A First-in-Class Pyrazole-isoxazole Enhanced Antifungal Activity of Voriconazole: Synergy Studies in an Azole-Resistant Strain, Computational Investigation and in Vivo Validation in a Fungal Infection Model.

The widespread and irrational use of azole antifungal agents has led to an increase of azole-resistant strains with an urgent need for combination drug therapy, enhancing the treatment efficacy. Here, we report the discovery of a first-in-class pyrazole-isoxazole, namely, , that showed remarkable growth inhibition against the . ATCC 10231 strain in combination with voriconazole, acting as a downregulator of ERG 11 () gene expression with a significant reduction of the yeast-to-hypha morphological transition.

Characterization of secretome during sublethal infection of larvae.

The fungal pathogen can induce prolonged colonization of the lungs of susceptible patients, resulting in conditions such as allergic bronchopulmonary aspergillosis and chronic pulmonary aspergillosis. Analysis of the secretome released during sub-lethal infection of larvae may give an insight into products released during prolonged human colonisation. larvae were infected with and the metabolism of host carbohydrate and proteins and production of fungal virulence factors were analysed.

A predictive signal model for dynamic cardiac magnetic resonance imaging.

Robust dynamic cardiac magnetic resonance imaging (MRI) has been a long-standing endeavor-as real-time imaging can provide information on the temporal signatures of disease we currently cannot assess-with the past decade seeing remarkable advances in acceleration using compressed sensing (CS) and artificial intelligence (AI). However, substantial limitations to real-time imaging remain and reconstruction quality is not always guaranteed. To improve reconstruction fidelity in dynamic cardiac MRI, we propose a novel predictive signal model that uses a priori statistics to adaptively predict temporal cardiac dynamics.

Prolonged Subculturing of on Extract Agar Results in Altered Virulence and Sensitivity to Antifungal Agents.

is an environmental saprophyte and opportunistic fungal pathogen of humans. The aim of the work presented here was to examine the effect of serially subculturing on agar generated from larvae in order to characterize the alterations in the phenotypes that might occur. The passaged strains showed alterations in virulence, antifungal susceptibility, and in protein abundances that may indicate adaptation after 25 passages over 231 days on extract agar.

Multifactor dimensionality reduction method identifies novel SNP interactions in the WNT protein interaction networks that are associated with recurrence risk in colorectal cancer.

Background: Interactions among genetic variants are rarely studied but may explain a part of the variability in patient outcomes.

Objectives: In this study, we aimed to identify 1 to 3 way interactions among SNPs from five Wnt protein interaction networks that predict the 5-year recurrence risk in a cohort of stage I-III colorectal cancer patients.

Methods: 423 patients recruited to the Newfoundland Familial Colorectal Cancer Registry were included.

Exposure of to Culture Filtrate Inhibits Growth and Stimulates Gliotoxin Production.

is an opportunistic fungal pathogen capable of inducing chronic and acute infection in susceptible patients. interacts with numerous bacteria that compose the microbiota of the lung, including and , both of which are common isolates from cystic fibrosis sputum. Exposure of to culture filtrate reduced fungal growth and increased gliotoxin production.

Examining SNP-SNP interactions and risk of clinical outcomes in colorectal cancer using multifactor dimensionality reduction based methods.

SNP interactions may explain the variable outcome risk among colorectal cancer patients. Examining SNP interactions is challenging, especially with large datasets. Multifactor Dimensionality Reduction (MDR)-based programs may address this problem.

Larvae as a Model for Investigating Fungal-Host Interactions.

larvae have become a widely accepted and utilised infection model due to the functional homology displayed between their immune response to infection and that observed in the mammalian innate immune response. Due to these similarities, comparable results to murine studies can be obtained using larvae in assessing the virulence of fungal pathogens and the toxicity or efficacy of anti-fungal agents. This coupled with their low cost, rapid generation of results, and lack of ethical/legal considerations make this model very attractive for analysis of host-pathogen interactions.

Primer and Historical Review on Rapid Cardiac CINE MRI.

Acceleration is an important consideration when imaging moving organs such as the heart. Not only does acceleration enable motion-free scans but, more importantly, it lies at the heart of capturing the dynamics of cardiac motion. For over three decades, various ingenious approaches have been devised and implemented for rapid CINE MRI suitable for dynamic cardiac imaging.

Magmatic gas percolation through the old lava dome of El Misti volcano.

The proximity of the major city of Arequipa to El Misti has focused attention on the hazards posed by the active volcano. Since its last major eruption in the fifteenth century, El Misti has experienced a series of modest phreatic eruptions and fluctuating fumarolic activity. Here, we present the first measurements of the compositions of gas emitted from the lava dome in the summit crater.