ADCY3: the pivotal gene in classical ketogenic diet for the treatment of epilepsy.

Objective: Epilepsy is a common neurological disorder characterized by recurrent epilepsy episodes. As a non-pharmacological treatment, the ketogenic diet has been widely applied in treating epilepsy. However, the exact therapeutic mechanism of the ketogenic diet for epilepsy remains unclear. This study investigates the molecular mechanisms of the ketogenic diet in regulating fatty acid metabolism and activating the ADCY3-initiated cAMP signaling pathway to enhance neuronal inhibition and thereby treat epilepsy. Methods and results: Meta-analysis reveals that the ketogenic diet is superior to the conventional diet in treating epilepsy. Animal experiments demonstrate that the ketogenic diet is more effective than the conventional diet in treating epilepsy, with the best results achieved using the classic ketogenic diet. Transcriptome sequencing analysis identifies six essential genes, among which ADCY3 shows increased expression in the ketogenic diet. In vivo experiments confirm that the activation of the cAMP-PKA signaling pathway by ADCY3 enhances neuronal inhibition and improves epilepsy control. Conclusion: Clinical observations indicate that the ketogenic diet improves patient epilepsy episodes by regulating the ADCY3-initiated cAMP signaling pathway.

Role of inflammatory cytokine in mediating the effect of plasma lipidome on epilepsy: a mediation Mendelian randomization study.

Background: Epilepsy is one of the most prevalent serious brain disorders globally, impacting over 70 million individuals. Observational studies have increasingly recognized the impact of plasma lipidome on epilepsy. However, establishing a direct causal link between plasma lipidome and epilepsy remains elusive due to inherent confounders and the complexities of reverse causality. This study aims to investigate the causal relationship between specific plasma lipidome and epilepsy, along with their intermediary mediators. Methods: We conducted a two-sample Mendelian randomization (MR) and mediation MR analysis to evaluate the causal effects of 179 plasma lipidomes and epilepsy, with a focus on the inflammatory cytokine as a potential mediator based on the genome-wide association study. The primary methodological approach utilized inverse variance weighting, complemented by a range of other estimators. A set of sensitivity analyses, including Cochran's Q test, I 2 statistics, MR-Egger intercept test, MR-PRESSO global test and leave-one-out sensitivity analyses was performed to assess the robustness, heterogeneity and horizontal pleiotropy of results. Results: Our findings revealed a positive correlation between Phosphatidylcholine (18:1_18:1) levels with epilepsy risk (OR = 1.105, 95% CI: 1.036-1.178, p = 0.002). Notably, our mediation MR results propose Tumor necrosis factor ligand superfamily member 12 levels (TNFSF12) as a mediator of the relationship between Phosphatidylcholine (18,1_18:1) levels and epilepsy risk, explaining a mediation proportion of 4.58% [mediation effect: (b = 0.00455, 95% CI: -0.00120-0.01030), Z = 1.552]. Conclusion: Our research confirms a genetic causal relationship between Phosphatidylcholine (18:1_18:1) levels and epilepsy, emphasizing the potential mediating role of TNFSF12 and provide valuable insights for future clinical investigations into epilepsy.

Genetic analysis of 37 cases with primary periodic paralysis in Chinese patients.

BACKGROUND: Primary periodic paralysis (PPP) is an inherited disorders of ion channel dysfunction characterized by recurrent episodes of flaccid muscle weakness, which can classified as hypokalemic (HypoPP), normokalemic (NormoPP), or hyperkalemic (HyperPP) according to the potassium level during the paralytic attacks. However, PPP is charactered by remarkable clinical and genetic heterogeneity, and the diagnosis of suspected patients is based on the characteristic clinical presentation then confirmed by genetic testing. At present, there are only limited cohort studies on PPP in the Chinese population. RESULTS: We included 37 patients with a clinical diagnosis of PPP. Eleven (29.7%) patients were tested using a specific gene panel and 26 (70.3%) by the whole-exome sequencing (WES). Twenty-two cases had a genetic variant identified, representing a diagnostic rate of 59.5% (22/37). All the identified mutations were either in the SCN4A or the CACNA1S gene. The overall detection rate was comparable between the panel (54.5%: 6/11) and WES (61.5%: 16/26). The remaining patients unresolved through panel sequencing were further analyzed by WES, without the detection of any mutation. The novel atypical splicing variant c.2020-5G > A affects the normal splicing of the SCN4A mRNA, which was confirmed by minigene splicing assay. Among 21 patients with HypoPP, 15 patients were classified as HypoPP-2 with SCN4A variants, and 6 HypoPP-1 patients had CACNA1S variants. CONCLUSIONS: Our results suggest that SCN4A alleles are the main cause in our cohort, with the remainder caused by CACNA1S alleles, which are the predominant cause in Europe and the United States. Additionally, this study identified 3 novel SCN4A and 2 novel CACNA1S variants, broadening the mutation spectrum of genes associated with PPP.

