Apelin/APJ system: a novel promising target for anti-oxidative stress in stroke.

The apelin/APJ system has garnered increasing attention in recent years. In this review, we comprehensively discuss the physiological and pathological mechanisms of the apelin/APJ system in stroke. The apelin/APJ system is widely expressed in the central nervous system (CNS).

Mechanisms of vagus nerve stimulation for the treatment of neurodevelopmental disorders: a focus on microglia and neuroinflammation.

The vagus nerve (VN) is the primary parasympathetic nerve, providing two-way communication between the body and brain through a network of afferent and efferent fibers. Evidence suggests that altered VN signaling is linked to changes in the neuroimmune system, including microglia. Dysfunction of microglia, the resident innate immune cells of the brain, is associated with various neurodevelopmental disorders, including schizophrenia, attention deficit hyperactive disorder (ADHD), autism spectrum disorder (ASD), and epilepsy.

TAD-SIE: sample size estimation for clinical randomized controlled trials using a Trend-Adaptive Design with a Synthetic-Intervention-Based Estimator.

Background: Phase-3 clinical trials provide the highest level of evidence on drug safety and effectiveness needed for market approval by implementing large randomized controlled trials (RCTs). However, 30-40% of these trials fail mainly because such studies have inadequate sample sizes, stemming from the inability to obtain accurate initial estimates of average treatment effect parameters.

Methods: To remove this obstacle from the drug development cycle, we present a new algorithm called Trend-Adaptive Design with a Synthetic-Intervention-Based Estimator (TAD-SIE) that powers a parallel-group trial, a standard RCT design, by leveraging a state-of-the-art hypothesis testing strategy and a novel trend-adaptive design (TAD).

Spatially resolved transcriptomics and graph-based deep learning improve accuracy of routine CNS tumor diagnostics.

The diagnostic landscape of brain tumors integrates comprehensive molecular markers alongside traditional histopathological evaluation. DNA methylation and next-generation sequencing (NGS) have become a cornerstone in central nervous system (CNS) tumor classification. A limiting requirement for NGS and methylation profiling is sufficient DNA quality and quantity, which restrict its feasibility.

Comparison of mNGS with conventional methods for diagnosis of cryptococcal meningitis: a retrospective study.

The application of metagenomic next-generation sequencing (mNGS) in the diagnosis of cryptococcal meningitis is relatively under characterized. Here, we retrospectively evaluated data from cryptococcal meningitis patients who were tested using mNGS and/or routine testing, including fungal culture, India ink staining, and cryptococcal antigen (CrAg) testing. The performance of mNGS was then assessed.

Latest clinical frontiers related to autism diagnostic strategies.

The diagnosis of autism is currently based on the developmental history, direct observation of behavior, and reported symptoms, supplemented by rating scales/interviews/structured observational evaluations-which is influenced by the clinician's knowledge and experience-with no established diagnostic biomarkers. A growing body of research has been conducted over the past decades to improve diagnostic accuracy. Here, we provide an overview of the current diagnostic assessment process as well as of recent and ongoing developments to support diagnosis in terms of genetic evaluation, telemedicine, digital technologies, use of machine learning/artificial intelligence, and research on candidate diagnostic biomarkers.

Regulatory T Cells for Stroke Recovery: A Promising Immune Therapeutic Strategy.

Background: Stroke remains a leading cause of mortality and disability among adults. Given the restricted therapeutic window for intravascular interventions and neuroprotection during the acute phase, there has been a growing focus on tissue repair and functional recovery in the subacute and chronic phases after stroke. The pro-inflammatory microglial polarization occurs in subacute and chronic phases after stroke and may represent therapeutic targets for stroke recovery.

User-Centered Design of Neuroprosthetics: Advancements and Limitations.

Neurological conditions resulting from severe spinal cord injuries, brain injuries, and other traumatic incidents often lead to the loss of essential bodily functions, including sensory and motor capabilities. Traditional prosthetic devices, though standard, have limitations in delivering the required dexterity and functionality. The advent of neuroprosthetics marks a paradigm shift, aiming to bridge the gap between prosthetic devices and the human nervous system.

From pain to meningitis: bacteria hijack nociceptors to promote meningitis.

