130,512 research outputs found
MARIPOSA: Can Amivantamab and Lazertinib Replace Osimertinib in the Front-Line Setting?
No full textDanielle Brazel,1 Misako Nagasaka2,3 1Department of Hematology/Oncology, Scripps Clinic/Scripps Green Hospital, La Jolla, CA, USA; 2Department of Hematology/Oncology, University of California Irvine School of Medicine, Chao Family Cancer Center, Orange, CA, USA; 3Department of Medicine, St. Marianna University School of Medicine, Kawasaki, JapanCorrespondence: Misako Nagasaka, University of California Irvine School of Medicine Chao Family Cancer Center, 101 The City Drive, Orange, CA, 92868, USA, Email [email protected]: Osimertinib is the current first-line treatment for EGFR-mutated NSCLC, however, patients frequently relapse due to acquired resistance mutations. Amivantamab is a bispecific antibody against EGFR and MET alterations. Lazertinib is a tyrosine kinase inhibitor active against EGFR mutations including common resistance mutations. The MARIPOSA trial was designed to study if the combination of amivantamab plus lazertinib in untreated epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients would provide improved progression-free survival. Here, we discuss the rationale for the study and the early results of MARIPOSA.Keywords: epidermal growth factor receptor (EGFR) mutations, first line treatment, bispecific antibod
MeSH term explosion and author rank improve expert recommendations
No full textInformation overload is an often-cited phenomenon that reduces the productivity, efficiency and efficacy of scientists. One challenge for scientists is to find appropriate collaborators in their research. The literature describes various solutions to the problem of expertise location, but most current approaches do not appear to be very suitable for expert recommendations in biomedical research. In this study, we present the development and initial evaluation of a vector space model-based algorithm to calculate researcher similarity using four inputs: 1) MeSH terms of publications; 2) MeSH terms and author rank; 3) exploded MeSH terms; and 4) exploded MeSH terms and author rank. We developed and evaluated the algorithm using a data set of 17,525 authors and their 22,542 papers. On average, our algorithms correctly predicted 2.5 of the top 5/10 coauthors of individual scientists. Exploded MeSH and author rank outperformed all other algorithms in accuracy, followed closely by MeSH and author rank. Our results show that the accuracy of MeSH term-based matching can be enhanced with other metadata such as author rank
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe 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
Genetic and epigenetic editing approach to characterise the nature and function of bivalent histone modifications
No full textIn eukaryotes, DNA is wrapped around a group of proteins termed histones
that are required to precisely control gene expression during development. The
amino acids of both the globular domains and unstructured tails of these histones can
be modified by chemical moieties, such as methylation, acetylation and
ubiquitination. The ‘histone code’ hypothesis proposes that specific combinations of
these and other histone modifications contain transcriptional information, which
guides the cell machinery to activate or repress gene expression in individual cell
types.
Chromatin immunoprecipitation (ChIP) experiments using undifferentiated
stem cell populations have identified the genomic co-localisation of histone
modifications reported to have opposing effects on transcription, which is known as
bivalency. The human α-globin promoter, a well-established model for the study of
transcriptional regulation, is bivalent in embryonic stem (ES) cells and this bivalency
is resolved once the ES cells terminally differentiate (i.e. only activating or
repressing marks remain). In a humanised mouse model, the deletion of a bone fide
enhancer within the human α-globin locus results in heterogeneous expression
patterns in primary erythroid cells. Notably, this correlates with an unresolved
bivalent state at this promoter in terminally differentiated cells.
Using this mouse model it is not feasible to ascertain whether the
transcriptional heterogeneity observed in the cells lacking an α-globin enhancer is
reflective of epigenetic heterogeneity (i.e. a mixed population of cells) rather than
co-localisation of bivalent histone modifications within the same cells. Furthermore,
the functional contribution of bivalency to development has yet to be described. To
address these difficulties, I aimed to generate a fluorescent reporter system for
human α-globin to facilitate the separation of transcriptionally heterogeneous
erythroid cells. This model will provide material for ChIP studies on transcriptionally
active and inactive populations to determine whether the epigenetic bivalency is
reflective of a mixed cell population or true bivalency. In addition, I aimed to
produce epigenetic editing tools to target bivalent promoters, which in combination
with in vitro differentiation assays would provide an interesting framework to test the
function of bivalency during development.
In this study, I extensively tested gene-editing strategies for generating a
fluorescent reporter knock-in in humanised mouse ES cells. I validated the suitability
of humanised mouse ES cell lines for gene targeting studies and optimised a robust
in vitro differentiation protocol for studying erythropoiesis. I utilised both
recombineering and CRISPR/Cas9 gene editing tools in tandem with PiggyBac
transposon technology, to knock-in the reporter gene. I made significant steps in
gene targeting and successfully inserted the reporter downstream of the α-globin
gene. I also generated a cloning system to express site-specific DNA-binding
domains (TALEs) fused to epigenetic regulators with the aim to resolve bivalent
histone modifications in vitro. From preliminary tests using these fusion proteins
targeting Nrp1, a bivalent promoter in mES cells, I observed mild but significant
changes in gene expression although histone modifications were unchanged. The
various tools generated and tested in this study provide a solid foundation for future
development of genetic and epigenetic editing at the human α-globin and other
bivalent loci
"Closing the R&D Gap, Evaluating the Sources of R&D Spending"
No full textBoth spending and tax policies have been implemented in the United States with the goal of stimulating private sector research and development (R&D). Karier questions whether current R&D policy, especially the research and experimentation tax credit, can contribute to closing the gap between nondefense expenditures on R&D in the United States and such expenditures in other countries, such as Japan and Germany. He also explores possible changes to our current R&D policy to make it more effective.
Dispelling the Myths Behind First-author Citation Counts
No full textWe 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
Scholarly Communication and Publishing Lunch and Learn Talk #11: The ULS Open Access Author Fee Fund
No full textAt the May 2014 talk, you will learn about the ULS Open Access Author Fee Fund--what it is, why we do it, how it works, and how the program is going so far
The R&D Tax Incentives
No full textThis article sets out some background information and reflections of the author on the R&D tax incentive schemes included in the Common Corporate Tax Base (CCTB) Proposal. In particular the author analyzes the stimulus to private R&D through ad hoc tax incentives included in the CCTB Proposal and dives into the actual provisions included in the Proposal highlighting the most relevant issues connected with their design and interpretation. Moreover, the author explores the interaction between the CCTB Proposal and the granting by Member States of domestic R&D tax incentives
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