Annotation and detection of drug effects in text for pharmacovigilance.

Pharmacovigilance (PV) databases record the benefits and risks of different drugs, as a means to ensure their safe and effective use. Creating and maintaining such resources can be complex, since a particular medication may have divergent effects in different individuals, due to specific patient characteristics and/or interactions with other drugs being administered. Textual information from various sources can provide important evidence to curators of PV databases about the usage and effects of drug targets in different medical subjects. However, the efficient identification of relevant evidence can be challenging, due to the increasing volume of textual data. Text mining (TM) techniques can support curators by automatically detecting complex information, such as interactions between drugs, diseases and adverse effects. This semantic information supports the quick identification of documents containing information of interest (e.g., the different types of patients in which a given adverse drug reaction has been observed to occur). TM tools are typically adapted to different domains by applying machine learning methods to corpora that are manually labelled by domain experts using annotation guidelines to ensure consistency. We present a semantically annotated corpus of 597 MEDLINE abstracts, PHAEDRA, encoding rich information on drug effects and their interactions, whose quality is assured through the use of detailed annotation guidelines and the demonstration of high levels of inter-annotator agreement (e.g., 92.6% F-Score for identifying named entities and 78.4% F-Score for identifying complex events, when relaxed matching criteria are applied). To our knowledge, the corpus is unique in the domain of PV, according to the level of detail of its annotations. To illustrate the utility of the corpus, we have trained TM tools based on its rich labels to recognise drug effects in text automatically. The corpus and annotation guidelines are available at: http://www.nactem.ac.uk/PHAEDRA/ .

Use of isolated mature osteoblasts in abundance acts as desired-shaped bone regeneration in combination with a modified poly-DL-lactic-co-glycolic acid (PLGA)-collagen sponge.

Controlled regeneration of bone or cartilage has recently begun to facilitate a host of novel clinical treatments. An osteoblast line, which we isolated is able to form new bone matrix in vivo within 2 days and exhibits a mature osteoblast phenotype both in vitro and in vivo. Using these cells, we show that cuboidal bones can be generated into a predesigned shaped-bone with high-density bone trabeculae when used in combination with a modified poly-DL-lactic-co-glycolic acid (PLGA)-collagen sponge. PLGA coated with collagen gel serves as a good scaffold for osteoblasts. These results indicate that mature osteoblasts, in combination with a scaffold such as PLGA-collagen sponge, show promise for use in a custom-shaped bone regeneration tool for both basic research into osteogenesis and for development of therapeutic applications.

Introduction and Expression of Recombinant ß-Galactosidase Genes in Cleavage Stage Mouse Embryos: (microinjection/mouse embryo/gene expression).

In an attempt to study gene regulation in very early stages of mouse embryogenesis, we injected genes constructed by joining the coding sequence of the bacterial ß-galactosidase gene to four different animal gene enhancers/promoters and to poly (A) signals, and examined the gene expression in cleavage stage embryos. With appropriate injection volumes for each embryonic stage, ranging from 0.2 to 1.3 pl, the majority of the injected embryos underwent at least one further cleavage. Expression of injected genes, which occurred transiently after injection, required the promoter sequences but without much distinction of the source of enhancer/promoter complexes. This result was in a sharp contrast to transfection of mouse cell lines where the recombinant genes were variably expressed reflecting differential enhancer effects. By injection at the 1-cell stage, expression of injected genes was low while the expression by injection at the 2-cell or later stages was several fold higher, which may correlate with the fact that most zygotic gene expression begins after the 2-cell stage. The low expression at the 1-cell stage was augmented by the conditions causing clea***age arrest such as inhibition of DNA synthesis with aphidicolin.