Epileptic Seizure Detection Based on Path Signature and Bi-LSTM Network With Attention Mechanism.

Automatic seizure detection using electroen-cephalogram (EEG) can significantly expedite the diagnosis of epilepsy, thereby facilitating prompt treatment and reducing the risk of future seizures and associated complications. While most existing EEG-based epilepsy detection studies employ deep learning models, they often ignore the chronological relationships between different EEG channels. To tackle this limitation, a novel automatic epilepsy detection method is proposed, which leverages path signature and Bidirectional Long Short-Term Memory (Bi-LSTM) neural network with an attention mechanism. The path signature algorithm is used to extract discriminative features for capturing the dynamic dependencies between different channels of EEG, while Bi-LSTM with attention further analyzes the inherent temporal dependencies hidden in EEG signal features. Our method is evaluated on two public EEG databases with different sizes (CHB-MIT and TUEP) and a private database from a local hospital. Two experimental settings are used, i.e., five-fold cross-validation and leave-one-out cross-validation. Experimental results show that our method achieves 99.09%, 95.60%, and 99.87% average accuracies on CHB-MIT, TUEP with 250Hz, and TUEP with 256Hz, respectively. On the private dataset, our method also achieves 99.40% average accuracy, which outperforms other methods. Furthermore, our method exhibits robustness in patients, as demonstrated by the evaluation results of cross-patient experiments.

Super resolution label-free dark-field microscopy by deep learning.

Dark-field microscopy (DFM) is a powerful label-free and high-contrast imaging technique due to its ability to reveal features of transparent specimens with inhomogeneities. However, owing to the Abbe's diffraction limit, fine structures at sub-wavelength scale are difficult to resolve. In this work, we report a single image super resolution DFM scheme using a convolutional neural network (CNN). A U-net based CNN is trained with a dataset which is numerically simulated based on the forward physical model of the DFM. The forward physical model described by the parameters of the imaging setup connects the object ground truths and dark field images. With the trained network, we demonstrate super resolution dark field imaging of various test samples with twice resolution improvement. Our technique illustrates a promising deep learning approach to double the resolution of DFM without any hardware modification.

Soil health benefits associated with urban horticulture.

As the global population grows and is increasingly concentrated in urban environments, the quality of urban horticultural soils is of mounting importance. Until now, most urban horticultural soil assessments have been applied in nations and continents outside North America, and none have been conducted in Canada-an important agricultural region. Here, we present the first Canadian study to evaluate soil health in urban horticultural soil (gardens producing fruit and vegetables), benchmarked against conventional agricultural soil in surrounding rural areas (producing cereals, oilseeds, and legumes). We assessed a range of soil health indicators (total C, soil organic C [SOC], active C, CO2 evolution, wet aggregate stability [WAS], total N, autoclave citrate extractable [ACE] protein, potentially mineralizable N [PMN], and N2O production), soil fertility indicators (inorganic N, available P, and available K), and inherent soil properties (texture, electrical conductivity [EC], and pH). We found that carbon- and nitrogen-based soil attributes in urban horticultural soils were 200 % that of the agricultural soils, indicating superior soil health-which had significant implications for interpreting soil health scores. As for soil fertility, inorganic N and available K did not differ between the two systems, but available P was 400 % higher in urban horticulture than agriculture soils, indicating that management practices which build soil health might risk also building excessive soil P levels. Our findings suggest that urban horticulture soils may provide superior ecosystem services and function as a reservoir for SOC, likely due to the soil health management practices implemented by gardeners-but care should be taken to manage soil health alongside managing soil fertility. Urban horticulture soil is an ideal platform for expanding research and governance not only for food production but for valuable ecosystem services.

Global calibration for non-targeted fraud detection in quinoa flour using portable hyperspectral imaging and chemometrics.

Quinoa is one of the highest nutritious grains, and global consumption of quinoa flour has increased as people pay more attention to health. Due to its high value, quinoa flour is susceptible to adulteration. Cross-contamination between quinoa flour and other flour can be easily neglected due to their highly similar appearance. Therefore, detecting adulteration in quinoa flour is important to consumers, industries, and regulatory agencies. In this study, portable hyperspectral imaging in the visible near-infrared (VNIR) spectral range (400-1000 nm) was applied as a rapid tool to detect adulteration in quinoa flour. Quinoa flour was adulterated with wheat, rice, soybean, and corn in the range of 0-98% with 2% increments. Partial least squares regression (PLSR) models were developed, and the best model for detecting the % authentic flour (quinoa) was obtained by the raw spectral data with R2p of 0.99, RMSEP of 3.08%, RPD of 8.77, and RER of 25.32. The model was improved, by selecting only 13 wavelengths using bootstrapping soft shrinkage (BOSS), to R2p of 0.99, RMSEP of 2.93%, RPD of 9.18, and RER of 26.60. A visualization map was also generated to predict the level of quinoa in the adulterated samples. The results of this study demonstrate the ability of VNIR hyperspectral imaging for adulteration detection in quinoa flour as an alternative to the complicated traditional method.