EEG microstates in epilepsy with and without cognitive dysfunction: Alteration in intrinsic brain activity.

OBJECTIVE: This study aims to investigate the difference between epilepsy comorbid with and without cognitive dysfunction. METHOD: Participants were classified into patients with epilepsy comorbid cognitive dysfunction (PCCD) and patients with epilepsy without comorbid cognitive dysfunction (nPCCD). Microstate analysis was applied based on 20-channel electroencephalography (EEG) to detect the dynamic changes in the whole brain. The coverage, occurrence per second, duration, and transition probability were calculated. RESULT: The occurrence per second and the coverage of microstate B in the PCCD group were higher than that of the nPCCD group. Coverage in microstate D was lower in the PCCD group than in the nPCCD group. In addition, the PCCD group has a higher probability of A to B and B to A transitions and a lower probability of A to D and D to A transitions. CONCLUSION: Our research scrutinizes the disparities observed within EEG microstates among epilepsy patients both with and without comorbid cognitive dysfunction. SIGNIFICANCE: EEG microstate analysis offers a novel metric for assessing neuropsychiatric disorders and supplies evidence for investigating the mechanisms and the dynamic change of epilepsy comorbid cognitive dysfunction.

Intrinsic brain activity differences in perampanel-responsive and non-responsive drug-resistant epilepsy patients: an EEG microstate analysis.

Background: Drug-resistant epilepsy (DRE) patients exhibit aberrant large-scale brain networks. Perampanel may be a therapeutic option for controlling seizures in these patients. Objective: We aim to explore the differences of resting-state electroencephalogram (EEG) microstate in perampanel-responsive and non-responsive DRE patients. Design: Retrospective study. Methods: Clinical data were collected from DRE patients who received perampanel treatment at the Fujian Medical University Union Hospital from June 2020 to September 2021, with a minimum follow-up of 6 months. Patients were classified into three groups based on the extent of reduction in seizure frequency: non-responsive (seizure reduction <50%), responsive (seizure reduction >50% but not seizure-free), and seizure-free. Resting-state EEG data sets of all participants were subjected to EEG microstate analysis. The study comprehensively compared the mean duration, frequency per second, and temporal coverage of each microstate among the three groups. Results: A total of 76 perampanel-treated DRE patients were categorized into three groups based on their response to treatment: non-responsive (n = 20), responsive (n = 36), and seizure-free (n = 20), according to the degree of seizure frequency reduction. The results of EEG microstate analysis revealed no statistically significant distinctions in frequency, duration, and coverage of microstate D in these DRE patients. However, the seizure-free group showed significantly increased duration and coverage of microstate A, frequency and coverage of microstate B, and significantly decreased duration, frequency, and coverage of microstate C when compared with the other groups. Conclusion: Microstate A, B, and D is associated with the sensorimotor network, visual network, salience network, and attention network, respectively. This study demonstrates statistically significant differences in the sensorimotor, visual, and salience networks, but not in the attention network, between perampanel-responsive and non-responsive DRE patients.

Achieving Bright and Long-Lived Aqueous Room-Temperature Phosphorescence of Carbon Nitrogen Dots Through In Situ Host-Guest Binding.

