Aplicaciones móviles en el proceso de Enseñanza Aprendizaje de las Matemáticas

Technological tools have transformed the educational world, however, in practice, few teachers use these resources to promote the teaching-learning process of mathematics. The present study was carried out with the purpose of evaluating the perception of the use of mobile applications in the teaching-learning process of mathematics in an educational institution in Guayaquil. The methodology used was positivist paradigm, quantitative approach. The type of research was descriptive-field, with a non-experimental-transactional design. A survey was used as a data collection technique, through a questionnaire with 10 questions. The sample consisted of all the 5th grade students (35) and the mathematics teachers (6) for which a census sample was used. The data was processed using descriptive statistics. The results revealed that mathematics teachers are willing to adopt applications as part of their methods but are not trained with strategies designed to monitor results on these mobile platforms; from the student perspective, enthusiasm prevails, but some resistance to the little motivation they receive.Las herramientas tecnológicas han transformado el mundo educativo, sin embargo, en la práctica, son pocos los docentes que emplean estos recursos para favorecer el proceso de enseñanza aprendizaje de las matemáticas. El presente estudio se realizó con el propósito de evaluar la percepción sobre el uso de aplicativos móviles en el proceso de enseñanza aprendizaje de las matemáticas en una institución educativa de Guayaquil. La metodología empleada fue de paradigma positivista, enfoque cuantitativo. El tipo de investigación fue descriptiva-de campo, con un diseño no experimental-transaccional. Se utilizo una encuesta como técnica de recolección de datos, mediante un cuestionario con 10 preguntas. La muestra estuvo conformada por la totalidad de los estudiantes de 5to grado la institución educativa (35) y los docentes de matemáticas (6) por lo que se empleó un muestreo censal. Los datos fueron procesados mediante la estadística descriptiva. Los resultados revelaron que los docentes de matemáticas están dispuestos a la adopción de aplicaciones como parte de sus métodos, pero no se encuentran capacitados con estrategias diseñadas para el seguimiento de resultados en dichas plataformas móviles; desde el enfoque estudiantil prevalece el entusiasmo, pero cierta resistencia ante la escasa motivación que reciben

Aplicaciones móviles en el proceso de Enseñanza Aprendizaje de las Matemáticas

Technological tools have transformed the educational world, however, in practice, few teachers use these resources to promote the teaching-learning process of mathematics. The present study was carried out with the purpose of evaluating the perception of the use of mobile applications in the teaching-learning process of mathematics in an educational institution in Guayaquil. The methodology used was positivist paradigm, quantitative approach. The type of research was descriptive-field, with a non-experimental-transactional design. A survey was used as a data collection technique, through a questionnaire with 10 questions. The sample consisted of all the 5th grade students (35) and the mathematics teachers (6) for which a census sample was used. The data was processed using descriptive statistics. The results revealed that mathematics teachers are willing to adopt applications as part of their methods but are not trained with strategies designed to monitor results on these mobile platforms; from the student perspective, enthusiasm prevails, but some resistance to the little motivation they receive.Las herramientas tecnológicas han transformado el mundo educativo, sin embargo, en la práctica, son pocos los docentes que emplean estos recursos para favorecer el proceso de enseñanza aprendizaje de las matemáticas. El presente estudio se realizó con el propósito de evaluar la percepción sobre el uso de aplicativos móviles en el proceso de enseñanza aprendizaje de las matemáticas en una institución educativa de Guayaquil. La metodología empleada fue de paradigma positivista, enfoque cuantitativo. El tipo de investigación fue descriptiva-de campo, con un diseño no experimental-transaccional. Se utilizo una encuesta como técnica de recolección de datos, mediante un cuestionario con 10 preguntas. La muestra estuvo conformada por la totalidad de los estudiantes de 5to grado la institución educativa (35) y los docentes de matemáticas (6) por lo que se empleó un muestreo censal. Los datos fueron procesados mediante la estadística descriptiva. Los resultados revelaron que los docentes de matemáticas están dispuestos a la adopción de aplicaciones como parte de sus métodos, pero no se encuentran capacitados con estrategias diseñadas para el seguimiento de resultados en dichas plataformas móviles; desde el enfoque estudiantil prevalece el entusiasmo, pero cierta resistencia ante la escasa motivación que reciben

