Search Results (14,292)

Pregnancy involves major cardiovascular adaptations, yet its long-term impact on maternal brain health remains poorly understood. The American Heart Association’s Life’s Simple 7 (LS7) and Life’s Essential 8 (LE8) are validated tools to assess cardiovascular and brain health, but their use in obstetric populations is limited. Following PRISMA-ScR guidelines, we searched three databases (2010–2024) for studies assessing ≥ 1 LS7/LE8 component during pregnancy with mid- or later-life cognitive or dementia outcomes; narrative synthesis and meta-analyses were conducted where feasible. Of 3940 screened abstracts, 30 studies met the inclusion criteria. Most examined hypertensive disorders of pregnancy (HDP), few assessed diabetes independently, and none evaluated the full LS7/LE8 construct. Meta-analyses showed that HDP was associated with increased risk of all-cause dementia (HR 1.34; 95% CI 1.11–1.62) and vascular dementia (HR 1.76; 95% CI 1.03–3.00; n = 3 studies), but not Alzheimer’s disease (HR 1.22; 95% CI 0.96–1.56). Although LS7/LE8 are established frameworks for cardiovascular and brain health, their application during pregnancy remains limited. Integrating LE8 into obstetric care may enable earlier identification of individuals at risk for later-life cognitive decline and inform strategies to promote maternal brain health across the lifespan. Full article

Background: Surgical resection remains the standard treatment for large brain metastases (LBMs), but many patients are not surgical candidates due to poor performance status or uncontrolled systemic disease. Gamma Knife-based hypofractionated stereotactic radiotherapy (GKRS) has emerged as a potential alternative; however, its clinical role in this population remains insufficiently defined. We evaluated whether a uniform daily 5-fraction GKRS provides effective and safe local treatment for surgery-ineligible LBMs. Methods: We retrospectively analyzed 100 patients with LBMs (>14 cm³) who underwent primary hypofractionated GKRS using a uniform daily 5-fraction schedule. Forty-six patients were male; the median age was 60 years. The median Karnofsky Performance Status (KPS) was 70 (60–100); a total of 47 patients (47%) had pre-GKRS neurological deficits. The most common primary sites were lung (41), breast (24), and kidney (14). The median tumor volume was 22.0 cm³ (14–70 cm³), and the marginal dose was 35.2 Gy (50% isodose line) in 5 fractions. The primary endpoints included local tumor control (LTC), intracranial progression-free survival (PFS), and overall survival (OS). Radiation necrosis (RN) was assessed as a key safety outcome. Results: At a median follow-up of 18 months, the overall LTC rate was 74%, with 1-, 2-, and 3-year rates of 73%, 65%, and 60%, respectively. Median PFS and OS were 7.5 and 16.3 months. Higher pre-treatment KPS and absence of neurological deficits were independently associated with improved OS (p = 0.003 and 0.025, respectively). RN occurred in 16% of patients, with 9% developing symptoms; all symptomatic cases were effectively managed with corticosteroids or bevacizumab. Most tumors demonstrated substantial volumetric reduction, with a median decrease of 80% and 30% achieving near-complete response (>95%). Conclusions: A uniform daily 5-fraction hypofractionated GKRS provides effective local control with acceptable toxicity in patients with LBMs. These findings support its role as a feasible local treatment option in selected patients who are not candidates for surgery. Integration with systemic therapies and prospective validation are warranted to refine patient selection and optimize outcomes. Full article

