acuerdo a la fecha de inicio de la quimioterapia, conformando la cohorte A los pacientes tratados de enero de 2002 hasta diciembre de 2006 y la cohorte B de enero de 2007 a diciembre de 2012. Se estableció estos periodos dado que representaba el cambio en los esquemas de tratamiento utilizados; es decir; la introducción de esquemas que incluyen antraciclinas, oxaliplatino, capecitabina y docetaxel.ResultadosRevisamos los expedientes de 291 pacientes con cáncer gástrico; excluimos a 221 pacientes por estar en etapas tempranas (i, ii o iii) resecables, recibir tratamiento con quimioterapia fuera de la unidad o no ser candidatos a quimioterapia. Finalmente incluimos 70 casos con tratamiento de primera línea. La mediana de SG para pacientes de la cohorte A fue de 11.2 vs. 10.5 meses para los pacientes de la cohorte B. La mediana de SLP en primera línea de tratamiento fue 8.5 vs. 5.2 meses respectivamente. Ambos resultados sin diferencia estadísticamente significativa.ConclusiónEn nuestro centro, no hay impacto de los nuevos esquemas de tratamiento en SLP o SG. Un tamaño de muestra pequeño y el hecho de que pacientes con pobre estado funcional recibieran quimioterapia podrían ser factores que influyeron en los resultados del estudio, en el cual se observó una tendencia a favor de los nuevos esquemas de quimioterapia, pero sin demostrar significación estadística.AbstractBackgroundThe introduction of new drugs for the treatment of patients with advanced, recurrent or metastatic gastric cancer has resulted in a small benefit in overall survival (OS) and progression free survival (PFS).ObjectiveTo determine the impact of new chemotherapy schedules on the OS of patients with advanced or metastic gastric cancer treated at the Centro Medico Nacional 20 de noviembre, ISSSTE.Material and methodologyRetrolective, descriptive study, the clinical files of patients with advanced, recurrent or metastatic gastric cancer treated with chemotherapy at the Centro Medico Nacional 20 de noviembre, ISSSTE, from january 2002 to december 2012, were analyzed. Chemotherapy schedules, OS and PFS were evaluated. Patients were assigned to two cohorts: those treated from january 2002 to december 2006 were included in cohort A and those treated from january 2007 to december 2012 in cohort B. These time periods were determined based on the years when newer chemotherapy agents (anthracyclines, oxaliplatin, capecitabine and docetaxel) were introduced in our institution.Results291 clinical files were analyzed; 221 patients were excluded for they had clinical stage I, II or resectable III disease, started first line chemotherapy as outpatients of our institution or were not candidates for chemotherapy. 70 cases treated with first line chemotherapy were included. OS for patients in cohort A was 11.2 months vs 10.5 months for patients in cohort B. PFS was 8.5 months vs 5.2, respectively. There was no statistical difference in either comparison.ConclusionThere was no impact of the introduction of newer chemotherapy agents in OS or PFS in patients treated in our institution. A small sample size and the fact that patients with poor performance status received chemotherapy could have had influenced the results of our study, in which tendency towards a better outcome for patients treated with newer chemotherapy schemes was observed, although a statistically significant benefit was not proven

