Suchergebnisse

Drug toxicity is a major concern for both regulatory agencies and the pharmaceutical industry. In this context, text-mining methods for the identification of drug side effects from free text are key for the development of up-to-date knowledge sources on drug adverse reactions. We present a new system for identification of drug side effects from the literature that combines three approaches: machine learning, rule- and knowledge-based approaches. This system has been developed to address the Task 3.B of Biocreative V challenge (BC5) dealing with Chemical-induced Disease (CID) relations. The first two approaches focus on identifying relations at the sentence-level, while the knowledge-based approach is applied both at sentence and abstract levels. The machine learning method is based on the BeFree system using two corpora as training data: the annotated data provided by the CID task organizers and a new CID corpus developed by crowdsourcing. Different combinations of results from the three strategies were selected for each run of the challenge. In the final evaluation setting, the system achieved the highest Recall of the challenge (63%). By performing an error analysis, we identified the main causes of misclassifications and areas for improving of our system, and highlighted the need of consistent gold standard data sets for advancing the state of the art in text mining of drug side effects. ; This work was supported by grants from the National Institutes of Health (GM114833, GM089820, TR001114); the Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional (PI13/00082 and CP10/00524 to A.B. and L.I.F.); the Innovative Medicines Initiative-Joint Undertaking (eTOX no. 115002, Open PHACTs no. 115191, EMIF no. 115372, iPiE no. 115735 to A.B. and L.I.F.), resources of which are composed of financial contributions from the European Union's Seventh Framework Programme (FP7/2007–13) and European Federation of Pharmaceutical Industries and Associations; and the European Union Horizon 2020 Programme 2014–20 (MedBioinformatics no. 634143 and Elixir-Excelerate no. 676559 to A.B. and L.I.F.). The Research Programme on Biomedical Informatics (GRIB) is a node of the Spanish National Institute of Bioinformatics (INB).

Nevirapine (NVP), a non-nucleoside reverse transcriptase inhibitor widely used in combined antiretroviral therapy and to prevent mother-to-child transmission of the human immunodeficiency virus type 1, is associated with several adverse side effects. Using 12-mesyloxy-nevirapine, a model electrophile of the reactive metabolites derived from the NVP Phase I metabolite, 12-hydroxy-NVP, we demonstrate that the nucleophilic core and C-terminal residues of histones are targets for covalent adduct formation. We identified multiple NVP-modification sites at lysine (e.g., H2BK47, H4K32), histidine (e.g., H2BH110, H4H76), and serine (e.g., H2BS33) residues of the four histones using a mass spectrometry-based bottom-up proteomic analysis. In particular, H2BK47, H2BH110, H2AH83, and H4H76 were found to be potential hot spots for NVP incorporation. Notably, a remarkable selectivity to the imidazole ring of histidine was observed, with modification by NVP detected in three out of the 11 histidine residues of histones. This suggests that NVP-modified histidine residues of histones are prospective markers of the drug's bioactivation and/or toxicity. Importantly, NVP-derived modifications were identified at sites known to determine chromatin structure (e.g., H4H76) or that can undergo multiple types of post-translational modifications (e.g., H2BK47, H4H76). These results open new insights into the molecular mechanisms of drug-induced adverse reactions. ; This work was supported in part by the PRIME-XS project, grant agreement number 262067, funded by the European Union seventh Framework Programme. We also thank Fundação para a Ciência e a Tecnologia (FCT), Portugal, for financial support through projects UID/QUI/00100/2020 (to CQE), RECI/QEQ-MED/0330/2012 and PTDC/QUI-QAN/32242/2017, as well as contract CEECIND/02001/2017 (to A.M.M.A) and doctoral fellowships SFRH/BD/80690/2011 (to SGH), SFRH/BD/75426/2010 (to ILM), and SFRH/BD/102846/2014 (to CC). Joint funding from FCT and the COMPETE Program through grant SAICTPAC/0019/2015 and RNEM-LISBOA-01-0145-FEDER-022125 funding are also gratefully acknowledged. The CRG/UPF Proteomics Unit is part of the "Plataforma de Recursos Biomoleculares y Bioinformáticos (ProteoRed)" supported by grant PT13/0001 of the Instituto de Salud Carlos III (ISCIII)

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disorder that commonly affects the skin, joints, kidneys, and central nervous system. Although great progress has been made over the years, patients still experience unfavorable secondary effects from medications, increased economic burden, and higher mortality rates compared to the general population. To alleviate these current problems, non-invasive, non-pharmacological interventions are being increasingly investigated. One such intervention is non-invasive vagus nerve stimulation, which promotes the upregulation of the cholinergic anti-inflammatory pathway that reduces the activation and production of pro-inflammatory cytokines and reactive oxygen species, culpable processes in autoimmune diseases such as SLE. This review first provides a background on the important contribution of the autonomic nervous system to the pathogenesis of SLE. The gross and structural anatomy of the vagus nerve and its contribution to the inflammatory response are described afterwards to provide a general understanding of the impact of stimulating the vagus nerve. Finally, an overview of current clinical applications of invasive and non-invasive vagus nerve stimulation for a variety of diseases, including those with similar symptoms to the ones in SLE, is presented and discussed. Overall, the review presents neuromodulation as a promising strategy to alleviate SLE symptoms and potentially reverse the disease ; Government of Catalonia under 2017SGR1551

FELD-MEDICAMENTEN-KATALOG Feld-Medicamenten-Katalog ([1]) Einband ( - ) Titelseite ([1]) I. Verzeichniß aller einfachen, zubereiteten, und zusammengesetzten Arzneystücke, welche in den k. k. Feldapotheken zu Fassungen aufbewahret werden, mit beygefügten Preisen nach der Militär-Taxe, ohne Zuschlag der Regiekosten. ([3]) II. Verzeichniß der für die k. k. Feld-Garnisons- und Regimentsspitäler bestimmten Arzneyformeln mit den beygesetzten Preisen nach der Militär-Taxe. Mit Zuschlag der Regiekosten. (17) Bemerkungen über die vorstehenden zwey Arzneytaxen, zur Nachricht für die k. k. Feldärzte und Feldapotheker. (19) Abschnitt ( - )

Two Poems by Alison Wong

THIS PAPER EXPLORES THE ACTUAL AND POTENTIAL USEFULNESS OF OPINION POLLS FOR ANALYZING WHO GAINS AND WHO LOSES WHEN COLLECTIVE GOODS ARE PROVIDED. THE AUTHOR ARGUES THAT ANSWERS TO OPINION POLLS CAN REVEAL SOMETHING ABOUT THE PERCEIVED DISTRIBUTION OF GAINS AND LOSSES AMONG PEOPLE OF VARIOUS AGES, INCOMES, RACES AND EDUCATIONAL GROUPS.