bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of Somatic Structural Variants Enables Quantification and Characterization of Circulating Tumor DNA in Children With Solid Tumors
Authors: Klega Kelly , Imamovic-Tuco Alma , Ha Gavin , Clapp Andrea N. , Meyer Stephanie , Ward Abigail , Clinton Catherine , Nag Anwesha , Van Allen Eliezer , Mullen Elizabeth , DuBois Steven G. , Janeway Katherine , Meyerson Matthew , Thorner Aaron R. , Crompton Brian D. 
Published: July 2018

Objective Liquid biopsies are being rapidly used in adult cancers as new biomarkers of disease. Circulating tumor DNA (ctDNA) levels have been reported to be proportional to disease burden, correlate with treatment response, and predict relapse. However, little is known about how frequently ctDNA is detectable in pediatric patients with solid tumors. Therefore, we developed a next-generation sequencing approach to detect and quantify ctDNA in the blood of patients with the most common pediatric solid tumors. Methods Detection of ctDNA requires assays sensitive to somatic events typically observed in the cancer type being studied. In pediatric solid tumors, structural variants are more common than recurrent point mutations. We adapted an ultralow passage whole-genome sequencing approach to capture copy number variants and a hybrid capture sequencing assay to detect translocations in liquid biopsy samples from pediatric patients. Results Copy number changes seen by ultralow passage whole-genome sequencing enabled detection of ctDNA in patients with osteosarcoma, neuroblastoma, alveolar rhabdomyosarcoma, and Wilms tumor. In Ewing sarcoma, detection of the EWSR1 translocation was a more sensitive approach. For patients with samples collected at multiple time points, changes in ctDNA levels corresponded to treatment response. We also found that disease-specific genomic biomarkers of prognosis were detectable in ctDNA. Conclusion This study demonstrates that liquid biopsy approaches that detect somatic structural variants are well suited to pediatric solid tumors. We show that children with the most common solid tumor malignancies have detectable levels of ctDNA, which may be used to track disease response and identify genomic subclassifiers of disease. Efforts to profile larger collections of clinically annotated specimens are under way to validate the clinical use of these assays.
Use of Low-Frequency Driver Mutations Detected by Cell-Free Circulating Tumor DNA to Guide Targeted Therapy in Non–Small-Cell Lung Cancer: A Multicenter Case Series
Authors: Jacobs Miriam T. , Mohindra Nisha A. , Shantzer Lindsey , Chen Ingrid L. , Phull Hardeep , Mitchell William , Raymond Victoria M. , Banks Kimberly C. , Nagy Rebecca J. , Lanman Richard B. , Christensen James , Patel Jyoti D. , Clarke Jeffrey , Patel Sandip P. 
Published: July 2018

Purpose To evaluate the clinical outcome of patients with non–small-cell lung cancer treated by targeting low variant allelic frequency (VAF) driver mutations identified through cell-free DNA (cfDNA) next-generation sequencing (NGS). Detection of driver mutations in cancer is critically important in the age of targeted therapy, where both tumor-based as well as cfDNA sequencing methods have been used for therapeutic decision making. We hypothesized that VAF should not be predictive of response and that low VAF alterations detected by cfDNA NGS can respond to targeted therapy. Patients and Methods A multicenter retrospective case review was performed to identify patients with non–small-cell lung cancer who received targeted molecular therapy on the basis of findings of low VAF alterations in cfDNA NGS. Mutations at low VAF were defined as < 0.2% mutated cfDNA molecules in a background of wild-type cfDNA. Results One hundred seventy-two patients underwent cfDNA NGS testing. Of the 172 patients, 12 were identified as having low VAF driver alterations and were considered for targeted therapy. The median progression-free survival (PFS) for all patients was 52 weeks (range, 17 to 88 weeks). For patients with EGFR exon 19 deletion (n = 7), the median PFS was 52 weeks (range, 17 to 60.5 weeks). For patients with EML4-ALK fusions (n = 3), the median PFS was 60 weeks (range, 18 to 88 weeks). The median overall survival for all patients after diagnosis was 57.6 weeks. Conclusion Targeted treatment response for driver mutations detected by cfDNA may be independent of VAF, even in relation to other higher VAF aberrations in plasma, and directly dependent on the underlying disease biology and ability to treat the patient with appropriate targeted therapy.
Clinical application and technical considerations of T
1 & T
2(*) mapping in cardiac, liver, and renal imaging
Authors: Dekkers Ilona A , Lamb Hildo J 
Published: July 2018

