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INTRODUCTION: Synaptic spine loss in Alzheimer's disease (AD) contributes to cognitive decline. p21-activated kinase 1 (PAK1), a regulator of spine integrity, is aberrantly activated in AD. We investigated whether PAK1 inhibition might preserve dendritic spines in vitro and in vivo.

ObjectivesCurrent pharmacological antidepressant treatments suffer from low remission rates and slow initiation of therapeutic effects. In addition, the development of new antidepressant treatments is confounded by the lack of consensus on efficient and valid neurophysiological targets. Temporal complexity is an alternative measure of dynamic brain activity that estimates brain signal variability at several timescales. It can be easily extracted from non-invasive brain recordings and provides...

CONCLUSION: All data, protocols, reagent sets, and chemical tools are made widely available on the AD Knowledge Portal with no intellectual property claims. Target Risk Scores and biodomains are accessible through Agora. For more information and the full target portfolio see www.treatad.org.

CONCLUSION: YCharOS has established characterization standards that align with funding and journal requirements, and is committed to identify reliable and accessible tools for AD research.

Tuberculosis (TB) is an ongoing global health threat that has been exacerbated by the COVID-19 pandemic. People with TB need comprehensive medical and social supports to ensure they can maintain and complete TB treatment. TB programs globally have turned to eHealth to bridge gaps in access and strengthen the circle of care around people with TB. This study evaluates the implementation of an intervention aimed at improving TB care in Shigatse, using the CFIR framework to identify factors...

CONCLUSION: Automated, AI-ENE node number is a novel risk factor for OPC that may better inform pretreatment risk stratification and decision-making.

CONCLUSION: These findings highlight the myelin-axon interface as a critical site of protein aggregation and disrupted neuro-glial communication in AD. The molecular architecture of the myelin-axon interface uncovered in this study provides a foundation for future mechanistic investigations in health and disease.

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Primary mismatch-repair-deficient high-grade gliomas (priMMRD-HGG) are lethal tumors characterized by hypermutation, resistance to chemoradiation and variable response to immunotherapy. To investigate the mechanisms governing the emergence of driver mutations and their impact on gliomagenesis and patient outcomes, we analyzed genomic and clinical data from 162 priMMRD-HGG. Here we identified three subgroups defined by secondary driver mutations in replicative DNA polymerases or IDH1. These...

Pulmonary fibrosis (PF) is a pathology associated with interstitial lung diseases (ILDs), including idiopathic pulmonary fibrosis (IPF). Fibrosis promotes continual secretion of extracellular matrix (ECM), producing nonfunctional scar tissue and causing organ failure. This study investigated the tyrosine kinase receptor Ephrin type-B receptor 4 (EphB4) as a mediator of PF. To this end, we generated mice with conditional Col1a2-driven deletion of Ephb4 and used a preclinical mouse model of PF,...

There is considerable heterogeneity in neurodevelopmental disorders (NDDs) that complicates research and clinical support. Although the biological mechanisms of NDDs remain uncertain, emerging studies suggest potential roles of hormone pathways as gonadal, thyroid, glucocorticoid and growth hormones all contribute to brain development. Alterations to these pathways and imbalances of hormones may modulate neural and behavioural development and contribute to the biology of NDDs. Importantly, the...

Mental and substance use disorders profoundly affect global population health, while there is a notable absence of systematic studies focusing on their burden in the Chinese population. We estimated the burden of Global Burden of Diseases (GBD) 2021 for 10 mental disorders and two types of substance use disorders in China from 1990 to 2021. We presented the numbers and rates of prevalence, disability-adjusted life years (DALYs), years of life lost (YLL) and years lived with disability (YLDs),...

A search for the dimuon decay of the Higgs boson is presented based on pp collision data recorded by ATLAS during Run 3 of the Large Hadron Collider, corresponding to an integrated luminosity of 165 fb^{-1} at sqrt[s]=13.6 TeV. To enhance the sensitivity, the results are combined with those from Run 2. An excess of events over the background is observed with a significance of 3.4σ (2.5σ expected). The best-fit signal strength is μ=1.4±0.4. This result provides evidence for the H→μμ decay with...

CONCLUSIONS: We identified 9 significantly mutated genes, some of which are known drug targets. Among individual genes, only the BRAF p.V600E mutation was significantly associated with DS-survival, suggesting a limited survival impact from mutations driving colorectal cancer development.

CONCLUSIONS AND RELEVANCE: Data and biospecimen sharing from registrational trials has been suboptimal. Improving clinical data, biospecimens, and biospecimens' related data sharing requires concrete actions and a multidimensional stakeholder approach to accelerate the impact of clinical cancer research on the quality of patient care.

We report an enantioselective protein affinity selection mass spectrometry screening approach (E-ASMS) that enables the detection of weak binders, informs on selectivity, and generates orthogonal confirmation of binding. After method development with control proteins, we screen 31 human proteins against a designed library of 8,217 chiral compounds. We identify 16 binders to 12 targets, including many proteins predicted to be "challenging to ligand", and confirm their interactions through...

Conceptual frameworks for cultural competence are essential in psychological care. The assessment of implementation efforts in pediatric neuropsychological contexts is particularly lacking. This study investigated an adapted training program for the Cultural Formulation Interview (CFI), including impact on provider cultural competence and perspectives on adaptation and implementation. Neuropsychological care providers (N = 16) participated in an adapted, group-based CFI training. The training...

Over a third of residues in the canonical human proteome are predicted to fall within intrinsically disordered protein regions (IDRs), which do not adopt stable folded structures. These IDRs play critical roles in biological regulation and organization, including as targets for post-translational modifications, scaffolds and mediators of biomolecular condensates. To address the pressing need for valid structural models providing biological relevance and enabling functional insight, we developed...

CONCLUSIONS: Our assay shows high specificity and sensitivity to detect HCV RNA directly from plasma within 45 min, and hence could be utilized for efficient screening and diagnosis of HCV infection globally.

Organisms regulate cell size and shape to function efficiently. Aberrant cell morphogenesis is commonly associated with disease, yet gene-regulatory mechanisms remain unknown. CISTR-ACT was the first lncRNA involved in inter-chromosomal proximities and Mendelian disease, and it is associated with mean corpuscular volume (red blood cell size). Here, functional dissection of CISTR-ACT's DNA- and RNA-encoded mechanisms by in vitro and in vivo perturbations reveals that CISTR-ACT regulates cell size...