The development of bright and long-lived aqueous room-temperature phosphorescent (RTP) materials holds paramount importance in broadening the application scope of RTP material system. However, the conventional RTP materials usually exhibit low efficiency and short lifetime in aqueous solution. Herein, an in situ host-guest strategy is proposed to achieve cyanuric acid (CA)-derived phosphorescent carbon nitrogen dots (CNDs) composite (CNDs@CA) that demonstrates a significant enhancement of both quantum yield (QY) and lifetime mediated by water. Detailed investigations reveal that the robust hydrogen bonding networks between CNDs@CA and water effectively stabilize triplet excitons and suppress nonradiative decays, as well as facilitate efficient energy transfer from CA to CNDs, thereby prolonging the lifetime and enhancing the efficiency of RTP. The phosphorescent QY and lifetime of CNDs@CA can be increased to 26.89% (3.9-fold increase) and 951.25 ms (5.5-fold increase), respectively, with the incorporation of 50 wt% water under ambient conditions. Even in fully aqueous environments (with up to 400 wt% water added), CNDs@CA exhibits persistent water-boosted RTP properties, demonstrating exceptional stability. The robust water-boosted RTP property of CNDs@CA in aqueous solutions presents significant potential for high signal-to-noise ratio afterglow bioimaging as well as advanced information encryption.

Pharmacological inhibition of S6K1 rescues synaptic deficits and attenuates seizures and depression in chronic epileptic rats.

BACKGROUND: Recent studies have shown that mTOR signaling plays an important role in synaptic plasticity. However, the function of S6K1, the mechanistic target of rapamycin kinase complex 1 (mTORC1) substrate, in epilepsy remains unknown. AIMS: Our present study aimed to explore the mechanism by which S6K1 is involved in chronic epilepsy. METHODS: First, immunostaining was used to measure neurite length and complexity in kainic acid (KA)-treated primary cultured neurons treated with PF-4708671, a highly selective S6K1 inhibitor. We obtained evidence for the role of S6K1 in protecting and promoting neuronal growth and development in vitro. Next, to explore the function and mechanism of the S6K1 inhibitor in epilepsy, a pilocarpine-induced chronic epileptic rat model was established. In vivo electrophysiology (including local field potentiation in CA1 and long-term potentiation), depression/anxiety-like behavior tests, and Golgi staining were performed to assess seizure behavior, power spectral density, depression/anxiety-like behavior, and synaptic plasticity. Furthermore, western blotting was applied to explore the potential molecular mechanisms. RESULTS: We found that inhibition of S6K1 expression significantly decreased seizures and depression-like behavior and restored power at low frequencies (1-80 Hz), especially in the delta, theta, and alpha bands, in chronic epileptic rats. In addition, PF-4708671 reversed the LTP defect in hippocampal CA3-CA1 and corrected spine loss and dendritic pathology. CONCLUSION: In conclusion, our data suggest that inhibition of S6K1 attenuates seizures and depression in chronic epileptic rats via the rescue of synaptic structural and functional deficits. Given the wide range of physiological functions of mTOR, inhibition of its effective but relatively simple functional downstream molecules is a promising target for the development of drugs for epilepsy.

A nomogram to predict the treatment benefit of perampanel in drug-resistant epilepsy patients.

Objective: The objective of this study was to identify the factors that affect the efficacy of added perampanel for the treatment of drug-resistant epilepsy (DRE), and to develop a reliable nomogram to predict the benefit of this addition. Methods: A retrospective clinical analysis was conducted on DRE patients who received perampanel treatment and who were followed up for at least 6 months from January 2020 and September 2023 at the Epilepsy Center of Fujian Medical University Union Hospital. Data from January 2020 to December 2021 were used as development dataset to build model, while the data from January 2022 to September 2023 were used as validation dataset for internal validation. The predictive factors that affected the efficacy of perampanel as DRE treatment were included in the final multivariate logistic regression model, and a derived nomogram was established. Results: A total of 119 DRE patients who received perampanel treatment were included in this study (development datasets: n = 76; validation data: n = 43). Among them, 72.3% (n = 86) showed a 50% or greater reduction in seizure frequency after perampanel treatment. Of all the parameters of interest, sex, age, history of generalized tonic-clonic seizures, and the number of antiseizure medications were identified as significant predictors for estimating the benefit of adding perampanel for the treatment of DRE. A model incorporating these four variables was developed, and a nomogram was constructed to calculate the probability of benefit of adding perampanel using the model coefficients. The C-index of the predictive model was 0.838, and the validation C-index was 0.756. The goodness-of-fit test showed good calibration of the model (p = 0.920, 0.752 respectively). Conclusion: The proposed nomogram has significant clinical potential for predicting the probability of benefit of perampanel as DRE treatment. This nomogram can be used to identify DRE patients who could benefit from the early addition of perampanel to their treatment regimen.