Pathological tissue alterations due to disease processes such as fibrosis, edema and infiltrative disease can be non-invasively visualized and quantified by MRI using T 1 and T 2 relaxation properties. Pixel-wise mapping of T 1 and T 2 image sequences enable direct quantification of T 1, T 2(*), and extracellular volume values of the target organ of interest. Tissue characterization based on T 1 and T 2(*) mapping is currently making the transition from a research tool to a clinical modality, as clinical usefulness has been established for several diseases such as myocarditis, amyloidosis, Anderson-Fabry and iron deposition. Other potential clinical applications besides the heart include, quantification of steatosis, cirrhosis, hepatic siderosis and renal fibrosis. Here, we provide an overview of potential clinical applications of T 1 andT 2(*) mapping for imaging of cardiac, liver and renal disease. Furthermore, we give an overview of important technical considerations necessary for clinical implementation of quantitative parametric imaging, involving data acquisition, data analysis, quality assessment, and interpretation. In order to achieve clinical implementation of these techniques, standardization of T 1 and T 2(*) mapping methodology and validation of impact on clinical decision making is needed.
Inferring the Economics of Store Density from Closures: The Starbucks Case
Authors: Guler Ali Umut 
Published: July 2018

This paper proposes a method that makes use of firms’ mass store closures to measure the store network effects of cannibalization and density economies. I calculate each store’s contribution to chain-level profits via one-store perturbations on the set of retained stores, and map these onto the firm’s closure choices. To separate the demand- and supply-side store network effects, I exploit the fact that the business-stealing effect intensifies with local network density, whereas the supply-side disadvantage prevails at sparse regions of the network. I apply the method to study the Starbucks chain. The average rate of cannibalization imposed by a neighbor outlet is 1.2% within one mile and 0.4% within one to three miles. For remote outlets, operation costs increase by 0.3% of revenues for each mile of distance from the network. Counterfactual analyses suggest that income level is a more important determinant of demand than population count at low levels of store penetration, whereas high-population regions can sustain denser store networks because of the softening of the cannibalization effect. Data are available at https://doi.org/10.1287/mksc.2017.1078 .
THE DISABLED POPULATION AND THEIR EDUCATIONAL STATUS IN INDIA
Authors: Lakshmana C M , Maruthi I 
Published: July 2018

De acordo com a Organização Mundial da Saúde (OMS), os deficientes são privados de todas as oportunidades de desenvolvimento social e econômico. Cerca de 400 milhões de pessoas com deficiência vivem no mundo em desenvolvimento. As instalações básicas, como saúde, educação e emprego são negadas a essa parte vulnerável da população. Cerca de 70% dos deficientes estão desempregados. De acordo com o Censo de 2011, a população total da Índia é de 1,23 bilhão de habitantes, na qual cerca de 2,1% (mais de 21 milhões de pessoas) sofrem de um ou outro tipo de deficiência. No entanto, o presente artigo enfoca a questão da deficiência e seu status educacional na Índia. Uma análise de estado-sábio foi feita para o estudo para entender a variação regional. Em todos os estados, o maior número de pessoas com deficiência é relatado em Uttar Pradesh, Maharashtra Andhra Pradesh, Bihar, Bengala Ocidental e Madhya Pradesh. Os dados do censo disponíveis foram usados para examinar a proporção de incapacidade e seu status educacional na Índia nas duas últimas décadas. O estudo constatou que, em um período de tempo, entre pessoas com deficiência, não apenas o status educacional da população com deficiência melhorou durante a década em análise, mas também aumentou o percentual de alfabetizados entre a população deficiente femininae masculina e o seu status, em níveis educacionais mais altos, também melhorou consequentemente.
Educação como Prática da Liberdade para Lésbicas, Gays, Bissexuais, Travestis e Transexuais: saberes, vivências e (re)leituras em Paulo Freire
Authors: Pereira Cleyton Feitosa , Lage Allene Carvalho 
Published: July 2018

