Real-Time Epileptic Seizure Detection Based on Deep Learning.

Epilepsy is one of the most common neurological diseases, and video EEG is the most commonly used examination method for epilepsy diagnosis. However, since the video EEG examination lasts for hours, the escort has a heavy burden, and the large amount of video EEG data needs to be visually checked by the doctor. The real-time detection of epileptic seizures can reduce the stress of the escort and provide a mark for the doctor to check the EEG efficiently. In this paper, we propose a deep neural network with specified signal representation for real-time seizure detection and add a smoothing filter on the model output to enhance performance. First, we compare the performance of real-time epileptic seizure detection model under different signal representations. Then we use the best signal representation for further analysis in real-time scenario. In the experiment, the EEG data of 9 patients in the CHB-MIT public data set was used, and a patient-specific neural network was trained for each individual. The recall was 97%, the false alarm was 0.219 times per hour, and the latency time was 3.4s for real-time seizure event detection. The results show that this method can realize the real-time detection of epileptic seizures, which is of great significance to the subsequent system design combined with actual scenes.

The carbon reduction effect of "Going Global" strategy: an empirical perspective on the carbon emission efficiency of OFDI in China.

Under the constraints of the "dual-carbon" objectives, how China can sustain economic development while concurrently achieving carbon emission reduction has become a pressing issue. With the rapid expansion of China's outward foreign direct investment (OFDI), elucidating its impact on carbon emission efficiency (CEE) assumes pronounced significance. Employing the systematic generalized method of moments (GMM) approach, based on panel data spanning the years 2006 to 2019 for China, this study primarily delves into the influence of OFDI on China's CEE. Furthermore, it probes into the mechanisms and asymmetries underpinning the relationship between OFDI and CEE. The principal findings are as follows: (1) augmentation of OFDI exerts a constructive effect on domestic carbon emission reduction, concomitantly yielding a discernible enhancement in CEE. A 1% increase in the magnitude of OFDI flow gives rise to a 0.009% improvement in CEE. (2) Mechanism verification reveals that heightened levels of OFDI operate through elevating green total factor productivity (GTFP), fostering optimal industrial structural adjustments, and invigorating green technological innovation, thereby elevating the CEE of the home country. (3) Asymmetry characterizes the impact of OFDI on domestic CEE, signifying a significant enhancement in regions with lower CEE while exhibiting less conspicuous effects in areas with higher CEE. This study furnishes policymakers with insights into leveraging OFDI to enhance CEE, thereby facilitating the attainment of the "dual-carbon" objectives.

Appraising the role of the digital economy in global decarbonization: A spatial non-linear perspective on globalization.

In the context of globalization, the role of the digital economy in carbon emissions may generate spatial spill over effects. This study comprehensively applies a spatial model to understand the nexus between the digital economy and carbon emissions in 67 economies from 2010 to 2019. Specifically, this study contributes by introducing a spatial panel threshold model, which helps to present the new evidence regarding decarbonization process. Empirical findings exemplify that the digital economy remarkably reduces local carbon emissions, with the positive spatial spill over effects being salient. The spatial moderating effect model uncover that globalization positively affects the nexus between the digital economy and carbon emissions. Interestingly, the spatial panel threshold model designates that the digital economy's reduction effect on local carbon emissions will be tightened, whereas the positive spatial spill over effects turn negative only when globalization surpasses a threshold. Our model has the potential to explain some results that traditional models cannot reach.

Unleashing the power of informatization: How does the "information benefiting people" policy affect green total factor productivity?

Information development is a necessary means for China to achieve technology force and an effective path toward sustainable development. Regarding the "information benefiting people" policy led by the Chinese government as a quasi-experiment of information technology, this study builds an analysis framework for the impact of informatization on green total factor productivity (GTFP). Based on panel data at the Chinese city level from 2006 to 2019, this study further empirically evaluates the mechanism path, heterogeneity, and spatial spillover effects between informatization and GTFP by using a difference-in-difference (DID) model, a mediating model, and a spatial DID model. The results show that (1) the information benefiting people policy contributes considerably to greater GTFP levels in the pilot cities; (2) the policy also promotes the rapid growth of GTFP by fostering the advancement of education, the share of the number of ICT employees, and green technology innovation; (3) the information benefiting people policy raises GTFP in the eastern cities, small cities, and non-old industrial based cities; and (4) the policies lead to a large rise in local GTFP levels, but a decline in GTFP in surrounding cities. This paper offers valuable reference suggestions for the Chinese government to implement informatization-policies to support green development.

