To study associations across tumor types between genome-wide loss of heterozygosity (gLOH) and alterations in homologous recombination repair (HRR)-associated genes beyond BRCA1 and BRCA2.
Genomic ...profiling using a targeted next-generation sequencing assay examining 324-465 genes (FoundationOne, FoundationOne Heme, and FoundationOne CDx; Foundation Medicine, Inc.) was performed in a cohort of 160,790 samples across different tumor types. Zygosity predictions and gLOH status were calculated and linked with alterations in 18 HRR-associated genes (BRCA1, BRCA2, PALB2, BARD1, ATR, ATRX, ATM, BAP1, RAD51B, RAD51C, RAD51D, BRIP1, NBN, CHEK1, CHEK2, FANCA, FANCC, MRE11) and other genomic features, using Fisher's exact test and Mann-Whitney U tests.
We identified a strong correlation between elevated gLOH and biallelic alterations in a core set of HRR-associated genes beyond BRCA1 and BRCA2, such as BARD1, PALB2, FANCC, RAD51C, and RAD51D (particularly in breast, ovarian, pancreatic, and prostate cancer). Monoallelic/heterozygous alterations in HRR-associated genes were not associated with elevated gLOH. gLOH was also independently associated with TP53 loss. Co-occurrence of TP53 loss and alterations in HRR-associated genes, and combined loss of TP53-PTEN or TP53-RB1, was associated with a higher gLOH than each of the events separately.
Biallelic alterations in core HRR-associated genes are frequent, strongly associated with elevated gLOH, and enriched in breast, ovarian, pancreatic, and prostate cancer. This analysis could inform the design of the next generation of clinical trials examining DNA repair-targeting agents, including PARP inhibitors.
Malignant melanoma (MM) is the most aggressive form of skin cancer, with increasing incidence worldwide. To date, there are no suitable clinical diagnostic, prognostic or predictive biomarkers for ...MM. Our data highlight the potential of metabolomic characterization of cancer stem cell‐ or serum‐derived exosomes using high‐resolution mass spectrometry for the discovery of clinically useful MM biomarkers.
Malignant melanoma (MM) is the most aggressive and life‐threatening form of skin cancer. It is characterized by an extraordinary metastasis capacity and chemotherapy resistance, mainly due to melanoma cancer stem cells (CSCs). To date, there are no suitable clinical diagnostic, prognostic or predictive biomarkers for this neoplasia. Therefore, there is an urgent need for new MM biomarkers that enable early diagnosis and effective disease monitoring. Exosomes represent a novel source of biomarkers since they can be easily isolated from different body fluids. In this work, a primary patient‐derived MM cell line enriched in CSCs was characterized by assessing the expression of specific markers and their stem‐like properties. Exosomes derived from CSCs and serums from patients with MM were characterized, and their metabolomic profile was analysed by high‐resolution mass spectrometry (HRMS) following an untargeted approach and applying univariate and multivariate statistical analyses. The aim of this study was to search potential biomarkers for the diagnosis of this disease. Our results showed significant metabolomic differences in exosomes derived from MM CSCs compared with those from differentiated tumour cells and also in serum‐derived exosomes from patients with MM compared to those from healthy controls. Interestingly, we identified similarities between structural lipids differentially expressed in CSC‐derived exosomes and those derived from patients with MM such as the glycerophosphocholine PC 16:0/0:0. To our knowledge, this is the first metabolomic‐based study aimed at characterizing exosomes derived from melanoma CSCs and patients' serum in order to identify potential biomarkers for MM diagnosis. We conclude that metabolomic characterization of CSC‐derived exosomes sets an open door to the discovery of clinically useful biomarkers in this neoplasia.
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An early diagnosis of cancer is fundamental not only in regard to reducing its mortality rate but also in terms of counteracting the progression of the tumor in the initial stages. Breast cancer (BC) ...is the most common tumor pathology in women and the second deathliest cancer worldwide, although its survival rate is increasing thanks to improvements in screening programs. However, the most common techniques to detect a breast tumor tend to be time-consuming, unspecific or invasive. Herein, the use of untargeted hydrophilic interaction liquid chromatography-mass spectrometry analysis appears as an analytical technique with potential use for the early detection of biomarkers in liquid biopsies from BC patients. In this research, plasma samples from 134 BC patients were compared with 136 from healthy controls (HC), and multivariate statistical analyses showed a clear separation between four BC phenotypes (LA, LB, HER2, and TN) and the HC group. As a result, we identified two candidate biomarkers that discriminated between the groups under study with a VIP > 1 and an AUC of 0.958. Thus, targeting the specific aberrant metabolic pathways in future studies may allow for better molecular stratification or early detection of the disease.
