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Increasing evidence documents turnover of the resting-state blood-oxygen-level dependent signal (TBOLD) as a key measure of local cortical brain status. Here we evaluated contemporaneous and lagged associations between TBOLD and cognitive function in 711 participants in the Human Connectome Project on Aging (HCP-A; 316 males and 395 females, age range 36-90 years). We found that TBOLD was negatively associated with Montreal Cognitive Assessment (MoCA) Total scores and with performance on 2 subscales, Delayed Recall and Visuospatial/Executive Function, controlling for sex, age, and handedness. This negative association was largely documented across brain areas and was significantly stronger in the left hemisphere compared to the right. In addition, analyses evaluating forward lagged crosscorrelations between TBOLD and cognitive performance demonstrated that TBOLD predicted decrements in future performance on MoCA Total score, Delayed Recall, and Visuospatial/Executive Function subscales, controlling for sex and handedness. Taken together, we found that increased TBOLD is associated with decreased cognitive performance contemporaneously and in the future. On the hypothesis that increased TBOLD is the outcome of neuroinflammatory processes, these findings provide a mechanism linking neuroinflammation with decreased cognitive performance. [ABSTRACT FROM AUTHOR]

Plain language summaries (PLSs) of clinical trial results are vital tools in the clinical development process for enhancing transparency and encouraging and facilitating patient engagement. The production of a PLS is now mandated in the EU for all interventional clinical trials by the European Medicines Agency under Regulation EU 536/2014 and became compulsory with the opening of the Clinical Trial Information System portal in January 2022. PLSs are intended to be accessible, comprehensible documents conveying complex trial findings to diverse audiences. This article explores the significance of PLSs, the importance of patient input in their production, and the role and concerns surrounding the use of artificial intelligence in generating them. [ABSTRACT FROM AUTHOR]

The article discusses the new government's approach to constitutional reform in the UK. The Labour party, which came to power in the 2024 general election, promised to restore trust in politics and deepen democracy through various reforms. However, there is a tension between the government's policy agenda and the incentives to retain power. The article examines three key areas for constitutional reform: the House of Lords, the House of Commons, and the standards system. It highlights the challenges and dilemmas faced by the government in achieving lasting change while balancing the desire for checks and balances with the need for a strong, centralized government. [Extracted from the article]

Objective: Host immunogenetics (Human Leukocyte Antigen, HLA) play a critical role in the human immune response to melanoma, influencing both melanoma prevalence and immunotherapy outcomes. Beneficial outcomes hinge on the successful binding of epitopes of melanoma antigens to HLA Class I molecules for an effective engagement of cytotoxic CD8+ lymphocytes and subsequent elimination of the cancerous cell. This study evaluated the binding affinity and immunogenicity of HLA Class I to melanoma tumor antigens to identify alleles best suited to facilitate elimination of melanoma antigens. Methods: In this study, we used freely available software tools to determine in silico the binding affinity and immunogenicity of 2462 reported HLA Class I alleles to all linear nonamer epitopes of 11 known antigens expressed in melanoma tumors (TRP2, S100, Tyrosinase, TRP1, PMEL(17), MAGE1, MAGE4, CTA, BAGE, GAGE/SSX2, Melan). Results: We identified the following 9 HLA Class I alleles with very high immunogenicity and binding affinity against all 11 melanoma antigens: A*02:14, B*07:10, B*35:10, B*40:10, B*40:12, B*44:10, C*07:11, and C*07:13, and C*07:14. Conclusion: These 9 HLA alleles possess the potential to aid in the elimination of melanoma both by themselves and by enhancing the beneficial effect of immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]