Recovering Arrhythmic EEG Transients from Their Stochastic Interference

Traditionally, the neuronal dynamics underlying electroencephalograms (EEG) have been understood as arising from \textit{rhythmic oscillators with varying degrees of synchronization}. This dominant metaphor employs frequency domain EEG analysis to identify the most prominent populations of neuronal current sources in terms of their frequency and spectral power. However, emerging perspectives on EEG highlight its arrhythmic nature, which is primarily inferred from broadband EEG properties like the ubiquitous $1/f$ spectrum. In the present study, we use an \textit{arrhythmic superposition of pulses} as a metaphor to explain the origin of EEG. This conceptualization has a fundamental problem because the interference produced by the superpositions of pulses generates colored Gaussian noise, masking the temporal profile of the generating pulse. We solved this problem by developing a mathematical method involving the derivative of the autocovariance function to recover excellent approximations of the underlying pulses, significantly extending the analysis of this type of stochastic processes. When the method is applied to spontaneous mouse EEG sampled at $5$ kHz during the sleep-wake cycle, specific patterns -- called $\Psi$-patterns -- characterizing NREM sleep, REM sleep, and wakefulness are revealed. $\Psi$-patterns can be understood theoretically as \textit{power density in the time domain} and correspond to combinations of generating pulses at different time scales. Remarkably, we report the first EEG wakefulness-specific feature, which corresponds to an ultra-fast ($\sim 1$ ms) transient component of the observed patterns. By shifting the paradigm of EEG genesis from oscillators to random pulse generators, our theoretical framework pushes the boundaries of traditional Fourier-based EEG analysis, paving the way for new insights into the arrhythmic components of neural dynamics.Comment: Original research manuscript in PDF format, 46 pages long, with 13 figures and one tabl

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

A Study on the Failure Analysis of the Neutron Embrittled Reactor Pressure Vessel Support Using Finite Element Analysis

One of the major degradation mechanisms in a nuclear power plant structural or mechanical component is the neutron embrittlement of the irradiated steel component. High energy neutrons change the microstructure of the steel, so the steel loses its fracture toughness. This neutron embrittlement increases the risk of the brittle fracture. Meanwhile, the reactor pressure vessel support is exposed in low temperature with high neutron irradiation environment which is an unfavorable condition for the fracture failure. In this study, the failure assessment of a reactor pressure vessel support was conducted using the fitness-for-service failure assessment diagram of API 579-1/ASME FFS-1(2016, API) with quantifying the structural margin under the maximum irradiation and extreme load events. Two interrelated studies were conducted. For the first investigation, the current analytical methods were reviewed to estimate the embrittled properties, such as fracture toughness and the yield strength incorporates the low irradiation temperature. The analytical results indicated that the reactor pressure vessel support may experience substantial fracture toughness decrease during the operation near the lower bound of the fracture toughness. A three-dimensional (3D) solid element finite element model was built for the linear stress analysis. Postulated cracks were located in the maximum stress region to compute the stress intensity and the reference stress ratio. Based on the stress result and the estimated physical properties, the structural margin of the reactor pressure vessel support was analyzed in the failure assessment diagram with respect to the types of the cracks, level of the applied load and the level of the neutron influence. The second study explored the structural stress analysis approaches at hot-spot which was found to be key parameter in failure analysis. Depending on the methods to remove the non-linear peak stress and the stress singularities, the accuracy of the failure assessment result varies. As an alternative proposal to evaluate the structural stress in 3D finite element analysis (FEA), the 3D model was divided into two-dimensional (2D) plane models. Five structural stress determination approaches were applied in 2D FEA for a comparison study, the stress linearization, the single point away approach, the stress extrapolation and the stress equilibrium method and the nodal force method. Reconstructing the structural stress in 3D was carried by the 3x3 stress matrix and compared to the 3D FEA results. The difference in 2D FEA structural stress results were eliminated by the constructing the stress in 3D. This study provides the failure assessment analysis of irradiated steel with prediction of the failure modes and safety margin. Through the failure assessment diagram, we could understand the effects of different levels of irradiation and loadings. Also, this study provides an alternative structural stress determination method, dividing the 3D solid element model into two 2D models, using the finite element analysis

