Integrative Model-based clustering of microarray methylation and expression data

In many fields, researchers are interested in large and complex biological processes. Two important examples are gene expression and DNA methylation in genetics. One key problem is to identify aberrant patterns of these processes and discover biologically distinct groups. In this article we develop a model-based method for clustering such data. The basis of our method involves the construction of a likelihood for any given partition of the subjects. We introduce cluster specific latent indicators that, along with some standard assumptions, impose a specific mixture distribution on each cluster. Estimation is carried out using the EM algorithm. The methods extend naturally to multiple data types of a similar nature, which leads to an integrated analysis over multiple data platforms, resulting in higher discriminating power.Comment: Published in at http://dx.doi.org/10.1214/11-AOAS533 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Malnutrición materno-fetal: Revisión de la bibliografía internacional y la urgencia de estudios, prevención e intervención en el Perú

Maternal-fetal malnutrition is common in Peru, but its prevention and possible intervention measures have not been investigated in Peru. We conducted a literature review on the topic to prevent and manage this serious public health problem.En el Perú, la malnutrición materno-fetal ocurre con frecuencia, pero su prevención, intervención y seguimiento no ha sido investigada en relación al conocimiento y experiencia de países emergentes. Los autores presentan una revisión actualizada de los avances científicos sobre malnutrición materno-fetal, con el fin de prevenir y manejar un empobrecido capital humano, que constituye nuestro principal y más urgente problema sanitario

Promoción científica, tecnológica y académica en la región NOA mediante repositorios digitales

El fuerte desarrollo de la producción científica así como la significativa expansión de la oferta educativa a nivel de grado y posgrado en la región del NOA en los últimos veinticinco años, han generado una urgente necesidad de crear un eficiente y efectivo sistema institucional de Repositorio Digital (RD), el cual enmarque e incluya a las relevantes universidades de la región. Atendiendo a esto, se presenta un proyecto de investigación aplicada, financiado por la Agencia Nacional de Promoción Científica y Tecnológica de la Argentina (PICTO-CIN 2010), cuyo propósito consiste en definir el diseño de un Repositorio Digital de las Universidades de la Región Noroeste de Argentina (NOA). En el mismo, se plantea crear un Repositorio Digital (RD) Institucional entre las universidades de la región NOA con el objetivo de mejorar la colaboración, desarrollo, enseñanza, aprendizaje, investigación y divulgación en las mismas. Servirá también para el desarrollo de un consorcio académico, científico y tecnológico que provea una colección balanceada y actualizada de la producción de las Universidades del NOA. Las principales variables a abordar en el estudio, se refieren a los mecanismos de recuperación y utilización de documentos digitales, de acuerdo con las normas, recomendaciones y estándares vigentes; principalmente los referidos a metadatos, interoperabilidad y accesibilidad de repositoriosEje: Tecnología informática aplicada en educaciónRed de Universidades con Carreras en Informática (RedUNCI

DNA Methylation Signatures Identify Biologically Distinct Subtypes in Acute Myeloid Leukemia

Abstract: We hypothesized that DNA methylation distributes into specific patterns in cancer cells, which reflect critical biological differences. We therefore examined the methylation profiles of 344 patients with acute myeloid leukemia (AML). Clustering of these patients by methylation data segregated patients into 16 groups. Five of these groups defined new AML subtypes that shared no other known feature. In addition, DNA methylation profiles segregated patients with CEBPA aberrations from other subtypes of leukemia, defined four epigenetically distinct forms of AML with NPM1 mutations, and showed that established AML1-ETO, CBFb-MYH11, and PML-RARA leukemia entities are associated with specific methylation profiles. We report a 15 gene methylation classifier predictive of overall survival in an independent patient cohort (p < 0.001, adjusted for known covariates)

H2.0-like Homeobox Regulates Early Hematopoiesis and Promotes Acute Myeloid Leukemia

