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The Mirror Neuron System (MNS) underlies important neurocognitive functions, such as imitation learning, social cognition and empathy, and may facilitate the recognition of emotional expressions via motor simulation. However, its development remains poorly understood. This study investigated functional connectivity maturation of MNS-related areas between early childhood and adulthood during an emotional faces task. Using the innovative magnetoencephalography approach of optically pumped...

BACKGROUND: Efinopegdutide is a pharmacologically distinct once-weekly GLP-1-glucagon receptor co-agonist with a relative receptor potency balance of approximately 2:1 under development for metabolic dysfunction-associated steatohepatitis (MASH). We aimed to investigate the efficacy and safety of efinopegdutide in adults with non-cirrhotic MASH.

Stroboscopic light stimulation (SLS) is a candidate non-pharmacological intervention that induces transient visual and affective experiences, with potential application in depression. Before efficacy testing, clinical development requires safety, tolerability, and feasibility data. We report a staged, single-site programme in adults reporting depressive symptoms. Study 1 tested 11 SLS parameter sets for safety and tolerability. Study 2 assessed whether an active comparator reduced subjective...

The construction of accurate enzyme-constrained genome-scale models (ecGEMs) remains a critical challenge in systems biology, limited by sparse kinetic data and the need for biologically meaningful representations. This work presents an integrated framework combining CPI-Pred, a deep learning model to predict kinetic parameters (kcat) from sequence and compound embeddings, with kinGEMs, a pipeline to incorporate these uncertainty-aware parameters into ecGEMs for metabolic optimization. By...

CONCLUSIONS: Humoral responses declined significantly within six months of vaccination. Cellular responses were comparable across vaccine status groups, yet vaccinated children tended to maintain higher levels for more than one-year post-vaccination. Hybrid immunity could contribute to a more robust and durable cellular response.

CONCLUSIONS: Over a decade, the proportion of children with CCCs needing PICU care has grown, with trends toward increasing prevalence in the clinically dominant categories of respiratory and hematology, immunodeficiency, and immunology, and the subcategories respiratory malformations, hereditary hemostasis anomalies, and home ventilation, and trends toward higher mortality rates following treatment withdrawal.

In this study, we employ Bayesian optimization to identify conditions for enzyme-catalyzed, site-selective esterifications of pyranoside derivatives. Our findings indicate that Bayesian algorithms facilitate these challenging optimizations, which involve simultaneous variation of enzyme identity, solvent, acyl donor loading, time and temperature, across a range of substrates with various configurations, protective groups and anomeric substituents. Using the experimental optimization data...

A common approach for detecting rare variants (RVs) associated with complex human diseases is to perform a gene-based analysis or a region-based test of association. Typically, in a gene-based analysis, all the RVs pertaining to the gene considered are included in the statistical test, which potentially reduces its power since most RVs are likely not associated with the outcome of interest. As paradigm shift, we propose to add a variable selection step to choose the RVs that compose the...

The phytopathogen Pseudomonas syringae must enter the leaf interior through natural openings such as stomata to cause disease. Plants restrict pathogen entry into the leaf through non-self-recognition-driven stomatal closure. P. syringae counters this stomatal immunity by deploying a range of toxins and effectors. Here, we show that stomatal immunity in Arabidopsis thaliana is reinforced upon recognition of the ubiquitous P. syringae type III effector AvrE1 by the resistance protein CAR1. CAR1...

CONCLUSIONS: Structural brain aging in MDD is age-dependent and most pronounced in a neuroanatomical phenotype associated with poorer key clinical outcomes. The findings are consistent with, but do not establish, neuroprogression models of MDD and demonstrate that cBAG is not a uniform feature of MDD, being more strongly expressed in a specifically clinically vulnerable disease phenotype.

CONCLUSIONS: Career sustainability requires reducing avoidable occupational load while preserving physical capacity and restoring function through recognition, modification, conditioning, recovery, assessment, and rehabilitation.

CONCLUSIONS: The C2PS is a pragmatic and reliable tool to harmonize heterogeneous neuropsychiatric phenotypic data for large multi-national studies. Observations in 1,325 individuals with CNVs at 16p11.2 or 22q11.2 reveal variant-specific psychiatric profiles, emphasize burden and impact of psychiatric multimorbidity, and provide insights beyond categorical diagnoses.

CONCLUSIONS: Proton re-RT demonstrated encouraging locoregional control and survival in heavily pretreated patients, although late toxicities remain important concerns (ClinicalTrials.gov identifier: NCT03217188).

Biophysical pleiotropy, the phenomenon in which a mutation affects multiple protein properties, underlies many genetic diseases and shapes protein evolution, yet remains poorly understood, limiting synthetic biology and therapeutic development. Although extensively studied in soluble proteins, little is known about how pleiotropic effects shaped the evolution of receptor protein functions. Here, we developed a cell-based assay designed to assess pleiotropic effects in G protein-coupled receptors...

CONCLUSIONS AND RELEVANCE: In this systematic analysis, the burden of bone cancer varied by age, geography, and time, underscoring global disparities. These findings provide valuable insights to inform health system planning and resource allocation tailored to different settings.

Proteins shuttle between the nucleus and cytoplasm through the nuclear pore and via nuclear transport receptors, termed importins and exportins. Although genetic alterations involving nucleoporins are enriched in pediatric, adolescent, and young adult (AYA) acute myeloid leukemia (AML), nucleocytoplasmic transport has not been extensively studied in this disease. We discover that genes encoding nucleocytoplasmic transport pathway components (Kyoto Encyclopedia of Genes and Genomes [KEGG]:...

Restricting the centromere-specific histone H3 variant Cse4 (CENP-A in human) to centromeric chromatin ensures faithful chromosome segregation. Mislocalization of overexpressed Cse4/CENP-A to non-centromeric regions contributes to chromosomal instability (CIN), an important hallmark of many cancers. Hence, defining mechanisms that prevent mislocalization of Cse4 is clinically significant. Here we report a role for YRA2 (Yeast RNA Annealing Protein 2) in ubiquitin mediated proteolysis of Cse4 to...

Recent advances in single-cell RNA sequencing and lineage tracing techniques have provided valuable insights into the temporal changes in gene expression during development, tumor progression, and disease onset. However, there are few computational methods available to analyze this information to help understand multicellular dynamics. We introduce Deep Lineage, a deep-learning method for analyzing time-series single-cell RNA sequencing with matched lineage tracing data. Our method accurately...

CONCLUSIONS AND RELEVANCE: This GBD 2023 analysis found that anorexia nervosa and bulimia nervosa contribute substantially to global nonfatal health loss. These findings support the integration of eating disorders into mental health surveillance, prevention, and service planning worldwide.