RetroFun-RVS: A Retrospective Family-Based Framework for Rare Variant Analysis Incorporating Functional Annotations.

A large proportion of genetic variations involved in complex diseases are rare and located within noncoding regions, making the interpretation of underlying biological mechanisms a daunting task. Although technical and methodological progress has been made to annotate the genome, current disease-rare-variant association tests incorporating such annotations suffer from two major limitations. First, they are generally restricted to case-control designs of unrelated individuals, which often require tens or hundreds of thousands of individuals to achieve sufficient power.

The Impact of Motivation on Sustained Attention in Very Preterm and Term-born Children: An ERP Study.

Objective: To compare the effect of motivational features on sustained attention in children born very preterm and at term.

Method: EEG was recorded while 34 8-to-11-year-old children born very preterm and 34 term-born peers completed two variants of a cued continuous performance task (CPT-AX); a standard CPT-AX with basic shape stimuli, and structurally similar variant, with a storyline, familiar characters, and feedback.

Results: Higher hit rates, quicker response times and larger event-related potential (ERP) amplitudes were observed during the motivating, compared with the standard, task.

Modeling Sporadic Progressive Supranuclear Palsy in 3D Midbrain Organoids: Recapitulating Disease Features for In Vitro Diagnosis and Drug Discovery.

Objective: Progressive Supranuclear Palsy (PSP) is a severe neurodegenerative disease characterized by tangles of hyperphosphorylated tau protein and tufted astrocytes. Developing treatments for PSP is challenging due to the lack of disease models reproducing its key pathological features. This study aimed to model sporadic PSP-Richardson's syndrome (PSP-RS) using multi-donor midbrain organoids (MOs).

Plant-based eating pattern and psychological symptoms: a cross-sectional survey among patients with migraine.

Objectives: The present study evaluated the association between plant-based diet index (PDI) and psychological symptoms, including depressive symptoms, stress, and anxiety among Iranian women diagnosed with migraine headaches.

Methods: A cross-sectional study was conducted on 262 patients with migraine (aged 20-50 years; body mass index, 18.5-30 kg/m²).

Language Mapping With rTMS in Healthy Pediatric Patients.

Purpose: Repetitive transcranial magnetic stimulation (rTMS) is a potentially effective, noninvasive tool for language mapping. However, there is a paucity of data in pediatric patients. In this study, we aimed to map language sites in healthy pediatric participants with navigated rTMS.

Cell-specific transcriptional signatures of vascular cells in Alzheimer's disease: perspectives, pathways, and therapeutic directions.

Alzheimer's disease (AD) is a debilitating neurodegenerative disease that is marked by profound neurovascular dysfunction and significant cell-specific alterations in the brain vasculature. Recent advances in high throughput single-cell transcriptomics technology have enabled the study of the human brain vasculature at an unprecedented depth. Additionally, the understudied niche of cerebrovascular cells, such as endothelial and mural cells, and their subtypes have been scrutinized for understanding cellular and transcriptional heterogeneity in AD.

Ibuprofen reduces inflammation, necroptosis and protects photoreceptors from light-induced retinal degeneration.

Background: The retinal degenerative diseases retinitis pigmentosa (RP) and atrophic age- related macular degeneration (AMD) are characterized by vision loss from photoreceptor (PR) degeneration. Unfortunately, current treatments for these diseases are limited at best. Genetic and other preclinical evidence suggest a relationship between retinal degeneration and inflammation.

NLRX1 limits inflammatory neurodegeneration in the anterior visual pathway.

Chronic innate immune activation in the central nervous system (CNS) significantly contributes to neurodegeneration in progressive multiple sclerosis (MS). Using multiple experimental autoimmune encephalomyelitis (EAE) models, we discovered that NLRX1 protects neurons in the anterior visual pathway from inflammatory neurodegeneration. We quantified retinal ganglion cell (RGC) density and optic nerve axonal degeneration, gliosis, and T-cell infiltration in Nlrx1 and wild-type (WT) EAE mice and found increased RGC loss and axonal injury in Nlrx1 mice compared to WT mice in both active immunization EAE and spontaneous opticospinal encephalomyelitis (OSE) models.

Marigold: a machine learning-based web app for zebrafish pose tracking.

Background: High-throughput behavioral analysis is important for drug discovery, toxicological studies, and the modeling of neurological disorders such as autism and epilepsy. Zebrafish embryos and larvae are ideal for such applications because they are spawned in large clutches, develop rapidly, feature a relatively simple nervous system, and have orthologs to many human disease genes. However, existing software for video-based behavioral analysis can be incompatible with recordings that contain dynamic backgrounds or foreign objects, lack support for multiwell formats, require expensive hardware, and/or demand considerable programming expertise.

NPT100-18A rescues mitochondrial oxidative stress and neuronal degeneration in human iPSC-based Parkinson's model.

Background: Parkinson's disease (PD) is a neurodegenerative disorder characterized by protein aggregates mostly consisting of misfolded alpha-synuclein (αSyn). Progressive degeneration of midbrain dopaminergic neurons (mDANs) and nigrostriatal projections results in severe motor symptoms. While the preferential loss of mDANs has not been fully understood yet, the cell type-specific vulnerability has been linked to a unique intracellular milieu, influenced by dopamine metabolism, high demand for mitochondrial activity, and increased level of oxidative stress (OS).

Sex-specific transcriptomic profiling reveals key players in bone loss associated with Alzheimer's disease.

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is frequently associated with musculoskeletal complications, including sarcopenia and osteoporosis, which substantially impair patient quality of life. Despite these clinical observations, the molecular mechanisms linking AD to bone loss remain insufficiently explored. In this study, we examined the femoral bone microarchitecture and transcriptomic profiles of APP/PS1 transgenic mouse models of AD to elucidate the disease's impact on bone pathology and identify potential gene candidates associated with bone deterioration.