Bacterial meningitis is a severe and life-threatening infection of the central nervous system (CNS), primarily caused by and . This condition carries a high risk of mortality and severe neurological sequelae, such as cognitive impairment and epilepsy. Pain, a central feature of meningitis, results from the activation of nociceptor sensory neurons by inflammatory mediators or bacterial toxins.

IDH-mutant gliomas in children and adolescents - from biology to clinical trials.

Gliomas account for nearly 30% of all primary central nervous system (CNS) tumors in children and adolescents and young adults (AYA), contributing to significant morbidity and mortality. The updated molecular classification of gliomas defines molecularly diverse subtypes with a spectrum of tumors associated with age-distinct incidence. In adults, gliomas are characterized by the presence or absence of mutations in isocitrate dehydrogenase (), with mutated (mIDH) gliomas providing favorable outcomes and avenues for targeted therapy with the emergence of mIDH inhibitors.

Raynaud Syndrome Associated with Medication for Attention-Deficit/Hyperactivity Disorder: A Systematic Review.

Background: Raynaud syndrome (RS) is a peripheral vasculopathy characterised be impaired acral perfusion typically manifesting as skin discolouration with pallor, cyanosis and/or erythema, and increased sensitivity to cold. RS may be primary or secondary to systemic disease, lifestyle and environmental factors or medication. RS has been reported with medication to treat ADHD, but we found no recent comprehensive overview of the literature.

The number of central nervous system-driven symptoms predicts subsequent chronic primary pain: evidence from UK Biobank.

Background: Chronic primary pain describes conditions where pain is the principal problem rather than a consequence of another disease. Primary pain is thought to be primarily owing to nociplastic pain (i.e.

Abnormal cardiovascular control during exercise: Role of insulin resistance in the brain.

During exercise circulatory adjustments to meet oxygen demands are mediated by multiple autonomic mechanisms, the skeletal muscle exercise pressor reflex (EPR), the baroreflex (BR), and by feedforward signals from central command neurons in higher brain centers. Insulin resistance in peripheral tissues includes sensitization of skeletal muscle afferents by hyperinsulinemia which is in part responsible for the abnormally heightened EPR function observed in diabetic animal models and patients. However, the role of insulin signaling within the central nervous system (CNS) is receiving increased attention as a potential therapeutic intervention in diseases with underlying insulin resistance.

Brain Function Outcomes of Recent and Lifetime Cannabis Use.

Importance: Cannabis use has increased globally, but its effects on brain function are not fully known, highlighting the need to better determine recent and long-term brain activation outcomes of cannabis use.

Objective: To examine the association of lifetime history of heavy cannabis use and recent cannabis use with brain activation across a range of brain functions in a large sample of young adults in the US.

Design, Setting, And Participants: This cross-sectional study used data (2017 release) from the Human Connectome Project (collected between August 2012 and 2015).

Current state and promise of user-centered design to harness explainable AI in clinical decision-support systems for patients with CNS tumors.

In neuro-oncology, MR imaging is crucial for obtaining detailed brain images to identify neoplasms, plan treatment, guide surgical intervention, and monitor the tumor's response. Recent AI advances in neuroimaging have promising applications in neuro-oncology, including guiding clinical decisions and improving patient management. However, the lack of clarity on how AI arrives at predictions has hindered its clinical translation.

Extracellular vesicles as drug and gene delivery vehicles in central nervous system diseases.

Extracellular vesicles (EVs) are secreted by almost all cell types and contain DNA, RNA, proteins, lipids and other metabolites. EVs were initially believed to be cellular waste but now recognized for their role in cell-to-cell communication. Later, EVs from immune cells were discovered to function similarly to their parent cells, paving the way for their use as gene and drug carriers.

Gut-brain axis and neuropsychiatric health: recent advances.

The gut–brain axis, a bidirectional communication pathway, permits the central nervous system (CNS) to exert influence over gastrointestinal function in response to stress, while the gut microbiota regulates the CNS via immune, neuroendocrine, and vagal pathways. Current research highlights the importance of the gut microbiota in stress-related disorders and the need for further research into the mechanisms of gut–brain communication, with potential therapeutic implications for a wide range of health conditions. This is a challenge taken on in this Collection on the Gut-Brain Axis.

