Cerebral Aneurysms and Arteriovenous Malformation: Preliminary Experience with the Use of Near-Infrared Fluorescence Imaging Applied to Endoscopy.

Indocyanine green video angiography, integrated into the operative microscope, is frequently used in cerebrovascular surgery. This technology is often preferred, for cost or availability, to Doppler or intraoperative DSA (digital subtraction angiography). With the same assumption it was possible, in our preliminary experience, to partially vicariate the aforementioned devices using the SPY mode of the Stryker endoscope; it allowed the visualization of fluorescence in high definition.

Statistical examination of shared loci in neuropsychiatric diseases using genome-wide association study summary statistics.

Continued methodological advances have enabled numerous statistical approaches for the analysis of summary statistics from genome-wide association studies. Genetic correlation analysis within specific regions enables a new strategy for identifying pleiotropy. Genomic regions with significant 'local' genetic correlations can be investigated further using state-of-the-art methodologies for statistical fine-mapping and variant colocalisation.

Sex-specific DNA methylation differences in Amyotrophic lateral sclerosis.

Sex is an important covariate in all genetic and epigenetic research due to its role in the incidence, progression and outcome of many phenotypic characteristics and human diseases. Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with a sex bias towards higher incidence in males. Here, we report for the first time a blood-based epigenome-wide association study meta-analysis in 9274 individuals after stringent quality control (5529 males and 3975 females).

Considerations in the search for epistasis.

Epistasis refers to changes in the effect on phenotype of a unit of genetic information, such as a single nucleotide polymorphism or a gene, dependent on the context of other genetic units. Such interactions are both biologically plausible and good candidates to explain observations which are not fully explained by an additive heritability model. However, the search for epistasis has so far largely failed to recover this missing heritability.

Identification of novel myelodysplastic syndromes prognostic subgroups by integration of inflammation, cell-type composition, and immune signatures in the bone marrow.

Mutational profiles of myelodysplastic syndromes (MDS) have established that a relatively small number of genetic aberrations, including SF3B1 and SRSF2 spliceosome mutations, lead to specific phenotypes and prognostic subgrouping. We performed a multi-omics factor analysis (MOFA) on two published MDS cohorts of bone marrow mononuclear cells (BMMNCs) and CD34 + cells with three data modalities (clinical, genotype, and transcriptomics). Seven different views, including immune profile, inflammation/aging, retrotransposon (RTE) expression, and cell-type composition, were derived from these modalities to identify the latent factors with significant impact on MDS prognosis.

Harnessing transcriptomic signals for amyotrophic lateral sclerosis to identify novel drugs and enhance risk prediction.

Introduction: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. This study integrates common genetic association results from the latest ALS genome-wide association study (GWAS) summary statistics with functional genomic annotations with the aim of providing mechanistic insights into ALS risk loci, inferring drug repurposing opportunities, and enhancing prediction of ALS risk and clinical characteristics.

Methods: Genes associated with ALS were identified using GWAS summary statistic methodology including SuSiE SNP-based fine-mapping, and transcriptome- and proteome-wide association study (TWAS/PWAS) analyses.

predicTTE: An accessible and optimal tool for time-to-event prediction in neurological diseases.

Time-to-event prediction is a key task for biological discovery, experimental medicine, and clinical care. This is particularly true for neurological diseases where development of reliable biomarkers is often limited by difficulty visualising and sampling relevant cell and molecular pathobiology. To date, much work has relied on Cox regression because of ease-of-use, despite evidence that this model includes incorrect assumptions.

Mutations in the tail and rod domains of the neurofilament heavy-chain gene increase the risk of ALS.

Objective: Neurofilament heavy-chain gene (NEFH) variants are associated with multiple neurodegenerative diseases, however, their relationship with ALS has not been robustly explored. Still, NEFH is commonly included in genetic screening panels worldwide. We therefore aimed to determine if NEFH variants modify ALS risk.

Selective Vestibular Neurectomy through the Presigmoid Retrolabyrinthine Approach in the Treatment of Meniere's Disease.

Background: Meniere's disease (MD) is a disabling disease, especially in patients who are refractory to medical therapy. Moreover, selective vestibular neurectomy (VN), in these selected cases, can be considered a surgical alternative which preserves hearing function and facial nerve.

Methods: We retrospectively studied 23 patients with MD diagnosis and history of failed extradural endolymphatic sac surgery (ELSS) who underwent combined micro-endoscopic selective VN, between January 2019 and August 2023, via a presigmoid retrolabyrinthine approach.

The Prognostic Role of Volumetric MRI Evaluation in the Surgical Treatment of Glioblastoma.

: Glioblastoma is the most common primary brain neoplasm in adults, with a poor prognosis despite a constant effort to improve patient survival. Some neuroradiological volumetric parameters seem to play a predictive role in overall survival (OS) and progression-free survival (PFS). The aim of this study was to analyze the impact of the volumetric areas of contrast-enhancing tumors and perineoplastic edema on the survival of patients treated for glioblastoma.