Resumo: Através de uma pesquisa bibliográfica, com foco nas obras “Educação como Prática da Liberdade” e “Pedagogia do Oprimido”, tecemos reflexões e conexões entre o pensamento freireano e a luta cotidiana do Movimento LGBT. As análises apontaram perspectivas de existir e estar no mundo - a integração ou a acomodação - e a relação que a população LGBT estabelece com o enfrentamento à heteronormatividade remetendo-nos à contradição opressor-oprimido. Entendemos essa complexa conjuntura violadora de direitos por aquilo que Freire chamou de “inexperiência democrática” como sendo parte da realidade construída historicamente por meio da colonização de povos latinoamericanos. Mas compreendemos também que a emancipação pode se dar através de uma educação horizontal, dialógica, plural e conscientizadora. Uma educação como prática da liberdade.Palavras-Chave: Educação. Diversidade sexual. Emancipação. Paulo Freire. Resumen: A través de una investigación bibliográfica, con foco en las obras "Educación como Práctica de la Libertad" y "Pedagogía del Oprimido", tejemos reflexiones y conexiones entre el pensamiento freireano y la lucha cotidiana del Movimiento LGBT. Los análisis apuntaron perspectivas de existir y estar en el mundo - la integración o el acomodamento - y la relación que la población LGBT establece con el enfrentamiento a la heteronormatividad remitiéndonos a la contradicción opresor-oprimido. Entendemos esa compleja coyuntura violadora de derechos por lo que Freire llamó "inexperiencia democrática" como parte de la realidad construida históricamente por medio de la colonización de pueblos latinoamericanos. Pero comprendemos también que la emancipación puede darse a través de una educación horizontal, dialógica, plural y concientizadora. Una educación como práctica de la libertad.Palabras clave: Educación. Diversidad sexual. Emancipación. Paulo Freire. Abstract: Through a bibliographical research, focusing on the works "Education as a Practice of Freedom" and "Pedagogy of the Oppressed", we weave reflections and connections between Freirean thinking and the daily struggle of the LGBT Movement. The analysis pointed to perspectives of existence and being in the world - integration or accommodation - and the relationship that the LGBT population establishes with the confrontation with heteronormativity, referring to the oppressive-oppressed contradiction. We understand this complex situation violating rights by what Freire called "democratic inexperience" as part of the reality historically built through the colonization of Latin American peoples. But we also understand that emancipation can take place through a horizontal, dialogical, pluralistic and conscientious education. An education as a practice of freedom.Keywords: Education. Sexual diversity. Emancipation. Paulo Freire.
Cytotoxic effect of 2, 5-dimethyl-celecoxib as a structural analog of celecoxib on human colorectal cancer (HT-29) cell line
Authors: Nikanfar Saba , Atari-hajipirloo Somayeh , Kheradmand Fatemeh , Rashedi Jalil , Heydari Amir 
Published: July 2018

Dimethyl-celecoxib (DMC), a close derivative of celecoxib (CXB) with a low COX-2 inhibitory function, exhibits signiï¬cant anti-neoplastic properties. In this study, we have investigated the effect of CXB and DMC on the human HT-29 cell line. The cellular viability, caspase-3 activity, and VEGF, NF-ÎºB, and COX-2 genes expressions were assessed respectively with MTT, colorimetric, and real-time RT-PCR methods. DMC, a close analogue of CXB, was more potent in inhibiting the growth of cells (IC50: 23.45 µM at 24 hr) than CXB (IC50: 30.41 µM at 24 hr). Both CXB and DMC caused a significant difference in caspase-3 activity compared to the control group. DMC significantly decreased the NF-ÎºB expression. Down-regulation of the COX-2 mRNA expression in the celecoxib-treated group was significant compared with that in the DMC-treated group. Alterations in the mRNA expression of VEGF were not significant between the groups. Owing to the more potent growth inhibitory effects of DMC compared to that of celecoxib, it may be important to conduct research on the anticancer application of this compound, which can reduce the side effects relating to COX2 inhibition.
ROS related enzyme levels and its association to molecular signaling pathway in the development of head and neck cancer
Authors: Iplik Elif Sinem , Ertugrul Baris , Candan Gonca , Pamuk Saim , Aydemir Levent , Celik Mehmet , Ulusan Murat , Ergen Arzu , Cakmakoglu Bedia 
Published: July 2018