A Through-Thickness Arrayed Carbon Fibers Elastomer with Horizontal Segregated Magnetic Network for Highly Efficient Thermal Management and Electromagnetic Wave Absorption.

Multifunctional thermal management materials with highly efficient electromagnetic wave (EMW) absorption performance are urgently required to tackle the heat dissipation and electromagnetic interference issues of high integrated electronics. However, the high thermal conductivity (λ) and outstanding EMW absorption performance are often incompatible with each other in a single material. Herein, a through-thickness arrayed NiCo2 O4 /graphene oxide/carbon fibers (NiCO@CFs) elastomer with integrated functionalities of high thermal conductivity, highly efficient EMW absorption, and excellent compressibility is reported. The NiCO@CFs elastomer realizes a high out-of-plane thermal conductivity of 15.55 W m-1  K-1 , due to the through-thickness vertically aligned CFs framework. Moreover, the unique horizontal segregated magnetic network effectively reduces the electrical contact between the CFs, which significantly enhances impedance matching of NiCO@CFs elastomer. As a result, the vertically arrayed NiCO@CFs elastomer synchronously exhibits ultrabroad effective absorption bandwidth of 8.25 GHz (9.75-18 GHz) at a thickness of 2.4 mm, good impedance matching, and a minimum reflection loss (RLmin ) of -55.15 dB. Given these outstanding findings, the multifunctional arrayed NiCO@CFs elastomer opens an avenue for applications in EMW absorption and thermal management. This strategy of constructing thermal/electrical/mechanical pathways provides a promising way for the high-performance multifunctional materials in electronic devices.

Quantifying the impacts of industrial convergence on air pollution: a quasi-experimental analysis of evidence from China's "Triple Play" reform.

Industrial structure change is an important cause of air pollution in China. Regarding the "Triple Play" reform (TPR) led by the Chinese government as a quasi-natural experiment of industrial convergence, this study constructs an analysis framework for the impact of industrial convergence on air pollution. Based on panel data at the Chinese city level from 2004 to 2016, this paper empirically examines the impact of industrial convergence on air pollution by using a difference-in-difference model, the propensity score matching method, and a mediation model. The results show that (1) the TPR significantly alleviates air pollution of cities; (2) the TPR reduces air pollution by improving green technological innovation and industrial structural upgrading; (3) the TPR significantly reduces air pollutants in the southern, coastal, non-resource-based cities and cities with higher technological absorption capacity, but its impact in the northern, inland, resource-based cities and cities with lower technological absorption capacity is not remarkable. This research provides feasible suggestions for the government to promote industrial convergence through deregulation policies and then reduce air pollution.

Giant axonal neuropathy (GAN) in an 8-year-old girl caused by a homozygous pathogenic splicing variant in GAN gene.

Giant axonal neuropathy (GAN) is a progressive disease that involves the peripheral and central nervous systems. This neurodegenerative disease is caused by variants in the GAN gene encoding gigaxonin, and is inherited in an autosomal recessive manner. Herein, we performed whole-exome sequencing on a 8-year-old child with dense, curly hair, weakness in both lower limbs, and abnormal MRI. The child was born to consanguineous parents. Our results revealed that the child carried the c.1373+1G>A homozygous pathogenic variant of the GAN gene, while both parents were heterozygous carriers. According to the validation at the cDNA levels, the splicing variant led to the skipping of exon 8 and affected the Kelch domain's formation. Unlike the previously reported cases of GAN, the child's clinical manifestations revealed peripheral nervous system involvement, no vertebral signs, cerebellar signs, and spasticity, but only MRI abnormalities. These results suggested that the patient's central nervous system was mildly involved, which may be related to the genotype. In order to further clarify the correlation between GAN genotype and phenotype, combined with this patient, 54 cases of reported homozygous variants of the GAN gene were merged for the analysis of genotype and phenotype. The results revealed a certain correlation between the GAN gene variant domain and the patient's clinical phenotype, such as central nervous system involvement and age of onset.

