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Obtaining a histological fingerprint from the in-vivo brain has been a long-standing target of magnetic resonance imaging (MRI). In particular, non-invasive imaging of iron and myelin, which are involved in normal brain functions and are histopathological hallmarks in neurodegenerative diseases, has practical utilities in neuroscience and medicine. Here, we propose a biophysical model that describes the individual contribution of paramagnetic (e.g., iron) and diamagnetic (e.g., myelin) susceptibility sources to the frequency shift and transverse relaxation of MRI signals. Using this model, we develop a method, χ-separation, that generates the voxel-wise distributions of the two sources. The method is validated using computer simulation and phantom experiments, and applied to ex-vivo and in-vivo brains. The results delineate the well-known histological features of iron and myelin in the specimen, healthy volunteers, and multiple sclerosis patients. This new technology may serve as a practical tool for exploring the microstructural information of the brain. [Display omitted]

Objectives: Recent case reports and series have shown that patients with neuromyelitis optica (NMO) experience clinical deterioration under interferon beta (IFN-β) treatment. The objective of the present study was to evaluate whether and to what extent IFN-β exacerbates NMO spectrum disorders (NMOSD). Methods: We retrospectively reviewed the medical records of 40 patients with NMOSD who had been treated with IFN-β for more than 6 months and whose disease duration was more than 1 year at the initiation of IFN-β treatment. We evaluated their annualized relapse rates (ARR) and Expanded Disability Status Scale (EDSS) scores before and after IFN-β treatment. Results: In total, 95% of patients exhibited an ineffective or exacerbated response to IFN-β treatment and the mean ARR significantly increased after IFN-β treatment (p = 0.002). The increased ARR > 50% under IFN-β treatment was observed in 20 patients (50%). The mean EDSS score significantly increased following IFN-β treatment (p < 0.001). Conclusion: In patients with NMOSD, IFN-β treatment is not only ineffective for preventing relapses but also may even increase relapses significantly. Thus, a more careful diagnostic approach to differentiate NMO from multiple sclerosis and attention to decision of treatment is warranted for patients at high risk of NMO.

We evaluated the association between hyponatremia and tuberculous meningitis (TBM) with the aim of providing additional information for differential diagnosis from other types of infectious meningitis, especially viral meningitis (VM). Cross-sectional and longitudinal data involving 5026 participants older than 18 years were analyzed in the total population and a propensity-matched population. The initial and lowest sodium levels and longitudinal changes in TBM, bacterial meningitis (BM), and VM patients were compared. Participants in the TBM group were enrolled when they were diagnosed as possible, probable, or definite TBM according to the Marais’ criteria. The initial serum sodium level was significantly lower in TBM patients than in BM and VM patients (136.9 ± 5.9 vs. 138.3 ± 4.7 mmol/L, p  < 0.001 for TBM vs. BM, and 139.0 ± 3.1, p  < 0.001 for TBM vs. VM), and it decreased significantly more steeply to lower levels in both the TBM and BM patients compared with VM patients. The lowest serum sodium level was in the order of TBM < BM < VM patients, and the change was statistically significant in all subgroups (131.8 ± 6.4, 133.1 ± 5.1, 137.4 ± 3.7, respectively, p  < 0.001). Participants with lower serum sodium level were more likely to have a diagnosis of TBM rather than VM, and this association was more pronounced for the lowest sodium level than the initial sodium level [OR 4.6 (95% CI 2.4–8.8, p  < 0.001)]. These findings indicate that baseline and longitudinal evaluation of serum sodium level can provide information for differential diagnosis of TBM from BM or VM.

In this study, various round-shaped ribs-round, double round, and point round-were proposed, and their heat transfer and pressure loss performances were experimentally compared with conventional orthogonal rib. The heat transfer coefficient (HTC) was measured using the transient liquid crystal technique, and the effects of ribbed channel configuration on flow field were analyzed using a commercial software. Results showed that the round-shaped ribbed channels showed up to a 16 % increase in the Nusselt number (Nu) ratio compared to the orthogonal ribbed channel. Despite the higher pressure loss, the round ribbed channel exhibited superior heat transfer, resulting in a thermal performance factor (TP) surpassing the orthogonal ribbed channel. The double round ribbed channel, on the other hand, indicated comparable TP with the orthogonal ribbed channel. The point round ribbed channel, benefiting from its low pressure loss, also achieved a higher TP than that of the orthogonal ribbed channel.