The Barker hypothesis links intrauterine conditions, mainly low birth weight, subject to poor nutrition with paradoxically improved standards of living and nutrition after World War II in Western countries, to adult disease, mainly coronary heart disease. The limitations of his hypothesis include the fact that it is based only on human epidemiological data and animal studies, and also that it is difficult to isolate the effect of the intrauterine environment from postnatal conditions, familial and genetic background. In the last 20 years, the introduction of ultrasound and Doppler techniques in the assessment of fetal and maternal vascularity added a major contribution to the evaluation of the intrauterine environment. Studies based on ultrasound and Doppler assist in differentiating between prematurity and fetal growth restriction (FGR), mainly in those with placental insufficiency, and postnatal morbidity and even mortality. In addition, the Pedersen hypothesis regarding fetuses with overgrowth, mainly with diabetic mothers, states that they are also prone to postnatal morbidity. However, most of the studies on the issue do not emphasize the effects of the intrauterine environment on fetal organs, such as the brain, heart, liver, kidneys and pancreas in FGR and fetal overgrowth, that may impose a different prognosis in later life. This narrative review aims to summarize current evidence from animal and human studies regarding the impact of intrauterine undernutrition and overnutrition on fetal organ development, and to evaluate how ultrasound and Doppler findings may contribute to understanding the link between the intrauterine environment and postnatal morbidity. Full article

Group 2 innate lymphoid cells (ILC2s) are tissue-resident immune cells that play a central role in type 2 immunity. Beyond cytokine signaling, they integrate inputs from lipids, nutrients, neuroendocrine mediators, and local metabolic cues, establishing cellular metabolism as a key regulator of their function. Immunometabolism provides a framework to understand how ILC2s adapt to diverse tissue environments such as the lung, adipose tissue, gut, skin, and brain, each defined by distinct nutrient availability, oxygen tension, and inflammatory conditions. Unlike many immune cells that primarily rely on glycolysis, ILC2s dynamically balance glycolysis, fatty acid oxidation (FAO), and oxidative phosphorylation (OXPHOS) depending on activation state and tissue context. Lipids not only serve as energy substrates but also regulate membrane organization, lipid raft–dependent signaling, and the generation of bioactive mediators, including eicosanoids, oxysterols, and sphingolipids. Emerging evidence linking cholesterol biosynthesis, steroid metabolism, and sphingolipid signaling to ILC2 function underscores the importance of lipid-dependent immune regulation. Dysregulation of these pathways contributes to chronic inflammatory diseases such as asthma, metabolic disorders, and fibrosis. Targeting metabolic pathways and checkpoints may therefore offer new strategies to modulate ILC2-driven pathology. This review summarizes current insights into metabolic programs governing ILC2 activation, survival, and plasticity and highlights emerging therapeutic opportunities. Full article

Background/Objectives: Posterior cortical atrophy, also referred to as Benson’s syndrome, is a presentation of Alzheimer’s disease that occurs in 5–15% of Alzheimer’s patients. Visual processing is the predominantly affected modality in posterior cortical atrophy, and symptoms such as prosopagnosia, simultanagnosia, alexia, optic ataxia, and visual hallucinations may occur, as well as blurred vision and visual distortions. Posterior cortical atrophy is considered to be a disease without a known cause or effective treatment. Methods: Here, we report a patient with posterior cortical atrophy who responded to a personalized, precision medicine protocol. Results: The patient had improved MRI volumetrics, symptoms, and cognitive testing. She regained the ability to read, use a computer, and undertake computer-based brain training, among other cognitive improvements. She has now sustained this improvement for over one year and continues to regain her independence and confidence. Conclusions: These results argue for additional laboratory testing in the evaluation of patients with posterior cortical atrophy, and they support the possibility of utilizing a similar approach in a proof-of-concept trial. Full article

Prion diseases are caused by self-propagating and transmissible alternative conformations of certain proteins, which induce neurotoxicity and lead to transmissible spongiform encephalopathy (TSE) in mammalian. Prions were also found in fungi, and in particular, the yeast Saccharomyces cerevisiae. Manganese (Mn) is an essential nutrient and plays crucial roles in central nervous system. However, high concentration of manganese is regarded as an environmental neuronal stressor which would induce striatal neurotoxicity. Long-term exposure to high concentration of manganese would increase the proportion of the infectiously pathogenic isoform (PrPSc) of prion protein. Additionally, increase of manganese levels was found to be age-related in human brain. Here, we studied the effect of manganese on prion using budding yeast prion [URE3] as model organism. We found the exposure to manganese can enhance the de novo generation and propagation of yeast prion [URE3], as well as the expression levels of chaperones Hsp104p and Hsp70p, in a dose-dependent manner. Full article

