1,721,053 research outputs found
Infectious complications in patients with lymphoproliferative syndromes treated with targeted therapies against specific targets
No full textTesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, leída el 05-06-2024. Tesis formato europeo (compendio de artículos)Los síndromes linfoproliferativos (SLP) constituyen un grupo de enfermedades con una marcada inmunodeficiencia, caracterizada por hipogammaglobulinemia, defectos cualitativos y cuantitativos de los linfocitos B y T, linfocitopenia CD4+, además de disfunción inmune innata y neutropenia. Estas alteraciones son el resultado de la propia enfermedad, de las comorbilidades del paciente y de los tratamientos dirigidos frente al proprio linfoma. La introducción en la última década de nuevas estrategias terapéuticas, como los fármacos dirigidos frente al receptor de la célula B (BCR) u otras vías de señalización intracelular como bcl2, así como la terapia celular, ha conseguido aumentar la eficacia antitumoral con respecto a la quimioterapia clásica, además de limitar las toxicidades de la misma. Sin embargo, el riesgo infeccioso de los nuevos fármacos no está claramente establecido; de hecho, hay pocos estudios, en general procedentes de ensayos clínicos, que describen el impacto de los nuevos fármacos en el riesgo infeccioso de estos pacientes...Lymphoproliferative syndromes constitute a group of diseases with marked immunodeficiency, characterized by hypogammaglobulinemia, qualitative and quantitative defects of B and Tlymphocytes, CD4+ lymphopenia, in addition to innate immune dysfunction and neutropenia. These alterations are the result of the disease itself, the patient's morbidities and anti-lymphoma treatments. The development, in the last decade, of new therapeutic strategies such as targeted drugs or cell therapy, has increased antitumor efficacy with respect to classical chemotherapy, in addition to limiting their toxicities. However, the infectious risk of new drugs is not clearly established, and there are few studies, generally extrapolated from clinical trials, that describe the impact of new drugs on the infectious risk of these patients...Fac. de MedicinaTRUEunpu
Estudio de los factores pronósticos genéticos de la leucemia linfática crónica e identificación de nuevos marcadores moleculares con relevancia clínica
Full text linkEn los últimos años, el conocimiento de la leucemia linfática crónica (LLC) ha experimentado un gran progreso y, en el campo de los factores pronósticos, tanto las técnicas de hibridación in situ fluorescente, el estado mutacional del gen de la cadena pesada de las inmunoglobulinas (IgVH) y la expresión de CD38 y el ZAP-70 han supuesto un gran avance. Aún así, hay pocas series publicadas que analicen un número amplio de pacientes que correlacionen los datos biológicos y el curso clínico. Nuestros resultados confirman el valor pronóstico de los estudios genético-moleculares en la LLC, por lo que el análisis de las alteraciones cromosómicas en 11q, cromosoma 12, 13q, 14q32 y 17p, así como el estudio de las mutaciones somáticas del gen IgVH, son pruebas necesarias a realizar en la valoración clínica, terapéutica y pronóstica de esta enfermedad. Además, la identificación del segmento genético VH puede añadir información adicional e independiente al estado mutacional de IgVH El subgrupo de pacientes con la traslocación 14q32 debe incluirse en la clasificación jerárquica entre los riesgos intermedio y desfavorable. Por otra parte, los enfermos con LLC y un número alto de pérdidas en el cromosoma 13q presentan una menor supervivencia global y tiempo hasta la progresión que los que tienen trisomía 12, citogenética normal o un porcentaje bajo de células con 13q-. Desde el punto de vista biológico, los pacientes con LLC y un número alto de pérdidas en 13q presentan más proliferación y menos apoptosis en los perfiles de expresión génicos, lo que podría justificar su peor pronóstico. Por último, los pacientes con LLC, de manera especial los casos con pérdidas en 13q, se caracterizan por la sobreexpresión del producto del proto-oncogén VAV. Es la primera ocasión en la que la expresión disregulada de este proto-oncogén se ha comunicado en una enfermedad hematológica.n recent years, the knowledge of chronic lymphoid leukemia (CLL) has improved. Thus, in the setting of prognostic factors, the use of fluorescence in situ hybridization (FISH), the immunoglobulin VH gene mutation status and the expression of CD38 and ZAP-70 antigens have implied a great advance. Even so, there are few published series with a high number of patients to correlate biological data and the clinical outcome. Our findings confirm the prognostic value of genetic and