John T.

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by Suqi Liu Ana Francis Carballo-Arce John T. Arnason and Ian M. Scott PEI Department of Agriculture, Charlottetown, PE C1A 7N8, Canada

Concerted examination of multiple collections of single-cell RNA sequencing (RNA-seq) data promises further biological insights that cannot be unco...

Objective:To assess safety and efficacy of deflazacort (DFZ) and prednisone (PRED) vs placebo in Duchenne muscular dystrophy (DMD).Methods:This phase III, double-blind, randomized, placebo-controlled, multicenter study evaluated muscle strength among 196 ...

Epithelial-to-Mesenchymal Transition (EMT) is a critical biological process by which cells acquire enhanced migratory and invasive properties. A key signaling pathway involved in EMT phenotypes includes transforming growth factor β (TGFβ) and transcription factors (TFs) such as SNAIL, ZEB, and TWIST. Additionally, microRNAs (miRNAs) – small, non-coding molecules that regulate gene expression by targeting mRNA transcripts – directly regulate genes central to the EMT process. Notably, miR-22 has been identified as a significant regulator of EMT through direct inhibition of EMT drivers like SNAI1 and indirect regulation of upstream genes. In this study, we performed CRISPR-based network rewiring by selectively removing an edge—the connection between two nodes—to investigate its impact on EMT dynamics. Specifically, we disrupted the connection between miR-22 and SNAI1 without affecting other interactions involving miR-22 or SNAI1 and examined the resulting effects on EMT. We demonstrate that the removal of the miR-22 target site from the SNAI1 gene renders cells more sensitive to TGFβ-mediated EMT. This finding highlights the unique advantage of edge-specific perturbation by ablating the direct regulatory connection between miR-22 and SNAI1. We demonstrate that all measured downstream effects on EMT can be attributed to this single interaction, independent of miR-22’s influence on other targets or indirect pathways. More generally, our results underscore the importance of CRISPR-mediated edge ablation for exploring the interactions that govern biological networks and highlight an underexplored opportunity to develop edge-based therapeutic modalities.

Background/objectives: This comprehensive study of infants with combinational deformational plagiocephaly with brachycephaly (cDPB) and combinational deformational brachycephaly with plagiocephaly (cDBP) examined the effectiveness of a custom, thermoplastic vacuum-formed cranial remolding orthosis and identified clinical predictive factors that affect treatment outcomes. In addition, a standardized classification scale for babies with combinational head shapes was developed for this study. Methods: This was a retrospective study of patients who were treated by Cranial Technologies between January 2014 and March 2025 and met the following inclusion criteria: (a) presented with a Cranial Vault Asymmetry Index (CVAI(S)) > 3.5 AND Cephalic Index (CI) > 90, (b) were compliant with the treatment protocol, (c) were nonsyndromic, and (d) did not have craniosynostosis. Infants with isolated plagiocephaly or isolated brachycephaly were excluded. Multiple linear regression (MLR) analyses and paired t-tests were used to model the effects of clinical predictive factors on CVAI(S) and CI outcomes and determine the change between pre- and post-treatment cranial anthropometric measurements, respectively. Results: N = 82,326 infants met the inclusion criteria for this study. The mean overall reduction in CVAI(S) was −3.64 (p 11 months −2.247 (p < 0.001). The mean overall reduction for CI was −3.84 (p < 0.001) and was not related to age. In terms of clinician-rated outcomes, 95–100% of babies who entered treatment at less than 6 months of age had a “good” or “great” outcome, while the “good” or “great” success rate dropped to less than 19% for babies who started treatment after 11 months of age. MLR (Adj. R2: 0.582) identified the following factors as significant predictors (p < 0.001) for change in CVAI(S): entry age (β = 0.008), left-sided plagiocephaly (β = −0.420), initial cephalic index (β = −0.056), initial CVAI(S) (β = −0.479), prematurity (β = −0.189), and the presence of torticollis or neck muscle involvement (β = 0.053). A second MLR for change in CI (Adj. R2: 0.217) observed significance (p < 0.001) for the following predictors: initial CI (β = −0.335), left-sided plagiocephaly (β = −0.332), multiple birth (β = −0.290), male sex (β = −0.158), initial CVAI(S) (β = −0.049), premature (β = −0.086), and neck muscle involvement (β = −0.106). Conclusions: CRO treatment for cDPB/cDBP resulted in highly significant improvement in both CVAI(S) and CI across all age groups with the youngest babies requiring the shortest treatment durations and demonstrating more favorable results, especially in correcting asymmetry. Overall, the mean reduction in CVAI(S) varied significantly between age groups, with younger babies experiencing greater change in CVAI(S) scores, whereas CI did not demonstrate the same relationship with entry age. This study proposed new terminology for infants who present with elements of both plagiocephaly and brachycephaly. The use of standardized terms such as cDPB/cDBP to describe a combinational head shape will enhance comparability across future studies, thus enabling better outcome reporting.

The brain has a higher energy demand per unit weight than any other organ in the body; however, links between metabolism, diet and neurological function have historically been underexplored. This partly stems from early assumptions that brain metabolism is primarily dependent on glucose and ketone bodies, whereas more recent evidence indicates broader metabolic flexibility and complex cell-type specialisation. In the past few decades, brain metabolism has become increasingly recognised as relevant to neurological and mental health, and many neurodegenerative disorders are accompanied by changes in brain energy utilisation. In parallel, epidemiological studies associate hypercaloric dietary patterns and metabolic disorders—particularly type-2 diabetes mellitus—with increased risk of later cognitive decline and sporadic Alzheimer’s disease, although causal pathways remain difficult to establish in humans. In this narrative review, we summarise selected findings linking “unhealthy” diets to synaptic function, focusing on synaptic plasticity, neuroinflammation and adult hippocampal neurogenesis, and we distinguish between evidence from human observational studies and mechanistic insights from animal and cellular models. We also discuss candidate mechanisms—including insulin resistance-linked signalling changes, lipid-driven inflammatory amplification, oxidative stress, and altered lipid handling—that may contribute to synaptic vulnerability. Finally, we outline translational considerations and key knowledge gaps (including physiological exposure levels and heterogeneity of experimental paradigms) that currently limit inference from preclinical models to clinical intervention.

Healthy midlife APOE ε4 carriers show higher network segregation cross-sectionally and longitudinal segregation loss, particularly in the default mode network, linking inherited Alzheimer’s risk to early brain changes decades before dementia onset

Carty et al. found that dehydration stress promotes intracellular lipid synthesis and favors glutamine oxidation as a carbon precursor for lipid synthesis via remodeling mitochondrial metabolism.

Globally, fires in 2025 burned the second-lowest area on record since 2002 and emitted the third-lowest CO total.