BCOR variants are associated with X-linked recessive partial epilepsy.

OBJECTIVE: BCOR gene, encoding a corepressor of BCL6, plays an important role in fetal development. BCOR mutations were previously associated with oculofaciocardiodental syndrome (OFCD or MCOPS2, OMIM# 300166). The BCOR protein is ubiquitously expressed in multiple areas, including the brain. However, the role of BCOR in neurological disorder remains elusive. METHODS: Trios-based whole-exome sequencing was performed in a cohort of 323 cases with partial epilepsy without acquired causes. RESULTS: Seven hemizygous missense BCOR variants, including c 0.103 G>C/p.Asp35His, c.1079 A>G/p.His360Arg, c 0.1097 C>T/p.Thr366Ile, c 0.3301 C>T/p.Pro1101Ser, c 0.3391 C>T/p.Arg1131Trp, c 0.4199 G>A/p.Arg1400Gln, and c 0.5254 G>A/p.Asp1752Asn, were identified in seven cases with partial epilepsy. Two patients presented partial seizures with generalized seizures and/or generalized discharges. One case showed cortical dysplasia in the right temporal-occipital area on MRI. Two cases presented mild developmental delay. However, all patients achieved seizure-free. The frequency of BCOR variants in the present cohort was significantly higher than that in the controls of healthy Chinese volunteers and all populations of Genome Aggregation Database (gnomAD). Computational modeling, including hydrogen bond and prediction of protein stability, implied that the variants lead to structural impairment. Previously, OFCD associated BCOR mutations were mostly destructive mutations in an X-linked dominant (XLD) pattern; in contrast, the BCOR variants identified in this study were all missense variants, which were associated with partial epilepsy in an X-linked recessive (XLR) pattern. The proportion of missense mutations in epilepsy was significantly higher than that in OFCD. CONCLUSIONS: BCOR was potentially a candidate pathogenic gene of partial epilepsy with or without developmental delay. The genotype-phenotype correlation helps understanding the mechanism underlying phenotypic variation.

Fourier Optical Spin Splitting Microscopy.

In this Letter, we propose a new quantitative phase imaging methodology named Fourier optical spin splitting microscopy (FOSSM). FOSSM relies on a metasurface located at the Fourier plane of a polarized microscope to separate the object image into two replicas of opposite circularly polarized states. The bias retardation between the two replicas is tuned by translating the metasurface or rotating the analyzer. Combined with a polarized camera, FOSSM can easily achieve single-shot quantitative phase gradient imaging, which greatly reduces the complexity of current phase microscope setups, paving the way for the next generation high-speed real-time multifunctional microscopy.

The twisting elevator mechanism of glutamate transporters reveals the structural basis for the dual transport-channel functions.

Glutamate transporters facilitate the removal of this excitatory neurotransmitter from the synapse. Increasing evidence indicates that this process is linked to intrinsic chloride channel activity that is thermodynamically uncoupled from substrate transport. A recent cryo-EM structure of GltPh - an archaeal homolog of the glutamate transporters - in an open channel state has shed light on the structural basis for channel opening formed at the interface of two domains within the transporter which is gated by two clusters of hydrophobic residues. These transporters cycle through several conformational states during the transport process, including the chloride conducting state, which appears to be stabilised by protein-membrane interactions and membrane deformation. Several point mutations that perturb the chloride conductance can have detrimental effects and are linked to the pathogenesis of the neurological disorder, episodic ataxia type 6.

Microscopic Characterization of the Chloride Permeation Pathway in the Human Excitatory Amino Acid Transporter 1 (EAAT1).

