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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Chang-Han Lee; Tae Hyun Kang; Ophélie Godon; Makiko Watanabe; +15 Authors

    The pharmacokinetic properties of antibodies are largely dictated by the pH-dependent binding of the IgG fragment crystallizable (Fc) domain to the human neonatal Fc receptor (hFcRn). Engineered Fc domains that confer a longer circulation half-life by virtue of more favorable pH-dependent binding to hFcRn are of great therapeutic interest. Here we developed a pH Toggle switch Fc variant containing the L309D/Q311H/N434S (DHS) substitutions, which exhibits markedly improved pharmacokinetics relative to both native IgG1 and widely used half-life extension variants, both in conventional hFcRn transgenic mice and in new knock-in mouse strains. engineered specifically to recapitulate all the key processes relevant to human antibody persistence in circulation, namely: (i) physiological expression of hFcRn, (ii) the impact of hFcγRs on antibody clearance and (iii) the role of competing endogenous IgG. DHS-IgG retains intact effector functions, which are important for the clearance of target pathogenic cells and also has favorable developability. International audience

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Nature Communications
    Article . 2019 . Peer-reviewed
    Data sources: PubMed Central
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Nature Communications
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    Nature Communications
    Article . 2019
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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    Nature Communications
    Article . 2019
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Nature Communications
    Article . 2019 . Peer-reviewed
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    Nature Communications
    Article . 2019 . Peer-reviewed
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    Nature Communications
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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      Nature Communications
      Article . 2019 . Peer-reviewed
      Data sources: PubMed Central
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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      Article . 2019
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      Article . 2019
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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      Article . 2019 . Peer-reviewed
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Nature Communications
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Lossio-Ventura, Juan Antonio, A; Bian, Jiang; Jonquet, Clement; Roche, Mathieu; +1 Authors

    [Departement_IRSTEA]Territoires [TR1_IRSTEA]SYNERGIE [Axe_IRSTEA]TETIS-SISO [ADD1_IRSTEA]Dynamiques spatiales d'anthropisation; International audience; Background: Rapid advancements in biomedical research have accelerated the number of relevant electronic documents published online, ranging from scholarly articles to news, blogs, and user-generated social media content. Nevertheless, the vast amount of this information is poorly organized, making it difficult to navigate. Emerging technologies such as ontologies and knowledge bases (KBs) could help organize and track the information associated with biomedical research developments. A major challenge in the automatic construction of ontologies and KBs is the identification of words with its respective sense(s) from a free-text corpus. Word-sense induction (WSI) is a task to automatically induce the different senses of a target word in the This paper is a significant extension of our previous studies published in the proceedings of: 1) The 10th International Conference on Language Resources and Evaluation (LREC'2016) titled, " Automatic biomedical term polysemy detection " ; and 2) The 19th International Conference on Extending Database Technology (EDBT'2016) titled, " A way to automatically enrich biomedical ontologies " , with new scientific methodologies and results. 2 Juan Antonio Lossio-Ventura et al. different contexts. In the last two decades, there have been several efforts on WSI. However, few methods are effective in biomedicine and life sciences. Methods: We developed a framework for biomedical entity sense induction using a mixture of natural language processing, supervised, and unsupervised learning methods with promising results. It is composed of three main steps: 1) a polysemy detection method to determine if a biomedical entity has many possible meanings; 2) a clustering quality index-based approach to predict the number of senses for the biomedical entity; and 3) a method to induce the concept(s) (i.e., senses) of the biomedical entity in a given context. Results: To evaluate our framework, we used the well-known MSH WSD polysemic dataset that contains 203 annotated ambiguous biomedical entities, where each entity is linked to 2 to 5 concepts. Our polysemy detection method obtained an F-measure of 98%. Second, our approach for predicting the number of senses achieved an F-measure of 93%. Finally, we induced the concepts of the biomedical entities based on a clustering algorithm and then extracted the keywords of reach cluster to represent the concept. Conclusions: We have developed a framework for biomedical entity sense induction with promising results. Our study results can benefit a number of downstream applications, for example, help to resolve concept ambiguities when building Semantic Web KBs from biomedical text.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Journal of Biomedica...arrow_drop_down
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    Journal of Biomedical Informatics
    Article . 2018 . Peer-reviewed
    License: Elsevier Non-Commercial
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Europe PubMed Central
    Other literature type . 2018
    Data sources: PubMed Central
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Pauli, R; Bowring, A; Reynolds, R; Chen, G; +2 Authors