Effect of Grape Seed Procyanidins Combined with Allicin on Lipid Levels in Hyperlipidemic Rats.

OBJECTIVES: To study the effects of grape seed proanthocyanidins (GSP) combined with allicin on serum lipids level and vascular damage in a rat model of hyperlipidemia. MATERIALS AND METHODS: SD rats(male, 170-220 gn= 40) were randomized into five groups (n = 8/group): modelhigh fat and cholesterol diet; controlnormal diet; model+low-dose (GSP+allicin )(GSP 45mg/kg, allicin 30mg/kg, orally); model+high-dose (GSP+allicin) (GSP180mg/kg, allicin 90mg/kg, orally) and positive control (model+simvastatin (4 mg/kg)). Normal control group was fed conventionally, and remaining four groups were fed high cholesterol and fat food to replicate the high fat model. After 9 weeks, the normal control group continued to receive regular feeding, while the other groups continued to receive high-fat feeding. At the same time, model and normal control groups were given equal volume of physiological saline by gavage, and the other treatment groups began to receive corresponding drugs by gavage once a day. After 4 weeks, serum levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) as well as high-density lipoprotein cholesterol (HDL-C) in rats were determined. And the body weight of rat, total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and malondialdehyde (MDA)in serum were identified. The level of endothelin-1(ET-1) was quantitative analysis by ELISA assay. RESULTS: In comparison to normal controls, the model group displayed a marked rise in body weight, an increment in serum concentrations of LDL-C, TG and TC, as well as a decline in HDL (P<0.01), demonstrating successful model replication; All doses of GSP in combination with allicin resulted in a reduction in TG, LDL-C, and TC and an enhancement in HDL-C in contrast to the model control (all P<0.05). High-dose (GSP+allicin ) decreased MDA, and increased T-AOC and SOD activity(all P<0.01). All doses of GSP combined with allicin decreased ET-1 (all P<0.05). In addition, the protective effect of GSP combined with allicin was dose-dependent. CONCLUSIONS: Studies have shown that GSP combined with allicin can significantly improve blood lipids in hyperlipidemic rats, and this mechanism may be related to antioxidants and reduced endothelial damage.

Spatially Resolved Organic Whispering-Gallery-Mode Hetero-Microrings for High-Security Photonic Barcodes.

Whispering-gallery-mode (WGM) microcavities featuring distinguishable sharp peaks in a broadband exhibit enormous advantages in the field of miniaturized photonic barcodes. However, such kind of barcodes developed hitherto are primarily based on microcavities wherein multiple gain medias were blended into a single matrix, thus resulting in the limited and indistinguishable coding elements. Here, a surface tension assisted heterogeneous assembly strategy is proposed to construct the spatially resolved WGM hetero-microrings with multiple spatial colors along its circular direction. Through precisely regulating the charge-transfer (CT) strength, full-color microrings covering the entire visible range were effectively acquired, which exhibit a series of sharp and recognizable peaks and allow for the effective construction of high-quality photonic barcodes. Notably, the spatially resolved WGM hetero-microrings with multiple coding elements were finally acquired through heterogeneous nucleation and growth controlled by the directional diffusion between the hetero-emulsion droplets, thus remarkably promoting the security strength and coding capacity of the barcodes. The results would be useful to fabricate new types of organic hierarchical hybrid WGM heterostructures for optical information recording and security labels.

Spectral properties and self-reduction of Eu3+ to Eu2+ in aluminosilicate oxyfluoride glass.