Differential Functional Changes of Nav1.2 Channel Causing SCN2A-Related Epilepsy and Status Epilepticus During Slow Sleep.

Background: Nav1.2 encoded by the SCN2A gene is a brain-expressed voltage-gated sodium channel known to be associated with neurodevelopment disorders ranging from benign familial neonatal infantile seizures (BFIS) to developmental and epileptic encephalopathy (DEE) and autism spectrum disorder. Interestingly, status epilepticus during slow sleep (ESES), which aggravates cognitive impairment, has been found in SCN2A-related epilepsy. However, the functional features and the relationship between SCN2A and ESES have not been researched. Method: We herein investigated the functional consequences of an unpublished de novo V911A and the other two published variants in patients with SCN2A-related disorder and ESES by whole-cell patch-clamp studies in transfected HEK293T cells. Results: The unpublished V911A and published K1933M variants detected in patients with DEE exhibited a profound gain-of-functional (GOF) change. Another published BFIS variant S863F significantly reduced current density as a loss-of-functional (LOF) change. The refractory epilepsy in the patient with V911A was controlled by using the precise treatment of oxcarbazepine (OXC) since the age of 3 months. ESES was found at 18 months during the seizure-free period. We finally chose an aggressive treatment for eliminating ESES by using methylprednisolone combined with levetiracetam and nitrazepam instead of the precise treatment of OXC. Conclusion: Both GOF and LOF variants in the SCN2A gene can lead to ESES among the phenotypes of DEE and BFIS. We should monitor the electroencephalogram regularly in the patients with SCN2A-related epilepsy even during their seizure-free period.

Establishment of an induced pluripotent stem cell line (ZJSHi001-A) from a patient with epileptic encephalopathy carrying KCNB1 Glu330Asp mutation.

Early infantile epileptic encephalopathy 26 (EE26) is a form of epileptic encephalopathy, a heterogeneous group of severe childhood-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. A recent study has shown that the KCNB1 gene mutation is associated with EE26; yet, the exact mechanism remains unclear. In this study, we produced an induced pluripotent stem cell line (iPSC) with a heterozygous variant of the KCNB1 gene (c.990G > T, p.Glu330Asp). Induced iPSCs were generated from peripheral blood mononuclear cells (PBMCs) obtained from a female child aged 6 with KCNB1 gene c. 990G > T and p.Glu330Asp heterozygous mutation.

Decoupling and decomposition analysis of investments and CO2 emissions in information and communication technology sector.

Organization of Economic Cooperation and Development (OECD) economies are facing a substantial increase in the information and communication technology (ICT) investments in the context of rapid spread of the Coronavirus Disease-2019 (COVID-2019) pandemic and constraints of emissions reduction. However, the mechanism of the impact of ICT investments on carbon dioxide is still unclear. Therefore, by employing the decoupling-factor model and Generalized Divisia Index Method, we explore the decoupling states of ICT investments and emission intensity, and the driving factors of ICT investments' scale, intensity, structure, and efficiency effects on carbon emissions in 20 OECD economies between 2000 and 2018. The results indicate that the number of economies with an ideal state of strong decoupling rose to nine between 2009 and 2018 compared to no economies between 2000 and 2009. The emission intensity of ICT investments contributes to a significant increase of carbon emissions, and the structure and efficiency of ICT investments always restrain the growth of carbon emissions. Significant emissions changes caused by the driving factors are shown in many economies before and after the crisis, reflecting the differences in the strategic choices of ICT investments and the impact on emissions due to the crisis such as the COVID-2019 pandemic. And policy implications for energy and carbon dioxide mitigation strategies in the post-COVID-2019 era are also provided.