molecular studies in this disease. So, the FISH analysis of chromosome aberrations in 11q, +12, 13q, 14q32 and 17p, and the determination of IgVH mutation status are mandatory in the clinical, therapeutic and prognostic evaluation of CLL. Moreover, the identification of VH usage can provide additional and independent information. The subgroup of patients with 14q32 translocation should be included between intermediate and high risk in the hierarchical classification. On the other hand, patients with CLL and a high number of losses in 13q chromosome have a shorter overall survival and time to first therapy than patients with +12, normal karyotype or a low percentage of 13q- cells. Biologically, the gene expression profile in this group of patients reveals more proliferation and less apoptosis. These features could determine a more aggressive clinical course and a worse outcome. Finally, CLL patients, mainly the cases with 13q deletion, are characterized by overexpression of the VAV proto-oncogene product. To the best of our knowledge, this is the first time the deregulated expression of the VAV proto-oncogene has been communicated in a hematological malignancy
Nuevas aportaciones de la hibridación in situ fluorescente y el estado mutacional del gen de las cadenas pesadas de inmunoglobulinas para predecir el curso clínico de los pacientes con leucemia linfocítica crónica
Full text linkTesis de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Medicina, leída el 30/11/2017La leucemia linfocítica crónica (LLC) es una enfermedad con un curso clínico extremadamente variable. Por este motivo, con el objetivo de predecir qué pacientes van a progresar en poco tiempo, en las últimas décadas se han identificado varios factores pronósticos de gran relevancia. Entre ellos, el estado mutacional de la cadena pesada de las inmunoglobulinas (IGHV) y las anomalías citogenéticas detectadas por hibridación in situ fluorescente (FISH) se han consolidado como dos de los más potentes. Además, en algunos casos indican la necesidad de un abordaje terapéutico diferente. En relación con el estado mutacional IGHV, el patrón no mutado se observa en aproximadamente la mitad de los pacientes con LLC y normalmente se caracteriza por presentar una enfermedad agresiva, al contrario que el patrón mutado. La FISH es capaz de detectar alteraciones genéticas clonales en aproximadamente el 80% de los sujetos con LLC. Estas alteraciones son, por orden de frecuencia: deleción de 13q (13q-), deleción de 11q (11q-), trisomía 12 (+12) y deleción de 17p (17p-), las cuales, junto a la ausencia de anormalidades citogenéticas, definen cinco grupos con pronóstico distinto. Además, el porcentaje de pérdidas en los casos de 11q-, 13qy 17p- también tiene valor pronóstico, de tal modo que los enfermos con un porcentaje elevado de células con deleción son los que presentan una evolución peor. Objetivos, material, métodos y resultados: El objetivo de esta Tesis Doctoral es analizar el impacto pronóstico de aspectos concretos y novedosos acerca del estado mutacional IGHV y de la FISH en pacientes con LLC. Se presentan a continuación los resúmenes de las publicaciones que han dado lugar a esta Tesis...Chronic lymphocytic leukemia (CLL) is a neoplasm with an extremely variable clinical course. For this reason, in the last decades, different prognostic factors have been investigated in order to predict which patients are going to progress in a short period of time. Among them, mutational status of the immunoglobulin heavy chain variable region (IGHV), and cytogenetic abnormalities detected by FISH have been consolidated as two of the most powerful factors. In addition, in some situations they indicate a different therapeutic approach. Mutations occur in approximately half of the cases, and usually present with nonprogressive disease, in contrast to patients with a non-mutated pattern. FISH studies are able to detect clonal genomic aberrations in the majority (>80%) of CLL patients. The most common recurrent chromosomal abnormalities include: 13q deletion (13q-); 11q deletion (11q-); trisomy 12 (+12); and 17p deletion (17p-), defining five prognostic categories with different survival times. Besides, the percentage of cells with the deletion in the cases of 11q-, 13q- and 17p- also adds prognostic value. Aim, material, methods and results: The aim of this Thesis is to analyze the prognostic impact of particular and novel aspects about the mutational status IGHV and FISH in patients with CLL. The abstracts of the papers that compose this Thesis are shown next...Depto. de MedicinaFac. de MedicinaTRUEunpu
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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