Co-targeting HSP90 alpha and CDK7 overcomes resistance against HSP90 inhibitors in BCR-ABL1+ leukemia cells.

HSP90 has emerged as an appealing anti-cancer target. However, HSP90 inhibitors (HSP90i) are characterized by limited clinical utility, primarily due to the resistance acquisition via heat shock response (HSR) induction. Understanding the roles of abundantly expressed cytosolic HSP90 isoforms (α and β) in sustaining malignant cells' growth and the mechanisms of resistance to HSP90i is crucial for exploiting their clinical potential.

Molecular dynamics analysis of superoxide dismutase 1 mutations suggests decoupling between mechanisms underlying ALS onset and progression.

Mutations in the superoxide dismutase 1 () gene are the second most common known cause of ALS. variants express high phenotypic variability and over 200 have been reported in people with ALS. It was previously proposed that variants can be broadly classified in two groups, 'wild-type like' (WTL) and 'metal binding region' (MBR) variants, based on their structural location and biophysical properties.

VariantSurvival: a tool to identify genotype-treatment response.

For a number of neurological diseases, such as Alzheimer's disease, amyotrophic lateral sclerosis, and many others, certain genes are known to be involved in the disease mechanism. A common question is whether a structural variant in any such gene may be related to drug response in clinical trials and how this relationship can contribute to the lifecycle of drug development. To this end, we introduce VariantSurvival, a tool that identifies changes in survival relative to structural variants within target genes.

SOD1-ALS-Browser: a web-utility for investigating the clinical phenotype in amyotrophic lateral sclerosis.

Variants in the superoxide dismutase () gene are among the most common genetic causes of amyotrophic lateral sclerosis. Reflecting the wide spectrum of putatively deleterious variants that have been reported to date, it has become clear that -linked ALS presents a highly variable age at symptom onset and disease duration. Here we describe an open access web tool for comparative phenotype analysis in ALS: https://sod1-als-browser.

Utility of line-field confocal optical coherence tomography in the pediatric population.

Background: In the last decades diagnosis of dermatological diseases has achieved a significant progress with the aid of imaging technologies. In pediatric population dermatologic procedural investigations require special considerations, skill sets, and knowledge. Avoiding unnecessary invasive procedures in children is highly recommended to reduce psychological disturbance and cosmetical scars.

DNAscan2: a versatile, scalable, and user-friendly analysis pipeline for human next-generation sequencing data.

Summary: The current widespread adoption of next-generation sequencing (NGS) in all branches of basic research and clinical genetics fields means that users with highly variable informatics skills, computing facilities and application purposes need to process, analyse, and interpret NGS data. In this landscape, versatility, scalability, and user-friendliness are key characteristics for an NGS analysis software. We developed DNAscan2, a highly flexible, end-to-end pipeline for the analysis of NGS data, which (i) can be used for the detection of multiple variant types, including SNVs, small indels, transposable elements, short tandem repeats, and other large structural variants; (ii) covers all standard steps of NGS analysis, from quality control of raw data and genome alignment to variant calling, annotation, and generation of reports for the interpretation and prioritization of results; (iii) is highly adaptable as it can be deployed and run via either a graphic user interface for non-bioinformaticians and a command line tool for personal computer usage; (iv) is scalable as it can be executed in parallel as a Snakemake workflow, and; (v) is computationally efficient by minimizing RAM and CPU time requirements.

Glioblastoma: A Retrospective Analysis of the Role of the Maximal Surgical Resection on Overall Survival and Progression Free Survival.

Background: Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults; despite advances in the understanding of GBM pathogenesis, significant achievements in treating this disease are still lacking. The aim of this study was to evaluate the prognostic significance of the extent of surgical resection (EOR), beyond the neoplastic mass, on the overall survival (OS).

Methods: A retrospective review of a single-institution glioblastoma patient database (January 2012-September 2021) was undertaken.

Large-scale analyses of CAV1 and CAV2 suggest their expression is higher in post-mortem ALS brain tissue and affects survival.

Caveolin-1 and Caveolin-2 (CAV1 and CAV2) are proteins associated with intercellular neurotrophic signalling. There is converging evidence that CAV1 and CAV2 (CAV1/2) genes have a role in amyotrophic lateral sclerosis (ALS). Disease-associated variants have been identified within CAV1/2 enhancers, which reduce gene expression and lead to disruption of membrane lipid rafts.

Managing Ventriculoperitoneal Shunt Exposure in Adult Patients: Surgical Options and Implant Removal Prevention.

Background: Ventriculoperitoneal (VP) shunt exposure is rare. Small series reporting on managing this complication mainly focus on the pediatric population, where wound breaks over cerebrospinal fluid (CSF) chambers are observed most frequently. However, case series on adult patients are missing.