    International audience; Data sharing is becoming a priority in functional Magnetic Resonance Imaging (fMRI) research, but the lack of a standard format for shared data is an obstacle (Poline et al., 2012; Poldrack and Gorgolewski, 2014). This is especially true for information about data provenance, including auxiliary information such as participant characteristics and task descriptions. The three most commonly used analysis software packages [AFNI1 (Cox, 1996), FSL2 (Jenkinson et al., 2012), and SPM3 (Penny et al., 2011)] broadly conduct the same analysis, but differ in how fundamental concepts are described, and have a myriad of differences in the pre-processing and modeling steps. The practical consequence is that sharing analyzed data is further complicated by the idiosyncrasies of the particular software used.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ CORE (RIOXX-UK Aggre...arrow_drop_down
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    Frontiers in Neuroinformatics
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    Frontiers in Neuroinformatics
    Article . 2016 . Peer-reviewed
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ CORE (RIOXX-UK Aggre...arrow_drop_down
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      Frontiers in Neuroinformatics
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Frontiers in Neuroinformatics
      Article . 2016 . Peer-reviewed
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: William N. William; Vassiliki A. Papadimitrakopoulou; J. Jack Lee; Li Mao; +20 Authors

    International audience; IMPORTANCE: Standard molecularly based strategies to predict and/or prevent oral cancer development in patients with oral premalignant lesions (OPLs) are lacking. OBJECTIVE: To test if the epidermal growth factor receptor inhibitor erlotinib would reduce oral cancer development in patients with high-risk OPLs defined by specific loss of heterozygosity (LOH) profiles. Secondary objectives included prospective determination of LOH as a prognostic marker in OPLs. DESIGN: The Erlotinib Prevention of Oral Cancer (EPOC) study was a randomized, placebo-controlled, double-bind trial. Accrual occurred from November 2006 through July 2012, with a median follow-up time of 35 months in an ambulatory care setting in 5 US academic referral institutions. Patients with OPLs were enrolled in the protocol, and each underwent LOH profiling (N = 379); they were classified as high-risk (LOH-positive) or low-risk (LOH-negative) patients based on their LOH profiles and oral cancer history. The randomized sample consisted of 150 LOH-positive patients. INTERVENTIONS: Oral erlotinib treatment (150 mg/d) or placebo for 12 months. MAIN OUTCOMES AND MEASURES: Oral cancer-free survival (CFS). RESULTS: A total of 395 participants were classified with LOH profiles, and 254 were classified LOH positive. Of these, 150 (59%) were randomized, 75 each to the placebo and erlotinib groups. The 3-year CFS rates in placebo- and erlotinib-treated patients were 74% and 70%, respectively (hazard ratio [HR], 1.27; 95% CI, 0.68-2.38; P = .45). The 3-year CFS was significantly lower for LOH-positive compared with LOH-negative groups (74% vs 87%, HR, 2.19; 95% CI, 1.25-3.83; P = .01). Increased EGFR gene copy number correlated with LOH-positive status (P \\textless .001) and lower CFS (P = .01). The EGFR gene copy number was not predictive of erlotinib efficacy. Erlotinib-induced skin rash was associated with improved CFS (P = .01). CONCLUSIONS AND RELEVANCE: In this trial, LOH was validated as a marker of oral cancer risk and found to be associated with increased EGFR copy number (the target of the intervention). Erlotinib did not, however, improve CFS in high-risk patients with LOH-positive or high-EGFR-gene-copy-number OPLs. These results support incorporation of LOH testing as a prognostic tool in routine clinical practice but do not support erlotinib use in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00402779

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ JAMA Oncologyarrow_drop_down
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    JAMA Oncology
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    Europe PubMed Central
    Other literature type . 2016
    Data sources: PubMed Central
    JAMA Oncology
    Article . 2016 . Peer-reviewed
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    Other literature type . 2015
    JAMA Oncology
    Article . 2016 . Peer-reviewed
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      JAMA Oncology
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      Europe PubMed Central
      Other literature type . 2016
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      JAMA Oncology
      Article . 2016 . Peer-reviewed
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      Other literature type . 2015
      JAMA Oncology
      Article . 2016 . Peer-reviewed
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    Authors: Joseph K. Pickrell; Nick Patterson; Chiara Barbieri; Falko Berthold; +17 Authors

    Southern and eastern African populations that speak non-Bantu languages with click consonants are known to harbour some of the most ancient genetic lineages in humans, but their relationships are poorly understood. Here, we report data from 23 populations analyzed at over half a million single nucleotide polymorphisms, using a genome-wide array designed for studying human history. The southern African Khoisan fall into two genetic groups, loosely corresponding to the northwestern and southeastern Kalahari, which we show separated within the last 30,000 years. We find that all individuals derive at least a few percent of their genomes from admixture with non-Khoisan populations that began approximately 1,200 years ago. In addition, the east African Hadza and Sandawe derive a fraction of their ancestry from admixture with a population related to the Khoisan, supporting the hypothesis of an ancient link between southern and eastern Africa To appear in Nature Communications