Homologous recombination DNA repair defects in PALB2-associated breast cancers

Mono-allelic germline pathogenic variants in the Partner And Localizer of BRCA2 (PALB2) gene predispose to a high-risk of breast cancer development, consistent with the role of PALB2 in homologous recombination (HR) DNA repair. Here, we sought to define the repertoire of somatic genetic alterations in PALB2-associated breast cancers (BCs), and whether PALB2-associated BCs display biallelic inactivation of PALB2 and/or genomic features of HR-deficiency (HRD). Twenty-four breast cancer patients with pathogenic PALB2 germline mutations were analyzed by whole-exome sequencing (WES, n = 16) or targeted capture massively parallel sequencing (410 cancer genes, n = 8). Somatic genetic alterations, loss of heterozygosity (LOH) of the PALB2 wild-type allele, largescale state transitions (LSTs) and mutational signatures were defined. PALB2-associated BCs were found to be heterogeneous at the genetic level, with PIK3CA (29%), PALB2 (21%), TP53 (21%), and NOTCH3 (17%) being the genes most frequently affected by somatic mutations. Bi-allelic PALB2 inactivation was found in 16 of the 24 cases (67%), either through LOH (n = 11) or second somatic mutations (n = 5) of the wild-type allele. High LST scores were found in all 12 PALB2-associated BCs with bi-allelic PALB2 inactivation sequenced by WES, of which eight displayed the HRD-related mutational signature 3. In addition, bi-allelic inactivation of PALB2 was significantly associated with high LST scores. Our findings suggest that the identification of bi-allelic PALB2 inactivation in PALB2- associated BCs is required for the personalization of HR-directed therapies, such as platinum salts and/or PARP inhibitors, as the vast majority of PALB2-associated BCs without PALB2 bi-allelic inactivation lack genomic features of HRD.. The authors thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (which has received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia, and the National Institute of Health (USA)) for their contributions to this resource, and the many families who contribute to kConFab. Research reported in this paper was supported in part by the Breast Cancer Research Foundation and the Sarah Jenkins Fund, a Cancer Center Support Grant of the National Institutes of Health/National Cancer Institute (grant No. P30CA008748; MSK), a grant of the Ministry of Health of the Czech Republic (NV15-29959A), Charles University projects PROGRES Q28/LF1 and SVV2019/260367, an HIR Grant UM.C/HlR/ MOHE/06 from the Ministry of Higher Education, Malaysia, and the National Health and Medical Research Council, Australia (NHMRC, Project Grant APP1029974). kConFab is supported by a grant from the National Breast Cancer Foundation, and previously by the NHMRC, the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, and the Cancer Foundation of Western Australia. W.D.F. was funded in part by Susan G Komen. A.L. was supported by the China Scholarship Council. T.N.-D. is an Early Career Fellow of the National Breast Cancer Foundation and M.S. is a NHMRC Senior Research Fellow of the National Health and Medical Research Council. M.T. was funded by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Addenbrooke’s Hospital and European Union Seventh Framework Program (2007–2013)/European Research Council (310018). S.P. was supported by the Swiss National Science Foundation (Ambizione grant number: PZ00P3_168165). J.S.R-F. is partly funded by the Breast Cancer Research Foundation and Britta Weigelt by Cycle for Survival

Whole‐exome sequencing and RNA sequencing analyses of acinic cell carcinomas of the breast

AimsAcinic cell carcinoma of the breast (ACC) is a rare histologic form of triple‐negative breast cancer (TNBC). Despite its unique histology, targeted sequencing analysis has failed to identify recurrent genetic alterations other than those found in common forms of TNBC. Here, we subjected three breast ACCs to whole‐exome and RNA‐sequencing, seeking to define whether they would harbor a pathognomonic genetic alteration.Methods and ResultsTumor and normal DNA and RNA samples from three breast ACCs were subjected to whole‐exome sequencing. Somatic mutations, copy number alterations, mutational signatures and fusion genes were determined using state‐of‐the‐art bioinformatics methods. Our analyses revealed TP53 hotspot mutations associated with loss of heterozygosity of the wild‐type allele in two cases. Mutations affecting homologous recombination (HR) DNA repair‐related genes were found in two cases, and an MLH1 pathogenic germline variant was detected in one case. In addition, copy number analysis revealed the presence of a somatic BRCA1 homozygous deletion and focal amplification of 12q14.3‐12q21.1, encompassing MDM2, HMGA2, FRS2 and PTPRB. No oncogenic in‐frame fusion transcript was identified in the three breast ACCs analyzed.ConclusionsNo pathognomonic genetic alterations were detected in the ACCs analyzed. These tumors have somatic genetic alterations similar to those of common forms of TNBC and may display HR deficiency or microsatellite instability. These findings provide further insights as to why ACCs which are usually clinically indolent may evolve into or in parallel with high‐grade TNBC