Electrophysiological features: The next precise step for SCN2A developmental epileptic encephalopathy.

BACKGROUND: To investigate the relationships among phenotypes, genotypes, and funotypes of SCN2A-related developmental epileptic encephalopathy (DEE). METHODS: We enrolled five DEE patients with five de novo variants of the SCN2A. Functional analysis and pharmacological features of Nav1.2 channel protein expressed in HEK293T cells were characterized by whole-cell patch-clamp recording. RESULTS: The phenotypes of c.4712T>C(p. I1571T), c.2995G>A(p.E999K), and c.4015A>G(p. N1339D) variants showed similar characteristics, including early seizure onset with severe to profound intellectual disability. Electrophysiological recordings revealed a hyperpolarizing shift in the voltage dependence of the activation curve and smaller recovery time constants of fast-inactivation than in wild type, indicating a prominent gain of function (GOF). Moreover, pharmacological electrophysiology showed that phenytoin inhibited over a 70% peak current and was more effective than oxcarbazepine and carbamazepine. In contrast, c.4972C>T (p.P1658S) and c.5317G>A (p.A1773T) led to loss of function (LOF) changes, showing reduced current density and enhanced fast inactivation. Both showed seizure onset after 3 months of age with moderate development delay. Interestingly, we discovered that choreoathetosis was a specific phenotype feature. CONCLUSION: These findings provided the insights into the phenotype-genotype-funotype relationships of SCN2A-related DEE. The preliminary evaluation using the distinct hints of GOF and LOF helped plan the treatment, and the next precise step should be electrophysiological study.

Autosomal dominant hereditary spastic paraplegia caused by mutation of UBAP1.

Hereditary spastic paraplegias (HSP) are a group of rare neurodegenerative diseases characterized by progressive spastic paraparesis. UBAP1 was recently found to induce a rare type of HSP (SPG80). We identified a family with eight inherited spastic paraplegic patients carrying a novel heterozygous mutation c.279delG (p.S94Vfs*9) of UBAP1. We demonstrated a lack of functional UBAP1 in these patients, resulting in the neurological disorder caused by interceptions of the ESCRT pathway. Extending from the older onset-age identified from this family, we found that comparing with the European and other populations, Asian patients displayed less proportion of severe patients and an older average age at onset. The origins of SPG80 patients associated with both their onset age and their disease severity, while the age at onset was not correlated with the disease severity.

[Correlation of phosphorylated S6 protein expression in blood and brain tissue in mice and rats with kainic acid-induced seizure].

OBJECTIVE: To determine the correlation of phosphorylated ribosomal S6 protein (P-S6) content in blood and brain tissue in mice and rats with seizure. METHODS: Seizure models were induced by intraperitoric injection of kainic acid (KA) in C57BL/mice and SD rats. Flow cytometry was used to detect the content of P-S6 in blood; Western blot was used to detect the expression of P-S6 in brain tissues. The correlation between P-S6 expression in blood and in brain tissue was examine by Pearson analysis, and the correlation between P-S6 expression in blood and the severity of seizure was also observed. RESULTS: Western blotting analysis showed that the expression of P-S6 was significantly increased in peripheral blood and brain tissue in mice 1 h after KA-induced seizure,and the expression levels increased to (1.49±0.45) times (P<0.05) and (2.55±0.66) times (P <0.01) of the control group, respectively. Flow cytometry showed that the positive percentage and average fluorescence intensity of P-S6 in the blood of mice increased significantly 1 h after KA-induced seizures (P<0.01), which was consistent with the expression of P-S6 in brain tissue (r=0.8474, P<0.01). Flow cytometry showed that the average fluorescence intensity of P-S6 in blood increased from 14.89±9.75 to 52.35±21.72 (P<0.01) in rats with seizure, which was consistent with the change of P-S6 in brain tissue (r=0.9385, P<0.01). Rats with higher levels of seizure were of higher levels of P-S6 in peripheral blood. CONCLUSIONS: Consistent correlation of P-S6 expression is demonstrated in peripheral blood and in brain tissue after KA-induced seizure, suggesting that the expression of P-S6 in blood can accurately reflect the changes of mTOR signaling pathway in brain tissue.