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    Nature Communications
    Article . 2012 . Peer-reviewed
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    arXiv.org e-Print Archive
    Other literature type . Preprint . 2012
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    DSpace@MIT
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    Nature Communications
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    https://doi.org/10.48550/arxiv...
    Article . 2012
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      Nature Communications
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      arXiv.org e-Print Archive
      Other literature type . Preprint . 2012
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      MPG.PuRe
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      DSpace@MIT
      Article . 2012
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      Nature Communications
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      MPG.PuRe
      Article . 2012
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      https://doi.org/10.48550/arxiv...
      Article . 2012
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Chang-Han Lee; Tae Hyun Kang; Ophélie Godon; Makiko Watanabe; +15 Authors

    The pharmacokinetic properties of antibodies are largely dictated by the pH-dependent binding of the IgG fragment crystallizable (Fc) domain to the human neonatal Fc receptor (hFcRn). Engineered Fc domains that confer a longer circulation half-life by virtue of more favorable pH-dependent binding to hFcRn are of great therapeutic interest. Here we developed a pH Toggle switch Fc variant containing the L309D/Q311H/N434S (DHS) substitutions, which exhibits markedly improved pharmacokinetics relative to both native IgG1 and widely used half-life extension variants, both in conventional hFcRn transgenic mice and in new knock-in mouse strains. engineered specifically to recapitulate all the key processes relevant to human antibody persistence in circulation, namely: (i) physiological expression of hFcRn, (ii) the impact of hFcγRs on antibody clearance and (iii) the role of competing endogenous IgG. DHS-IgG retains intact effector functions, which are important for the clearance of target pathogenic cells and also has favorable developability. International audience

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    Nature Communications
    Article . 2019 . Peer-reviewed
    Data sources: PubMed Central
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    Nature Communications
    Article . 2019
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    Nature Communications
    Article . 2019
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    Nature Communications
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    Nature Communications
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      Nature Communications
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    Authors: Lossio-Ventura, Juan Antonio, A; Bian, Jiang; Jonquet, Clement; Roche, Mathieu; +1 Authors

    [Departement_IRSTEA]Territoires [TR1_IRSTEA]SYNERGIE [Axe_IRSTEA]TETIS-SISO [ADD1_IRSTEA]Dynamiques spatiales d'anthropisation; International audience; Background: Rapid advancements in biomedical research have accelerated the number of relevant electronic documents published online, ranging from scholarly articles to news, blogs, and user-generated social media content. Nevertheless, the vast amount of this information is poorly organized, making it difficult to navigate. Emerging technologies such as ontologies and knowledge bases (KBs) could help organize and track the information associated with biomedical research developments. A major challenge in the automatic construction of ontologies and KBs is the identification of words with its respective sense(s) from a free-text corpus. Word-sense induction (WSI) is a task to automatically induce the different senses of a target word in the This paper is a significant extension of our previous studies published in the proceedings of: 1) The 10th International Conference on Language Resources and Evaluation (LREC'2016) titled, " Automatic biomedical term polysemy detection " ; and 2) The 19th International Conference on Extending Database Technology (EDBT'2016) titled, " A way to automatically enrich biomedical ontologies " , with new scientific methodologies and results. 2 Juan Antonio Lossio-Ventura et al. different contexts. In the last two decades, there have been several efforts on WSI. However, few methods are effective in biomedicine and life sciences. Methods: We developed a framework for biomedical entity sense induction using a mixture of natural language processing, supervised, and unsupervised learning methods with promising results. It is composed of three main steps: 1) a polysemy detection method to determine if a biomedical entity has many possible meanings; 2) a clustering quality index-based approach to predict the number of senses for the biomedical entity; and 3) a method to induce the concept(s) (i.e., senses) of the biomedical entity in a given context. Results: To evaluate our framework, we used the well-known MSH WSD polysemic dataset that contains 203 annotated ambiguous biomedical entities, where each entity is linked to 2 to 5 concepts. Our polysemy detection method obtained an F-measure of 98%. Second, our approach for predicting the number of senses achieved an F-measure of 93%. Finally, we induced the concepts of the biomedical entities based on a clustering algorithm and then extracted the keywords of reach cluster to represent the concept. Conclusions: We have developed a framework for biomedical entity sense induction with promising results. Our study results can benefit a number of downstream applications, for example, help to resolve concept ambiguities when building Semantic Web KBs from biomedical text.

