Investigating the frequency of neural autoantibodies in refractory focal epilepsy.

Objectives: There have been conflicting reports about the frequency of neural autoantibodies in epilepsy cohorts, which is confounded by the lack of clear distinction of epilepsy from acute symptomatic seizures due to encephalitis. The aim of this study was to determine the frequency of neural autoantibodies in a well characterised population of refractory focal epilepsy of known and unknown cause.

Methods: Cases were recruited from epilepsy outpatient clinics at the Princess Alexandra, Mater, Royal Brisbane and Women's and Cairns Base Hospitals from 2021 - 2023.

Child Neurology: Severe -Related Congenital Muscular Dystrophy With Rapidly Progressive Encephalopathy Leading to Infantile Death.

Pathogenic variants in cause congenital muscular dystrophy through hypoglycosylation of alpha-dystroglycan (OMIM #615350). The established phenotypic spectrum of GMPPB-related disorders includes recurrent rhabdomyolysis, limb-girdle muscular dystrophy, neuromuscular transmission abnormalities, and congenital muscular dystrophy with variable brain and eye anomalies. We report a 9-month-old male infant with congenital muscular dystrophy, infantile spasms, and compound heterozygous pathogenic variants (c.

Environmental exposures and the risk of hepatocellular carcinoma.

The global epidemiology of HCC is shifting due to changes in both established and emerging risk factors. This transformation is marked by an emerging prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes, alongside traditional risks such as viral hepatitis (HBV and HCV), and exposure to chemical agents like aflatoxin, alcohol, tobacco, and air pollution. This review examines how environmental exposures and evolving liver pathology, exacerbated by lifestyle and metabolic conditions, are contributing to the rising worldwide incidence of HCC.

Unveiling degenerative bone changes in the condyle: a texture analysis approach using cone-beam computed tomography.

Purpose: The degenerative joint disease is a temporomandibular disorder. By analysing texture parameters, it becomes possible to characterize and differentiate various tissues, based on their textural properties according to cone-beam computed tomography (CBCT). This study evaluated degenerative diseases in the temporomandibular joint through texture analysis.

Three-dimensional measurement of the depth of invasion in oral squamous cell carcinoma samples using Lugol's iodine-enhanced micro-computed tomography: an original study.

Objectives: Depth of invasion (DOI) in oral squamous cell carcinoma (OSCC) guides treatment and prognosis but lacks three-dimensional (3D) insight. Thus, this study aimed to investigate the feasibility and accuracy of Lugol's iodine-enhanced micro-computed tomography (CT) for the 3D measurement of DOI in OSCC samples.

Methodology: In total, 50 in vitro OSCC samples from Nanjing Stomatological Hospital (July 2022 to January 2024) were subjected to micro-CT imaging with a slice thickness of 50 μm following 3% Lugol iodine staining for 12 h, followed by pathological examination and staining.

Spine-Abductor Syndrome: Novel Associations Between Lumbar Spine Disease and Hip Gluteal Muscle Pathology.

Background: Risk factors for gluteal tears include age-related deterioration, female sex, and increased body mass index. As the literature that supports the sagittal relationship between the lumbar spine and the hip is increasing, there may be a parallel relationship between the perturbations in spinopelvic alignment caused by lumbar spine disease and gluteal muscle tears. Because no prior studies other than single-institution series have reported on this phenomenon, we investigated spine-abductor syndrome at the population level.

Transient interactions between the fuzzy coat and the cross-β core of brain-derived Aβ42 filaments.

Several human disorders, including Alzheimer's disease (AD), are characterized by the aberrant formation of amyloid fibrils. In many cases, the amyloid core is flanked by disordered regions, known as fuzzy coat. The structural properties of fuzzy coats, and their interactions with their environments, however, have not been fully described to date.

SMARCA4 regulates the NK-mediated killing of senescent cells.

Induction of senescence by chemotherapeutic agents arrests cancer cells and activates immune surveillance responses to contribute to therapy outcomes. In this investigation, we searched for ways to enhance the NK-mediated elimination of senescent cells. We used a staggered screen approach, first identifying siRNAs potentiating the secretion of immunomodulatory cytokines to later test for their ability to enhance NK-mediated killing of senescent cells.

Amphiphilic hemicyanine molecular probes crossing the blood-brain barrier for intracranial optical imaging of glioblastoma.