SummaryHomeobox domain-containing transcription factors are important regulators of hematopoiesis. Here, we report that increased levels of nonclustered H2.0-like homeobox (HLX) lead to loss of functional hematopoietic stem cells and formation of aberrant progenitors with unlimited serial clonogenicity and blocked differentiation. Inhibition of HLX reduces proliferation and clonogenicity of leukemia cells, overcomes the differentiation block, and leads to prolonged survival. HLX regulates a transcriptional program, including PAK1 and BTG1, that controls cellular differentiation and proliferation. HLX is overexpressed in 87% of patients with acute myeloid leukemia (AML) and independently correlates with inferior overall survival (n = 601, p = 2.3 × 10−6). Our study identifies HLX as a key regulator in immature hematopoietic and leukemia cells and as a prognostic marker and therapeutic target in AML

A distinct epigenetic program underlies the 1;7 translocation in myelodysplastic syndromes

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El modelo sistémico de aprendizaje y enseñanza, como apoyo en la inserción laboral

The main objective of the research was to find out how the systemic process influences with the teaching and learning approach, in the labor inclusion of graduates of the Faculty of Law of the National University Hermilio Valdizán. To achieve this, the study was developed based on a descriptive explanatory type, under a non-experimental, correlational and cross-sectional design, for which we worked with a population of 121 graduates and the sample consisted of 37 graduates from the years 2016 and 2017, being of the non-probabilistic type, which were constructed two questionnaires, a questionnaire to measure the systematic teaching-learning process variable, another questionnaire to measure the job placement opportunity variable, all to qualify the level of influence. Sperman's Ro test was applied to evaluate the hypothesis. As a result, our results confirmed the study hypothesis, showing that the systemic teaching-learning process shows a significant relationship with job placement and that there is a positive influence between both variables. Reaching the conclusion that exercising a systemic process in teaching and learning generates opportunity in labor inclusion.La investigación tuvo como objetivo principal buscar cómo influye el proceso sistémico con el enfoque de enseñanza y aprendizaje, en la inclusión laboral de los egresados de la Facultad de Derecho de la Universidad Nacional Hermilio Valdizán. Para lograrlo, se desarrolló el estudio en base a tipo descriptivo explicativo, bajo un diseño no experimental, correlacional &nbsp;y de tipo transversal, para lo cual se trabajó con una población de 121 egresados y la muestra estuvo constituida por 37 egresados de los años 2016 y 2017, siendo del tipo no probabilístico, los cuales se construyeron dos cuestionarios, un cuestionario para medir la variable proceso sistemático de enseñanza-aprendizaje, otro cuestionario para medir la variable oportunidad de inserción laboral, todo ello para calificar el nivel de influencia. Para evaluar la hipótesis se aplicó la prueba Ro de Sperman. A raíz de ello nuestros resultados confirmaron la hipótesis de estudio, demostrando que el proceso sistémico de enseñanza-aprendizaje muestra una relación significativa con la inserción laboral y que existe influencia positiva entre ambas variables. Llegando a la conclusión que ejercer un proceso sistémico en la enseñanza y aprendizaje genera oportunidad en la inclusión laboral

Analysis of candidate genes for macular telangiectasia type 2

Purpose: To find the gene(s) responsible for macular telangiectasia type 2 (MacTel) by a candidate-gene screening approach.Methods: Candidate genes were selected based on the following criteria: those known to cause or be associated with diseases with phenotypes similar to MacTel, genes with known function in the retinal vasculature or macular pigment transport, genes that emerged from expression microarray data from mouse models designed to mimic MacTel phenotype characteristics, and genes expressed in the retina that are also related to diabetes or hypertension, which have increased prevalence in MacTel patients. Probands from eight families with at least two affected individuals were screened by direct sequencing of 27 candidate genes. Identified nonsynonymous variants were analyzed to determine whether they cosegregate with the disease in families. Allele frequencies were determined by TaqMan analysis of the large MacTel and control cohorts.Results: We identified 23 nonsynonymous variants in 27 candidate genes in at least one proband. Of these, eight were known single nucleotide polymorphisms (SNPs) with allele frequencies of >0.05; these variants were excluded from further analyses. Three previously unidentified missense variants, three missense variants with reported disease association, and five rare variants were analyzed for segregation and/or allele frequencies. No variant fulfilled the criteria of being causal for MacTel. A missense mutation, p.Pro33Ser in frizzled homolog (Drosophila) 4 (FZD4), previously suggested as a disease-causing variant in familial exudative vitreoretinopathy, was determined to be a rare benign polymorphism.Conclusions: We have ruled out the exons and flanking intronic regions in 27 candidate genes as harboring causal mutations for MacTel

