Clinicopathological characterization of vacuolar tauopathy associated with VCP D395G.

Introduction: The clinical, radiological, and pathological features have not been well documented for the recently discovered autosomal-dominant vacuolar tauopathy (VT) harboring the Valosin-containing protein (VCP) p.Asp395Gly variant.

Methods: We investigated the clinical, neuropsychological, physiological, laboratory, and radiological data and neuropathological findings in five symptomatic VT cases who met the diagnostic criteria for frontotemporal dementia (FTD).

Charcot-Marie-Tooth-like presentation in giant axonal neuropathy: clinical variability and prevalence in a large Japanese case series.

Background: Giant axonal neuropathy 1 (GAN) is a rare neurodegenerative disorder with autosomal recessive inheritance and significant phenotypic heterogeneity, ranging from milder presentations resembling Charcot-Marie-Tooth disease (CMT) to classical presentations involving central and peripheral nervous systems. We investigated the genetic and clinical spectrum of GAN in Japanese patients with inherited peripheral neuropathies (IPNs).

Methods: We conducted genetic screening of 3315 Japanese patients diagnosed with IPNs between 2007 and 2023 using targeted next-generation or whole-exome sequencing.

Raman Imaging of an Amphotericin B Potentiator in Single-Cell .

Nectriatide, a fungal cyclotetrapeptide, was previously found to enhance the antifungal activity of amphotericin B (AmB), with nectriatide linear derivatives (NLDs) exhibiting even stronger potentiation. Although we showed that NLDs have an affinity for ergosterol , the precise mechanism underlying these interactions within living fungal cells remained elusive. Here, we demonstrate for the first time a label-free, single-cell Raman microspectroscopic imaging approach to visualize how NLD-1 colocalizes with ergosterol in .

Brain biopsy and metagenomic sequencing enhance aetiological diagnosis of encephalitis.

Identifying the aetiology of CNS diseases, regardless of their infectious or non-infectious nature, is often intricate. Next-generation sequencing (NGS) has emerged as a powerful tool for sensitive and unbiased screening of tissue or body fluid specimens. This study aimed to investigate the underlying aetiology of patients with suspected infectious CNS diseases.

Pleiotropic effects of MORC2 derive from its epigenetic signature.

Heterozygous missense mutations in MORC2 have been implicated in various clinical entities, ranging from early-onset neurodevelopmental disorders to late-onset neuropathies. The mechanism underlying the phenotypic heterogeneity and pleiotropic effects of MORC2 has remained elusive. Here, we analyzed blood and fibroblast DNA methylation, transcriptomes, proteomes, and phenotypes of 53 MORC2 patients.

Visual evoked potential in myelin oligodendrocyte glycoprotein antibody-associated disease.

The visual evoked potential (VEP) patterns of optic neuritis are known to often differ between multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) but have been less reported in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). This study aimed to characterize the VEP pattern in MOGAD and evaluate its utility in distinguishing MOGAD from MS and NMOSD. We retrospectively reviewed the clinical manifestations and VEP findings in patients with MS (n = 29), NMOSD (n = 14), and MOGAD (n = 10).

SOD1-related inherited peripheral neuropathies in a Japanese cohort: genetic variants and clinical insights.

Background: Inherited peripheral neuropathies (IPNs) encompass a wide range of disorders affecting the peripheral nervous system, often with complex genetic causes and frequent underdiagnosis. The variants in the superoxide dismutase 1 (SOD1) gene, primarily linked to amyotrophic lateral sclerosis (ALS), have also been associated with peripheral neuropathy. The recent approval of Tofersen, targeting SOD1-related ALS, highlights the importance of precise genetic diagnosis.

Molecular Fingerprinting of Mouse Brain Using Ultrabroadband Coherent Anti-Stokes Raman Scattering (CARS) Microspectroscopy Empowered by Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS).

The Raman fingerprint spectral region provides abundant structural information on molecules. However, analyzing vibrational images within this region using coherent Raman imaging remains challenging due to the small Raman cross section and congested spectral features. In this study, we combined ultrabroadband coherent anti-Stokes Raman scattering (CARS) microspectroscopy across the spectral range of 500-4000 cm with multivariate curve resolution-alternating least-squares (MCR-ALS) to reveal hidden Raman bands in the fingerprint region.

Raman Hyperspectral Analysis of Microbial Colonies for Secondary Metabolites Screening.

Since the discovery of penicillin, a vast array of microbial antibiotics has been identified and applied in the medical field. Globally, the search for drug candidates microbial screening is ongoing. Traditional screening methods, however, are time-consuming and require labor-intensive sample processing, significantly reducing throughput.

Genetic and pathophysiological insights from autopsied patient with primary familial brain calcification: novel MYORG variants and astrocytic implications.

Primary familial brain calcification (PFBC) is a genetic neurological disorder characterized by symmetric brain calcifications that manifest with variable neurological symptoms. This study aimed to explore the genetic basis of PFBC and elucidate the underlying pathophysiological mechanisms. Six patients from four pedigrees with brain calcification were enrolled.

