Identification of four biotypes in temporal lobe epilepsy via machine learning on brain images.

Artificial intelligence provides an opportunity to try to redefine disease subtypes based on similar pathobiology. Using a machine-learning algorithm (Subtype and Stage Inference) with cross-sectional MRI from 296 individuals with focal epilepsy originating from the temporal lobe (TLE) and 91 healthy controls, we show phenotypic heterogeneity in the pathophysiological progression of TLE. This study was registered in the Chinese Clinical Trials Registry (number: ChiCTR2200062562). We identify two hippocampus-predominant phenotypes, characterized by atrophy beginning in the left or right hippocampus; a third cortex-predominant phenotype, characterized by hippocampus atrophy after the neocortex; and a fourth phenotype without atrophy but amygdala enlargement. These four subtypes are replicated in the independent validation cohort (109 individuals). These subtypes show differences in neuroanatomical signature, disease progression and epilepsy characteristics. Five-year follow-up observations of these individuals reveal differential seizure outcomes among subtypes, indicating that specific subtypes may benefit from temporal surgery or pharmacological treatment. These findings suggest a diverse pathobiological basis underlying focal epilepsy that potentially yields to stratification and prognostication - a necessary step for precise medicine.

Analysis of Amplitude Modulation of EEG Based on Holo-Hilbert Spectrum Analysis During General Anesthesia.

OBJECTIVE: The study aims to investigate the relationship between amplitude modulation (AM) of EEG and anesthesia depth during general anesthesia. METHODS: In this study, Holo-Hilbert spectrum analysis (HHSA) was used to decompose the multichannel EEG signals of 15 patients to obtain the spatial distribution of AM in the brain. Subsequently, HHSA was applied to the prefrontal EEG (Fp1) obtained during general anesthesia surgery in 15 and 34 patients, and the α-θ and α-δ regions of feature (ROFs) were defined in Holo-Hilbert spectrum (HHS) and three features were derived to quantify AM in ROFs. RESULTS: During anesthetized phase, an anteriorization of the spatial distribution of AMs of α-carrier in brain was observed, as well as AMs of α-θ and α-δ in the EEG of Fp1. The total power ([Formula: see text]), mean carrier frequency ([Formula: see text]) and mean amplitude frequency ([Formula: see text]) of AMs changed during different anesthesia states. CONCLUSION: HHSA can effectively analyze the cross-frequency coupling of EEG during anesthesia and the AM features may be applied to anesthesia monitoring. SIGNIFICANCE: The study provides a new perspective for the characterization of brain states during general anesthesia, which is of great significance for exploring new features of anesthesia monitoring.

Study of the Structural Changes and Internal Activator Transport Behavior after Activation of Aluminum-Based Flameless Ration Heaters: Experimental and Molecular Dynamics Simulations.

Aluminum-based flameless ration heaters (AFRHs) are heating elements in food packaging. Water is used to activate AFRHs. The material properties of each region of AFRHs were determined by X-ray diffraction, scanning electron microscopy, and hydrogen and heat generation. The results show that the internal cross-section shows stratification with hydrogen and heat production capacities of 105.2 ± 9.7 mL/g and 1435.0 ± 30.3 J/g for the outer layer, 27.1 ± 4.4 mL/g and 80.4 ± 3.1 J/g for the inner layer, and 1.1 ± 0.01 mL/g and 1.2 ± 0.05 J/g for the middle layer, respectively. According to the correspondence between aluminum and hydrogen in the aluminum-water reaction relationship, the reaction efficiency of the outer layer and the inner layer is as low as 64 and 80%, which is an indication of low reaction efficiency. To analyze the reasons for low reaction efficiency, a pore channel model of 3.5 nm tricalcium aluminate (C3A) was developed using molecular dynamics (MD) to reveal the adsorption behavior of the activator in the pore channel. The results show that the activator is subject to solid surface adsorption in the pore channel with a low diffusion coefficient. Oxygen atoms on the surface adsorb hydrogen atoms to form hydrogen bonds and sodium ions to form ionic bonds with calcium ions. This increases the retention time of the activator on the surface. The MD results explain the low reaction efficiency of AFRHs at the microscopic scale. Moreover, it provides ideas and a basis for the optimization of AFRHs.