Reduced expression of the RNA helicase DDX5 associated with increased hepatocellular carcinoma (HCC) tumor grade and poor patient survival following treatment with sorafenib. While immunotherapy is the first-line treatment for HCC, sorafenib and other multi-tyrosine kinase inhibitors (mTKIs) are widely used when immunotherapy is contra-indicated or fails. Herein, we elucidate the role of DDX5 in sensitizing HCC to sorafenib, offering new therapeutic strategies. Treatment of various human HCC cell lines with sorafenib/mTKIs downregulated DDX5 in vitro and in preclinical HCC models. Conversely, DDX5 overexpression reduced the viability of sorafenib-treated cells via ferroptosis, suggesting a role for DDX5 in sorafenib sensitivity. RNAseq of wild-type vs . DDX5-knockdown cells treated with or without sorafenib identified a set of common genes repressed by DDX5 and upregulated by sorafenib. This set significantly overlaps with Wnt signaling genes, including Disheveled-1 (DVL1) , an indispensable Wnt activator and prognostic indicator of poor survival for sorafenib-treated patients. DDX5-knockout (DDX5 KO ) HCC cells exhibited DVL1 induction, Wnt/β-catenin pathway activation, and ferroptosis upon inhibition of canonical Wnt signaling. Consistently, xenograft HCC tumors exhibited reduced growth by inhibition of Wnt/β-catenin signaling via induction of ferroptosis. Significantly, overexpression of DDX5 in HCC xenografts repressed DVL1 expression and increased ferroptosis, resulting in reduced tumor growth by sorafenib. We conclude that DDX5 downregulation by sorafenib mediates adaptive resistance by activating Wnt/β-catenin signaling, leading to ferroptosis escape. Conversely, overexpression of DDX5 in vivo enhances the anti-tumor efficacy of sorafenib by suppressing Wnt/β-catenin activation and induction of ferroptosis. Thus, DDX5 overexpression in combination with mTKIs is a promising therapeutic strategy for HCC.

This study aimed to evaluate the incidence and likelihood of antibiotic-associated encephalopathy (AAE), comparing rates among the classes of antibiotics in monotherapy or in combination therapy. We also investigated the associations between the incidence of AAE and the glomerular filtration rate (GFR) and electroencephalogram features. Consecutive admissions that used any kind of antibiotics to treat infectious diseases were identified from six hospitals. We classified antibiotics according to three distinct pathophysiologic mechanisms and clinical subtypes. We searched for the incidence of AAE as the primary outcome. A total of 97,433 admission cases among 56,038 patients was identified. Cases that received type 1 antibiotics had significantly more frequent AAE compared to those that received type 2 antibiotics (adjusted odds ratio [OR], 2.62; 95% confidence interval [CI] 1.15–5.95; P  = 0.021). Combined use of type 1 + 2 antibiotics was associated with a significantly higher incidence of AAE compared to the use of type 2 antibiotics alone (adjusted OR, 3.44; 95% CI 1.49–7.93; P  = 0.004). Groups with GFR < 60 mL/min/1.73 m 2 had significantly higher incidence rates of AAE compared to those with GFRs ≥ 90 mL/min/1.73 m 2 among cases that received type 1 + 2 antibiotics. Detection of spike-and-wave or sharp-and-wave patterns on electroencephalogram was significantly more common in the combination therapy group. Combination use of antibiotics was associated with a higher incidence of AAE compared to monotherapy. The incidence of AAE significantly increased as renal function decreased, and epileptiform discharges were more likely to be detected in cases receiving combined antibiotics.

Purpose: Patients with epilepsy frequently experience autonomic dysfunction, closely related to sudden unexplained death in epilepsy (SUDEP). SUDEP occurs most often at night or during sleep, and frequent nocturnal seizures are an established risk factor. This study investigated the influence of nocturnal seizures on autonomic dysfunction in epilepsy. Patients and Methods: This retrospective study enrolled frontal lobe epilepsy (FLE) patients who performed 24-hour EEG monitoring. All participants were divided into nocturnal FLE (NFLE, > 90% of seizures occurring during sleep) or diurnal FLE (DFLE) groups. EEG and ECG signals were simultaneously obtained during waking and sleep stages. EEG current density source and connectivity analysis of the autonomic network were performed. ECG was analyzed across time and frequency domains heart rate variability (HRV) analysis method was used. The obtained parameters were compared between the NFLE and DFLE groups. Results: Fifteen NFLE and 16 DFLE patients were enrolled with no significant difference in age, sex, disease duration, seizure frequency, or the number of anti-seizure medications between the two groups. During sleep, a decrease in HRV parameters and an increase of the beta-1 (13-22 Hz) current source density power in the bilateral paracentral lobule (BA4,5,6), precuneus (BA7), and cingulate (BA31) were observed in the NFLE group compared to DFLE group. The NFLE group also showed hyperconnectivity in the central autonomic (12 edges distributed over 10 nodes), sympathetic (2 edges distributed over 3 nodes), and parasympathetic (4 edges distributed over 6 nodes) beta-1 frequency band networks during sleep. During wakefulness, central and cardiac autonomic variables were not significantly different between the NFLE and DFLE groups. Conclusion: Interictal cardiac and central autonomic dysfunction occurred simultaneously and can be attributed to the brain-heart autonomic axis. Our findings suggest that nocturnal seizures may contribute to interictal autonomic dysfunction during sleep in people with epilepsy. Keywords: nocturnal seizure, heart rate variability, central autonomic network, sleep, autonomic dysfunction