Eu-doped aluminosilicate oxyfluoride glass prepared via a melt-quenching method was investigated using X-ray diffraction, absorption spectroscopy, X-ray fluorescence spectrometry, photoluminescence spectroscopy and fluorescence decay curves. We found that the reduction of Eu3+ to Eu2+ ions occurred in the glass prepared in air. The emission spectra showed that the intensity of 4f65d → 4f7 transition of Eu2+ ions varied with increasing incident beam wavelength. Meanwhile, the fluorescence lifetimes of Eu3+: 5D0 → 7F2 monitored at 617 nm in the glass change with the variation of excitation wavelength. The energy transfer between Eu2+ and Eu3+ and the emission mechanisms of Eu2+ ions in the glass were also discussed.

Vertical Phase Regulation with 1,3,5-Tribromobenzene Leads to 18.5% Efficiency Binary Organic Solar Cells.

The sequential deposition method assists the vertical phase distribution in the photoactive layer of organic solar cells, enhancing power conversion efficiencies. With this film coating approach, the morphology of both layers can be fine-tuned with high boiling solvent additives, as frequently applied in one-step casting films. However, introducing liquid additives can compromise the morphological stability of the devices due to the solvent residuals. Herein, 1,3,5-tribromobenzene (TBB) with high volatility and low cost, is used as a solid additive in the acceptor solution and combined thermal annealing to regulate the vertical phase in organic solar cells composed of D18-Cl/L8-BO. Compared to the control cells, the devices treated with TBB and those that underwent additional thermal processing exhibit increased exciton generation rate, charge carrier mobility, charge carrier lifetime, and reduced bimolecular charge recombination. As a result, the TBB-treated organic solar cells achieve a champion power conversion efficiency of 18.5% (18.1% averaged), one of the highest efficiencies in binary organic solar cells with open circuit voltage exceeding 900 mV. This study ascribes the advanced device performance to the gradient-distributed donor-acceptor concentrations in the vertical direction. The findings provide guidelines for optimizing the morphology of the sequentially deposited top layer to achieve high-performance organic solar cells.

[Clinical features and genetic analysis of a child with glycogen storage disease type VI].

OBJECTIVE: To explore the clinical features and genetic etiology of a child with glycogen storage disease VI (GSD-VI). METHODS: Clinical data and laboratory results of the patient were collected. Whole exome sequencing (WES) was carried out for the patient. Candidate variant and its parental origin was verified by Sanger sequencing. RESULTS: The patient was a 3-year-and-9-month old boy whom has featured abdominal distention, hepatomegaly, short stature and elevated hepatic transaminase. WES revealed the he has harbored compound heterozygous variants of the PYGL gene, namely c.697G>A (p.Gly233Ser) and c.320dupA (p.Asn107fs). Sanger sequencing has verified that the two variants have derived from his father and mother, respectively. The c.320dupA (p.Asn107fs) variant was unreported previously. CONCLUSION: The compound heterozygous variants of the PYGL gene probably underlay the GSD-VI in this patient. Above finding has enriched the spectrum of PYGL gene variants and provided a basis for the treatment and genetic counseling.

Coordination-Assistant Chiral Agent Anchoring on Amphiphilic Graphitic Phase Carbon Nitride Membrane for Multiple Molecular Separation.

Membranes composed of two-dimensional (2D) materials suffer from low stability and structural swelling and are usually restricted to applications in aqueous systems. Among various 2D materials, graphitic phase carbon nitride (GCN, g-C3N4) has shown great application potential owing to its structural tunability. Herein, we develop a coordination-assisted strategy to regulate the GCN layer spacing and chemical environment via copper ion (Cu2+) coordination-assisted intercalation of enantiopure (1S,2S)-(-)-1,2-diphenyl-1,2-ethanediamine (DPE) between GCN nanosheets. The obtained GCN-Cu-DPE membrane is continuous and intact, free of cracks and pinholes, stable under acidic and alkaline conditions, and exhibits water permeability above 215 L m-2 h-1 bar-1 and a high rejection rate to dye molecules. The membrane is amphiphilicity and thus allows both polar solvent (water) and nonpolar solvent (hexane) to freely pass through. Remarkably, the permeation rate is proportional to the viscosity of the solvent. Benefiting from the chiral space between nanosheets, the GCN-Cu-DPE membrane shows selective permeation of aspartic acid racemate in aqueous systems and limonene racemate in the organic phase. Our work demonstrates a general and promising strategy for chiral membrane fabrication toward high-value-added chiral separation, especially in the pharmaceutical industry.

