107 research outputs found

    The American Psychiatric Association’s Guideline for Major Depressive Disorder: A Commentary

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    The American Psychiatric Association (APA) published a new guideline for Major Depressive Disorder (MDD) which will undoubtedly be used by many practitioners to guide clinical decision-making. In fact, it is non-psychiatrist clinicians who prescribe the majority of antidepressants (AD). We review the APA’s most recent guideline on MDD and report on our observations

    GOAnnotator: linking protein GO annotations to evidence text

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    BACKGROUND: Annotation of proteins with gene ontology (GO) terms is ongoing work and a complex task. Manual GO annotation is precise and precious, but it is time-consuming. Therefore, instead of curated annotations most of the proteins come with uncurated annotations, which have been generated automatically. Text-mining systems that use literature for automatic annotation have been proposed but they do not satisfy the high quality expectations of curators. RESULTS: In this paper we describe an approach that links uncurated annotations to text extracted from literature. The selection of the text is based on the similarity of the text to the term from the uncurated annotation. Besides substantiating the uncurated annotations, the extracted texts also lead to novel annotations. In addition, the approach uses the GO hierarchy to achieve high precision. Our approach is integrated into GOAnnotator, a tool that assists the curation process for GO annotation of UniProt proteins. CONCLUSION: The GO curators assessed GOAnnotator with a set of 66 distinct UniProt/SwissProt proteins with uncurated annotations. GOAnnotator provided correct evidence text at 93% precision. This high precision results from using the GO hierarchy to only select GO terms similar to GO terms from uncurated annotations in GOA. Our approach is the first one to achieve high precision, which is crucial for the efficient support of GO curators. GOAnnotator was implemented as a web tool that is freely available at

    Toward the Restoration of Hand Use to a Paralyzed Monkey: Brain-Controlled Functional Electrical Stimulation of Forearm Muscles

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    Loss of hand use is considered by many spinal cord injury survivors to be the most devastating consequence of their injury. Functional electrical stimulation (FES) of forearm and hand muscles has been used to provide basic, voluntary hand grasp to hundreds of human patients. Current approaches typically grade pre-programmed patterns of muscle activation using simple control signals, such as those derived from residual movement or muscle activity. However, the use of such fixed stimulation patterns limits hand function to the few tasks programmed into the controller. In contrast, we are developing a system that uses neural signals recorded from a multi-electrode array implanted in the motor cortex; this system has the potential to provide independent control of multiple muscles over a broad range of functional tasks. Two monkeys were able to use this cortically controlled FES system to control the contraction of four forearm muscles despite temporary limb paralysis. The amount of wrist force the monkeys were able to produce in a one-dimensional force tracking task was significantly increased. Furthermore, the monkeys were able to control the magnitude and time course of the force with sufficient accuracy to track visually displayed force targets at speeds reduced by only one-third to one-half of normal. Although these results were achieved by controlling only four muscles, there is no fundamental reason why the same methods could not be scaled up to control a larger number of muscles. We believe these results provide an important proof of concept that brain-controlled FES prostheses could ultimately be of great benefit to paralyzed patients with injuries in the mid-cervical spinal cord

    Phosphatidylinositol 3-kinase pathway activation in breast cancer brain metastases

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    Activation status of the phosphatidylinositol 3-kinase (PI3K) pathway in breast cancer brain metastases (BCBMs) is largely unknown. We examined expression of phospho(p)-AKT, p-S6, and phosphatase and tensin homologue (PTEN) in BCBMs and their implications for overall survival (OS) and survival after BCBMs. Secondary analyses included PI3K pathway activation status and associations with time to distant recurrence (TTDR) and time to BCBMs. Similar analyses were also conducted among the subset of patients with triple-negative BCBMs. METHODS: p-AKT, p-S6, and PTEN expression was assessed with immunohistochemistry in 52 BCBMs and 12 matched primary BCs. Subtypes were defined as hormone receptor (HR)+/HER2-, HER2+, and triple-negative (TNBC). Survival analyses were performed by using a Cox model, and survival curves were estimated with the Kaplan-Meier method. RESULTS: Expression of p-AKT and p-S6 and lack of PTEN (PTEN-) was observed in 75%, 69%, and 25% of BCBMs. Concordance between primary BCs and matched BCBMs was 67% for p-AKT, 58% for p-S6, and 83% for PTEN. PTEN- was more common in TNBC compared with HR+/HER2- and HER2+. Expression of p-AKT, p-S6, and PTEN- was not associated with OS or survival after BCBMs (all, P > 0.06). Interestingly, among all patients, PTEN- correlated with shorter time to distant and brain recurrence. Among patients with TNBC, PTEN- in BCBMs was associated with poorer overall survival. CONCLUSIONS: The PI3K pathway is active in most BCBMs regardless of subtype. Inhibition of this pathway represents a promising therapeutic strategy for patients with BCBMs, a group of patients with poor prognosis and limited systemic therapeutic options. Although expression of the PI3K pathway did not correlate with OS and survival after BCBM, PTEN- association with time to recurrence and OS (among patients with TNBC) is worthy of further study

    The American Psychiatric Association’s Guideline for Major Depressive Disorder: A Commentary

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    The American Psychiatric Association (APA) published a new guideline for Major Depressive Disorder (MDD) which will undoubtedly be used by many practitioners to guide clinical decision-making. In fact, it is non-psychiatrist clinicians who prescribe the majority of antidepressants (AD). We review the APA’s most recent guideline on MDD and report on our observations

    Verification of Uncurated Protein Annotations

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    Molecular Biology research projects produced vast amounts of data, part of which has been preserved in a variety of public databases. However, a large portion of the data contains a significant number of errors and therefore requires careful verification by curators, a painful and costly task, before being reliable enough to derive valid conclusions from it. On the other hand, research in biomedical information retrieval and information extraction are nowadays delivering Text Mining solutions that can support curators to improve the efficiency of their work to deliver better data resources. Over the past decades, automatic text processing systems have successfully exploited biomedical scientific literature to reduce the researchers’ efforts to keep up to date, but many of these systems still rely on domain knowledge that is integrated manually leading to unnecessary overheads and restrictions in its use. A more efficient approach would acquire the domain knowledge automatically from publicly available biological sources, such as BioOntologies, rather than using manually inserted domain knowledge. An example of this approach is GOAnnotator, a tool that assists the verification of uncurated protein annotations. It provided correct evidence text at 93% precision to the curators and thus achieved promising results. GOAnnotator was implemented as a web tool that is freely available at http://xldb.di.fc.ul.pt/rebil/tools/goa/
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