Tolerability and efficacy of switching anti-fibrotic treatment from nintedanib to pirfenidone for idiopathic pulmonary fibrosis.

Background: In real-world studies, the rate of discontinuation of nintedanib (NT) varies from 4% to 53%. Switching anti-fibrotic treatment in patients with idiopathic pulmonary fibrosis (IPF) has not been adequately investigated, and data on the tolerability and efficacy of changes in anti-fibrotic treatment is limited in clinical practice.

Objective: To identify factors associated with poor continuation of NT, efficacy and predictors of deterioration after switching from NT to pirfenidone (PFD) in patients with IPF.

A novel homozygous HPDL variant in Japanese siblings with autosomal recessive hereditary spastic paraplegia: case report and literature review.

Biallelic variants of 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) gene have been linked to neurodegenerative disorders ranging from severe neonatal encephalopathy to early-onset spastic paraplegia. We identified a novel homozygous variant, c.340G > T (p.

CANVAS-related RFC1 mutations in patients with immune-mediated neuropathy.

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) has recently been attributed to biallelic repeat expansions in RFC1. More recently, the disease entity has expanded to atypical phenotypes, including chronic neuropathy without cerebellar ataxia or vestibular areflexia. Very recently, RFC1 expansions were found in patients with Sjögren syndrome who had neuropathy that did not respond to immunotherapy.

Dystonia and Parkinsonism in COA7-related disorders: expanding the phenotypic spectrum.

Background And Objective: Biallelic mutations in the COA7 gene have been associated with spinocerebellar ataxia with axonal neuropathy type 3 (SCAN3), and a notable clinical diversity has been observed. We aim to identify the genetic and phenotypic spectrum of COA7-related disorders.

Methods: We conducted comprehensive genetic analyses on the COA7 gene within a large group of Japanese patients clinically diagnosed with inherited peripheral neuropathy or cerebellar ataxia.

Microbleed clustering in thalamus sign in CADASIL patients with R75P mutation.

Background And Objective: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral microvascular disease characterized by the development of vascular dementia and lacunar infarctions. This study aimed to identify the genetic and clinical features of CADASIL in Japan.

Methods: We conducted genetic analysis on a case series of patients clinically diagnosed with CADASIL.

[Involvement of autonomic nervous system since middle age in elderly patient with giant axonal neuropathy caused by novel genetic mutation].

A 69-year-old man began to experience difficulty with walking at the age of 5 years and started use of a cane at around 13 years, then finally started using a wheelchair at 17 years old. A diagnosis of Charcot-Marie-Tooth disease was previously determined at another hospital, though neither peripheral nerve biopsy nor gene analysis was conducted. He visited our institution at the age of 54 years and irregular outpatient examinations were started, which indicated slowly progressive muscle weakness and sensory disturbance of the limbs, leading to a decline in activities of daily living.

Siblings with Cockayne Syndrome B Type III Presenting with Slowly Progressive Cerebellar Ataxia.

Two patients, 48- and 50-year-old sisters, presented with a characteristic facial appearance with slowly progressive deafness and cerebellar ataxia starting in their 30s. Genetic testing identified compound heterozygous pathogenic variants in the ERCC6 gene: c.1583G>A (p.

Single-Cell Level Raman Molecular Profiling Reveals the Classification of Growth Phases of .

Harmful algal blooms (HABs) are a natural phenomenon caused by outbreaks of algae, resulting in serious problems for aquatic ecosystems and the coastal environment. () is one of the diatoms responsible for HABs. The growth curve of can be observed from beginning to end of HABs: therefore, detailed analysis is necessary to characterize each growth phase of .

White spot syndrome virus (WSSV) modulates lipid metabolism in white shrimp.

In addition to the Warburg effect, which increases the availability of energy and biosynthetic building blocks in WSSV-infected shrimp, WSSV also induces both lipolysis at the viral genome replication stage (12 hpi) to provide material and energy for the virus replication, and lipogenesis at the viral late stage (24 hpi) to complete virus morphogenesis by supplying particular species of long-chain fatty acids (LCFAs). Here, we further show that WSSV causes a reduction in lipid droplets (LDs) in hemocytes at the viral genome replication stage, and an increase in LDs in the nuclei of WSSV-infected hemocytes at the viral late stage. In the hepatopancreas, lipolysis is triggered by WSSV infection, and this leads to fatty acids being released into the hemolymph.

Successful baricitinib treatment of refractory anti-synthetase syndrome associated with interstitial lung disease.

A 47-year-old Japanese man was admitted with dyspnoea on exertion (DOE), skin rash and myalgia. Clinical findings of Gottron's sign and mechanic's hands were observed, with increased serum levels of Krebs von den Lungen-6, surfactant protein-D, creatine kinase, and anti-EJ on laboratory tests. In both lungs, chest computed tomography revealed diffuse reticular opacities and lower lobe predominance.