1,721,052 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
Abstract 418: Adaptive resistance to chemotherapy in triple-negative breast cancer revealed by single cell DNA and RNA sequencing
No full textAbstract
Triple-negative breast cancer (TNBC) is an aggressive subtype that displays extensive intratumor heterogeneity and frequently (46%) develops resistance to neoadjuvant chemotherapy (NAC). Currently, the genomic basis of chemoresistance remains poorly understood. An important question is whether resistance to chemotherapy is driven by the selection of rare pre-existing subclones with genomic mutations and transcriptional programs that confer resistance to chemotherapy (adaptive resistance) or by the spontaneous induction of new mutations and expression changes that confer a resistant phenotype (acquired resistance). To investigate this question we applied single cell DNA and RNA sequencing methods and deep-exome sequencing to longitudinal time-point samples collected from a cohort of 20 TNBC patients. Deep-exome sequencing of the cohort at three time points revealed a random death model, wherein multiple clones were targeted, as opposed to the selection of specific somatic mutations. In contrast, single cell copy number profiling of ~800 cells from 8 patients identified an adaptive resistance model, wherein minor subclones from the pre-treatment tumors were selected and expanded in response to NAC. Similarly, single cell RNA sequencing of ~8000 cells from 8 patients identified subclones with chemoresistant phenotypes that were selected in response to NAC, resulting in the expansion of the resistant tumor mass. These data suggest that chemoresistance evolves through the selection of copy number changes and expression changes in signaling pathways associated with chemoresistance, rather than point mutations. This adaptive resistance model has important translational implications in clinical diagnostics, by suggesting that resistant clones can be detected in TNBC patients prior to the administration of chemotherapy.
Citation Format: Charissa Kim, Ruli Gao, Emi Sei, Rachel Brandt, Nicola Crosetto, Theodoros Foukakis, Nicholas Navin. Adaptive resistance to chemotherapy in triple-negative breast cancer revealed by single cell DNA and RNA sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 418. doi:10.1158/1538-7445.AM2017-418</jats:p
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
Basic and translational studies of follicular thyroid neoplasia
No full textThyroid tumors occur frequently in the general population and although the majority represents benign follicular adenomas (FTA), thyroid cancer constitutes 1% of all malignancies worldwide. Among the differentiated cancers, three main types are recognized, including the papillary and follicular forms (PTC and FTC) that originate from the follicular thyrocytes, and the medullary carcinoma that arises from the C-cells. The undifferentiated form, i.e. anaplastic carcinoma (ATC), is a highly aggressive cancer of sometimes unknown cellular origin.The overall goal of this thesis was to investigate the alternative genetic pathways leading to follicular thyroid tumorigenesis and thereby identify clinically relevant biomarkers. A large panel of primary non-medullary thyroid tumors of different histopathological diagnoses as well as human thyroid cell lines were analyzed.In Paper I, cytogenetic analyses of primary thyroid tumors and of the established thyroid cancer cell lines DRO, ARO and CGTH W- 1 were performed. Five of the 16 primary tumors revealed an abnormal karyotype including a FTC with a somatic translocation involving chromosomes 2, 5 and 10 and a PTC with a balanced translocation t(3;15).In Paper II, a panel of 87 follicular thyroid tumors was screened for the presence of PAX8PPARgamma chromosomal translocation. Interphase fluorescence in situ hybridization (iFISH), RTPCR followed by sequencing and Western blotting were used for the detection of the PAX8PPARgamma fusion on the DNA, RNA and protein level, respectively. The rearrangement was detected in 10 of 34 (29%) FTCs and in one of 20 (5%) atypical FTAs, but not in any of the 20 regular FTAs or 13 ATCs studied. The findings suggest that PAX8-PPARgamma occurs frequently in FTC and is highly suggestive of a malignant tumor.Subsequently, the functional consequences of PAX8-PPARgamma were explored (Paper III). Using highdensity oligonucleotide arrays, the gene expression profiles of FTCs bearing a PAX8-PPARgamma fusion were compared with FTCs lacking this fusion. Unsupervised clustering and multidimensional scaling analyses showed that PAX8-PPARgamma positive FTCs have a highly uniform and distinct gene expression signature and are likely to constitute a distinct biological entity. Notably, a large number of ribosomal protein and translation-associated genes were concurrently under-expressed in the FTCs with the fusion.In Paper IV, the role of Ras and its pro-apoptotic effectors NORE1A and RASSF1A in FTC development was investigated. Dramatically reduced mRNA expression of NORE1A was evident in all PAX8-PPARgamma positive FTCs, while RAS mutations and PAX8-PPARgamma fusion were mutually exclusive events. RASSF1A expression was reduced in the majority of the FTCs analyzed.In Paper V, expression of the PTEN tumor suppressor gene was analyzed in 87 sporadic thyroid tumors. Complete loss of PTEN mRNA expression was evident in six of the tumors and the transcriptional silencing of PTEN was significantly associated with the anaplastic subtype. No association was observed between the expression, loss of heterozygosity, and mutation status of PTEN in the 3 3 cases in which these parameters were compared.In Paper VI, 26 potential markers of malignancy were evaluated in 75 follicular thyroid tumors by TaqMan quantitative RT-PCR. A combination of five genes (TERT, TFF3, PPARgamma, EGR2 and CITED1) could accurately predict aggressive FTC, while two genes (TERT and TFF3) specifically detected malignant tumors.List of scientific papersI. Foukakis T, Thoppe SR, Lagercrantz S, Dwight T, Weng WH, Svensson A, Hoog A, Zedenius J, Wallin G, Lui WO, Larsson C (2005). Molecular cytogenetic characterization of primary cultures and established cell lines from non-medullary thyroid tumors. Int J Oncol. 26(1): 141-9. https://pubmed.ncbi.nlm.nih.gov/15586234 II. Dwight T, Thoppe SR, Foukakis T, Lui WO, Wallin G, Hoog A, Frisk T, Larsson C, Zedenius J (2003). Involvement of the PAX8/peroxisome proliferator-activated receptor gamma rearrangement in follicular thyroid tumors. J Clin Endocrinol Metab. 88(9): 4440-5. https://doi.org/10.1210/jc.2002-021690 III. Lui WO, Foukakis T, Liden J, Thoppe SR, Dwight T, Hoog A, Zedenius J, Wallin G, Reimers M, Larsson C (2005). Expression profiling reveals a distinct transcription signature in follicular thyroid carcinomas with a PAX8-PPAR(gamma) fusion oncogene. Oncogene. 24(8): 1467-76. https://doi.org/10.1038/sj.onc.1208135 IV. Foukakis T, Wallin G, Geli J, Au A, Robinson BG, Lui WO, Zedenius J, Larsson C (2005). The NORE1A RAS effector is suppressed in follicular thyroid carcinomas with a PAX8-PPARgamma fusion. [Submitted]V. Frisk T, Foukakis T, Dwight T, Lundberg J, Hoog A, Wallin G, Eng C, Zedenius J, Larsson C (2002). Silencing of the PTEN tumor-suppressor gene in anaplastic thyroid cancer. Genes Chromosomes Cancer. 35(1): 74-80. https://doi.org/10.1002/gcc.10098 VI. Foukakis T, Gusnanto A, Au A, Hogg A, Lui WO, Larsson C, Wallin G, Zedenius J (2005). PCR based expression signature of malignancy in follicular thyroid tumors. [Submitted]</p
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
- …