Excitatory somatostatin interneurons in the dentate gyrus drive a widespread seizure network in cortical dysplasia.

Seizures due to cortical dysplasia are notorious for their poor prognosis even with medications and surgery, likely due to the widespread seizure network. Previous studies have primarily focused on the disruption of dysplastic lesions, rather than remote regions such as the hippocampus. Here, we first quantified the epileptogenicity of the hippocampus in patients with late-stage cortical dysplasia. We further investigated the cellular substrates leading to the epileptic hippocampus, using multiscale tools including calcium imaging, optogenetics, immunohistochemistry and electrophysiology. For the first time, we revealed the role of hippocampal somatostatin-positive interneurons in cortical dysplasia-related seizures. Somatostatin-positive were recruited during cortical dysplasia-related seizures. Interestingly, optogenetic studies suggested that somatostatin-positive interneurons paradoxically facilitated seizure generalization. By contrast, parvalbumin-positive interneurons retained an inhibitory role as in controls. Electrophysiological recordings and immunohistochemical studies revealed glutamate-mediated excitatory transmission from somatostatin-positive interneurons in the dentate gyrus. Taken together, our study reveals a novel role of excitatory somatostatin-positive neurons in the seizure network and brings new insights into the cellular basis of cortical dysplasia.

The Recretohalophyte Tamarix TrSOS1 Gene Confers Enhanced Salt Tolerance to Transgenic Hairy Root Composite Cotton Seedlings Exhibiting Virus-Induced Gene Silencing of GhSOS1.

The salt overly sensitive 1 (SOS1) gene encodes the plasma membrane Na+/H+ antiporter, SOS1, that is mainly responsible for extruding Na+ from the cytoplasm and reducing the Na+ content in plants under salt stress and is considered a vital determinant in conferring salt tolerance to the plant. However, studies on the salt tolerance function of the TrSOS1 gene of recretohalophytes, such as Tamarix, are limited. In this work, the effects of salt stress on cotton seedlings transformed with tobacco-rattle-virus-based virus-induced gene silencing (VIGS) of the endogenous GhSOS1 gene, or Agrobacterium rhizogenes strain K599-mediated TrSOS1-transgenic hairy root composite cotton plants exhibiting VIGS of GhSOS1 were first investigated. Then, with Arabidopsis thaliana AtSOS1 as a reference, differences in the complementation effect of TrSOS1 or GhSOS1 in a yeast mutant were compared under salt treatment. Results showed that compared to empty-vector-transformed plants, GhSOS1-VIGS-transformed cotton plants were more sensitive to salt stress and had reduced growth, insufficient root vigor, and increased Na+ content and Na+/K+ ratio in roots, stems, and leaves. Overexpression of TrSOS1 enhanced the salt tolerance of hairy root composite cotton seedlings exhibiting GhSOS1-VIGS by maintaining higher root vigor and leaf relative water content (RWC), and lower Na+ content and Na+/K+ ratio in roots, stems, and leaves. Transformations of TrSOS1, GhSOS1, or AtSOS1 into yeast NHA1 (Na+/H+ antiporter 1) mutant reduced cellular Na+ content and Na+/K+ ratio, increased K+ level under salt stress, and had good growth complementation in saline conditions. In particular, the ability of TrSOS1 or GhSOS1 to complement the yeast mutant was better than that of AtSOS1. This may indicate that TrSOS1 is an effective substitute and confers enhanced salt tolerance to transgenic hairy root composite cotton seedlings, and even the SOS1 gene from salt-tolerant Tamarix or cotton may have higher efficiency than salt-sensitive Arabidopsis in regulating Na+ efflux, maintaining Na+ and K+ homeostasis, and therefore contributing to stronger salt tolerance.

Clinical characteristics, treatments, and outcomes of patients with anti-N-methyl-d-aspartate receptor encephalitis: A systematic review of reported cases.