Given the prevalence and annual incidence of cancer, head and neck cancer is affecting more than 600,000 people each year. In this research, it was decided to investigate that which genes are involved and how MPO, NQO1, SOD2 enzyme levels effective to develop of head and neck cancer and for the first time at the tissue level. 35 tumor tissues in all head and neck anatomy and their surrounding tissue (70 in total) were enclosed the research that received surgery. Determination of the apoptosis genes expression levels (Mtch1, Akt1, Caspase3, Caspase9, Bcl2, Mdm2, mTOR) were determined by RT-PCR techniques and the same patients' sample used for ROS associated oxidant-antioxidant system by using MPO, NQO1, SOD2 enzyme levels using ELISA method. According to statistical results, caspase 9 gene was found statistically high expressed in early stage in contrast to late stage (p=0,013). Level of SOD2, NQO1 and MPO was determined and only MPO level was found significantly important on tumor tissues p=0,008). Specially, our findings for high expression of Cas9 on early stage were thought to be the target for treatment with its well-known initiator role of the apoptosis. Our results suggest that the higher level of MPO in tumor tissues and indicates that it has some role on pathology of head and neck cancers. We believe that, our research will lead the proposal in-vivo studies and will open new areas on therapeutic targets.
Management of occupational noise induced hearing loss in the mining sector in South Africa: Where are the audiologists?
Authors: Moroe Nomfundo , Khoza-Shangase Katijah 
Published: July 2018

Abstract

Objective
This study was conducted to explore the scope of practice for occupational audiologists in the mining industry and the audiologists’ involvement in hearing conservation programmes in South African mines. Additionally, this study investigated the mining industry’s role in the audiologists’ involvement, and assessed the audiologists’ levels of preparedness for working in occupational audiology.

Methods
In-depth, qualitative telephone and face-to face interviews were conducted with seven occupational audiologists involved in the management of occupational, noise-induced hearing loss (ONIHL) in the South African mining sector. Snowball sampling was utilized to recruit possible participants for this study. Data were analysed using inductive thematic analysis.

Results
The following themes were identified: scope-context misalignment, juniorization of the experts, audiologists are important… but for what?, and limited training in occupational audiology.

Conclusions
Our evidence highlights important gaps in HCPs in South Africa. The fact that the audiologists responsible for the management of ONIHL are only minimally and peripherally involved may play a significant role in the lack of progress reported in the management of ONIHL in the South African mining sector.
La unión hace la fuerza: bases para un pleno desarrollo de la indagación científica en Latinoamérica
Authors: Ibañez-Marti Juan José 
Published: July 2018

En un artículo precedente (“La ciencia en Latinoamérica: tendencias y patrones”) se analiza con ciertas herramientas estadísticas sencillas, el estado de la ciencia y, en menor grado, de la tecnología en la región. Partiendo de los resultados obtenidos, en este nuevo artículo se indaga las bondades y debilidades del sistema de “Ciencia, Tecnología e Innovación” (CTI), intentando entender los pasos que debieran seguir los países de LA para engancharse al tren de los Estados más prósperos y desarrollados. La conclusión es clara: por si solos, cada uno de ellos difícilmente podría lograr progresar significativamente en estas materias. Actualmente la CTI depende de contextos económicos y geopolíticos, y demanda esfuerzos colectivos, a no ser que se trate de Estados muy industrializados y extensos como China o EE.UU, por citar tan solo dos ejemplos. Con vistas a exponer estos hechos, se explica cómo han logrado salir del ostracismo y mejorar palmariamente sus CIT países latinos europeos como España y Portugal. Su integración en una mancomunidad de países como lo es la Unión Europea (UE), así como una estabilidad democrática dilatada en el tiempo, resultaron imprescindibles. Más aun, el esfuerzo colectivo de la UE demuestra, sin la menor duda, que la integración de todos los países de la región en una Unión Latinoamericana (ULA), con una gobernanza supranacional en diversas materias (y entre ellas la CIT) es el único pilar fundamental que ofrece garantías. Este modo de proceder, aunando esfuerzos, atesora enormes posibilidades para fortalecer LA en todos los sentidos. Los efectos de tal estrategia son explicados con cierto detalle. Adicionalmente, con vistas a desbrozar un poco el camino, se han desglosado las bondades y debilidades de la CIT en LA (sistemas educativos, cultura digital, problemas de género, producción de patentes, dependencia económica exterior y estratégica de organismos internacionales -FMI, Banco Mundial, etc.-, como también de las inversiones de grandes compañías multinacionales, riesgo de las privatizaciones de centros y actividades previamente Estatales, etc., etc.). Con vistas a encuadrar tal información en un contexto global, se ha escogido como contrapunto la estrategia exitosa (aunque a menudo reprobable respecto a la reducción de desigualdades sociales) que han logrado lanzar el CIT en diversos países del SE asiático.
Caracterización de la prosa de Tucidides
Authors: Jiménez Vásquez José María 
Published: July 2018