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Malignant melanoma (MM) can spread to other organs and is resistant in part due to the presence of cancer stem cell subpopulations (CSCs). While a controversial high dose of interferon-alpha (IFN-α) ...has been used to treat non-metastatic high-risk melanoma, it comes with undesirable side effects. In this study, we evaluated the effect of low and high doses of IFN-α on CSCs by analyzing ALDH activity, side population and specific surface markers in established and patient-derived primary cell lines. We also assessed the clonogenicity, migration and tumor initiation capacities of IFN-α treated CSCs. Additionally, we investigated genomic modulations related to stemness properties using microRNA sequencing and microarrays. The effect of IFN-α on CSCs-derived exosomes was also analyzed using NanoSight and liquid chromatography (LC-HRMS)-based metabolomic analysis, among others. Our results showed that even low doses of IFN-α reduced CSC formation and stemness properties, and led to a significant decrease in the ability to form tumors in mice xenotransplants. IFN-α also modulated the expression of genes and microRNAs involved in several cancer processes and metabolomics of released exosomes. Our work suggests the utility of low doses of interferon, combined with the analysis of metabolic biomarkers, as a potential clinical approach against the aggressiveness of CSCs in melanoma.
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Resumen El presente trabajo es un estudio orientado a identificar las principales dificultades que muestran los estudiantes al resolver problemas algorítmicos o algebraicos. Se ha tomado como ...referencia la base de datos que contiene la información sobre la aplicación de pruebas estandarizadas de matemáticas, a escala nacional, de estudiantes de 7° a 9° grado (doce a quince años) de la educación básica en Honduras. Después de un análisis de los parámetros estadísticos de dificultad, correlación, así como del análisis gráfico de las opciones de cada ítem, se seleccionaron los ítems contestados de forma incorrecta por estudiantes que tienen altos puntajes en las pruebas aplicadas, lo que permitió analizarlos tomando como referencia investigaciones realizadas en otros contextos. Los resultados muestran que estudiantes de alto desempeño cometen errores en problemas básicos de aritmética y álgebra. Consideramos que reconocer estos errores es un buen camino para orientar procesos de formación y capacitación docente, así como para fortalecer estrategias didácticas encaminadas a evitar los errores identificados.
Abstract This work is a study aimed at identifying the main difficulties that students show when solving algorithmic or algebraic problems. As a reference point, we used the database that contains the results of the application of standardized mathematics tests on basic education students from 7th to 9th grade (ages 12 to 15) in Honduras. After an analysis of the statistical parameters of difficulty, correlation, as well as the graphical analysis of the options of each item, the items answered incorrectly by students who had high scores in the applied tests were selected, which allowed them to be analyzed taking as reference the research carried out in other contexts. The results show that high performance students make mistakes in basic problems of arithmetic and algebra. We believe that recognizing these errors is a good way to guide teacher education and training processes, as well as to strengthen teaching strategies aimed at avoiding the identified errors.
Este trabajo está orientado a una valoración del alineamiento o coherencia, a nivel de demanda cognitiva, entre los estándares educativos y las tareas o actividades que proponen los libros de texto ...oficiales para la enseñanza de las Matemáticas para el bloque de Álgebra en los grados 7°, 8°y 9° de la Educación Básica en Honduras. Si se asegura un verdadero alineamiento entre los estándares educativos, los libros de texto y las evaluaciones, se ayuda a mejorar los procesos de implementación del curriculo, a valorar con mejor criterio los resultados de las evaluaciones y a involucrar a los docentes en los procesos de mejora. Con la ayuda de veinte docentes de Matemáticas, hondurenos, con amplia experiencia en estos grados y aplicando el modelo propuesto por Webb (1997), se clasificaron, según el nivel de demanda cognitiva, treinta estándares del boque de Álgebra y 110 preguntas de las pruebas nacionales de evaluación. A partir de esta clasificación fueron evaluadas, posteriormente, 1912 tareas similares a las propuestas en dichas pruebas y recogidas en los libros de texto oficiales para los grados en estudio. Los resultados encontrados indican que no existe un adecuado alineamiento a nivel de demanda cognitiva, en el bloque de Álgebra, entre estándares educativos y actividades propuestas en los libros de texto. Consideramos que la metodologia utilizada puede resultar útil para extenderla a otros bloques de Matemáticas, asi como a otras áreas de la educación básica.
