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CONCLUSIONS: The implementation of Interact-North represents a scalable model to address the gap in psychosocial support for families, but funding remains a barrier.

Lysine demethylase 2A (KDM2A) is a key epigenetic regulator and promising target for inhibition since its loss is selectively lethal in cancers reliant on Alternative Lengthening of Telomeres (ALT). Here we investigated the mechanism of compound 183c, a potent KDM2A inhibitor described in the patent literature. Biophysical studies showed that 183c requires the co-factor 2-oxoglutarate (2OG) for binding. A 2.2 Å crystal structure of the KDM2A-183c-2OG ternary complex explained the selectivity of...

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Temperate inland wetlands have long been viewed as climate regulators, with sustained CO₂ sequestration offsetting continuous CH₄ emissions over centennial-millennial timescales. However, the net climatic effect of these opposing fluxes remains uncertain under anthropogenic warming as they differ in both magnitude and atmospheric lifetime. We combine 19,000 CH₄ chamber measurements from 202 temperate inland wetlands with carbon burial rates from 16 dated sediment cores in North America's Prairie...

CONCLUSIONS: AI-assisted wbMRI interpretation can improve tumour detection in pediatric cancer surveillance by reducing false negatives. However, its influence on workflow efficiency and inter-radiologist variability highlights the importance of careful implementation. Successful integration requires addressing challenges such as improving the predictive precision of AI models, offering intuitive end-user designs and instructions, and building trust in AI outputs. AI outputs can influence...

The liver is composed of diverse cell populations that coordinate essential metabolic and immune functions. Single-cell transcriptomics has advanced characterization of liver cellular composition, but dissociation of tissue to single-cells can introduce biases through the enrichment or depletion of cell types. Spatial transcriptomics is a complementary approach to avoid inherent bias for cell populations and to add important spatial context. The Visium HD spatial transcriptomics technology from...

Ensuring defensible policy inferences and robust decision reliability is fundamental for multi-criteria decision-making activities, particularly in transport safety engineering. This study developed a hybrid preference function-nested and machine learning-embedded decision model, i.e., EXPROM II-K-means with a linear discriminant analysis, to provide a robust support system for policy setting and decision making. The proposed model incorporates a refined nonparametric preference function into...

The rules of prokaryotic cell design remain elusive. Here, a theory is presented for interpreting growth rate, overflow metabolism, respiration efficiency, and maintenance energy flux based on cell dimensions, membrane protein crowding, and metabolism. The theory employs biophysical properties and systems analysis to successfully interpret phenotypes of Escherichia coli K-12 strains MG1655 and NCM3722. These strains are genetically similar but differ in surface area-to-volume (SA : V) ratios (~...

Epithelial cancers such as stomach and ovarian cancer tend to metastasize to the peritoneum, often leading to intractable disease and poor survival. The mechanisms that enable gastric cancer cells to implant, invade, and survive in the peritoneal niche are poorly understood. We developed a novel human peritoneal explant model using freshly harvested peritoneal tissue samples. GFP-labeled human gastric adenocarcinoma cells (AGS) were co-cultured with the peritoneal samples, and 2% of these cells...

Single-cell RNA sequencing has advanced our understanding of cellular heterogeneity. Ensuring the replicability of identified cell clusters across studies is essential for determining their biological robustness. We assess the replicability of cell clusters identified in two large mouse brain atlases, one generated using single-cell RNA sequencing and the other with single nuclei. Both profile over 4 million cells and group them into over 5,000 clusters. Using transcriptome-wide neighbor voting,...

Children with severe self-injurious behaviour (SIB) are at risk of permanent injury and lack effective treatment options. Neuromodulation of the nucleus accumbens (NAc), a key node in reward and behavioural regulation circuits, may directly modulate the drivers of SIB. We report long-term outcomes from a first-in-human, single-centre trial of deep brain stimulation (DBS) targeting the NAc in children and adolescents with profound autism and treatment-refractory SIB (NCT03982888). Six...

Machine learning on electronic health records (EHR) is constrained by limited data, strict privacy regulations, and distribution shifts across sites and time. Synthetic data offer a potential solution, but existing tabular generators often struggle in the small sample size in EHR regime. We propose MEDPFN, a distribution-aware synthetic EHR generator built on top of the TabPFN tabular foundation model. MEDPFN uses TabPFN as a learned compatibility score over EHR and adds a Mahalanobis...

Electronic Health Records (EHR) contain abundant structured tabular data, yet developing accurate predictive models on small clinical datasets remains challenging. Foundation models have transformed natural language and imaging tasks by leveraging pretraining on large-scale data, and they are increasingly explored in healthcare as a route toward generalist medical AI. However, this paradigm remains largely unexplored for structured EHR data. In this study, we explore the adaptation of a tabular...

CONCLUSION: These gene-specific DNAm signatures improve variant interpretation and diagnosis, especially for uncertain and atypical cases, underscoring the utility of integrating epigenetic, genetic, and phenotypic data in clinical diagnostics.

Prostate cancer is characterized by profound clinical and molecular heterogeneity. While its genomic heterogeneity is well-characterized, its epigenomic heterogeneity remains less understood. We therefore created a compendium of 3,001 multi-ancestry prostate methylomes spanning normal tissue through localized disease of all grades to poly-metastatic disease. A subset of 884 samples had multi-omic DNA and/or RNA characterization. We identify four epigenomic subtypes that risk-stratify patients...

CONCLUSIONS AND RELEVANCE: The 6 outcome domains identified through a Delphi consensus are recommended for reporting in future facial aging trials to ensure that outcomes that matter most to patients and clinicians are measured and that results are comparable across interventions.

CONCLUSION: The consensus highlights the potential of auditory-perceptual assessment and acoustic metrics to inform screening for swallowing dysfunction in older adults and offers expert insights for clinical investigators who aim to analyze voice, speech, and/or cough sounds as clinically meaningful indicators of laryngeal function to improve early detection and intervention, thereby enhancing patient outcomes.

Plants respond to environmental cues, such as light and temperature, which regulate their growth and development. In the model plant Arabidopsis (Arabidopsis thaliana), PHYTOCHROME-INTERACTING FACTORS (PIFs) are central regulators of both shade-avoidance and thermomorphogenesis. However, their functional roles in crop species are less well known. Here, we generated a tomato (Solanum lycopersicum) mutant lacking all eight known PIF genes (slpifo), to investigate their roles under controlled and...

PTCHD1 is an X-linked three-exon gene associated with autism spectrum disorder (ASD) and/or intellectual disability (ID). Mice lacking Ptchd1 exon 2 (Ptchd1^(Δexon2)) exhibit hyperactivity and learning impairments, but do not recapitulate ASD-like traits. Through mapping of clinically reported loss-of-function mutations in human patients, we determined that PTCHD1 exon 3 is a high-risk locus. We therefore generated an alternative Ptchd1 knockout mouse model by targeting Ptchd1 exon 3...

While COVID-19 mortality was relatively low in many Sub-Saharan African countries during the first wave of the pandemic, SARS-CoV-2 transmission was extensive. We hypothesized that female sex workers (FSWs) would be at enhanced risk of acquisition of this novel respiratory viral infection, due to intimate contact with multiple sexual partners and solicitation of clients in crowded venues. Here we describe the seroincidence, socio-behavioural associations and clinical outcomes of SARS-CoV-2...