Treatment preferences of patients with muscle invasive bladder cancer: A discrete choice experiment.

Background: When faced with treatment options, patients are asked to participate in decision-making. We sought to determine which treatment aspects matter most for individuals treated for muscle invasive bladder cancer (MIBC), with an aim to improve understanding of patient preferences and what trade-offs patients are willing to accept. Our study consisted of a discrete choice experiment (DCE): a type of questionnaire used to elicit preferences in the absence of real-world choice.

USP28 deletion and small-molecule inhibition destabilizes c-MYC and elicits regression of squamous cell lung carcinoma.

Lung squamous cell carcinoma (LSCC) is a considerable global health burden, with an incidence of over 600,000 cases per year. Treatment options are limited, and patient's 5-year survival rate is less than 5%. The ubiquitin-specific protease 28 (USP28) has been implicated in tumourigenesis through its stabilization of the oncoproteins c-MYC, c-JUN, and Δp63.

Synthesis of natural/C-enriched d-tagatose from natural/C-enriched d-fructose.

A concise, easily scalable synthesis of a rare ketohexose, d-tagatose, was developed, that is compatible with the preparation of d-[UL-C]tagatose. Epimerization of the widely available and inexpensive ketohexose d-fructose at the C-4 position via an oxidation/reduction (Dess-Martin periodinane/NaBH) was a key step in the synthesis. Overall, fully protected natural d-tagatose (3.

Hydrate Growth on Methane Gas Bubbles in the Presence of Salt.

Methane bubble dispersions in a water column can be observed in both vertical subsea piping as well as subsea gas seepages. Hydrate growth has been shown to occur at the gas-water interface under flowing conditions, yet the majority of the current literature is limited to quiescent systems. Gas hydrate risks in subsea piping have been shown to increase in late life production wells with increased water content and with gas-in-water bubble dispersions.

FPR1 is the plague receptor on host immune cells.

The causative agent of plague, Yersinia pestis, uses a type III secretion system to selectively destroy immune cells in humans, thus enabling Y. pestis to reproduce in the bloodstream and be transmitted to new hosts through fleabites. The host factors that are responsible for the selective destruction of immune cells by plague bacteria are unknown.

Molecular basis of USP7 inhibition by selective small-molecule inhibitors.

Ubiquitination controls the stability of most cellular proteins, and its deregulation contributes to human diseases including cancer. Deubiquitinases remove ubiquitin from proteins, and their inhibition can induce the degradation of selected proteins, potentially including otherwise 'undruggable' targets. For example, the inhibition of ubiquitin-specific protease 7 (USP7) results in the degradation of the oncogenic E3 ligase MDM2, and leads to re-activation of the tumour suppressor p53 in various cancers.

Glutathionylation of LcrV and Its Effects on Plague Pathogenesis.

Glutathionylation, the formation of reversible mixed disulfides between glutathione and protein cysteine residues, is a posttranslational modification previously observed for intracellular proteins of bacteria. Here we show that LcrV, a secreted protein capping the type III secretion machine, is glutathionylated at Cys and that this modification promotes association with host ribosomal protein S3 (RPS3), moderates type III effector transport and killing of macrophages, and enhances bubonic plague pathogenesis in mice and rats. Secreted LcrV was purified and analyzed by mass spectrometry to reveal glutathionylation, a modification that is abolished by the codon substitution CysAla in Moreover, the mutation enhanced the survival of animals in models of bubonic plague.

Quantitative Lipoproteomics in Clostridium difficile Reveals a Role for Lipoproteins in Sporulation.

Bacterial lipoproteins are surface exposed, anchored to the membrane by S-diacylglyceryl modification of the N-terminal cysteine thiol. They play important roles in many essential cellular processes and in bacterial pathogenesis. For example, Clostridium difficile is a Gram-positive anaerobe that causes severe gastrointestinal disease; however, its lipoproteome remains poorly characterized.

Transcatheter aortic valve implantation and simultaneous closure of associated paravalvular leak.

Paravalvular aortic regurgitation (PAR) following transcatheter aortic valve implantation (TAVI) is a complication which is associated with increased late mortality. When PAR is severe and refractory to standard corrective measures, case reports have now described the successful use of vascular plugs to treat PAR as a follow-up procedure. We describe a case of vascular plug implantation to reduce PAR immediately after implantation of the transcatheter aortic valve prosthesis.

The impact of HIV infection and antiretroviral therapy on the predicted risk of Down syndrome.

Objective: The aim of this study was to assess predicted Down syndrome risk, based on three serum analytes (triple test), with HIV infection status and antiretroviral therapy regimen.

Methods: Screening results in 72 HIV-positive women were compared with results from age-matched and race-matched HIV-negative controls. Mean concentrations of each analyte were compared by serostatus and antiretroviral therapy.

Using social cognitive theory to explain discretionary, "leisure-time" physical exercise among high school students.

Purpose: To examine whether knowledge of high school students' actions of self-regulation, and perceptions of self-efficacy to overcome exercise barriers, social situation, and outcome expectation will predict non-school related moderate and vigorous physical exercise.

Methods: High school students enrolled in introductory Physical Education courses completed questionnaires that targeted selected Social Cognitive Theory variables. They also self-reported their typical "leisure-time" exercise participation using a standardized questionnaire.