Brain and muscle Arnt-like protein 1 (BMAL1) is a transcription factor that forms heterodimers with circadian locomotor output cycles kaput (CLOCK) and drives transcription from E-box elements, thereby regulating the circadian rhythms of gene expression. The kidney expresses numerous rhythmic genes and exhibits circadian physiological function regulation. Circadian rhythm abnormalities, such as sleep disorders and excessive daytime sleepiness, are particularly frequent in patients with chronic kidney disease (CKD). Furthermore, reduced amplitude and phase disruption in clock gene expression rhythms have been reported in mouse CKD models. These results suggest that circadian disruption is associated with renal pathophysiology. However, the role of BMAL1 in the repair process following acute kidney injury (AKI) remains unclear; therefore, this study aimed to elucidate its role in kidney repair following ischemia–reperfusion injury (IRI). We found that the tamoxifen (TAM)-inducible global Bmal1 knockout (BKO) mouse kidneys exhibited increased lipid accumulation, enhanced fibrosis, and delayed kidney repair post-IRI, and that these abnormalities were associated with reduced Peroxisome proliferator-activated receptor alpha (Pparα) expression. Furthermore, treatment with a PPARα agonist reduced these abnormalities in BKO mice. Collectively, our findings demonstrate that the BMAL1–PPARα axis promotes post-AKI kidney repair. Full article

Magnetic resonance imaging (MRI) remains one of the most important tests for diagnosing and monitoring various diseases. In recent years, machine learning methods have been widely applied to automate MRI analysis. It supports decision-making by predicting disease and highlighting relevant regions. However, the proper use of feature extraction methods can improve the performance of the model. This paper proposes a WaveletFusion architecture that combines a two-dimensional Haar wavelet decomposition with a convolutional neural network (CNN) for classification. The approach was demonstrated on the Brain Tumor MRI dataset and further examined on the Br35H :: Brain Tumor Detection 2020 (Br35H). The model decomposes each MRI slice into approximation and directional detail subbands and fuses multi-scale wavelet features within the convolutional pipeline. To evaluate the effect of decomposition depth, WaveletFusion variants from one to eight levels were compared with a Baseline CNN model under the same training protocol. The results showed that performance improved progressively with increasing decomposition depth up to level 7, whereas the 8-level configuration consistently declined, indicating that excessive decomposition introduces information loss and over-compression in the deepest approximation pathway. The best-performing configuration, which outperformed both the Baseline CNN and the WaveletFusion variations in five independent runs, was the 7-level WaveletFusion model, achieving a test accuracy of 0.94 ± 0.01 and test macro-F1 of 0.93 ± 0.02. A similar tendency was observed on the Br35H dataset, where the 7-level model achieved a 0.97 ± 0.01 test accuracy and 0.97 ± 0.01 test macro-F1, while the 8-level configuration remained weaker on both datasets. These results show that multi-scale wavelet fusion can improve Brain Tumor MRI classification while maintaining a compact model size and a fair comparison setting, and that the decomposition depth must be selected carefully. Full article