Excitatory amino acid transporters (EAATs) are glutamate transporters that belong to the solute carrier 1A (SLC1A) family. They couple glutamate transport to the cotransport of three sodium (Na+) ions and one proton (H+) and the counter-transport of one potassium (K+) ion. In addition to this coupled transport, binding of cotransported species to EAATs activates a thermodynamically uncoupled chloride (Cl-) conductance. Structures of SLC1A family members have revealed that these transporters use a twisting elevator mechanism of transport, where a mobile transport domain carries substrate and coupled ions across the membrane, while a static scaffold domain anchors the transporter in the membrane. We recently demonstrated that the uncoupled Cl- conductance is activated by the formation of an aqueous pore at the domain interface during the transport cycle in archaeal GltPh. However, a pathway for the uncoupled Cl- conductance has not been reported for the EAATs, and it is unclear if such a pathway is conserved. Here, we employ all-atom molecular dynamics (MD) simulations combined with enhanced sampling, free-energy calculations, and experimental mutagenesis to approximate large-scale conformational changes during the transport process and identified a Cl--conducting conformation in human EAAT1 (hEAAT1). Sampling the large-scale structural transitions in hEAAT1 allowed us to capture an intermediate conformation formed during the transport cycle with a continuous aqueous pore at the domain interface. The free-energy calculations performed for the conduction of Cl- and Na+ ions through the captured conformation highlight the presence of two hydrophobic gates that control low-barrier movement of Cl- through the aqueous pathway. Overall, our findings provide insights into the mechanism by which a human neurotransmitter transporter supports functional duality of active transport and passive Cl- permeation and confirm the commonality of this mechanism in different members of the SLC1A family.

Ataxia-linked SLC1A3 mutations alter EAAT1 chloride channel activity and glial regulation of CNS function.

Glutamate is the predominant excitatory neurotransmitter in the mammalian central nervous system (CNS). Excitatory amino acid transporters (EAATs) regulate extracellular glutamate by transporting it into cells, mostly glia, to terminate neurotransmission and to avoid neurotoxicity. EAATs are also chloride (Cl-) channels, but the physiological role of Cl- conductance through EAATs is poorly understood. Mutations of human EAAT1 (hEAAT1) have been identified in patients with episodic ataxia type 6 (EA6). One mutation showed increased Cl- channel activity and decreased glutamate transport, but the relative contributions of each function of hEAAT1 to mechanisms underlying the pathology of EA6 remain unclear. Here we investigated the effects of 5 additional EA6-related mutations on hEAAT1 function in Xenopus laevis oocytes, and on CNS function in a Drosophila melanogaster model of locomotor behavior. Our results indicate that mutations resulting in decreased hEAAT1 Cl- channel activity but with functional glutamate transport can also contribute to the pathology of EA6, highlighting the importance of Cl- homeostasis in glial cells for proper CNS function. We also identified what we believe is a novel mechanism involving an ectopic sodium (Na+) leak conductance in glial cells. Together, these results strongly support the idea that EA6 is primarily an ion channelopathy of CNS glia.

Two-dimensional optical spatial differentiation and high-contrast imaging.

Optical analog signal processing technology has been widely studied and applied in a variety of science and engineering fields, with the advantages of overcoming the low-speed and high-power consumption associated with its digital counterparts. Much attention has been given to emerging metasurface technology in the field of optical imaging and processing systems. Here, we demonstrate, for the first time, broadband two-dimensional spatial differentiation and high-contrast edge imaging based on a dielectric metasurface across the whole visible spectrum. This edge detection method works for both intensity and phase objects simply by inserting the metasurface into a commercial optical microscope. This highly efficient metasurface performing a basic optical differentiation operation opens up new opportunities in applications of fast, compactible and power-efficient ultrathin devices for data processing and biological imaging.

CHD4 variants are associated with childhood idiopathic epilepsy with sinus arrhythmia.

AIMS: CHD4 gene, encoding chromodomain helicase DNA-binding protein 4, is a vital gene for fetal development. In this study, we aimed to explore the association between CHD4 variants and idiopathic epilepsy. METHODS: Trios-based whole-exome sequencing was performed in a cohort of 482 patients with childhood idiopathic epilepsy. The Clinical Validity Framework of ClinGen and an evaluating method from five clinical-genetic aspects were used to determine the association between CHD4 variants and epilepsy. RESULTS: Four novel heterozygous missense mutations in CHD4, including two de novo mutations (c.1597A>G/p.K533E and c.4936G>A/p.E1646K) and two inherited mutations with co-segregation (c.856C>G/p.P286A and c.4977C>G/p.D1659E), were identified in four unrelated families with eight individuals affected. Seven affected individuals had sinus arrhythmia. From the molecular sub-regional point of view, the missense mutations located in the central regions from SNF2-like region to DUF1087 domain were associated with multisystem developmental disorders, while idiopathic epilepsy-related mutations were outside this region. Strong evidence from ClinGen Clinical Validity Framework and evidences from four of the five clinical-genetic aspects suggested an association between CHD4 variants and epilepsy. CONCLUSIONS: CHD4 was potentially a candidate pathogenic gene of childhood idiopathic epilepsy with arrhythmia. The molecular sub-regional effect of CHD4 mutations helped explaining the mechanisms underlying phenotypic variations.

Glutamate transporters have a chloride channel with two hydrophobic gates.