[Ultrasonographic manifestation and genetic analysis of a fetus with Stickler syndrome].

OBJECTIVE: To carry out genetic analysis for a family with a fetus manifesting micrognathia and a previous history for fetal micromandibular deformity. METHODS: Systematic ultrasound examination was carried out for the fetus, and the prenatal and postnatal phenotype of the first fetus were retrospectively analyzed. The fetus and his parents were subjected to whole exome sequencing (WES) to identify potential pathogenic variants. Candidate variants were verified by Sanger sequencing. RESULTS: Fetal ultrasound has indicated micrognathia. The first fetus was found to have micrognathia by prenatal ultrasonography and have featured macrosomia and dyspnea due to with tongue retraction, high palatal arch and small mandibular deformity. WES revealed that the fetus has a harbored a c.3G>C (p.Met1?) variant of the COL2A1 gene, which was inherited from the father who had myopia and retinal detachment. CONCLUSION: Stickler syndrome is mainly characterized prenatally by micrognathia, in addition with a variety of postnatal anomalies. The c.3G>C (p.Met1?) variant probably underlay the Stickler syndrome in this pedigree.

Genetic Surveillance of Five SARS-CoV-2 Clinical Samples in Henan Province Using Nanopore Sequencing.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread and poses a major threat to public health worldwide. The whole genome sequencing plays a crucial role in virus surveillance and evolutionary analysis. In this study, five genome sequences of SARS-CoV-2 were obtained from nasopharyngeal swab samples from Zhengzhou, China. Following RNA extraction and cDNA synthesis, multiplex PCR was performed with two primer pools to produce the overlapped amplicons of ~1,200 bp. The viral genomes were obtained with 96% coverage using nanopore sequencing. Forty-five missense nucleotide mutations were identified; out of these, 5 mutations located at Nsp2, Nsp3, Nsp14, and ORF10 genes occurred with a <0.1% frequency in the global dataset. On the basis of mutation profiles, five genomes were clustered into two sublineages (B.1.617.2 and AY.31) or subclades (21A and 21I). The phylogenetic analysis of viral genomes from several regions of China and Myanmar revealed that five patients had different viral transmission chains. Taken together, we established a nanopore sequencing platform for genetic surveillance of SARS-CoV-2 and identified the variants circulating in Zhengzhou during August 2021. Our study provided crucial support for government policymaking and prevention and control of COVID-19.

Photoinduced Rechargeable Lithium-Ion Battery.

Lithium-ion battery (LIB) design is the predominant technology to power portable and mobile electric devices/equipment. Fast charging and self-powering of LIBs are significant but challenging features to be addressed for meeting the fast-paced society and emerging demands. Herein, we report a rational photorechargeable lithium-ion battery (photo-LIB) design using LiV2O5 as a photocathode by directly modifying a commercial LIB without using any additives, which works in both photoassisted fast charging and photo-only charging modes. The photo-LIB attains a high specific capacity of 185 mAh g-1 in as fast as 5 min under illumination, an enhancement of 270% referring to that in dark. Under the photo-only charging mode, the device achieves a highest full-spectrum photo-energy conversion efficiency of 9% so far, demonstrating a highly efficient self-powering mode. We reveal that the improved performance of photo-LIB is due to reversible vanadium intervalence charge transfer and Li+ insertion/deinsertion in LiV2O5 under illumination.

Molecular analysis and novel variation identification of Chinese pedigrees with mucopolysaccharidosis using targeted next-generation sequencing.