Intracranial optical imaging of glioblastoma (GBM) is challenging due to the scarcity of effective probes with blood-brain barrier (BBB) permeability and sufficient imaging depth. Herein, we describe a rational strategy for designing optical probes crossing the BBB based on an electron donor-π-acceptor system to adjust the lipid/water partition coefficient and molecular weight of probes. The amphiphilic hemicyanine dye (namely, IVTPO), which exhibits remarkable optical properties and effective BBB permeability, is chosen as an efficient fluorescence/photoacoustic probe for in vivo real-time imaging of orthotopic GBM with high resolution through the intact skull.

Targeting TRPC channels for control of arthritis-induced bone erosion.

Arthritis leads to bone erosion due to an imbalance between osteoclast and osteoblast function. Our prior investigations revealed that the Ca-selective ion channel, Orai1, is critical for osteoclast maturation. Here, we show that the small-molecule ELP-004 preferentially inhibits transient receptor potential canonical (TRPC) channels.

Engineered extracellular vesicles with DR5 agonistic scFvs simultaneously target tumor and immunosuppressive stromal cells.

Small extracellular vesicles (sEVs) are nanosized vesicles. Death receptor 5 (DR5) mediates extrinsic apoptosis. We engineer DR5 agonistic single-chain variable fragment (scFv) expression on the surface of sEVs derived from natural killer cells.

A population of c-kit IL-17A ILC2s in sputum from individuals with severe asthma supports ILC2 to ILC3 trans-differentiation.

In prednisone-dependent severe asthma, uncontrolled sputum eosinophilia is associated with increased numbers of group 2 innate lymphoid cells (ILC2s). These cells represent a relatively steroid-insensitive source of interleukin-5 (IL-5) and IL-13 and are considered critical drivers of asthma pathology. The abundance of ILC subgroups in severe asthma with neutrophilic or mixed granulocytic (both eosinophilic and neutrophilic) airway inflammation, prone to recurrent infective exacerbations, remains unclear.

Inhaled xenon modulates microglia and ameliorates disease in mouse models of amyloidosis and tauopathy.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder. Antiamyloid antibody treatments modestly slow disease progression in mild dementia due to AD. Emerging evidence shows that homeostatic dysregulation of the brain immune system, especially that orchestrated by microglia, plays an important role in disease onset and progression.

regulates melanocortin 4 receptor transcription and energy homeostasis.

Disruption of hypothalamic melanocortin 4 receptors (MC4Rs) causes obesity in mice and humans. Here, we investigated the transcriptional regulation of in the hypothalamus. In mice, we show that the homeodomain transcription factor Orthopedia (OTP) is enriched in MC4R neurons in the paraventricular nucleus (PVN) of the hypothalamus and directly regulates transcription.

Epithelial OPA1 links mitochondrial fusion to inflammatory bowel disease.

Dysregulation at the intestinal epithelial barrier is a driver of inflammatory bowel disease (IBD). However, the molecular mechanisms of barrier failure are not well understood. Here, we demonstrate dysregulated mitochondrial fusion in intestinal epithelial cells (IECs) of patients with IBD and show that impaired fusion is sufficient to drive chronic intestinal inflammation.

Gene therapy ameliorates bowel dysmotility and enteric neuron degeneration and extends survival in lysosomal storage disorder mouse models.

Children with neurodegenerative disease often have debilitating gastrointestinal symptoms. We hypothesized that this may be due at least in part to underappreciated degeneration of neurons in the enteric nervous system (ENS), the master regulator of bowel function. To test this hypothesis, we evaluated mouse models of neuronal ceroid lipofuscinosis type 1 and 2 (CLN1 and CLN2 disease, respectively), neurodegenerative lysosomal storage disorders caused by deficiencies in palmitoyl protein thioesterase-1 and tripeptidyl peptidase-1, respectively.

MmuPV1 infection of Tmc6/Ever1 or Tmc8/Ever2 deficient FVB mice as a model of βHPV in typical epidermodysplasia verruciformis.

Typical epidermodysplasia verruciformis (EV) is a rare, autosomal recessive disorder characterized by an unusual susceptibility to infection with specific skin-trophic types of human papillomavirus, principally betapapillomaviruses, and a propensity for developing malignant skin tumors in sun exposed regions. Its etiology reflects biallelic loss-of-function mutations in TMC6 (EVER1), TMC8 (EVER2) or CIB1. A TMC6-TMC8-CIB1 protein complex in the endoplasmic reticulum is hypothesized to be a restriction factor in keratinocytes for βHPV infection.

3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity.