Dengue (DEN) is an infectious disease caused by the DEN virus (DENV), which belongs to the Flavivirus genus in the family Flaviviridae. It has a (+) sense RNA genome and is mainly transmitted to ...humans by the vector mosquito Aedes aegypti. Dengue fever (DF) and dengue hemorrhagic fever (DHF) are caused by one of four closely related virus serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Epidemiological and evolutionary studies have indicated that host and viral factors are involved in determining disease outcome and have proved the importance of viral genotype in causing severe epidemics. Host immune status and mosquito vectorial capacity are also important influences on the severity of infection. Therefore, an understanding of the relationship between virus variants with altered amino acids and high pathogenicity will provide more information on the molecular epidemiology of DEN. Accordingly, knowledge of the DENV serotypes and genotypes circulating in the latest DEN outbreaks around the world, including Mexico, will contribute to understanding DEN infections.
1. We obtained 88 isolates of DENV, 27 from Oaxaca and 61 from Veracruz. 2. Of these 88 isolates, 16 were serotype 1; 62 serotype 2; 7 serotype 3; and 2 serotype 4. One isolate had 2 serotypes (DENV-2 and -1). 3. Partial nucleotide sequences of the genes encoding C- prM (14 sequences), the NS3 helicase domain (7 sequences), the NS5 S-adenosyl methionine transferase domain (7 sequences) and the RNA-dependent RNA polymerase (RdRp) domain (18 sequences) were obtained. Phylogenetic analysis showed that DENV-2 isolates belonged to the Asian/American genotype. In addition, the Asian/American genotype was divided into two clusters, one containing the isolates from 2001 and the other the isolates from 2005-2006 with high bootstrap support of 94%.
DENV-2 was the predominant serotype in the DF and DHF outbreak from 2005 to 2006 in Oaxaca State as well as in the 2006 outbreak in Veracruz State, with the Asian/American genotype prevalent in both states. Interestingly, DENV-1 and DENV-2 were the only serotypes related to DHF cases. In contrast, DENV-3 and DENV-4 were poorly represented according to epidemiological data reported in Mexico. We found that isoleucine was replaced by valine at residue 106 of protein C in the isolates from these 2005-2006 outbreaks and in those from the 1997, 1998 and 2001 outbreaks in the Caribbean islands. We suggested that this amino acid change may be used as a signature for isolates arising in the Caribbean islands and pertaining to the Asian/American genotype. Other amino acid changes are specific for the Asian/American, Asian and American strains.
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Introducción: las investigaciones empíricas demuestran que la autoeficacia percibida es una variable importante en el mantenimiento y la reducción del peso. Existen instrumentos que evalúan la ...autoeficacia percibida y su relación con la obesidad, pero en México aún son insuficientes.Objetivo: el propósito de la presente investigación es analizar las propiedades psicométricas de la versión mexicana del inventario de autoeficacia para el control de peso (AP-CP) en estudiantes universitarios del área de la salud.Métodos: en el estudio participaron 872 estudiantes universitarios de la Escuela de Ciencias de la Salud con edades comprendidas entre 17 y 47 (20,07 ± 2,61) años. Para evaluar la pertinencia del análisis factorial se realizó la prueba de esfericidad de Bartlett. Para evaluar el ajuste de los puntajes en factores específicos se llevó a cabo el método de componentes principales con rotación Varimax.Resultados: el análisis del índice de consistencia interna (coeficiente alfa de Cronbach) muestra adecuadas propiedades psicométricas para los tres factores resultantes: 0,856 para el factor “estilo de alimentación y externalidad”, 0,85 para el factor “actividad física programada” y 0,671 para el factor “actividad física cotidiana”.Conclusión: los hallazgos de este estudio muestran que el AP-CP es un instrumento confiable y válido para medir el nivel de autoeficacia para el control de peso en estudiantes universitarios mexicanos del área de la salud.
