Thalamocortical relationship in epileptic patients with generalized spike and wave discharges — A multimodal neuroimaging study

AbstractUnlike focal or partial epilepsy, which has a confined range of influence, idiopathic generalized epilepsy (IGE) often affects the whole or a larger portion of the brain without obvious, known cause. It is important to understand the underlying network which generates epileptic activity and through which epileptic activity propagates. The aim of the present study was to investigate the thalamocortical relationship using non-invasive imaging modalities in a group of IGE patients. We specifically investigated the roles of the mediodorsal nuclei in the thalami and the medial frontal cortex in generating and spreading IGE activities. We hypothesized that the connectivity between these two structures is key in understanding the generation and propagation of epileptic activity in brains affected by IGE. Using three imaging techniques of EEG, fMRI and EEG-informed fMRI, we identified important players in generation and propagation of generalized spike-and-wave discharges (GSWDs). EEG-informed fMRI suggested multiple regions including the medial frontal area near to the anterior cingulate cortex, mediodorsal nuclei of the thalamus, caudate nucleus among others that related to the GSWDs. The subsequent seed-based fMRI analysis revealed a reciprocal cortical and bi-thalamic functional connection. Through EEG-based Granger Causality analysis using (DTF) and adaptive DTF, within the reciprocal thalamocortical circuitry, thalamus seems to serve as a stronger source in driving cortical activity from initiation to the propagation of a GSWD. Such connectivity change starts before the GSWDs and continues till the end of the slow wave discharge. Thalamus, especially the mediodorsal nuclei, may serve as potential targets for deep brain stimulation to provide more effective treatment options for patients with drug-resistant generalized epilepsy

Spatial distribution and diversity of the heterotrophic flagellates in the Cosmonaut Sea, Antarctic

As predators of bacteria and viruses and as food sources for microzooplankton, heterotrophic flagellates (HFs) play an important role in the marine micro-food web. Based on the global climate change’s impact on marine ecosystems, particularly sea ice melting, we analyzed the community composition and diversity of heterotrophic flagellates, focusing on the Antarctic Cosmonaut Sea. During the 36th China Antarctic research expedition (2019-2020), we collected seawater samples, subsequently analyzing HFs through IlluminaMiSeq2000 sequencing to assess community composition and diversity. Notable variations in HFs abundance were observed between the western and eastern sectors of the Cosmonaut Sea, with a distinct concentration at a 100-meter water depth. Different zones exhibited diverse indicators and dominants taxa influenced by local ocean currents. Both the northern Antarctic Peninsula and the western Cosmonaut Sea, where the Weddell Eddy and Antarctic Land Slope Current intersect, showcased marine stramenopiles as dominant HFs species. Our findings offer insights into dominant taxa, spatial distribution patterns among heterotrophic flagellates, correlations between taxa distribution and environmental factors, and the exploration of potential indicator taxa

Analysis of the association between testosterone and cardiovascular disease potential risk factor apolipoprotein B in adult males without cancer: national health and nutrition examination survey 2011-2016

BackgroundOver the years, there has been extensive exploration of the association between testosterone and lipid profiles, yet the precise mechanisms underlying their interaction remain incompletely elucidated. Similarly, there is a dearth of research on the correlation between serum apolipoprotein B (apoB) and serum total testosterone (TT), particularly within specific populations.MethodsWe conducted a cross-sectional study to assess the relationship between serum TT concentration and serum apoB concentration. Using the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016, we employed weighted generalized linear models, weighted univariate, weighted multivariate analysis, and smooth curve fitting to assist in exploring the relationship between serum TT and apoB. Serum apoB concentration served as the independent variable, and serum TT concentration as the dependent variable. ApoB was divided into four quartiles—Q1 (<0.7g/L, N=691), Q2 (≥0.7g/L to <0.9g/L, N=710), Q3 (≥0.9g/L to <1.1g/L, N=696), and Q4 (≥1.1g/L, N=708)—thereby further solidifying the stable association between the two. Additionally, the application of smooth curve fitting will contribute to a more detailed elucidation of the specific relationship between serum TT concentration and serum apoB concentration under different factors (Drinking, Smoke, Diabetes, Hypertension, and High cholesterol level.).ResultsThe results indicate a negative correlation between serum TT concentration and apoB concentration (β=-113.4; 95% CI: -146.6, -80.2; P<0.001). After adjusting for confounding variables, the negative correlation between apoB concentration and TT concentration remains significant (β=-61.0; 95% CI: -116.7, -5.2; P=0.040). When apoB concentration was converted from a continuous variable to a categorical variable (quartiles: Q1<0.7g/L; Q2:≥0.7g/L to<0.9g/L; Q3:≥0.9g/L to <1.1g/L; Q4: ≥1.1g/L), TT level of participants in the highest quartile (≥1.1g/L) was -47.2 pg/mL (95% CI: -91.2, -3.3; P=0.045) lower than that in the lowest quartile (<0.7g/L). The smooth curve fitting diagram revealed differences in the relationship between TT concentration and apoB among individuals with different cardiovascular disease (CVD) risk factors.ConclusionsThis study elucidates a robust inverse correlation between serum TT concentration and apoB concentration, maintaining statistical significance even upon adjustment for confounding factors. These findings present a promising avenue for addressing the prevention and treatment of low testosterone and CVD