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a recently recognized autoimmune disorder which is responsive to immunotherapy. However, the outcomes of different immunotherapies have not been defined and there have been few studies that carried out a comparison among them. To provide an overview of the clinical characteristics, treatments, and outcomes of anti-NMDAR encephalitis, we systematically reviewed the literature in the PubMed, Medline, Embase, Cochrane Library, BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), and Wan-fang databases. Eighty-three studies with a total of 432 patients were included. The median age was 22years. Two hundred ninety-three (68%) patients were female, 87 (21%) of 412 patients had a tumor, including 68 (78%) patients with ovarian teratoma. Pediatric patients had a higher ratio of seizures to psychiatric symptoms as the initial manifestation (p=0.0012), a lower proportion with a tumor (p<0.0001) and CSF pleocytosis (p=0.0163), and a better outcome (p=0.0064) than adults. Patients who died had a higher proportion of CSF pleocytosis than the patients who survived (p=0.0021). There were no significant differences among three first-line immunotherapy used alone (p=0.9172) or among combinations of every two of them (p=0.3059). With regard to the use of corticosteroid and IVIG, there were no significant differences between the outcomes of early combined treatment and sequential treatment (p=0.7277), or between using corticosteroid first and IVIG first (p=0.5422). Our findings suggest that the clinical characteristics and outcomes for pediatric patients were different from adult patients, and no significant differences were found among different immunotherapies.

Fabrication of selenium-deposited and chitosan-coated titania nanotubes with anticancer and antibacterial properties.

To exploit titanium materials with anticancer and antibacterial properties, TiO(2) nanotubes arrays as nanoreservoirs for deposition of selenium were generated onto titanium substrates and then covered with chitosan layer. The deposition of selenium in TiO(2) nanotubes was performed with electrodeposition. The physical properties (surface morphologies, chemical compositions and wettability) of the substrates were characterized by field-emission scanning electron microscopy (FE-SEM) equipped with energy dispersive X-ray spectroscopy (EDS) and contact angle measurement, respectively. The growth behaviors of both healthy osteoblasts and cancerous osteoblasts on the substrates were investigated in vitro. The selenium-deposited and chitosan-coated TiO(2) nanotubes substrates (TiO(2) nanotubes-Se-Chi) demonstrated great potential for promoting the proliferation of healthy osteoblasts and inhibiting the growth of cancerous osteoblasts. Meanwhile, the TiO(2) nanotubes-Se-Chi substrates displayed a sustained release of selenium for 21 days. The antibacterial properties of the prepared substrates were evaluated with Escherichia coli (E. coli). The result showed that TiO(2) nanotubes-Se-Chi substrates had long term antibacterial capacity. The approach in this study provides an alternative to fabricate anticancer and antibacterial titanium-based implants for potential clinical application.

Etiologic features of newly diagnosed epilepsy: hospital-based study of 892 consecutive patients in West China.

PURPOSE: We evaluated data from a large cohort of newly diagnosed epilepsy patients from the biggest epilepsy center in West China. The aim was to determine the most prevalent etiologic factors in this region. METHODS: From May 2008 to May 2010, the clinical data of patients with newly diagnosed epilepsy were consecutively, systematically and prospectively recorded in a database. The data were analyzed according to sex, age, seizure type, etiology, and other factors. RESULTS: The present study examined 892 patients with newly diagnosed epilepsy. Among these patients, 346 (38.8%) were confirmed as symptomatic, with the largest constituent ratio among the elderly (63.2%). In this symptomatic group, central nervous system (CNS) infections and traumatic brain injuries (TBI) were the two most common etiologies. When analyzed according to age bracket, cortical dysplasia, mesial temporal sclerosis, and CNS infection were the most frequent causes among young patients (<18 years). On the other hand, CNS infection and TBI were the two most common causes in patients between 18 and 60 years. Stroke was the most common cause of newly diagnosed symptomatic epilepsy in the elderly (>60 years). CONCLUSIONS: More than 30% of newly diagnosed epilepsy cases were shown to be symptomatic by medical history as well as careful clinical and laboratory examination. Detailed epilepsy assessments are essential to formulate a therapeutic plan and to improve prognosis. The etiology spectrum found in this large cohort forms a comparative baseline for future studies.