Molecular diagnosis has advanced rapidly in neurogenetic disorders, yet translating genotype into patient-specific predictions of brain network dysfunction and progression remains limited. Virtual brain models provide a structured solution by embedding individual anatomy and connectomics into biophysical whole-brain simulations. The critical step is to position genetics not as a diagnostic label, but as a constructive input to model design. This review outlines a genetics-centered framework for virtual brain modeling. First, atlas-derived transcriptomic and cell-type maps can define region-specific molecular priors, constraining vulnerability or excitability parameters and reducing model degeneracy. Second, when reproducible genotype-linked network phenotypes exist, mutation groups can inform stratified initialization and progression regimes. Third, at the patient level, exome and CNV data—summarized as pathway burdens and, where appropriate, calibrated polygenic modifiers—can be translated into individualized priors or regularizers, provided that mapping rules are explicit and externally validated. By integrating genetics at multiple levels of evidence, virtual brain models gain mechanistic plausibility, improved calibration, and explicit uncertainty quantification. The most realistic impact over the next few years is likely to be improved stratification, progression-aware forecasting, and scenario-based decision support in rare neurogenetic diseases, especially where longitudinal cohort infrastructure and validated biomarker inputs are already available, rather than deterministic individual prediction. Full article

The Bacillus Calmette–Guérin (BCG) vaccine, originally developed for tuberculosis (TB) prevention, has recently attracted attention due to its broader immunomodulatory properties. In addition to its role in TB control, BCG induces trained immunity, a process involving epigenetic and metabolic reprogramming of innate immune cells that leads to altered systemic inflammatory responses. Increasing evidence suggests that these long-term immune adaptations may influence the central nervous system by modulating microglial activation and neuroinflammatory pathways implicated in neurodegenerative diseases. In parallel, chronic infections such as TB are associated with persistent systemic inflammation and immune dysregulation, which may contribute to microglial priming and increased vulnerability to neurodegeneration. This narrative review, based on a targeted literature search of PubMed, Scopus, Web of Science, Embase, and relevant preprint servers, synthesizes current evidence on the relationships between BCG vaccination, trained immunity, and neuroimmune interactions. We focus on studies addressing systemic immune reprogramming, microglial responses, and neuroinflammatory mechanisms relevant to neurodegenerative disorders. The available data suggest that BCG-induced immune modulation may exert context-dependent effects on the brain, with potential neuroprotective implications under certain conditions. However, the evidence remains heterogeneous and largely observational, and causality cannot yet be established. Further mechanistic and prospective studies are required to clarify whether BCG-induced trained immunity can modify the risk or progression of age-related neurodegenerative diseases. Full article

Formaldehyde (HCHO) is a typical volatile organic compound (VOC) that poses significant risks to human health. Long-term exposure, even at low concentrations, has been associated with various malignant diseases, including nasopharyngeal, colon, and brain cancers. Common technologies for HCHO abatement include ventilation, adsorption, photocatalysis, and catalytic oxidation. Among these methods, catalytic oxidation is regarded as the most promising due to its high removal efficiency, low cost, minimal energy consumption, and no toxic by-products. In recent years, supported catalysts with excellent room-temperature activity and high dispersibility have attracted considerable attention. These catalysts can usually be divided into two categories: noble metal catalysts and non-noble metal catalysts. Zirconia (ZrO₂) has become an ideal support owing to its advantages of high specific surface area, abundant and tunable acid–base sites, and strong metal–support interaction (SMSI). Various modification strategies have been developed to improve the catalytic performance of ZrO₂-based systems, such as the construction of phase interfaces and the stabilization of single-atom species. This review summarizes the recent research progress of ZrO₂-based systems for the catalytic oxidation of formaldehyde. It provides a detailed discussion of the physicochemical properties of ZrO₂ supports and the reaction mechanisms involved, and highlights achievements in crystal phase regulation, elemental doping, metal–support interaction, and composite modification. Finally, future challenges and development directions for these catalysts are also outlined. Full article

