RuBi-Ruxolitinib: A Photoreleasable Antitumor JAK Inhibitor

We describe the synthesis and biological testing of ruthenium-bipyridine ruxolitinib (RuBiRuxo), a photoreleasable form of ruxolitinib, a JAK inhibitor used as an antitumoral agent in cutaneous T-cell lymphomas (CTCL). This novel caged compound is synthesized efficiently, is stable in aqueous solution at room temperature, and is photoreleased rapidly by visible light. Irradiation of RuBiRuxo reduces cell proliferation and induces apoptosis in a light- and time-dependent manner in a CTCL cell line. This effect is specific and is mediated by a decreased phosphorylation of STAT proteins. Our results demonstrate the potential of ruthenium-based photocompounds and light-based therapeutic approaches for the potential treatment of cutaneous lymphomas and other pathologies

Development of the Valued Living Questionnaire – Comprehension Support version (VLQ-CS) and validation in adults with acquired brain injury

Valued living (acting in accordance with personal values) is associated with better outcomes after acquired brain injury (ABI), but its measurement using the Valued Living Questionnaire (VLQ) may not be valid due to comprehension errors relating to structure and content. We aimed to modify the VLQ to improve its accessibility and evaluate construct validity and reliability in an ABI cohort. Adaptations made in the VLQ – Comprehension Support version (VLQ-CS) used established communication support methods and addressed common comprehension errors. 103 community-dwelling participants (34% female; mean age 52.17, range 19–79) with ABI (66% stroke, 16% TBI, 18% other) completed the VLQ-CS, and measures of convergent (valued living, mood, wellbeing, psychological inflexibility) and divergent validity (subjective memory). Test-retest reliability was evaluated with repeated administrations 6–8 weeks apart for a subset of participants (n = 44), using Intraclass Correlation Coefficients (ICCs). Convergent validity was supported; VLQ-CS scores were positively correlated with measures of valued living (r=.60–.65) and wellbeing (r=.64–.67), and negatively correlated with depression (r=-0.56–.58), anxiety (r=-0.35–.38) and psychological inflexibility (r=-0.37–.41). Divergent validity was marginal (r=-0.29). Test-retest reliability was good for the VLQ-CS Composite score (ICC=.80). The VLQ-CS shows promise as a valid, reliable measure of valued living post-ABI. Future research should extend to neurotypical and other clinical populations. Valued living or values-based action is associated with better functional and psychosocial outcomes after acquired brain injury (ABI) and is therefore an important target for intervention.Measurement of valued living needs to be clear, easily understood, and relevant for people with cognitive and communication impairments associated with ABI and other conditions.The Valued Living Questionnaire – Comprehension Support version (VLQ-CS) was developed to optimise accessibility and reduce comprehension errors.The VLQ-CS is valid, reliable and fit-for-purpose as a measure of valued living for people with ABI. Valued living or values-based action is associated with better functional and psychosocial outcomes after acquired brain injury (ABI) and is therefore an important target for intervention. Measurement of valued living needs to be clear, easily understood, and relevant for people with cognitive and communication impairments associated with ABI and other conditions. The Valued Living Questionnaire – Comprehension Support version (VLQ-CS) was developed to optimise accessibility and reduce comprehension errors. The VLQ-CS is valid, reliable and fit-for-purpose as a measure of valued living for people with ABI.</p

Additional file 1: of MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data

Supplemental methods, extended derivations, and supplementary figures and tables. (PDF 3940 kb