Stromal MED12 exon 2 mutations in complex fibroadenomas of the breast

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.Aims: Here we explore the presence of mediator complex subunit 12 (MED12) exon 2 and telomerase reverse transcriptase (TERT) promoter hotspot mutations in complex fibroadenomas (CFAs) of the breast. Methods: The stromal components from 18 CFAs were subjected to Sanger sequencing of MED12 exon 2 and the TERT promoter hotspot loci. The epithelial and stromal components of two MED12 mutated CFAs were subjected to laser capture microdissection, and Sanger sequencing of MED12 exon 2, TERT promoter and PIK3CA exons 9 and 20, separately. Results: MED12 exon 2 mutations were identified in the stroma of 17% of CFAs. The analyses of epithelial and stromal components, microdissected separately, revealed that MED12 mutations were restricted to the stroma. No TERT promoter or PIK3CA mutations in exons 9 and 20 were detected in analysed CFAs. Conclusions: Like conventional fibroadenomas, MED12 exon 2 mutations appear to be restricted to the stromal component of CFAs, supporting the notion that CFAs are stromal neoplasms.This study was funded by the Breast Cancer Research Foundation. BW is funded by a Cycle for Survival grant, CS by a Fundação para a Ciência e Tecnologia grant (SFRH/BDE/110544/2015). FP is partially funded by a K12 CA184746 grant. The research reported in this paper was supported in part by a Cancer Centre Support Grant of the National Institutes of Health/National Cancer Institute (grant No P30CA008748).info:eu-repo/semantics/publishedVersio

MYBL1 rearrangements and MYB amplification in breast adenoid cystic carcinomas lacking the MYB–NFIB fusion gene

Breast adenoid cystic carcinoma (AdCC), a rare type of triple-negative breast cancer, has been shown to be driven by MYB pathway activation, most often underpinned by the MYB–NFIB fusion gene. Alternative genetic mechanisms, such as MYBL1 rearrangements, have been reported in MYB–NFIB-negative salivary gland AdCCs. Here we report on the molecular characterization by massively parallel sequencing of four breast AdCCs lacking the MYB–NFIB fusion gene. In two cases, we identified MYBL1 rearrangements (MYBL1–ACTN1 and MYBL1–NFIB), which were associated with MYBL1 overexpression. A third AdCC harboured a high-level MYB amplification, which resulted in MYB overexpression at the mRNA and protein levels. RNA-sequencing and whole-genome sequencing revealed no definite alternative driver in the fourth AdCC studied, despite high levels of MYB expression and the activation of pathways similar to those activated in MYB–NFIB-positive AdCCs. In this case, a deletion encompassing the last intron and part of exon 15 of MYB, including the binding site of ERG-1, a transcription factor that may downregulate MYB, and the exon 15 splice site, was detected. In conclusion, we demonstrate that MYBL1 rearrangements and MYB amplification probably constitute alternative genetic drivers of breast AdCCs, functioning through MYBL1 or MYB overexpression. These observations emphasize that breast AdCCs probably constitute a convergent phenotype, whereby activation of MYB and MYBL1 and their downstream targets can be driven by the MYB–NFIB fusion gene, MYBL1 rearrangements, MYB amplification, or other yet to be identified mechanisms. Copyright © 2017 Pathological Society of Great Britain and Ireland

Phyllodes tumors with and without fibroadenoma-like areas display distinct genomic features and may evolve through distinct pathways