Regular Exercise as a Secondary Practical Treatment for Nonalcoholic Fatty Liver Disease

A novel notion has arisen in clinical medicine: non-alcoholic fatty liver disease (NAFLD), representing a spectrum of conditions ranging from asymptomatic simple steatosis to steatohepatitis and cirrhosis. Even though there is a pressing need to treat this disease, the treatment options are limited. Previous studies have confirmed that weight loss via lifestyle management has proven to be successful. This is now accepted as the first-line therapy. In those studies, improvements of liver function and hepatic steatosis were noted when weight loss of around 3% to 10% of body weight was achieved. However, optimum weight loss and its management are difficult to accomplish. Subsequent studies showed that when weight loss was achieved independent of exercise, additional beneficial effects were observed in addition to weight loss. Exercise with a diet regimen brought even more benefits. Because of this substantial evidence, exercise should be proposed as another strategy for NAFLD treatment, regardless of weight loss. This review was aimed at providing a succinct, comprehensive overview of the diagnosis and management of NAFLD, highlighting the need for routinization of the role of exercise in NAFLD management, and at elucidating the mechanisms behind the benefits of exercise, with relevant studies

RNF213 R4810K Variant in Suspected Unilateral Moyamoya Disease Predicts Contralateral Progression

Background Early‐stage unilateral moyamoya disease (MMD) is difficult to discriminate from isolated intracranial atherosclerotic stenosis, and identification of contralateral progression may aid in the diagnosis of MMD. The RNF213 (ring finger protein 213) R4810K variant is a strong genetic susceptibility factor for MMD; however, the role of contralateral progression in unilateral MMD is unknown. Methods and Results Patients who had undergone RNF213 R4810K genotyping with suspected unilateral MMD between January 2017 and August 2021 from 2 tertiary university hospitals were retrospectively reviewed. We compared the clinical features and radiographic outcomes of patients with and without this variant. The risk factors of contralateral progression in patients with suspected unilateral MMD were evaluated. The RNF213 R4810K variant was observed in 72 of 123 patients with suspected unilateral MMD, all of which were heterozygous. The allele frequency of the R4810K variant was significantly higher in the suspected unilateral MMD group compared with the historical control group (29.3% versus 1.2%; P<0.0001). Family history of MMD was significantly more common in patients with the variant than in those without (17% versus 4%; P=0.003). Eleven of 72 patients with the variant developed contralateral progression, whereas only 1 of 51 patients without the variant developed contralateral progression during a median follow‐up period of 28 months (log‐rank test; P=0.03). The presence of the RNF213 R4810K variant significantly correlated with contralateral progression (adjusted odds ratio, 6.39 [95% CI, 1.11–36.63]; P=0.04). Conclusions Contralateral progression is more likely to occur in patients with suspected unilateral MMD with the RNF213 R4810K variant than in those without the variant. However, because our study used a small sample size, this finding should be carefully interpreted and requires further studies with more patients and longer follow‐up periods

Signaling Pathways Regulated by UBR Box-Containing E3 Ligases

UBR box E3 ligases, also called N-recognins, are integral components of the N-degron pathway. Representative N-recognins include UBR1, UBR2, UBR4, and UBR5, and they bind destabilizing N-terminal residues, termed N-degrons. Understanding the molecular bases of their substrate recognition and the biological impact of the clearance of their substrates on cellular signaling pathways can provide valuable insights into the regulation of these pathways. This review provides an overview of the current knowledge of the binding mechanism of UBR box N-recognin/N-degron interactions and their roles in signaling pathways linked to G-protein-coupled receptors, apoptosis, mitochondrial quality control, inflammation, and DNA damage. The targeting of these UBR box N-recognins can provide potential therapies to treat diseases such as cancer and neurodegenerative diseases

Prediction of Insulin Resistance by Modified Triglyceride Glucose Indices in Youth