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    Journal of Biomedical Informatics
    Article . 2018 . Peer-reviewed
    License: Elsevier Non-Commercial
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    Europe PubMed Central
    Other literature type . 2018
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    Authors: Pauli, R; Bowring, A; Reynolds, R; Chen, G; +2 Authors

    International audience; Data sharing is becoming a priority in functional Magnetic Resonance Imaging (fMRI) research, but the lack of a standard format for shared data is an obstacle (Poline et al., 2012; Poldrack and Gorgolewski, 2014). This is especially true for information about data provenance, including auxiliary information such as participant characteristics and task descriptions. The three most commonly used analysis software packages [AFNI1 (Cox, 1996), FSL2 (Jenkinson et al., 2012), and SPM3 (Penny et al., 2011)] broadly conduct the same analysis, but differ in how fundamental concepts are described, and have a myriad of differences in the pre-processing and modeling steps. The practical consequence is that sharing analyzed data is further complicated by the idiosyncrasies of the particular software used.

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    Frontiers in Neuroinformatics
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    Frontiers in Neuroinformatics
    Article . 2016 . Peer-reviewed
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      Frontiers in Neuroinformatics
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    Authors: William N. William; Vassiliki A. Papadimitrakopoulou; J. Jack Lee; Li Mao; +20 Authors

    International audience; IMPORTANCE: Standard molecularly based strategies to predict and/or prevent oral cancer development in patients with oral premalignant lesions (OPLs) are lacking. OBJECTIVE: To test if the epidermal growth factor receptor inhibitor erlotinib would reduce oral cancer development in patients with high-risk OPLs defined by specific loss of heterozygosity (LOH) profiles. Secondary objectives included prospective determination of LOH as a prognostic marker in OPLs. DESIGN: The Erlotinib Prevention of Oral Cancer (EPOC) study was a randomized, placebo-controlled, double-bind trial. Accrual occurred from November 2006 through July 2012, with a median follow-up time of 35 months in an ambulatory care setting in 5 US academic referral institutions. Patients with OPLs were enrolled in the protocol, and each underwent LOH profiling (N = 379); they were classified as high-risk (LOH-positive) or low-risk (LOH-negative) patients based on their LOH profiles and oral cancer history. The randomized sample consisted of 150 LOH-positive patients. INTERVENTIONS: Oral erlotinib treatment (150 mg/d) or placebo for 12 months. MAIN OUTCOMES AND MEASURES: Oral cancer-free survival (CFS). RESULTS: A total of 395 participants were classified with LOH profiles, and 254 were classified LOH positive. Of these, 150 (59%) were randomized, 75 each to the placebo and erlotinib groups. The 3-year CFS rates in placebo- and erlotinib-treated patients were 74% and 70%, respectively (hazard ratio [HR], 1.27; 95% CI, 0.68-2.38; P = .45). The 3-year CFS was significantly lower for LOH-positive compared with LOH-negative groups (74% vs 87%, HR, 2.19; 95% CI, 1.25-3.83; P = .01). Increased EGFR gene copy number correlated with LOH-positive status (P \\textless .001) and lower CFS (P = .01). The EGFR gene copy number was not predictive of erlotinib efficacy. Erlotinib-induced skin rash was associated with improved CFS (P = .01). CONCLUSIONS AND RELEVANCE: In this trial, LOH was validated as a marker of oral cancer risk and found to be associated with increased EGFR copy number (the target of the intervention). Erlotinib did not, however, improve CFS in high-risk patients with LOH-positive or high-EGFR-gene-copy-number OPLs. These results support incorporation of LOH testing as a prognostic tool in routine clinical practice but do not support erlotinib use in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00402779

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    JAMA Oncology
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    Europe PubMed Central
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    JAMA Oncology
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    Other literature type . 2015
    JAMA Oncology
    Article . 2016 . Peer-reviewed
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      Europe PubMed Central
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      JAMA Oncology
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    Authors: Joseph K. Pickrell; Nick Patterson; Chiara Barbieri; Falko Berthold; +17 Authors

    Southern and eastern African populations that speak non-Bantu languages with click consonants are known to harbour some of the most ancient genetic lineages in humans, but their relationships are poorly understood. Here, we report data from 23 populations analyzed at over half a million single nucleotide polymorphisms, using a genome-wide array designed for studying human history. The southern African Khoisan fall into two genetic groups, loosely corresponding to the northwestern and southeastern Kalahari, which we show separated within the last 30,000 years. We find that all individuals derive at least a few percent of their genomes from admixture with non-Khoisan populations that began approximately 1,200 years ago. In addition, the east African Hadza and Sandawe derive a fraction of their ancestry from admixture with a population related to the Khoisan, supporting the hypothesis of an ancient link between southern and eastern Africa To appear in Nature Communications

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    Nature Communications
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    Other literature type . Preprint . 2012
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    https://doi.org/10.48550/arxiv...
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      MPG.PuRe
      Article . 2012
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      https://doi.org/10.48550/arxiv...
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