1,721,005 research outputs found
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Hypertranscription in Human Cancer
Get PDFCancer is a disease driven by aberrant gene expression leading to uncontrolled cellular proliferation. To date, tens-of-thousands of patient tumors have undergone RNA-sequencing, creating a catalog of the genes and pathways differentially expressed in cancer tissues. Despite these significant advances, a fundamental aspect of gene regulation remains poorly characterized: the overall expression level across all genes. Recent work has demonstrated that certain oncogenes, such as MYC, might drive tumor growth by globally increasing transcription of all active genes, a phenomenon known as hypertranscription. While hypertranscription has been studied in model systems and cell lines, where drugs that dampen global transcription have shown promise against aggressive ‘transcriptionally addicted’ cancers, hypertranscription has never been characterized in human patients. Thus, we do not know hypertranscription’s prevalence across cancer types, its drivers, or its impact on patient outcomes. This gap in knowledge is driven in large part by the absence of appropriate methods to accurately measure global transcription. Nearly all reported gene expression estimates incorrectly assume relatively equal RNA output across samples.
In Chapter 2, a novel computational method is developed that allows joint measurement of global and focal gene expression changes in patient tumor RNA-sequencing data. Critically, this method accounts for differences in tumor purity and ploidy, providing a direct fold-change measure in overall cancer-cell transcription. In Chapter 3, this method is applied to 7,494 tumor samples spanning 31 types, revealing that hypertranscription is a hallmark of aggressive cancers, with over 40% of all cancers harboring hypertranscription levels of at least 2-fold. Investigation of single-cell RNA-sequencing data revealed hypertranscriptional clones that dominated transcript production regardless of their size. Exploration of transcription factors revealed that loss of transcriptional suppression may be fundamental to the hypertranscriptional phenotype. In Chapter 4, the clinical implications of hypertranscription are explored. Hypertranscription defined patient subgroups with worse survival across multiple cancers, even within well-established subtypes. Finally, patients with hypertranscribed mutations have improved response to immune checkpoint therapy. Taken together, this work provides fundamental insights into gene dysregulation across human cancers and may prove useful in identifying patients that would benefit from novel therapies.Ph.D
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe 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
Mutation Evolution and Genomic Patterns of Recurrence in Ewing Sarcoma and Leiomyosarcoma
No full textSarcomas are a highly heterogeneous group of tumours of the bone and soft tissue whose mutation evolution has been unexplored in the majority of subtypes. From a molecular perspective, sarcomas are sub-classified in two categories: (1) those with disease-defining genetic alterations (commonly translocation-associated gene fusions) and overall quiet genomes and (2) those with no disease-defining alterations and numerous other genetic changes. The work in this thesis centered on a representative sarcoma from each category. First, the genomes of Ewing sarcoma (ES), the second most frequent bone cancer of childhood, were explored. ES represents a prototypical fusion-driven sarcoma as it is characterized and driven by the EWSR1-ETS fusion. Secondly, leiomyosarcoma (LMS), an adult soft-tissue cancer, was examined. LMS is a malignant neoplasm that affects smooth muscle tissue and has a high risk of metastatic relapse. The aim of this research was to advance our knowledge of the basic biology of these two sarcoma subtypes, including the initiating events of sarcomagenesis, the subsequent order of mutations, and the ongoing mutagenic processes in primary, relapse and metastatic ES and LMS.
Chapter 1 provides a comprehensive background on the current knowledge of cancer genomics and an introduction to general sarcoma biology, followed by an overview of the clinical and genomic intricacies of ES and LMS. Chapter 2 provides a synthesis of the informatics tools and approaches developed to detect and characterize mutations in the cancer genome. Chapter 3 describes the patterns of mutations in ES tumours. This chapter reports that in several sarcomas, canonical fusions frequently emerge from rearrangement bursts, also called ‘chromoplexy’, creating complex genomic loops and disrupting additional genes. The transcriptional heterogeneity and cellular lineages of LMS molecular subtypes are presented in Chapter 4. Additionally, the genomic mutation signatures and the mutation dynamics contributing to relapse and metastatic spread are described. Lastly, Chapter 5 examines future directions for ES and LMS genomics research. Overall, this thesis highlights recent advances in ES and LMS genomics and provides the molecular framework for future work in patient stratification and early cancer detection in these subtypes.Ph.D.2022-06-22 00:00:0
Studies on the Evolution of and Mutational Processes Driving Childhood Cancer in the Context of Genetic Predisposition
Get PDFCancer predisposition syndromes (CPSs) are caused by heritable mutations, often affecting DNA-repair pathways, which dramatically increase cancer risk. Once diagnosed, screening of additional family members combined with cancer surveillance protocols have shown significant survival benefits. However, CPSs are largely underdiagnosed due to clinical heterogeneity and variants of uncertain significance. In this thesis I explore the hypothesis that CPS-associated cancers exhibit characteristic DNA-repair-associated mutational signatures—patterns of somatic mutation related to mutation aetiology¬— and/or evolutionary dynamics, which may be exploited to aid in CPS diagnosis and management. To address this hypothesis, I studied two model CPSs—constitutional mismatch repair deficiency (CMMRD) and Li-Fraumeni syndrome (LFS).
CMMRD results from biallelic germline mutations in one of four mismatch repair genes, and is associated with childhood brain, colorectal and lymphocytic neoplasms. Recent work has shown cancers developing in CMMRD patients to possess recurrent somatic mutations in POLE/POLD1 and massively elevated numbers of somatic point mutations (hypermutation). To assess the frequency, timing, and aetiology of hypermutation in adult and childhood cancer, I performed a comprehensive analysis of hypermutation across >80,000 human cancers. Our work identified CMMRD in 15 patients, resulting in their enrollment on a surveillance protocol and immune checkpoint inhibitor trial, which has shown sustained responses for CMMRD patients.
Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by germline mutations in the TP53 tumor suppressor gene, and is associated with a wide range of cancers, including sarcomas, breast cancers, adrenocortical carcinomas and brain tumours. To investigate somatic mutational events driving tumourigenesis in LFS, I performed whole-genome sequencing (WGS) analysis of bulk and multi-region dissections of tumours derived from childhood and young adult patients with germline TP53 mutations. Our analyses revealed that the life history of LFS cancers is marked by early loss of heterozygosity of TP53, mutational signatures related to homologous recombination repair deficiency and in some cases previous chemotherapeutic treatment. In summary, my thesis research demonstrated CPS-related malignancies are often mutationally and evolutionarily distinct entities. The unique molecular features of these tumours reveal aspects of their aetiology and in some cases can be used to aid in diagnosing and treating these patients.Ph.D.2022-11-30 00:00:0
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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