The limit of disease-modifying therapeutic strategies against epilepsy has prompted mainstream epilepsy research toward understanding the pathways contributing to epileptic seizures. Microglia, the powerhouse of the brain’s innate immune system, is known for its role in epileptic seizures, contributing via neuroinflammation, neuronal death, and neurogenesis. Therapeutic targeting of microglia with its inhibitor and therapeutic compounds modulating its activation reduces the development of spontaneous recurrent seizure after status epilepticus in a pre-clinical model. Herein, we review various aspects of microglia in epilepsy, including their contribution to seizure-induced neuronal death and neurogenesis, the outcome of depleting microglia (both pharmacologically and genetically), the aspects of microglia–astrocyte interaction, and promising therapeutic outcomes achieved by targeting microglia. Full article

Background/Objectives: Pediatric cancers are disorders of dysregulated development driven largely by genomic and epigenetic alterations. Precisely modeling these developmental differences is essential for understanding the unique biology of childhood cancers. Patient-derived organoids (PDOs) offer a powerful in vitro platform that recapitulates tumor heterogeneity, plasticity, microenvironment (including immune cells) and disease-relevant features. Methods: Here, we describe a step-by-step protocol for the establishment of PDOs from cells derived from pediatric brain tumors and extracranial solid tumor biopsies and bone marrow aspirates, including tumor processing, organoid culture/subculture, and cryopreservation. Results: Furthermore, we present the use of PDOs for further experimental analysis such as fluorescence imaging, Western blotting, flow cytometry, and immunohistochemistry (IHC) to investigate the underlying pathophysiology of tumorigenesis. Conclusions: Expanding the application of organoids to childhood malignancies holds exceptional promise for elucidating pediatric tumor biology and advancing therapeutic strategies, representing the long-overdue convergence of technology and clinical need. Full article

Background: Gliomas are the most common malignant brain tumors in adults, characterized by a poor prognosis. Although the current World Health Organization (WHO) classification provides clear guidelines for classifying oligodendroglioma, astrocytoma, and glioblastoma patients, significant heterogeneity persists within each class, limiting the effectiveness of current treatment strategies. With the increasing availability of large-scale multi-omics datasets resulting from advancements in sequencing technologies and online repositories that provide them, such as The Cancer Genome Atlas (TCGA), it is now possible to investigate these tumors at multiple molecular levels. Methods: In this work, we apply integrative multi-omics analysis to explore the interplay between genomic (mutations), epigenomic (DNA methylation), and transcriptomic (mRNA and miRNA) layers. Our approach relies on Multi-Omics Factor Analysis (MOFA), a Bayesian latent factor analysis model designed to capture sources of variation across different omics types. Results: Our results highlight distinct molecular profiles across the three glioma types and identify potential relationships between methylation and genetic expression. In particular, we uncover novel candidate biomarkers associated with survival as well as a transcriptional profile associated with neural system development. Conclusions: These findings may contribute to more personalized therapeutic strategies, potentially improving treatment effectiveness and survival outcomes in this disease. Full article

Hyaluronan (HA) is a ubiquitous extracellular matrix (ECM) component that is gaining significant attention for its diverse roles in cell signalling and disease. The biological functions of HA are dependent on its molecular weight (M_w): low M_w polysaccharide chains drive stimulatory processes such as inflammation and angiogenesis, whereas high M_w HA is stabilising and anti-inflammatory. Growing evidence indicates that HA is integral to brain function. The composition of HA in the brain is regulated by the balance of enzymatic synthesis and degradation, mediated by different isoforms of hyaluronan synthase (HAS) and hyaluronidase (HYAL) respectively. Fluctuating expression of the genes encoding the HAS and HYAL enzymes has been implicated in neuropathology and ageing, with some studies providing evidence towards epigenetic regulation of these genes. The regulatory environment of the brain confers a unique balance of enhanced protection alongside the requirement for maximum flexibility. This scoping review focuses on summarising current knowledge regarding epigenetic regulation of HAS and HYAL genes in neural contexts, as well as identifying gaps in knowledge against which future research can be directed. Understanding how these genes are regulated, particularly through epigenetic mechanisms, provides insight into how HA is regulated in the brain, facilitating understanding regarding its function in brain health and disease. Full article