Comparative study on the influence of final use structure on carbon emissions in the Beijing-Tianjin-Hebei region.

The Beijing-Tianjin-Hebei region's rapid economic development has led to a dramatic increase in its CO2 emissions, which is closely related to various regions' consumption habits and structures. In this paper, the decomposition analysis method based on input and output (IO-SDA) was applied to decompose the CO2 emissions change of the Beijing-Tianjin-Hebei region from 1997 to 2012 into five driving factors: population, carbon emission efficiency, production structure, final use structure and per capita regional GDP, and then the final use structure factor was further analyzed. The results show that: (1) the population and per capita regional GDP promote the CO2 emissions of all regions; Carbon emission efficiency is the biggest offsetting factor; The effect of final use structure changes on the growth of CO2 emissions in Beijing and Hebei remains unchanged. The effect on Tianjin was from 0.7Mt offset to 0.8Mt promotion. (2) Urban household consumption is the most important factor offsetting CO2 emissions in Beijing. Investment and export are the most important final use types for promoting the growth of CO2 emissions in Tianjin and Hebei, with the contribution of 95.78% and 88.09%, respectively. (3) From the sectoral perspective: The construction sector has the greatest impact on the total capital formation of the three regions. In terms of exports, Beijing's tertiary industry has the largest offsetting effect, while Tianjin and Hebei mainly rely on the promotion of metal smelting and other manufacturing industries. Finally, some policy implications for low carbonization are proposed in the Beijing-Tianjin-Hebei region.

Exploring the changes and driving forces of water footprints in China from 2002 to 2012: A perspective of final demand.

Due to economic development and population growth, the water shortage in China has gradually become increasingly severe. In this paper, by developing an environmentally expanded input-output (IO) model, water footprint in China during 2002-2012 is calculated from the perspective of final demand. Furthermore, a structural decomposition analysis (SDA) model is used to study the driving factors of the water footprint of rural and urban household consumption, gross fixed capital formation and exports. The findings indicate that: 1) the water footprint driven by final demand in China increased by 18.3% during 2002-2012, reaching 617.68 billion m3 in 2012, of which urban household consumption accounts for the highest proportion. 2) Of the different sectors, agricultural commodities have the highest water footprint, accounting for 35% of national water footprint in 2012. 3) In terms of the driving factors, water efficiency inhibits the increase of water footprint regardless of final demand types, while GDP per capita makes a great contribution to its rise. 4) As for rural household consumption, the most important driving factor is the inhibition effects of consumption pattern in water footprint. For urban household consumption, the water footprint is inhibited by consumption pattern but promoted by production structure during 2002-2010. However, it is no longer the case during 2010-2012 that consumption pattern becomes a promoting factor, with production structure being inhibiting one. 5) Regarding gross fixed capital formation, its water footprint increase driven by consumption pattern is only 12.4 billion m3 during 2007-2010. As for exports, consumption pattern causes the decline of water footprint after 2005 and the overall water footprint of exports declines during 2007-2012. Finally, this paper provides policy implications with respect to the promotion of China's water footprint conservation.

Genotype and phenotype analysis using an epilepsy-associated gene panel in Chinese pediatric epilepsy patients.

Epilepsy is a common and genetically heterogeneous disorder among children. Advances in next-generation sequencing have revealed that numerous epilepsy genes, helped us improve the understanding of mechanisms underlying epileptogenesis, and guided the development of treatments. We identified 39 candidate variants in 21 genes, including 37 that were pathogenic or likely pathogenic variants according to the American College of Medical Genetics and Genomics scoring system and two variants of uncertain significance that were considered causative after they were associated with clinical characteristics. Thirty were de novo variants (76.9%), and 20 variants had not previously been reported (51.3%). We obtained a diagnosis in 39 of the 141 probands (27.7%). The most frequently mutated gene was SCN1A; KCNQ2, KCNT1, PCDH19, STXBP1, SCN2A, TSC2, and PRRT2 were mutated in more than one individual; ANKRD11, CDKL5, DCX, DEPDC5, GABRB3, GRIN2A, IQSEC2, KCNA2, KCNB1, KCNJ6, TSC1, SCN9A, and SCN1B were mutated in a single individual. In addition, we detected a nonsense variant in a candidate gene KCND1 and considered it as a new candidate epilepsy gene, which needed further functional study. Consequently, large number of unreported variants were detected, diverse phenotypes were associated with known epilepsy genes. Changes in clinical management beyond genetic counseling were suggested.