Association between childhood trauma and mental health disorders in adolescents during the second pandemic wave of COVID-19, Chiclayo-Peru

"Introduction: The COVID-19 pandemic has significantly affected mental health, with children and adolescents being particularly vulnerable. Evidence on the association between childhood trauma and mental health outcomes in schoolchildren during the pandemic is limited. This study aimed to evaluate this relationship in Chiclayo city, northern Peru, during the second wave of COVID-19. Methods: A cross-sectional secondary data study was conducted, measuring childhood trauma using the Marshall’s Trauma Scale, depressive symptomatology (PHQ-9), and anxiety symptomatology (GAD-7). Additional variables assessed were alcohol use (AUDIT), resilience (abbreviated CD-RISC), and socio-educational data. Prevalence ratios were estimated using generalized linear models. Results: Among 456 participants, 88.2% were female, with a mean age of 14.5 years (SD: 1.33). Depressive symptomatology prevalence was 76.3% (95%CI: 72.14– 80.15) and increased by 23% in schoolchildren with childhood trauma (PR: 1.23; 95%CI: 1.10–1.37). Factors positively associated with depressive symptomatology included increasing age, seeking mental health help during the pandemic, and severe family dysfunction. Anxiety symptomatology prevalence was 62.3% (95%CI: 57.65–66.75) and increased by 55% in schoolchildren with childhood trauma (PR: 1.55; 95%CI: 1.31–1.85). Anxiety symptomatology was positively associated with mild, moderate, and severe family dysfunction. Conclusion: Schoolchildren exposed to childhood trauma are at increased risk for depressive and anxiety symptoms. Monitoring the impact of the COVID-19 pandemic on adolescent mental health is vital. These findings can assist schools in establishing effective measures to prevent mental health outcomes

Gene Expression Signature of Cigarette Smoking and Its Role in Lung Adenocarcinoma Development and Survival

Tobacco smoking is responsible for over 90% of lung cancer cases, and yet the precise molecular alterations induced by smoking in lung that develop into cancer and impact survival have remained obscure.We performed gene expression analysis using HG-U133A Affymetrix chips on 135 fresh frozen tissue samples of adenocarcinoma and paired noninvolved lung tissue from current, former and never smokers, with biochemically validated smoking information. ANOVA analysis adjusted for potential confounders, multiple testing procedure, Gene Set Enrichment Analysis, and GO-functional classification were conducted for gene selection. Results were confirmed in independent adenocarcinoma and non-tumor tissues from two studies. We identified a gene expression signature characteristic of smoking that includes cell cycle genes, particularly those involved in the mitotic spindle formation (e.g., NEK2, TTK, PRC1). Expression of these genes strongly differentiated both smokers from non-smokers in lung tumors and early stage tumor tissue from non-tumor tissue (p<0.001 and fold-change >1.5, for each comparison), consistent with an important role for this pathway in lung carcinogenesis induced by smoking. These changes persisted many years after smoking cessation. NEK2 (p<0.001) and TTK (p = 0.002) expression in the noninvolved lung tissue was also associated with a 3-fold increased risk of mortality from lung adenocarcinoma in smokers.Our work provides insight into the smoking-related mechanisms of lung neoplasia, and shows that the very mitotic genes known to be involved in cancer development are induced by smoking and affect survival. These genes are candidate targets for chemoprevention and treatment of lung cancer in smokers