Patients with neurological or psychiatric complications of COVID-19 have worse long-term functional outcomes: COVID-CNS-A multicentre case-control study.

It is established that patients hospitalised with COVID-19 often have ongoing morbidity affecting activity of daily living (ADL), employment, and mental health. However, little is known about the relative outcomes in patients with COVID-19 neurological or psychiatric complications. We conducted a UK multicentre case-control study of patients hospitalised with COVID-19 (controls) and those who developed COVID-19 associated acute neurological or psychiatric complications (cases).

Trace amine signaling in zebrafish models: CNS pharmacology, behavioral regulation and translational relevance.

Tyramine, β-phenylethylamine, octopamine and other trace amines are endogenous substances recently recognized as important novel neurotransmitters in the brain. Trace amines act via multiple selective trace amine-associated receptors (TAARs) of the G protein-coupled receptor family. TAARs are expressed in various brain regions and modulate neurotransmission, neuronal excitability, adult neurogenesis, cognition, mood, locomotor activity and olfaction.

Highly Optimized CNS Penetrant Inhibitors of EGFR Exon20 Insertion Mutations.

Despite recent advances in the inhibition of EGFR (epidermal growth factor receptor), there remains a clinical need for new EGFR Exon20 insertion (Ex20Ins) inhibitors that spare EGFR WT. Herein, we report the discovery and optimization of two chemical series leading to ether and biaryl as potent, selective, and brain-penetrant inhibitors of Ex20Ins mutants. Building on our earlier discovery of alkyne which allowed access to CNS property space for an Ex20Ins inhibitor, we utilized structure-based design to move to lower lipophilicity and lower CL compounds while maintaining a WT selectivity margin.

Morphological Characteristics and Extracellular Matrix Abnormalities in Astrocytes Derived From iPSCs of Children With Alexander Disease.

Aims: Alexander disease (AxD) is a leukodystrophy caused by mutations in the astrocytic filament gene GFAP. There are currently no effective treatments for AxD. Previous studies have rarely established AxD models with the patient's original GFAP mutations.

Central nervous system posttransplant lymphoproliferative disorder following allogeneic hematopoietic stem cell transplantation successfully treated with combination therapy of acalabrutinib and immunochemotherapy: A case report and literature review.

Here, we report a case of Epstein-Barr virus-positive central nervous system-post-transplant lymphoproliferative disorder (CNS-PTLD) patient who failed to achieve complete metabolic remission (CMR) after successively trying a methotrexate-based regimen combined with orelabrutinib or whole-brain radiotherapy and encountered intracranial hemorrhage during orelabrutinib treatment. Ultimately, the patient achieved CMR after one cycle of acalabrutinib in combination with temozolomide, teniposide, liposomal doxorubicin, dexamethasone, and rituximab (TEDDi-R). Following another cycle of TEDDi-R treatment, he has been receiving acalabrutinib maintenance up to now and remained in CMR.

Fluorescent Particles Based on Aggregation-Induced Emission for Optical Diagnostics of the Central Nervous System.

In 2001, Tang's team discovered a unique type of luminogens with substantial enhanced fluorescence upon aggregation and introduced the concept of "aggregation-induced emission (AIE)". Unlike conventional fluorescent materials, AIE luminogens (AIEgens) emit weak or no fluorescence in solution but become highly fluorescent in aggregated or solid states, due to a mechanism known as restriction of intramolecular motions (RIM). Initially considered a purely inorganic chemical phenomenon, AIE was later applied in biomedicine to improve the sensitivity of immunoassays.

BoNT/Action beyond neurons.

Botulinum neurotoxin type A (BoNT/A) has expanded its therapeutic uses beyond neuromuscular disorders to include treatments for various pain syndromes and neurological conditions. Originally recognized for blocking acetylcholine release at neuromuscular junctions, BoNT/A's effects extend to both peripheral and central nervous systems. Its ability to undergo retrograde transport allows BoNT/A to modulate synaptic transmission and reduce pain centrally, influencing neurotransmitter systems beyond muscle control.