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BackgroundReliable detection of huntingtin (HTT) is essential for understanding Huntington's disease (HD) biology and for evaluating therapeutic strategies. However, high-quality monoclonal antibodies (mAbs) against the HTT C-terminal domain remain limited.ObjectiveWe sought to generate and validate novel monoclonal antibodies targeting the HTT C-terminal HEAT-containing domain to better detect HTT independently of potential effects of polyglutamine length that can impact some N-terminally...

Although the genetic code is degenerate, codon selection is nonrandom and reflects significant functional constraints. Codon-usage bias (CUB) acts as a layer of post-transcriptional regulation, influencing messenger RNA (mRNA) stability, translation kinetics, and co-translational protein folding. While CUB is well-characterized in unicellular organisms, its regulatory scope and functional consequences in humans remain complex and less defined. Our study offers a comprehensive evaluation of human...

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Digital, self-guided, single-session interventions (SSIs) deliver structured psychological support within one interaction. Here we crowdsourced 66 diverse 10-min SSIs for depression and, with input from researchers and lived-experience experts, selected 11 for testing in a preregistered online randomized controlled trial (ClinicalTrials.gov ID: NCT06856668 ). US adults (N = 7,505) experiencing elevated depressive symptoms were randomly assigned to 1 of the 11 crowdsourced SSIs, a validated...

CONCLUSIONS: Real-world data from the Canadian population suggest a low level of long-term persistence on selexipag, although the level of persistence is similar to reported rates for other PAH therapies. Further research into predictors of selexipag persistence is needed to help optimize potential treatment outcomes.

CONCLUSION: A population-based approach provided new evidence for accumulating illnesses over young adulthood, supporting the need for novel models of anticipatory care for adults with 22q11.2 microdeletion. A similar genetics-first strategy, defining cohorts with shared genetic changes, may facilitate understanding of premature aging mechanisms relevant to the general population.

RESEARCH AIMS: The benefits of parenting interventions for child and family outcomes following pediatric brain injury are well documented. However, training in pediatric neuropsychology largely emphasizes a focus on assessment, as well as syndrome- or disorder-specific interventions. Greater attention to transdiagnostic intervention is warranted, particularly pediatric neurorehabilitation programs that are family-centered and evidence-based. This study evaluated the acceptability of a didactic...

The Reactome Pathway Knowledgebase (www.reactome.org) provides expert-curated information on human biological pathways, molecular interactions, and disease mechanisms. However, its complex data model and keyword-based search interface present accessibility barriers for non-expert users. In contrast, general-purpose conversational AI systems offer intuitive natural language interfaces but lack the domain-specificity, transparent sourcing, and factual reliability required for scientific...

CONCLUSION: These results highlight that a large proportion of P/LP variation is either absent or has conflicting evidence for pathogenicity in ClinVar, emphasising the importance of periodic reassessment, discrepancy resolution and updates to ensure completeness and accuracy of public databases.

CONCLUSIONS: These findings indicate that the presence of dietary n-3 PUFA plays a key role in modulating mammary tumour development, which may be further influenced by the underlying n-6 PUFA background. The associated changes in immune markers suggest that n-3 PUFA exert anticancer effects in part by shifting the tumour immune microenvironment toward an anti-tumour phenotype and modulating cannabinoid receptor signalling. Collectively, this work informs future human studies investigating the...

HTD1265 is a newly identified antifungal compound that displays potent activity against Candida krusei, a clinically challenging non-albicans species. To elucidate its mechanism of action, we applied an integrative phenotypic approach combining high-resolution morphological profiling, pathway inference, and genetic validation in Saccharomyces cerevisiae. Morphological signature extraction revealed a characteristic defect in nuclear positioning upon HTD1265 treatment. Integration of nuclear...

CONCLUSION: Collectively, our results establish EP300 as a key regulator of IR state identity in GSCs and provide a mechanistic basis for therapeutic targeting of aggressive cellular states in GBM.