In advanced hepatocellular carcinoma (HCC), RNA helicase DDX5 regulates the Wnt/β-catenin-ferroptosis axis, influencing the efficacy of the multi-tyrosine kinase inhibitor (mTKI) sorafenib. DDX5 inhibits Wnt/β-catenin signaling, preventing sorafenib-induced ferroptosis escape. Sorafenib/mTKIs reduce DDX5 expression, correlating with poor patient survival post-sorafenib treatment. Notably, DDX5-knockout in HCC cells activates Wnt/β-catenin signaling persistently. Herein, we investigate the mechanistic impact of Wnt/β-catenin activation resulting from DDX5 downregulation in the progression and treatment of HCC. RNAseq analyses identified shared genes repressed by DDX5 and upregulated by sorafenib, including Wnt signaling genes, NF-κB-inducing kinase ( NIK) essential for non-canonical NF-κB (p52/RelB) activation, and cytoprotective transcription factor NRF2 . We demonstrate, Wnt/β-catenin activation induced NIK transcription, leading to non-canonical NF-κB activation, which subsequently mediated NRF2 transcription. Additionally, DDX5 deficiency extended NRF2 protein half-life by inactivating KEAP1 through p62/SQSTM1 stabilization. In a preclinical HCC mouse model, NRF2 knockdown or DDX5 overexpression restricted tumor growth upon sorafenib treatment, via induction of ferroptosis. Importantly, DDX5-knockout HCC cells exhibited elevated expression of Wnt signaling genes, NIK, p52/RelB , and NRF2-regulated genes, regardless of sorafenib treatment. Transcriptomic analyses of HCCs from TCGA and the Stelic Animal Model (STAM) of non-alcoholic steatohepatitis revealed elevated expression of these interconnected pathways in the context of DDX5 downregulation. In conclusion, DDX5 deficiency triggers Wnt/β-catenin signaling, promoting p52/RelB and NRF2 activation, thereby enabling ferroptosis evasion upon sorafenib treatment. Similarly, independent of sorafenib, DDX5 deficiency in liver tumors enhances activation and gene expression of these interconnected pathways, underscoring the clinical relevance of DDX5 deficiency in HCC progression and therapeutic response.

Background: Although neuromyelitis optica (NMO) is a central nervous system (CNS) autoimmune disease distinct from multiple sclerosis (MS). NMO and NMO spectrum disorder (NMOSD) sometimes show asymptomatic lesions on brain magnetic resonance imaging (MRI) at onset, and even present with symptomatic brain involvement. Objectives: We investigated whether brain MRI at onset can be helpful for the differentiation of MS and NMOSD. Methods: We retrospectively analyzed initial brain MRIs, performed within three months of onset, in patients with MS (n = 51) and anti-aquaporin4-antibody-positive patients with NMOSD (n = 67). Results: NMOSD patients met the Paty (37%) and Barkhof (13%) criteria, and the criteria of the European Magnetic Imaging in MS (MAGNIMS) study group (9%), for MS. Ovoid lesions perpendicular to the lateral ventricle, isolated juxtacortical lesions in U-fibers and isolated ovoid/round cortical lesions were found only in MS patients, whereas longitudinal corticospinal tract lesions, extensive hemispheric lesions, periependymal lesions surrounding the lateral ventricle and cervicomedullary lesions were found only in NMOSD patients. Conclusions: Our study suggests that it is difficult to differentiate MS from NMOSD by the fulfillment of the MRI criteria for MS on brain MRI at onset; however, the characteristic morphology of brain lesions is highly useful for the early differentiation of the two disorders.