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An all-optical format conversion (AOFC) scheme for the input 30 Gbit/s rectangular 8-ary quadrature amplitude modulation (8QAM) signal is proposed and numerically investigated based on phase-sensitive amplification (PSA) and nonlinear Mach-Zehnder interferometer (MZI). Firstly, the input rectangular 8QAM signal is orthogonal decomposed into the in-phase and quadrature components based on PSA, respectively. The in-phase component is the 4-ary amplitude and phase shift keying (4APSK) signal and the quadrature component is the binary phase shift keying (BPSK) signal. Secondly, the converted 4APSK signal is transmitted into one piece of highly nonlinear fiber (HNLF) to obtain the phase-distorted two-amplitude and two-phase (2A-2P) signal based on the self-phase modulation (SPM) effect. After adjusting the power of the 2A-2P signal, it is injected into one nonlinear MZI to eliminate the amplitude difference of the inner and the outer rings of the 2A-2P signal. The 2A-2P signal can be converted into the regular quadrature phase shift keying (QPSK) signal by the nonlinear MZI with phase preservation. Thirdly, the converted BPSK and QPSK signals are coherently superposed in one 3-dB optical coupler (OC) to get the aggregated rectangular 8QAM signal and other types of 8QAM signals. The proposed scheme can also be extended to realize the AOFC from the 16-ary quadrature amplitude modulation (16QAM) signal to two QPSK signals. The constellation diagrams, amplitude and phase histograms, error vector magnitude (EVM) and bit error rate (BER) of the relevant optical signals are measured to evaluate the system performance. The proposed scheme can be equipped with the optical gateway to enable all-optical interconnection of optical networks with different modulation formats.

ObjectiveMultiple system atrophy (MSA) is a degenerative disease. Immune dysfunction found to play a crucial role in the pathogenesis of this disease in the literature, while the characteristics of peripheral immune function remain unclear. This study aimed to investigate the characteristics and alterations of peripheral immune function in patients with MSA.MethodsA case–control study was conducted between January 2021 to December 2022 at SanBo Brain Hospital, Capital Medical University, Beijing, China. A total of 74 participants were recruited, including 47 MSA patients and 27 non-MSA participants. Peripheral blood samples were collected from each participant. A total of 29 types of immune cells were measured using the flow cytometry analysis technology. Single-factor analysis and multiple-factor analysis (multiple linear regression models) were performed to determine the differences and risk factors in immune cells between the MSA and non-MSA groups.ResultsAlterations of the count or percentage of CD19+ B lymphocytes and CD3−CD56+ B lymphocytes in MSA patients were found in this study. The reductions of the count and percentage of CD19+ B lymphocytes were still robust after adjusting for variables of age, gender, body mass index, albumin, and hemoglobin. Furthermore, the reductions in the count and percentage of CD19+ B lymphocytes in the MSA patients were more significant in women and individuals aged 60 years old or above than in the non-MSA participants.ConclusionOur findings suggested that MSA patients may be influenced by B lymphocytes, particularly CD19+ cells. Therefore, the reductions in immune cells should be considered in the diagnosis and treatment of MSA. Further studies are warranted to confirm and expand upon these findings.

An air-trenches/holes assisted depressed-core few-mode fiber (AT-AH-DC-FMF) that features some asymmetrical air trenches, air holes and a depressed step-index core is proposed in this paper. The AT and DC can produce great contribution in separating the non-degenerated LP modes and spatial modes, thus suppressing the crosstalk efficiently. Based on AT and AH, the bending loss values of AT-AH-DC-FMF can be satisfied with the ITU-T recommendations of G. 654. The simulation results indicate that our proposed fiber can support 12 spatial modes with the effective index difference between adjacent LP modes ( $\Delta \text{n}_{\mathrm {eff}}$ ) larger than $1.03\times 10^{-3}$ and the effective index difference between adjacent spatial modes ( $\delta \text{n}_{\mathrm {eff}}$ ) larger than $1.24\times 10^{-4}$ . The broadband characteristics such as $\Delta \text{n}_{\mathrm {eff}}$ , $\delta \text{n}_{\mathrm {eff}}$ , chromatic dispersion and effective mode field area (Aeff) over the whole C and L band are comprehensively investigated. Moreover, fabrication methods and birefringence are detailed discussed. Our proposed AT-AH-DC-FMF possesses great potential to be applied to less multiple-input multiple-output (MIMO-less) space-division multiplexing (SDM), thus enlarging optical communication capacity and simplifying the system complexity.