New prioritized value iteration for Markov decision processes

The problem of solving large Markov decision processes accurately and quickly is challenging. Since the computational effort incurred is considerable, current research focuses on finding superior acceleration techniques. For instance, the convergence properties of current solution methods depend, to a great extent, on the order of backup operations. On one hand, algorithms such as topological sorting are able to find good orderings but their overhead is usually high. On the other hand, shortest path methods, such as Dijkstra's algorithm which is based on priority queues, have been applied successfully to the solution of deterministic shortest-path Markov decision processes. Here, we propose an improved value iteration algorithm based on Dijkstra's algorithm for solving shortest path Markov decision processes. The experimental results on a stochastic shortest-path problem show the feasibility of our approach. © Springer Science+Business Media B.V. 2011.García Hernández, MDG.; Ruiz Pinales, J.; Onaindia De La Rivaherrera, E.; Aviña Cervantes, JG.; Ledesma Orozco, S.; Alvarado Mendez, E.; Reyes Ballesteros, A. (2012). New prioritized value iteration for Markov decision processes. Artificial Intelligence Review. 37(2):157-167. doi:10.1007/s10462-011-9224-zS157167372Agrawal S, Roth D (2002) Learning a sparse representation for object detection. In: Proceedings of the 7th European conference on computer vision. Copenhagen, Denmark, pp 1–15Bellman RE (1954) The theory of dynamic programming. Bull Amer Math Soc 60: 503–516Bellman RE (1957) Dynamic programming. Princeton University Press, New JerseyBertsekas DP (1995) Dynamic programming and optimal control. Athena Scientific, MassachusettsBhuma K, Goldsmith J (2003) Bidirectional LAO* algorithm. In: Proceedings of indian international conferences on artificial intelligence. p 980–992Blackwell D (1965) Discounted dynamic programming. Ann Math Stat 36: 226–235Bonet B, Geffner H (2003a) Faster heuristic search algorithms for planning with uncertainty and full feedback. In: Proceedings of the 18th international joint conference on artificial intelligence. Morgan Kaufmann, Acapulco, México, pp 1233–1238Bonet B, Geffner H (2003b) Labeled RTDP: improving the convergence of real-time dynamic programming. In: Proceedings of the international conference on automated planning and scheduling. Trento, Italy, pp 12–21Bonet B, Geffner H (2006) Learning depth-first search: a unified approach to heuristic search in deterministic and non-deterministic settings and its application to MDP. In: Proceedings of the 16th international conference on automated planning and scheduling. Cumbria, UKBoutilier C, Dean T, Hanks S (1999) Decision-theoretic planning: structural assumptions and computational leverage. J Artif Intell Res 11: 1–94Chang I, Soo H (2007) Simulation-based algorithms for Markov decision processes Communications and control engineering. Springer, LondonDai P, Goldsmith J (2007a) Faster dynamic programming for Markov decision processes. Technical report. Doctoral consortium, department of computer science and engineering. University of WashingtonDai P, Goldsmith J (2007b) Topological value iteration algorithm for Markov decision processes. In: Proceedings of the 20th international joint conference on artificial intelligence. Hyderabad, India, pp 1860–1865Dai P, Hansen EA (2007c) Prioritizing bellman backups without a priority queue. In: Proceedings of the 17th international conference on automated planning and scheduling, association for the advancement of artificial intelligence. Rhode Island, USA, pp 113–119Dibangoye JS, Chaib-draa B, Mouaddib A (2008) A Novel prioritization technique for solving Markov decision processes. In: Proceedings of the 21st international FLAIRS (The Florida Artificial Intelligence Research Society) conference, association for the advancement of artificial intelligence. Florida, USAFerguson D, Stentz A (2004) Focused propagation of MDPs for path planning. In: Proceedings of the 16th IEEE international conference on tools with artificial intelligence. pp 310–317Hansen EA, Zilberstein S (2001) LAO: a heuristic search algorithm that finds solutions with loops. Artif Intell 129: 35–62Hinderer K, Waldmann KH (2003) The critical discount factor for finite Markovian decision processes with an absorbing set. Math Methods Oper Res 57: 1–19Li L (2009) A unifying framework for computational reinforcement learning theory. PhD Thesis. The state university of New Jersey, New Brunswick. NJLittman ML, Dean TL, Kaelbling LP (1995) On the complexity of solving Markov decision problems.In: Proceedings of the 11th international conference on uncertainty in artificial intelligence. Montreal, Quebec pp 394–402McMahan HB, Gordon G (2005a) Fast exact planning in Markov decision processes. In: Proceedings of the 15th international conference on automated planning and scheduling. Monterey, CA, USAMcMahan HB, Gordon G (2005b) Generalizing Dijkstra’s algorithm and gaussian elimination for solving MDPs. Technical report, Carnegie Mellon University, PittsburghMeuleau N, Brafman R, Benazera E (2006) Stochastic over-subscription planning using hierarchies of MDPs. In: Proceedings of the 16th international conference on automated planning and scheduling. Cumbria, UK, pp 121–130Moore A, Atkeson C (1993) Prioritized sweeping: reinforcement learning with less data and less real time. Mach Learn 13: 103–130Puterman ML (1994) Markov decision processes. 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Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit

Gene silencing of Nox4 by CpG island methylation during hepatocarcinogenesis in rats

The association between the downregulation of genes and DNA methylation in their CpG islands has been extensively studied as a mechanism that favors carcinogenesis. The objective of this study was to analyze the methylation of a set of genes selected based on their microarray expression profiles during the process of hepatocarcinogenesis. Rats were euthanized at: 24 h, 7, 11, 16 and 30 days and 5, 9, 12 and 18 months post-treatment. We evaluated the methylation status in the CpG islands of four deregulated genes (Casp3, Cldn1, Pex11a and Nox4) using methylation-sensitive high-resolution melting technology for the samples obtained from different stages of hepatocarcinogenesis. We did not observe methylation in Casp3, Cldn1 or Pex11a. However, Nox4 exhibited altered methylation patterns, reaching a maximum of 10%, even during the early stages of hepatocarcinogenesis. We observed downregulation of mRNA and protein of Nox4 (97.5% and 40%, respectively) after the first carcinogenic stimulus relative to the untreated samples. Our results suggest that Nox4 downregulation is associated with DNA methylation of the CpG island in its promoter. We propose that methylation is a mechanism that can silence the expression of Nox4, which could contribute to the acquisition of neoplastic characteristics during hepatocarcinogenesis in rats

The Genomes of Three Uneven Siblings: Footprints of the Lifestyles of Three Trichoderma Species.

The genus Trichoderma contains fungi with high relevance for humans, with applications in enzyme production for plant cell wall degradation and use in biocontrol. Here, we provide a broad, comprehensive overview of the genomic content of these species for "hot topic" research aspects, including CAZymes, transport, transcription factors, and development, along with a detailed analysis and annotation of less-studied topics, such as signal transduction, genome integrity, chromatin, photobiology, or lipid, sulfur, and nitrogen metabolism in T. reesei, T. atroviride, and T. virens, and we open up new perspectives to those topics discussed previously. In total, we covered more than 2,000 of the predicted 9,000 to 11,000 genes of each Trichoderma species discussed, which is >20% of the respective gene content. Additionally, we considered available transcriptome data for the annotated genes. Highlights of our analyses include overall carbohydrate cleavage preferences due to the different genomic contents and regulation of the respective genes. We found light regulation of many sulfur metabolic genes. Additionally, a new Golgi 1,2-mannosidase likely involved in N-linked glycosylation was detected, as were indications for the ability of Trichoderma spp. to generate hybrid galactose-containing N-linked glycans. The genomic inventory of effector proteins revealed numerous compounds unique to Trichoderma, and these warrant further investigation. We found interesting expansions in the Trichoderma genus in several signaling pathways, such as G-protein-coupled receptors, RAS GTPases, and casein kinases. A particularly interesting feature absolutely unique to T. atroviride is the duplication of the alternative sulfur amino acid synthesis pathway

Integrated genomic and transcriptomic analysis reveals mycoparasitism as the ancestoral life style of Trichoderma

Mycoparasitism, a lifestyle where one fungus is parasitic on another fungus has special relevance when the prey is a plant pathogen, providing a strategy for biological control of pests for plant protection. Probably, the most studied biocontrol agents are species of the genus Hypocrea/Trichoderma

Diminishing benefits of urban living for children and adolescents’ growth and development

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background: Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods: We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5-19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI &lt;18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For school-aged children and adolescents, we report thinness (BMI &lt;2 SD below the median of the WHO growth reference) and obesity (BMI &gt;2 SD above the median). Findings: From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation: The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesity. Funding: UK Medical Research Council, UK Research and Innovation (Research England), UK Research and Innovation (Innovate UK), and European Union