Breast fibroepithelial lesions (fibroadenomas and phyllodes tumors) are underpinned by recurrent; MED12; exon 2 mutations, which are more common in fibroadenomas and benign phyllodes tumors.; TERT; promoter hotspot mutations have been documented in phyllodes tumors, and found to be more frequent in borderline and malignant lesions. Several lines of evidence suggest that a subset of phyllodes tumors might arise from fibroadenomas. Here we sought to investigate the genetic differences between phyllodes tumors with fibroadenoma-like areas vs. those without. We retrieved data for 16 borderline/ malignant phyllodes tumors, including seven phyllodes tumors with fibroadenoma-like areas and nine phyllodes tumors without fibroadenoma-like areas, which had been previously subjected to targeted capture massively parallel sequencing. Whilst; MED12; exon 2 mutations were significantly more frequent in tumors with fibroadenoma-like areas (71 vs. 11%), an enrichment in genetic alterations targeting; bona fide; cancer genes was found in those without fibroadenoma-like areas, in particular in; EGFR; mutations and amplifications (78 vs. 14%). No significant difference in the frequency of; TERT; genetic alterations was observed (71% in cases with fibroadenoma-like areas vs 56% in those without fibroadenoma-like areas). Our data suggest that the development of phyllodes tumors might follow two different evolutionary pathways: a; MED12; -mutant pathway that involves the progression from a fibroadenoma to a malignant phyllodes tumor; and a; MED12; -wild-type pathway, where malignant phyllodes tumors arise de novo through the acquisition of genetic alterations targeting cancer genes. Additional studies are warranted to confirm our observations and define whether the outcome differs between both pathways

Genomic profiling of primary and recurrent Adult Granulosa Cell Tumors of the Ovary

Adult-type granulosa cell tumor (aGCT) is a rare malignant ovarian sex cord-stromal tumor, harboring recurrent FOXL2 c.C402G/p.C134W hotspot mutations in 97% of cases. These tumors are considered to have a favorable prognosis, however aGCTs have a tendency for local spread and late recurrences, which are associated with poor survival rates. We sought to determine the genetic alterations associated with aGCT disease progression. We subjected primary non-recurrent aGCTs (n = 7), primary aGCTs that subsequently recurred (n = 9) and their matched recurrences (n = 9), and aGCT recurrences without matched primary tumors (n = 10) to targeted massively parallel sequencing of ≥410 cancer-related genes. In addition, three primary non-recurrent aGCTs and nine aGCT recurrences were subjected to FOXL2 and TERT promoter Sanger sequencing analysis. All aGCTs harbored the FOXL2 C134W hotspot mutation. TERT promoter mutations were found to be significantly more frequent in recurrent (18/28, 64%) than primary aGCTs (5/19, 26%, p = 0.017). In addition, mutations affecting TP53, MED12, and TET2 were restricted to aGCT recurrences. Pathway annotation of altered genes demonstrated that aGCT recurrences displayed an enrichment for genetic alterations affecting cell cycle pathway-related genes. Analysis of paired primary and recurrent aGCTs revealed that TERT promoter mutations were either present in both primary tumors and matched recurrences or were restricted to the recurrence and absent in the respective primary aGCT. Clonal composition analysis of these paired samples further revealed that aGCTs display intra-tumor genetic heterogeneity and harbor multiple clones at diagnosis and relapse. We observed that in a subset of cases, recurrences acquired additional genetic alterations not present in primary aGCTs, including TERT, MED12, and TP53 mutations and CDKN2A/B homozygous deletions. Albeit harboring relatively simple genomes, our data provide evidence to suggest that aGCTs are genetically heterogeneous tumors and that TERT promoter mutations and/or genetic alterations affecting other cell cycle-related genes may be associated with disease progression and recurrences

ERα-LBD, an isoform of estrogen receptor alpha, promotes breast cancer proliferation and endocrine resistance

Estrogen receptor alpha (ER alpha) drives mammary gland development and breast cancer (BC) growth through an evolutionarily conserved linkage of DNA binding and hormone activation functions. Therapeutic targeting of the hormone binding pocket is a widely utilized and successful strategy for breast cancer prevention and treatment. However, resistance to this endocrine therapy is frequently encountered and may occur through bypass or reactivation of ER-regulated transcriptional programs. We now identify the induction of an ER alpha isoform, ER alpha-LBD, that is encoded by an alternative ESR1 transcript and lacks the activation function and DNA binding domains. Despite lacking the transcriptional activity, ER alpha-LBD is found to promote breast cancer growth and resistance to the ER alpha antagonist fulvestrant. ER alpha-LBD is predominantly localized to the cytoplasm and mitochondria of BC cells and leads to enhanced glycolysis, respiration and stem-like features. Intriguingly, ER alpha-LBD expression and function does not appear to be restricted to cancers that express full length ER alpha but also promotes growth of triple-negative breast cancers and ER alpha-LBD transcript (ESR1-LBD) is also present in BC samples from both ER alpha(+) and ER alpha(-) human tumors. These findings point to ER alpha-LBD as a potential mediator of breast cancer progression and therapy resistance