Exploring potential EQ-5D bolt-on dimensions with a qualitative approach: an interview study in Hong Kong SAR, China.

PURPOSE: The introduction of bolt-on dimensions in EQ-5D instruments is growing common, but most bolt-on studies have targeted the diseased population and obtained bolt-on from other existing Health-related Quality of Life (HRQoL) instruments. As the qualitative approach offers important evidence to support the consistency and design of the potential bolt-on items, this paper studies the Hong Kong SAR community's perception of the current EQ-5D-5 L instrument and identifies potential bolt-on via a qualitative approach. METHODS: A representative sample mix was recruited based on the age group, gender, and education level composition of the Hong Kong SAR community by quota sampling. Semi-structured interviews were conducted and the interviews were transcribed and coded to identify emergent and recurrent themes. RESULTS: Thirty interviews were conducted and the majority of the interviewees considered the EQ-5D-5 L insufficiently comprehensive to illustrate their HRQoL. While some key HRQoL aspects included in the EQ-5D matched with the community's HRQoL perception, respondents showed concern about the potential overlap of the existing HRQoL dimension, the optimal number or attributes, and the appropriateness of the EQ-VAS. Among the potential bolt-on dimensions that emerged, 'Sleep', 'Interpersonal Relationship', and 'Satisfaction' were the key potential bolt-on dimensions identified and emphasized in the interviews. CONCLUSIONS: The qualitative findings of the study illustrate the possible gap between EQ-5D-5 L measurements and community HRQoL perception, while the findings support the development of EQ-5D bolt-on dimensions in the target community with content and face validity.

CAR-T cell therapy targeting surface expression of TYRP1 to treat cutaneous and rare melanoma subtypes.

A major limitation to developing chimeric antigen receptor (CAR)-T cell therapies for solid tumors is identifying surface proteins highly expressed in tumors but not in normal tissues. Here, we identify Tyrosinase Related Protein 1 (TYRP1) as a CAR-T cell therapy target to treat patients with cutaneous and rare melanoma subtypes unresponsive to immune checkpoint blockade. TYRP1 is primarily located intracellularly in the melanosomes, with a small fraction being trafficked to the cell surface via vesicular transport. We develop a highly sensitive CAR-T cell therapy that detects surface TYRP1 in tumor cells with high TYRP1 overexpression and presents antitumor activity in vitro and in vivo in murine and patient-derived cutaneous, acral and uveal melanoma models. Furthermore, no systemic or off-tumor severe toxicities are observed in an immunocompetent murine model. The efficacy and safety profile of the TYRP1 CAR-T cell therapy supports the ongoing preparation of a phase I clinical trial.

Enterococci as indicators of Lake Michigan recreational water quality: comparison of two methodologies and their impacts on public health regulatory events.

The frequency of poor-water-quality advisories issued in Milwaukee and Racine, Wisconsin, in the absence of identifiable sources of contamination brought into question the reliability of the present indicator organism, Escherichia coli. Enteroccoci have been suggested as an alternative to E. coli for freshwater monitoring due to their direct correlation to swimmer-associated gastroenteritis. The purpose of this research was threefold: (i) to explore enterococci as an alternative to E. coli for monitoring freshwater Lake Michigan beaches, (ii) to evaluate the impact of the two indicators on regulatory decisions, and (iii) to compare membrane filtration m-enterococcus agar with indoxyl-beta-D-glucoside to a chemical substrate technique (Enterolert) for the recovery of enterococci. Recreational water samples from Milwaukee (n = 305) and Racine (n = 153) were analyzed for the enumeration of E. coli and enterococci using IDEXX Colilert-18 and Enterolert. Correlation between the indicators was low (R(2) = 0.60 and 0.69). Based on U.S. Environmental Protection Agency bacterial indicator threshold levels of risk for full body immersion, using enterococci would have resulted in 56 additional unsafe-recreational-water-quality advisories compared to the total from using E. coli and the substrate-based methods. A comparison of the two enterococcal methods (n = 124) yielded similar results (R(2) = 0.62). This was further confounded by the frequent inability to verify enterococci from those wells producing fluorescence by the defined substrate test using conventional microbiological methods. These results suggest that further research is necessary regarding the use of defined substrate technology interchangeably with the U.S. Environmental Protection Agency-approved membrane filtration test for the detection of enterococci from fresh surface water.