An online multidomain lifestyle intervention to prevent cognitive decline in at-risk older adults: a randomized controlled trial.

Effective, scalable dementia prevention interventions are needed to address modifiable risk factors given global burden of dementia and challenges in developing disease-modifying treatments. A single-blind randomized controlled trial assessed an online multidomain lifestyle intervention to prevent cognitive decline over 3 years. Participants were dementia-free community-dwelling Australians aged 55-77 years with modifiable dementia risk factors.

Predisposing Factors of Progression from Refractory Status Epilepticus to Super-Refractory Status Epilepticus in ICU-Admitted Patients: Multicenter Retrospective Cohort Study in a Resource-Limited Setting.

Background: Super-refractory status epilepticus (SRSE) is an extremely serious neurological emergency. Risk factors and mechanisms involved in transition from refractory status epilepticus (RSE) to SRSE are insufficiently studied.

Methods: This was a multicenter retrospective cohort study of consecutive patients diagnosed and treated for RSE at two reference hospital over 5 years in Ecuador.

Can response to ADHD medication be predicted?

Predictors for the pharmacological effect of ADHD medication in children and adolescents are lacking. This study examined clinically relevant factors in a large (N = 638) prospective cohort reflecting real-world evidence. Children and adolescents aged 6-17 diagnosed with ADHD were evaluated at baseline and three months following ADHD medication initiation.

fMRI data acquisition and analysis for task-free, anesthetized rats.

Templates for the acquisition of large datasets such as the Human Connectome Project guide the neuroimaging community to reproducible data acquisition and scientific rigor. By contrast, small animal neuroimaging often relies on laboratory-specific protocols, which limit cross-study comparisons. The establishment of broadly validated protocols may facilitate the acquisition of large datasets, which are essential for uncovering potentially small effects often seen in functional MRI (fMRI) studies.

Aging disrupts the coordination between mRNA and protein expression in mouse and human midbrain.

Age-related dopamine (DA) neuron loss is a primary feature of Parkinson's disease. However, whether similar biological processes occur during healthy aging, but to a lesser degree, remains unclear. We therefore determined whether midbrain DA neurons degenerate during aging in mice and humans.

The architecture of the human default mode network explored through cytoarchitecture, wiring and signal flow.

The default mode network (DMN) is implicated in many aspects of complex thought and behavior. Here, we leverage postmortem histology and in vivo neuroimaging to characterize the anatomy of the DMN to better understand its role in information processing and cortical communication. Our results show that the DMN is cytoarchitecturally heterogenous, containing cytoarchitectural types that are variably specialized for unimodal, heteromodal and memory-related processing.

Esketamine alleviates depressive-like behavior in neuropathic pain mice through the METTL3-GluA1 pathway.

Esketamine, a newly developed antidepressant, is the subject of this research which seeks to explore its impact on depressive symptoms in neuropathic pain mice and the potential molecular mechanisms involved. Through transcriptome sequencing and bioinformatics analysis combined with in vivo studies, it was identified that esketamine markedly boosts the levels of the m6A methyltransferase METTL3 and the AMPA receptor GluA1 subunit. Esketamine activates METTL3, allowing it to bind with GluA1 mRNA, promoting m6A modification, thereby enhancing GluA1 expression at synapses.

Investigating time-independent and time-dependent diffusion phenomena using steady-state diffusion MRI.

Diffusion MRI is a leading method to non-invasively characterise brain tissue microstructure across multiple domains and scales. Diffusion-weighted steady-state free precession (DW-SSFP) is an established imaging sequence for post-mortem MRI, addressing the challenging imaging environment of fixed tissue with short T and low diffusivities. However, a current limitation of DW-SSFP is signal interpretation: it is not clear what diffusion 'regime' the sequence probes and therefore its potential to characterise tissue microstructure.

Working capacity level defines the specific impairment profile of the comprehensive ICF core set for multiple sclerosis.

Multiple sclerosis (MS) unfavorably affects working capacity. The Comprehensive International Classification of Functioning, Disability and Health Core Set for MS (cICF-MS), issued by the World Health Organization, has not yet been extended to evaluate working capacity level (WCL). To evaluate the relative importance of cICF-MS categories in relation to WCL.

Identifying factors that contribute to collision avoidance behaviours while walking in a natural environment.

Busy walking paths, like in a park, city centre, or shopping mall, frequently necessitate collision avoidance behaviour. Lab-based research has shown how different situation- and person-specific factors, typically studied independently, affect avoidance behaviour. What happens in the real world is unclear.

Neural circuits underlying context-dependent competition between defensive actions in Drosophila larvae.

To ensure their survival, animals must be able to respond adaptively to threats within their environment. However, the precise neural circuit mechanisms that underlie flexible defensive behaviors remain poorly understood. Using neuronal manipulations, machine learning-based behavioral detection, electron microscopy (EM) connectomics and calcium imaging in Drosophila larvae, we map second-order interneurons that are differentially involved in the competition between defensive actions in response to competing aversive cues.

Sub-cellular population imaging tools reveal stable apical dendrites in hippocampal area CA3.

Apical and basal dendrites of pyramidal neurons receive anatomically and functionally distinct inputs, implying compartment-level functional diversity during behavior. To test this, we imaged in vivo calcium signals from soma, apical dendrites, and basal dendrites in mouse hippocampal CA3 pyramidal neurons during head-fixed navigation. To capture compartment-specific population dynamics, we developed computational tools to automatically segment dendrites and extract accurate fluorescence traces from densely labeled neurons.