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El presente trabajo expone los resultados obtenidos de un estudio de investigación orientado a explorar las principales creencias y concepciones de los profesores que enseñan matemáticas en el nivel ...de secundaria en Honduras (alumnos de 13 a 18 años), en relación con la enseñanza, el aprendizaje y la evaluación de las matemáticas.Los resultados muestran, entre otros aspectos, que para los profesores hondureños el aprendizaje de las matemáticas se logra por la participación del alumno, creencia que está más acentuada en los profesores con formación de licenciatura, y que la evaluación es un proceso que mejora la enseñanza y el aprendizaje, aunque debe tratarse con mucho cuidado por los errores y las imprecisiones existentes.Como conclusiones, destacamos la necesidad de mejorar la formación inicial y continua de los profesores de manera que utilicen recursos que favorezcan la participación de los alumnos, y mejoren los procesos de evaluación.
This paper presents the results obtained from a research study aimed at exploring the main beliefs and conceptions of teachers who teach mathematics at the secondary level in Honduras (students from 13 to 18 years old), in relation to teaching, learning and the assessment of mathematics. The results show, among other aspects, that for Honduran teachers, learning mathematics is achieved through student participation, a belief that is more accentuated in teachers with a bachelor's degree, and that evaluation is a process that improves teaching. and learning, although it must be treated with great care due to errors and inaccuracies. As conclusions, we highlight the need to improve the initial and continuous training of teachers so that they use resources that favor student participation, and improve evaluation processes.
Este trabalho apresenta os resultados de um estudo de pesquisa teve como objetivo explorar as principaiscrenças e concepções que têm professores que ensinam matemática para o ensino secundário e nível médioem Honduras (estudantes de 13 a 18 anos), em relação ao ensino/aprendizagem e avaliação da matemática.Entre outros aspetos, os resultados mostram que para os professores hondurenhos a aprendizagem damatemática é alcançada pela participação ativa do aluno, uma crença que está mais acentuada nosprofessores com licenciatura, e que a avaliação é um processo que melhoria do ensino e da aprendizagemque fornece resultados úteis mas que devem ser tratados com grande cuidado pelos erros e imprecisõesque sempre existem.Como conclusões, destaca-se a necessidade de melhorar a formação inicial e continuada dos professores,a fim de utilizar recursos que favoreçam a participação ativa dos estudantes e melhorar os processos deavaliação.
Este trabalho apresenta os resultados de um estudo de pesquisa teve como objetivo explorar as principaiscrenças e concepções que têm professores que ensinam matemática para o ensino secundário e nível médioem Honduras (estudantes de 13 a 18 anos), em relação ao ensino/aprendizagem e avaliação da matemática.Entre outros aspetos, os resultados mostram que para os professores hondurenhos a aprendizagem damatemática é alcançada pela participação ativa do aluno, uma crença que está mais acentuada nosprofessores com licenciatura, e que a avaliação é um processo que melhoria do ensino e da aprendizagemque fornece resultados úteis mas que devem ser tratados com grande cuidado pelos erros e imprecisõesque sempre existem.Como conclusões, destaca-se a necessidade de melhorar a formação inicial e continuada dos professores,a fim de utilizar recursos que favoreçam a participação ativa dos estudantes e melhorar os processos deavaliação.
empirical research shows that perceived self-efficacy is an important variable in maintaining and reducing weight. There are available instruments to measure perceived self-efficacy and its relation ...to obesity, but in Mexico it is still insufficient.
the purpose of the current research is to analyze the psychometric properties of the Mexican version of the self-efficacy inventory for weight control (SEI-WC) in university students in the health area.
participants in this study were 872 university students from the School of Health Sciences, aged between 17 and 47 (20.07 ± 2.61) years. Bartlett's sphericity test was performed to evaluate the relevance of the factor analysis. The principal component analysis with Varimax rotation was used to evaluate the adjustment of the scores on each factor.
internal consistency (Cronbach's alpha) shows adequate psychometric properties for the three final factors: 0.856 for the factor "feeding style and externality", 0.85 for "programmed physical activity" and 0.671 for "daily physical activity".
the findings of this study show that the SEI-WC is a reliable and valid instrument to measure the level of self-efficacy for weight control in Mexican university students in the health area.
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