Riemannian Surface on Carbon Anodes Enables Li-Ion Storage at −35 °C

Since sluggish Li$^{+}$ desolvation leads to severe capacity degradation of carbon anodes at subzero temperatures, it is urgently desired to modulate electron configurations of surface carbon atoms toward high capacity for Li-ion batteries. Herein, a carbon-based anode material (O-DF) was strategically synthesized to construct the Riemannian surface with a positive curvature, which exhibits a high reversible capacity of 624 mAh g$^{-1}$ with an 85.9% capacity retention at 0.1 A g$^{-1}$ as the temperature drops to −20 °C. Even if the temperature drops to −35 °C, the reversible capacity is still effectively retained at 160 mAh g$^{-1}$ after 200 cycles. Various characterizations and theoretical calculations reveal that the Riemannian surface effectively tunes the low-temperature sluggish Li$^{+}$ desolvation of the interfacial chemistry via locally accumulated charges of non-coplanar sp$^{x}$ (2 < x < 3) hybridized orbitals to reduce the rate-determining step of the energy barrier for the charge-transfer process. Ex-situ measurements further confirm that the sp$^{x}$-hybridized orbitals of the pentagonal defect sites should denote more negative charges to solvated Li$^{+}$ adsorbed on the Riemannian surface to form stronger Li–C coordinate bonds for Li$^{+}$ desolvation, which not only enhances Li-adsorption on the curved surface but also results in more Li$^{+}$ insertion in an extremely cold environment

TWIN: TWo-stage Interest Network for Lifelong User Behavior Modeling in CTR Prediction at Kuaishou

Life-long user behavior modeling, i.e., extracting a user's hidden interests from rich historical behaviors in months or even years, plays a central role in modern CTR prediction systems. Conventional algorithms mostly follow two cascading stages: a simple General Search Unit (GSU) for fast and coarse search over tens of thousands of long-term behaviors and an Exact Search Unit (ESU) for effective Target Attention (TA) over the small number of finalists from GSU. Although efficient, existing algorithms mostly suffer from a crucial limitation: the \textit{inconsistent} target-behavior relevance metrics between GSU and ESU. As a result, their GSU usually misses highly relevant behaviors but retrieves ones considered irrelevant by ESU. In such case, the TA in ESU, no matter how attention is allocated, mostly deviates from the real user interests and thus degrades the overall CTR prediction accuracy. To address such inconsistency, we propose \textbf{TWo-stage Interest Network (TWIN)}, where our Consistency-Preserved GSU (CP-GSU) adopts the identical target-behavior relevance metric as the TA in ESU, making the two stages twins. Specifically, to break TA's computational bottleneck and extend it from ESU to GSU, or namely from behavior length $10^2$ to length $10^4-10^5$, we build a novel attention mechanism by behavior feature splitting. For the video inherent features of a behavior, we calculate their linear projection by efficient pre-computing \& caching strategies. And for the user-item cross features, we compress each into a one-dimentional bias term in the attention score calculation to save the computational cost. The consistency between two stages, together with the effective TA-based relevance metric in CP-GSU, contributes to significant performance gain in CTR prediction.Comment: Accepted by KDD 202

Case report: Successful and effective percutaneous closure of a deep femoral artery pseudoaneurysm using proglide device

A 61-year-old man developed severe swelling in the left lower extremity after interventional embolization of liver tumor. Ultrasound examination showed a pseudoaneurysm and thrombosis in the upper thigh on the left. To recognize the causes and determine the effective therapy, lower extremity arteriography was performed. The results revealed a pseudoaneurysm arised from deep femoral artery. Considering of the size of cavity and symptoms of patient, a new method was tried instead of traditional treatment using PROGLIDE device. Postoperative angiography showed a powerful blocking effect. This case study provide us a specific treatment for pseudoaneurysm, and this method provide us a new therapeutic strategy in clinical practice