Glutamate is the most abundant excitatory neurotransmitter in the central nervous system, and its precise control is vital to maintain normal brain function and to prevent excitotoxicity1. The removal of extracellular glutamate is achieved by plasma-membrane-bound transporters, which couple glutamate transport to sodium, potassium and pH gradients using an elevator mechanism2-5. Glutamate transporters also conduct chloride ions by means of a channel-like process that is thermodynamically uncoupled from transport6-8. However, the molecular mechanisms that enable these dual-function transporters to carry out two seemingly contradictory roles are unknown. Here we report the cryo-electron microscopy structure of a glutamate transporter homologue in an open-channel state, which reveals an aqueous cavity that is formed during the glutamate transport cycle. The functional properties of this cavity, combined with molecular dynamics simulations, reveal it to be an aqueous-accessible chloride permeation pathway that is gated by two hydrophobic regions and is conserved across mammalian and archaeal glutamate transporters. Our findings provide insight into the mechanism by which glutamate transporters support their dual function, and add information that will assist in mapping the complete transport cycle shared by the solute carrier 1A transporter family.

Amino Acid Transporters and Exchangers from the SLC1A Family: Structure, Mechanism and Roles in Physiology and Cancer.

The Solute Carrier 1A (SLC1A) family includes two major mammalian transport systems-the alanine serine cysteine transporters (ASCT1-2) and the human glutamate transporters otherwise known as the excitatory amino acid transporters (EAAT1-5). The EAATs play a critical role in maintaining low synaptic concentrations of the major excitatory neurotransmitter glutamate, and hence they have been widely researched over a number of years. More recently, the neutral amino acid exchanger, ASCT2 has garnered attention for its important role in cancer biology and potential as a molecular target for cancer therapy. The nature of this role is still being explored, and several classes of ASCT2 inhibitors have been developed. However none have reached sufficient potency or selectivity for clinical use. Despite their distinct functions in biology, the members of the SLC1A family display structural and functional similarity. Since 2004, available structures of the archaeal homologues GltPh and GltTk have elucidated mechanisms of transport and inhibition common to the family. The recent determination of EAAT1 and ASCT2 structures may be of assistance in future efforts to design efficacious ASCT2 inhibitors. This review will focus on ASCT2, the present state of knowledge on its roles in tumour biology, and how structural biology is being used to progress the development of inhibitors.

Optical edge detection based on high-efficiency dielectric metasurface.

Optical edge detection is a useful method for characterizing boundaries, which is also in the forefront of image processing for object detection. As the field of metamaterials and metasurface is growing fast in an effort to miniaturize optical devices at unprecedented scales, experimental realization of optical edge detection with metamaterials remains a challenge and lags behind theoretical proposals. Here, we propose a mechanism of edge detection based on a Pancharatnam-Berry-phase metasurface. We experimentally demonstrated broadband edge detection using designed dielectric metasurfaces with high optical efficiency. The metasurfaces were fabricated by scanning a focused laser beam inside glass substrate and can be easily integrated with traditional optical components. The proposed edge-detection mechanism may find important applications in image processing, high-contrast microscopy, and real-time object detection on compact optical platforms such as mobile phones and smart cameras.

Derivation of a Prediction Rule for Unfavorable Outcome after Ischemic Stroke in the Chinese Population.

BACKGROUND: Efficient assessment of patients after ischemic stroke has important reference value for doctors to choose appropriate treatment for patients. Our study aimed to develop a new prognostic model for predicting outcomes 3 months after ischemic stroke among Chinese Population. METHODS: A prospective observational cohort study among ischemic stroke patients presenting to Emergency Department in the Second Affiliated Hospital of Guangzhou Medical University was conducted from May 2012 to June 2013. Demographic data of ischemic stroke patients, assessment of NIHSS and laboratory results were collected. Based on 3-month modified Rankin Scale (mRS) ischemic stroke patients were divided into either favorable outcome (mRS: 0-2) or unfavorable outcome groups (mRS: 3-6). The variables closely associated with prognosis of ischemic stroke were selected to develop the new prognostic model (NAAP) consisted of 4 parameters: NIHSS, age, atrial fibrillation, and prealbumin. The prognostic value of the modified prognostic model was then compared with NIHSS alone. RESULTS: A total of 454 patients with suspected stroke were recruited. One hundred eighty-six patients with ischemic stroke were included in the final analysis. A new prognostic model, NAAP was developed. The area under curve (AUC) of NAAP was .861 (95%confidence interval: .803-.907), whilst the AUC of NIHSS was .783 (95%CI: .717-.840), (P = .0048). Decision curve analysis showed that NAAP had a higher net benefit for threshold probabilities of 65% for predictive risk of poor outcomes. CONCLUSIONS: The modified prognostic model, NAAP may be a better prognostic tool for predicting 3-month unfavorable outcomes for ischemic stroke than NIHSS alone.