1,721,107 research outputs found
Update on the pathogenesis of osteolysis in multiple myeloma patients
No full textMultiple myeloma (MM) is a plasma cell malignancy characterized by the high capacity to induce osteolytic bone lesions that mainly result from an increased bone resorption related to the stimulation of osteoclast recruitment and activity. Although it is known that myeloma cells induce osteoclastic bone resorption, the biological mechanisms involved in the pathophysiology of MM-induced bone resorption have been unclear for several years. Recently, new data seem to elucidate which mechanism is critically involved in the activation of osteoclastic cells in MM. The critical osteoclastogenetic factor RANKL and its soluble antagonist osteoprotegerin (OPG) are the major candidates in the pathophysiology of MM bone disease. Human MM cells induce an imbalance in the RANKL/OPG ratio in the bone marrow environment that triggers the osteoclast formation and activation leading to bone destruction. The role or RANKL/OPG system and other osteoclast stimulating factors in the pathophysiology of MM bone disease are summarized in this update
Angiogenic switch in multiple myeloma
No full textAngiogenesis is the hallmark of cancer. Growing evidence indicates that an imbalance between pro- and anti-angiogenic molecules triggers the angiogenic switch during tumor progression. Several molecules, able to affect vascular formation and function, are now beginning to be elucidated. Recent data indicate that angiogenesis also occurs in hematological malignancies. In multiple myeloma it has been demonstrated that patients with active disease have an increase in bone marrow angiogenesis correlated with the progression of disease and an adverse prognosis. The pathophysiology of myeloma-induced angiogenesis is complex and involves either the direct production of angiogenic molecules by myeloma cells or their induction in the microenvironment. In this review we have focalized our attention on the main factors involved in the angiogenic switch that occurs in MM patients
RNA processing: A new player of genomic instability in multiple myeloma
No full textGenomic instability, a hallmark of almost all cancers, originates from the combined effects of a deregulated DNA damage response, DNA repair defects, and a failure of cell-cycle checkpoints before the damaged DNA is propagated to daughter cells [1]. Alterations in this network of genomic integrity-preserving pathways lead to the accumulation of mutations, aneuploidy, and chromosomal alterations, the main causes of cancer. Multiple myeloma (MM) is a clonal malignancy of terminally differentiated plasma cells that reside and expand in the bone marrow. MM cells are characterized by a high aneuploidy incidence and recurrent structural chromosomal alterations, features that reflect these cells' underlying genomic instability [2]
New insight in the mechanism of osteoclast activation and formation in multiple myeloma: focus on the receptor activator of NF-kappaB ligand (RANKL)
No full textThe increase of osteoclast activation and formation is mainly involved in the development of the osteolytic bone lesions that characterize multiple myeloma (MM) patients. The mechanisms by which myeloma cells induce bone resorption have not been clear for many years. Recently, new evidence has elucidated which factors are critically involved in the activation of osteoclastic cells in MM. The potential role of the critical osteoclastogenic factor, the receptor activator of NF-kappaB ligand (RANKL), and its soluble antagonist osteoprotegerin (OPG) in the activation of bone resorption in MM is summarized in this review. It has been demonstrated that human MM cells induce an imbalance in the bone marrow environment of the RANKL/OPG ratio in favor of RANKL that triggers the osteoclast formation and activation leading to bone destruction. The direct production of the chemokine macrophage inflammatory protein-1 alpha (MIP-1alpha) by myeloma cells, in combination with the RANKL induction in BM stromal cells in response to myeloma cells, are critical in osteoclast activation and osteoclastogenesis
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
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