The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities of type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome-wide association study (GWAS) efforts for childhood obesity revealed 19 independent signals for the trait; however, the mechanism of action of these loci remains to be elucidated. To molecularly characterize these childhood obesity loci, we sought to determine the underlying causal variants and the corresponding effector genes within diverse cellular contexts.

CFTR dictates monocyte adhesion by facilitating integrin clustering but not activation.

Monocytes are critical in controlling tissue infections and inflammation. Monocyte dysfunction contributes to the inflammatory pathogenesis of cystic fibrosis (CF) caused by CF transmembrane conductance regulator (CFTR) mutations, making CF a clinically relevant disease model for studying the contribution of monocytes to inflammation. Although CF monocytes exhibited adhesion defects, the precise mechanism is unclear.

Soil microbiome bacteria protect plants against filamentous fungal infections via intercellular contacts.

Bacterial-fungal interaction (BFI) has significant implications for the health of host plants. While the diffusible antibiotic metabolite-mediated competition in BFI has been extensively characterized, the impact of intercellular contact remains largely elusive. Here, we demonstrate that the intercellular contact is a prevalent mode of interaction between beneficial soil bacteria and pathogenic filamentous fungi.

A histochemical approach to activity-based copper sensing reveals cuproplasia-dependent vulnerabilities in cancer.

Copper is an essential nutrient for sustaining vital cellular processes spanning respiration, metabolism, and proliferation. However, loss of copper homeostasis, particularly misregulation of loosely bound copper ions which are defined as the labile copper pool, occurs in major diseases such as cancer, where tumor growth and metastasis have a heightened requirement for this metal. To help decipher the role of copper in the etiology of cancer, we report a histochemical activity-based sensing approach that enables systematic, high-throughput profiling of labile copper status across many cell lines in parallel.

Hypochlorous Acid-Activatable NIR Fluorescence/Photoacoustic Dual-Modal Probe with High Signal-to-Background Ratios for Imaging of Liver Injury and Plasma Diagnosis of Sepsis.

Hypochlorous acid can be employed as a biomarker for blood infection (such as sepsis) and tissue damage (such as drug-induced liver injury, DILI), and the diagnosis of tissue damage or blood infection can be achieved through the detection of hypochlorous acid in relevant biological samples. Considering the complex environment and the diverse interferences in living organisms and blood plasma, developing new detection methods for HClO with high signal-to-background ratios is particularly important, and it can improve the accuracy of detection and quality of imaging based on a higher contrast, which makes the detection of HClO clearer and more accurate. Here, based on the advantages of the NIR fluorescence/photoacoustic dual-modal probe, we reported a hypochlorous acid-activatable NIR fluorescence/photoacoustic dual-modal probe (NIRF-PA-HClO) based on the spirolactam ring-opening strategy in this paper.

Gene expression analysis reveals mir-29 as a linker regulatory molecule among rheumatoid arthritis, inflammatory bowel disease, and dementia: Insights from systems biology approach.

Background: Rheumatoid arthritis (RA) is a degenerative autoimmune disease, often managed through symptomatic treatment. The co-occurrence of the reported extra-articular comorbidities such as inflammatory bowel disease (IBD), and dementia may complicate the pathology of the disease as well as the treatment strategies. Therefore, in our study, we aim to elucidate the key genes, and regulatory elements implicated in the progression and association of these diseases, thereby highlighting the linked potential therapeutic targets.

Long-term survival of participants in the PASART-1 and PASART-2 trials of neo-adjuvant pazopanib and radiotherapy in soft tissue sarcoma.

Objective: This study aims to assess the long-term safety and efficacy of adding pazopanib to neo-adjuvant radiotherapy followed by surgery in patients with high-risk non-metastatic soft tissue sarcoma of the trunk and extremities treated in the PASART-1 and PASART-2 trials, as well as to compare the PASART cohorts to a control cohort receiving standard treatment during the same time period from the Netherlands Cancer Registry (IKNL) to investigate if adding pazopanib improves Overall Survival (OS).

Methods: Updated follow-up data on disease control, survival and long-term toxicities of the PASART-trials were extracted from electronic patient records. The effect of adding pazopanib to neo-adjuvant radiotherapy on OS was investigated by comparing the combined PASART cohorts to the IKNL cohort via direct comparison and exact matching analysis.

Maintenance treatment with trofosfamide in patients with advanced soft tissue sarcoma - a retrospective single-centre analysis.

Background: The prognosis of patients with advanced soft tissue sarcoma (STS) remains dismal. Trofosfamide (TRO) has been proposed as a well-tolerated oral maintenance therapy. This retrospective analysis aims to determine the value of this therapy.