BACKGROUND: Mucopolysaccharidosis (MPS) refers to a group of lysosomal storage disorders for which seven types and 11 subtypes are currently recognized. Targeted next-generation sequencing (NGS) offers an important method of disease typing, diagnosis, prenatal diagnosis, and treatment. METHODS: Gene variations in 48 Chinese MPS patients were evaluated using NGS, and the pathogenicity of the DNA alterations was evaluated using PolyPhen2, SIFT, and Mutation Taster. The effect of amino acid substitution on protein structure was also assessed. RESULTS: Four pedigrees with MPS I (8.3%), 28 with MPS II (58.3%), two with MPS IIIA (4.2%), two with MPS IIIB (4.2%), six with MPS IVA (12.5%), one with MPS IVB (2.1%), and five with MPS VI (10.4%) were identified. Of the 69 variations identified, 11 were novel variants (three in IDUA, five in IDS, and three in GALNS), all of which were predicted to be disease-causing except for one, and were associated with impaired protein structure and function. CONCLUSIONS: Targeted NGS technology is effective for the gene-based testing of MPS disorders, which show high allelic heterogeneity. MPS II was the predominant form in Chinese. Our study expands the existing variation spectrum of MPS, which is important for disease management and genetic counseling.

Predicting cognitive impairment in outpatients with epilepsy using machine learning techniques.

Many studies report predictions for cognitive function but there are few predictions in epileptic patients; therefore, we established a workflow to efficiently predict outcomes of both the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) in outpatients with epilepsy. Data from 441 outpatients with epilepsy were included; of these, 433 patients met the 12 clinical characteristic criteria and were divided into training (n = 304) and experimental (n = 129) groups. After descriptive statistics were analyzed, cross-validation was used to select the optimal model. The random forest (RF) algorithm was combined with the redundancy analysis (RDA) algorithm; then, optimal feature selection and resampling were carried out after removing linear redundancy information. The features that contributed more to multiple outcomes were selected. Finally, the external traceability of the model was evaluated using the follow-up data. The RF algorithm was the best prediction model for both MMSE and MoCA outcomes. Finally, seven markers were screened by overlapping the top ten important features for MMSE ranked by RF modeling, those ranked for MoCA ranked by RF modeling, and those for both assessments ranked by RDA. The optimal combination of features were namely, sex, age, age of onset, seizure frequency, brain MRI abnormalities, epileptiform discharge in EEG and usage of drugs. which was the most efficient in predicting outcomes of MMSE, MoCA, and both assessments.

Sequencing of neurofilament genes identified NEFH Ser787Arg as a novel risk variant of sporadic amyotrophic lateral sclerosis in Chinese subjects.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with neuronal cell inclusions composed of neurofilaments and other abnormal aggregative proteins as pathological hallmarks. Approximately 90% of patients have sporadic cases (sALS), and at least 4 genes, i.e. C9orf72, SOD1, FUS and TARDBP, have been identified as the main causative genes, while many others have been proposed as potential risk genes. However, these mutations could explain only ~ 10% of sALS cases. The neurofilament polypeptides encoded by NEFH, NEFM, and NEFL are promising protein biomarkers for ALS and other degenerative diseases. However, whether the genetic variants of these genes were associated with ALS remain ambiguous. METHODS: Here, we used PCR-Sanger to sequence the exons of these three genes in a cohort of 371 sALS patients and 711 healthy controls (Phase I) and validated the risk variant in another 300 sALS patients and 1076 controls (Phase II). RESULTS: A total of 92 variants were identified, including 36 rare heterozygous variants in NEFH, 27 in NEFM, and 16 in NEFL, and only rs568759161 (p.Ser787Arg) in NEFH reached nominal statistical power (P = 0.02 at Phase I, P = 0.009 at Phase II) in the case-control comparison. Together, the Phase I and II studies showed the significantly higher frequency of the variant in cases (9/1342, 0.67%) than in controls (2/3574, 0.07%) (OR 12.06; 95% CI 2.60-55.88; P = 0.0003). No variants passed multiple testing in the discovery cohort, but rs568759161 was associated with ALS in a replication cohort. CONCLUSIONS: Our results confirmed that NEFH Ser787Arg is a novel sALS risk variant in Chinese subjects, but NEFM and NEFL were not associated with sALS. These data may have implications for genetic counselling and for understanding the pathogenesis of sALS.