Use of gene therapy for optic nerve protection: Current concepts

Gene therapy has become an essential treatment for optic nerve injury (ONI) in recent years, and great strides have been made using animal models. ONI, which is characterized by the loss of retinal ganglion cells (RGCs) and axons, can induce abnormalities in the pupil light reflex, visual field defects, and even vision loss. The eye is a natural organ to target with gene therapy because of its high accessibility and certain immune privilege. As such, numerous gene therapy trials are underway for treating eye diseases such as glaucoma. The aim of this review was to cover research progress made in gene therapy for ONI. Specifically, we focus on the potential of gene therapy to prevent the progression of neurodegenerative diseases and protect both RGCs and axons. We cover the basic information of gene therapy, including the classification of gene therapy, especially focusing on genome editing therapy, and then we introduce common editing tools and vector tools such as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) -Cas9 and adeno-associated virus (AAV). We also summarize the progress made on understanding the roles of brain derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), phosphatase-tensin homolog (PTEN), suppressor of cytokine signal transduction 3 (SOCS3), histone acetyltransferases (HATs), and other important molecules in optic nerve protection. However, gene therapy still has many challenges, such as misalignment and mutations, immunogenicity of AAV, time it takes and economic cost involved, which means that these issues need to be addressed before clinical trials can be considered

Quantitative mapping of genetic similarity in human heritable diseases by shared mutations

Many genetic diseases exhibit considerable epidemiological comorbidity and common symptoms, which provokes debate about the extent of their etiological overlap. The rapid growth in the number of known disease-causing mutations in the Human Gene Mutation Database (HGMD) has allowed us to characterize genetic similarities between diseases by ascertaining the extent to which identical genetic mutations are shared between diseases. Using this approach, we show that 41.6% of disease pairs in all possible pairs (42, 083) exhibit a significant sharing of mutations (P value < 0.05). These mutation-related disease pairs are in agreement with heritability-based disease–disease relations in 48 neurological and psychiatric disease pairs (Spearman's correlation coefficient = 0.50; P value = 3.4 × 10−5), and share over-expressed genes significantly more often than unrelated disease pairs (1.5–1.8-fold higher; P value ≤ 1.6 × 10−4). The usefulness of mutation-related disease pairs was further demonstrated for predicting novel mutations and identifying individuals susceptible to Crohn disease. Moreover, the mutation-based disease network concurs closely with that based on phenotypes

Elevated Serum Growth Differentiation Factor 15 Levels in Hyperthyroid Patients

Background: Recent studies have shown that growth differentiation factor 15 (GDF15), a member of the transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) superfamily, plays an important role in appetite, type 2 diabetes, and cardiovascular diseases. Since thyroid hormone has pleiotropic effects on whole-body energy metabolism, we aimed to explore the effect of thyroid hormone on circulating GDF15 levels in humans and GDF15 genes expression in C57BL/6 mice.Methods: A total of 134 hyperthyroid patients and 105 healthy subjects were recruited. Of them, 43 hyperthyroid patients received thionamide treatment for 3 months until euthyroidism. Serum GDF15 levels were determined using the enzyme-linked immunosorbent assay (ELISA) method. To determine the source for the increased circulating GDF15, C57BL/6 mice were treated with T3, and GDF15 gene expressions in the liver, skeletal muscle, brown adipose tissue (BAT), inguinal white adipose tissue (iWAT), epididymal white adipose tissue (eWAT) were analyzed by quantitative real-time polymerase chain reaction (PCR).Results: Serum GDF15 levels were significantly elevated in hyperthyroid patients as compared with healthy subjects (326.06 ± 124.13 vs. 169.24 ± 82.96 pg/mL; P &lt; 0.001). After thionamide treatment, GDF15 levels in hyperthyroid patients declined markedly from 293.27 ± 119.49 to 118.10 ± 71.83 pg/mL (P &lt; 0.001). After adjustment for potential confounders, serum GDF15 levels were independently associated with hyperthyroidism. T3 treatment increased GDF15 expression in the brown adipose tissue of C57BL/6 mice.Conclusions: Serum GDF15 levels were elevated in patients with hyperthyroidism and declined after thionamide treatment. Thyroid hormone treatment upregulated GDF15 expression in mice. Therefore, our results present the clinical relevance of GDF15 in humans under the condition of hyperthyroidism