Este artículo consiste en un análisis de las características más sobresalientes de la prosa del famoso historiador Tucídides, en el que se analiza las principales características del estilo, morfosintaxis y léxico-fonética utilizados por el autor de la Guerra del Peloponeso, el principal escritor de prosa Ático en antigua, así como su representante más famoso.This article consists of an anlysis of the most outstanding characteristics of the prose of the famous historian Thucydides, in which is discussed the principal features of style, morpho-sintax and lexicophonetics used by the author of the Peloponnesian War, the main prose writer in Ancient Attic, as well as its most famous representative.
La lengua española en la educación costarricense, redefinición
Authors: Sánchez Corrales Victor Manuel 
Published: July 2018

La planificación lingüística que se ocupa de la enseñanza del español en Costa Rica se ha basado directamente en los dogmas prescriptivos de la Real Academia Española y, en menor medida, en las aportaciones teóricas de Bello. En este artículo, me propongo un cambio paradigmático y sostengo que la competencia comunicativa basada en la interacción lingüística de los miembros de una comunidad lingüística, en este caso Costa Rica, debe sustituir prescriptivismo como la piedra angular de la enseñanza de la lengua materna en las escuelas. Language planning concerned with the teaching of Spanish in Costa Rica has been based squarely on the prescriptive dogmas of the Royal Spanish Academy and, to a lesser degree, on the theoretical contributions of Bello. In this article, I propose a paradigmatic change and argue that communicative competence based on the linguistic interaction of the members of a speech community, in this case Costa Rica, should replace prescriptivism as the cornerstone of mother-tongue instruction in the schools.
The lost steps of <i>The great Gatsby</i>
Authors: Pacheco Gilda 
Published: July 2018

En este artículo se presenta un análisis comparativo de El gran Gatsby de F. Scott Fitzgerald y Los pasos perdidos de Alejo Carpentier. Al comparar y contrastar personajes, escenarios, imágenes y arquetipos, es posible ver las bases para el fracaso del mito llamado "sueño americano", un tema clásico en la literatura de Estados Unidos, también se encuentra en la obra del novelista cubano. Dualismo, el individualismo, la búsqueda de la identidad, así como la ambición, la indiferencia y la esperanza son elementos ESENCIALES en ambas obras que conducen al fracaso del mito. Así es como dos regiones diferentes, dos escritores con fondo diferente, la cultura y el entorno, y dos novelas escritas con veinticinco años de diferencia muestran además el mismo distorsionado sueño corrompido y perdido: un sueño inaccesible e inalcanzable implícito en el título irónico y melancólico del artículo.This articles presents a comparative analysis of F. Scott Fitzgerald's The Great Gatsby and Alejo Carpentier Los pasos perdidos. By comparing and contrasting characters, scenarios, images and archetypes, it is possible to see that the bases for the failure the myth called "the American dream", a classical topics in US. literature, are also found in the work by the Cuban novelist. Dualísm, individualism, the search for identity, as well as ambition, indifference and hope are essential elements in both works which lead to the failure of the myth. That is how two different regions, two writers with different background, culture and setting, and two novels written twenty five years apart show the same distorted, corrupted and lost dream: an inaccessible and unreachable dream implicit in the ironic and melancholic title of the article.
Respuesta de la Secretaría de la Academia Costarricense de la Lengua al discurso de don Jézer González Picado
Authors: Sandoval de Fonseca Virginia 
Published: July 2018

Me cabe el privilegio de dar la bienvenida al colega don Jézer González Picado. Su discurrir de hoy revela, en primer término, dos prendas que adornan su espíritu: el agradecimiento y la humildad. Lo primero, cuando emocionadamente recuerda haber sido discípulo de Carlos Luis Sáenz, la segunda, al atribuir los juicios que emite en el presente trabajo, al afecto, más que a la habilidad. Así es don Jézer. Por supuesto que no menosprecia del todo su obra, pero tampoco la sobrevalora. Quienes hemos tenido la suerte de trabajar con él, ya como compañeros, ya al cobijo de su jerarquía, sabemos qué de intuiciones brillantes le brotan en el trato crítico-literario con la obra y cómo las sistematiza luego en sus muchos y variados estudios. Testimonios de ello son sus libros, sus artículos, sus conferencias, los prólogos de muchos libros que andan por allí en la República de las Letras, las incontables tesis de grado que han dirigido, tanto de licenciatura como de posgrado.