The triglyceride glucose (TyG) index, derived from a combination of fasting glucose and triglycerides, has been suggested as a useful marker for insulin resistance (IR), in addition to modified TyG indices that combine obesity parameters. This study investigated the association and utility of TyG and modified TyG indices for IR prediction in youth. Based on the Korea National Health and Nutritional Examination Survey, the data of 3728 youth aged 10–19 years were analyzed. Odds ratios (ORs) and 95% confidence intervals (CIs) of tertiles 2 and 3 for each parameter were calculated and compared with tertile 1 as a reference. To compare the parameters for identifying IR, receiver operating characteristic curves were plotted and the area under the curve (AUC) was calculated. The ORs and 95% CIs for insulin resistance (IR) progressively increased across tertiles of each parameter. Overall, all modified TyG indices presented higher ORs and AUC than the TyG index. The TyG-body mass index standard deviation score showed the largest AUC for IR detection in all subjects. In conclusion, TyG and modified TyG indices could be used as valuable markers for the prediction of IR in youth. Moreover, modified TyG indices had better diagnostic accuracy than the TyG index

B. longum CKD1 enhances the efficacy of anti-diabetic medicines through upregulation of IL- 22 response in type 2 diabetic mice

ABSTRACTThe gut microbiota plays a pivotal role in metabolic disorders, notably type 2 diabetes mellitus (T2DM). In this study, we investigated the synergistic potential of combining the effects of Bifidobacterium longum NBM7–1 (CKD1) with anti-diabetic medicines, LobeglitazoneⓇ (LO), SitagliptinⓇ (SI), and MetforminⓇ (Met), to alleviate hyperglycemia in a diabetic mouse model. CKD1 effectively mitigated insulin resistance, hepatic steatosis, and enhanced pancreatic β-cell function, as well as fortifying gut-tight junction integrity. In the same way, SI-CKD1 and Met- CKD1 synergistically improved insulin sensitivity and prevented hepatic steatosis, as evidenced by the modulation of key genes associated with insulin signaling, β-oxidation, gluconeogenesis, adipogenesis, and inflammation by qRT-PCR. The comprehensive impact on modulating gut microbiota composition was observed, particularly when combined with MetforminⓇ. This combination induced an increase in the abundance of Rikenellaceae and Alistipes related negatively to the T2DM incidence while reducing the causative species of Cryptosporangium, Staphylococcaceae, and Muribaculaceae. These alterations intervene in gut microbiota metabolites to modulate the level of butyrate, indole-3-acetic acid, propionate, and inflammatory cytokines and to activate the IL-22 pathway. However, it is meaningful that the combination of B. longum NBM7–1(CKD1) reduced the medicines’ dose to the level of the maximal inhibitory concentrations (IC50). This study advances our understanding of the intricate relationship between gut microbiota and metabolic disorders. We expect this study to contribute to developing a prospective therapeutic strategy modulating the gut microbiota

Comparison of the Modified TyG Indices and Other Parameters to Predict Non-Alcoholic Fatty Liver Disease in Youth

We investigated the modified triglycerides-glucose (TyG) indices and other markers for non-alcoholic fatty liver disease (NAFLD) in 225 participants aged 10–19 years, and the participants were divided into subgroups according to their NAFLD grade. We performed logistic regression analysis and calculated the odds ratios (ORs) with 95% confidence intervals (CIs) of tertiles 2 and 3 for each parameter, with those of tertile 1 as a reference. The area under the receiver operating characteristic (ROC) curve was calculated to compare the parameters for identifying NAFLD. TyG and modified indices, aspartate transaminase-to-platelet ratio index (APRI)-body mass index (BMI), APRI-BMI standard deviation score (SDS), APRI waist-to-hip ratio, fibrosis-4 index (FIB)-4, and hepatic steatosis index (HSI) were higher in participants with NAFLD than in those without NAFLD. The ORs and 95% CIs for NAFLD progressively increased across tertiles of each parameter. TyG and modified TyG indices, FIB-4, HSI, and modified APRIs, except APRI waist-to-height ratio, predicted NAFLD significantly through ROC curves. Modified TyG indices, APRI-BMI SDS, and HSI were superior to the other markers for NAFLD prediction. Modified TyG indices, APRI-BMI SDS, and HSI appear to be useful for assessing NAFLD in youths