[Effects of Honokiol on cognitive function in mice with kainic acid-induced epilepsy].

OBJECTIVE: To investigate the effects of Honokiol on cognitive function in mice with epilepsy. METHODS: Kainic acid (38 mg/kg) was intraperitoneally injected in 5 weeks old male ICR mice to induce epilepsy. Honokiol at dose of 3, 10, 30 mg/kg was given to epilepic mice by intraperitoneal injection for 10 days. Fluoro-Jade B staining was used to assess neuronal death; Morris water maze and Y maze tests were used to measure cognitive function such as learning and memory; Western blot was performed to detect the expression of acetylated superoxide dismutase (SOD), microtubule associated protein 1 light chain 3-Ⅱ (LC3-Ⅱ) and P62 in hippocampus tissue; thiobarbituric acid and WST-1 methods were used to detect malondialdehyde (MDA) and SOD. RESULTS: Compared with control group, the levels of acetylated-SOD, MDA, LC3-Ⅱ, P62 and neuronal death increased, cognitive function and SOD decreased in model group (P<0.05 or P<0.01). Honokiol at the dose of 10 mg/kg and 30 mg/kg decreased SOD acetylation, MDA content, expression of LC3-Ⅱ and P62, as well as neuronal death, and the cognitive function was improved (P<0.05 or P<0.01), especially in 30 mg/kg Honokiol group. CONCLUSIONS: Honokiol alleviates oxidative stress and autophagy degradation disorder, decreases neuronal death, and therefore improves cognitive function in epilepsy mice.

A pivotal role of FOS-mediated BECN1/Beclin 1 upregulation in dopamine D2 and D3 receptor agonist-induced autophagy activation.

Autophagy dysfunction is implicated in the pathogenesis of Parkinson disease (PD). BECN1/Beclin 1 acts as a critical regulator of autophagy and other cellular processes; yet, little is known about the function and regulation of BECN1 in PD. In this study, we report that dopamine D2 and D3 receptor (DRD2 and DRD3) activation by pramipexole and quinpirole could enhance BECN1 transcription and promote autophagy activation in several cell lines, including PC12, MES23.5 and differentiated SH-SY5Y cells, and also in tyrosine hydroxylase positive primary midbrain neurons. Moreover, we identified a novel FOS (FBJ murine osteosarcoma viral oncogene homolog) binding sequence (5'-TGCCTCA-3') in the rat and human Becn1/BECN1 promoter and uncovered an essential role of FOS binding in the enhancement of Becn1 transcription in PC12 cells in response to the dopamine agonist(s). In addition, we demonstrated a critical role of intracellular Ca2+ elevation, followed by the enhanced phosphorylation of CAMK4 (calcium/calmodulin-dependent protein kinase IV) and CREB (cAMP responsive element binding protein) in the increases of FOS expression and autophagy activity. More importantly, pramipexole treatment ameliorated the SNCA/α-synuclein accumulation in rotenone-treated PC12 cells that overexpress wild-type or A53T mutant SNCA by promoting autophagy flux. This effect was also demonstrated in the substantia nigra and the striatum of SNCAA53T transgenic mice. The inhibition of SNCA accumulation by pramipexole was attenuated by cotreatment with the DRD2 and DRD3 antagonists and Becn1 siRNAs. Thus, our findings suggest that DRD2 and DRD3 agonist(s) may induce autophagy activation via a BECN1-dependent pathway and have the potential to reduce SNCA accumulation in PD.