The pivotal phase 3 True North (TN) study demonstrated the efficacy and safety of ozanimod in patients with moderately to severely active ulcerative colitis. This analysis assessed ozanimod during TN and the ongoing open-label extension (OLE) in patients with active disease who were naive to advanced therapies (ATs).
The role of topological heterogeneity in the origin of extreme events in a network is investigated here. The dynamics of the oscillators associated with the nodes are assumed to be identical and influenced by mean-field repulsive interactions. An interplay of topological heterogeneity and the repulsive interaction between the dynamical units of the network triggers extreme events in the nodes when each node succumbs to such events for discretely different ranges of repulsive coupling. A high degree node is vulnerable to weaker repulsive interactions, while a low degree node is susceptible to stronger interactions. As a result, the formation of extreme events changes position with increasing strength of repulsive interaction from high to low degree nodes. Extreme events at any node are identified with the appearance of occasional large-amplitude events (amplitude of the temporal dynamics) that are larger than a threshold height and rare in occurrence, which we confirm by estimating the probability distribution of all events. Extreme events appear at any oscillator near the boundary of transition from rotation to libration at a critical value of the repulsive coupling strength. To explore the phenomenon, a paradigmatic second-order phase model is used to represent the dynamics of the oscillator associated with each node. We make an annealed network approximation to reduce our original model and, thereby, confirm the dual role of the repulsive interaction and the degree of a node in the origin of extreme events in any oscillator associated with a node.
Poster presentationsFigure 1.Kaplan Meier analysis displaying adalimumab failure in relation to prior ATI formation.Figure 2. Kaplan Meier analysis displaying adalimumab failure in relation to the reason for infliximab failure.
<div>Abstract<p>Lung squamous carcinoma (LUSC) is a highly metastatic disease with a poor prognosis. Using an integrated screening approach, we found that miR-671-5p reduces LUSC metastasis by inhibiting a circular RNA (circRNA), CDR1as. Although the putative function of circRNA is through miRNA sponging, we found that miR-671-5p more potently silenced an axis of CDR1as and its antisense transcript, cerebellar degeneration related protein 1 (CDR1). Silencing of CDR1as or CDR1 significantly inhibited LUSC metastases and CDR1 was sufficient to promote migration and metastases. CDR1, which directly interacted with adaptor protein 1 (AP1) complex subunits and coatomer protein I (COPI) proteins, no longer promoted migration upon blockade of Golgi trafficking. Therapeutic inhibition of the CDR1as/CDR1 axis with miR-671-5p mimics reduced metastasis <i>in vivo</i>. This report demonstrates a novel role for CDR1 in promoting metastasis and Golgi trafficking. These findings reveal an miRNA/circRNA axis that regulates LUSC metastases through a previously unstudied protein, CDR1.</p>Significance:<p>This study shows that circRNA, CDR1as, promotes lung squamous migration, metastasis, and Golgi trafficking through its complimentary transcript, CDR1.</p></div>
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