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Institution

Novartis

CompanyBasel, Switzerland
About: Novartis is a company organization based out in Basel, Switzerland. It is known for research contribution in the topics: Alkyl & Population. The organization has 41930 authors who have published 50566 publications receiving 1978996 citations. The organization is also known as: Novartis International AG.


Papers
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Journal ArticleDOI
TL;DR: An antagonist for the metabotropic glutamate receptor may improve symptoms in patients with fragile X syndrome whose FMR1 promoters are fully methylated, a sign that gene expression is completely silenced, and provides the basis for a larger study to test whether methylation can serve as a predictor of a positive antagonist response in a population of patients with Fragile X syndrome.
Abstract: Fragile X syndrome (FXS) is an X-linked condition associated with intellectual disability and behavioral problems. It is caused by expansion of a CGG repeat in the 5′ untranslated region of the fragile X mental retardation 1 (FMR1) gene. ThismutationisassociatedwithhypermethylationattheFMR1promoterandresultanttranscriptionalsilencing.FMR1 silencinghasmanyconsequences,includingup-regulationofmetabotropicglutamatereceptor5(mGluR5)–mediated signaling. mGluR5 receptor antagonists have shown promise in preclinical FXS models and in one small open-label study of FXS. We examined whether a receptor subtype–selective inhibitor of mGluR5, AFQ056, improves the behavioral symptoms of FXS in a randomized, double-blind, two-treatment, two-period, crossover study of 30 male FXS patients aged 18 to 35 years. We detected no significant effects of treatment on the primary outcome measure, the Aberrant Behavior Checklist–Community Edition (ABC-C) score, at day 19 or 20 of treatment. In an exploratory analysis, however, seven patients with full FMR1 promoter methylation and no detectable FMR1 messenger RNA improved, as measured with the ABC-C, significantly more after AFQ056 treatment than with placebo (P <0 .001). We detected no response in 18 patients with partial promoter methylation. Twenty-four patients experienced an adverse event, which was mostly mild to moderately severe fatigue or headache. If confirmed in larger and longer-term studies, these results suggest that blockade of the mGluR5 receptor in patients with full methylation at the FMR1 promoter may show improvement in the behavioral attributes of FXS.

611 citations

Journal ArticleDOI
TL;DR: These two phase 3 studies show the efficacy and safety of canakinumab in systemic JIA with active systemic features, and among the 100 patients who underwent randomization in the withdrawal phase, the risk of flare was lower among patients who continued to receive canakinUMab than among those who were switched to placebo.
Abstract: A B S T R AC T BACKGROUND Interleukin-1 is pivotal in the pathogenesis of systemic juvenile idiopathic arthritis (JIA). We assessed the efficacy and safety of canakinumab, a selective, fully human, anti–interleukin-1β monoclonal antibody, in two trials. METHODS In trial 1, we randomly assigned patients, 2 to 19 years of age, with systemic JIA and active systemic features (fever; ≥2 active joints; C-reactive protein, >30 mg per liter; and glucocorticoid dose, ≤1.0 mg per kilogram of body weight per day), in a double-blind fashion, to a single subcutaneous dose of canakinumab (4 mg per kilo gram) or placebo. The primary outcome, termed adapted JIA ACR 30 response, was defined as improvement of 30% or more in at least three of the six core criteria for JIA, worsening of more than 30% in no more than one of the criteria, and resolution of fever. In trial 2, after 32 weeks of open-label treatment with canakinumab, pa tients who had a response and underwent glucocorticoid tapering were randomly assigned to continued treatment with canakinumab or to placebo. The primary outcome was time to flare of systemic JIA. RESULTS At day 15 in trial 1, more patients in the canakinumab group had an adapted JIA ACR 30 response (36 of 43 [84%], vs. 4 of 41 [10%] in the placebo group; P<0.001). In trial 2, among the 100 patients (of 177 in the open-label phase) who underwent randomization in the withdrawal phase, the risk of flare was lower among patients who continued to receive canakinumab than among those who were switched to pla cebo (74% of patients in the canakinumab group had no flare, vs. 25% in the pla

611 citations

Journal ArticleDOI
01 May 2016-Leukemia
TL;DR: Long-term results support the positive benefit-risk profile of frontline nilotinib 300 mg twice daily in patients with CML-CP, and few deaths in any arm were associated with CVEs, infections or pulmonary diseases.
Abstract: Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial

609 citations

Journal ArticleDOI
TL;DR: In this article, a graph convolutional model that consistently matches or outperforms models using fixed molecular descriptors as well as previous graph neural architectures on both public and proprietary data sets is presented.
Abstract: Advancements in neural machinery have led to a wide range of algorithmic solutions for molecular property prediction. Two classes of models in particular have yielded promising results: neural networks applied to computed molecular fingerprints or expert-crafted descriptors and graph convolutional neural networks that construct a learned molecular representation by operating on the graph structure of the molecule. However, recent literature has yet to clearly determine which of these two methods is superior when generalizing to new chemical space. Furthermore, prior research has rarely examined these new models in industry research settings in comparison to existing employed models. In this paper, we benchmark models extensively on 19 public and 16 proprietary industrial data sets spanning a wide variety of chemical end points. In addition, we introduce a graph convolutional model that consistently matches or outperforms models using fixed molecular descriptors as well as previous graph neural architectures on both public and proprietary data sets. Our empirical findings indicate that while approaches based on these representations have yet to reach the level of experimental reproducibility, our proposed model nevertheless offers significant improvements over models currently used in industrial workflows.

605 citations

Journal ArticleDOI
TL;DR: expression of a large number of genes changes in response to enrichment training, many of which can be linked to neuronal structure, synaptic plasticity, and transmission and may play important roles in modulating learning and memory capacity.
Abstract: An enriched environment is known to promote structural changes in the brain and to enhance learning and memory performance in rodents [Hebb, D. O. (1947) Am. Psychol. 2, 306–307]. To better understand the molecular mechanisms underlying these experience-dependent cognitive changes, we have used high-density oligonucleotide microarrays to analyze gene expression in the brain. Expression of a large number of genes changes in response to enrichment training, many of which can be linked to neuronal structure, synaptic plasticity, and transmission. A number of these genes may play important roles in modulating learning and memory capacity.

605 citations


Authors

Showing all 41972 results

NameH-indexPapersCitations
Irving L. Weissman2011141172504
Peter J. Barnes1941530166618
Paul G. Richardson1831533155912
Kenneth C. Anderson1781138126072
Jie Zhang1784857221720
Lei Jiang1702244135205
Marc A. Pfeffer166765133043
Jorge E. Cortes1632784124154
Ian A. Wilson15897198221
Peter G. Schultz15689389716
Bruce D. Walker15577986020
Timothy P. Hughes14583191357
Kurt Wüthrich143739103253
Leonard Guarente14335280169
Christopher D.M. Fletcher13867482484
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202318
202285
20211,321
20201,377
20191,376
20181,456