The TSC1 gene is a tumor suppressor gene that encodes for the growth inhibitory protein hamartin. It was founded clinically relevant to tuberous sclerosis complex (TSC) and related epilepsy. Variants in TSC1 resulted in tuberous sclerosis, focal cortical dysplasia (FCD) Type II, pulmonary lymphangioleiomyomatosis and change in everolimus sensitivity. Here, we generated induced pluripotent stem cells (iPSC) from a normal individual by electroporation of peripheral blood mononuclear cells (PBMC), and further generated TSC1-knockout human iPSC line via CRISPR/Cas9 gene editing. The resulting iPSCs had normal karyotype, free of genomically integrated epitomal plasmids, expressed pluripotency markers, and maintained trilineage differentiation potential.

ObjectiveTo validate the reliability and efficiency of clinical diagnosis in practice based on a well-established system for the automatic segmentation of cerebral microbleeds (CMBs).MethodThis is a retrospective study based on Magnetic Resonance Imaging-Susceptibility Weighted Imaging (MRI-SWI) datasets from 1,615 patients (median age, 56 years; 1,115 males, 500 females) obtained between September 2018 and September 2019. All patients had been diagnosed with cerebral small vessel disease (CSVD) with clear cerebral microbleeds (CMBs) on MRI-SWI. The patients were divided into training and validation cohorts of 1,285 and 330 patients, respectively, and another 30 patients were used for internal testing. The model training and validation data were labeled layer by layer and rechecked by two neuroradiologists with 15 years of work experience. Afterward, a three-dimensional convolutional neural network (CNN) was applied to the MRI data from the training and validation cohorts to construct a deep learning system (DLS) that was tested with the 72 patients, independent of the aforementioned MRI cohort. The DLS tool was used as a segmentation program for these 72 patients. These results were evaluated and revised by five neuroradiologists and subjected to an output analysis divided into the missed label, incorrect label, and correct label. The interneuroradiologists DLS agreement rate, which was assessed using the interrater agreement kappas test, was used for the quality analysis.ResultsIn the detection and segmentation of the CMBs, the DLS achieved a Dice coefficient of 0.72. In the evaluation of the independent clinical data, the neuroradiologists reported that more than 90% of the lesions were directly detected and less than 10% of lesions were incorrectly labeled or the label was missed by our DLS. The kappa value for interneuroradiologist DLS agreement reached 0.79 on average.ConclusionBased on the results, the automatic detection and segmentation of CMBs are feasible. The proposed well-trained DLS system might represent a trusted tool for the segmentation and detection of CMB lesions.

A novel lensless imaging approach based on ptychography and wavefront separation is proposed in this paper, which was characterized by rapid convergence and high-quality imaging. In this method, an amplitude modulator was inserted between the light source and the sample for light wave modulation. By laterally translating this unknown modulator to different positions, we acquired a sequence of modulated intensity images for quantitative object recovery. In addition, to effectively separate the object and modulator wavefront, a couple of diffraction patterns without modulation were recorded. Optical experiments were performed to verify the feasibility of our approach by testing a resolution plate, a phase object, and an agaricus cell.

Background. Non-small-cell lung cancer (NSCLC) is the most common malignant tumor among males and females worldwide. Hypoxia is a typical feature of the tumor microenvironment, and it affects cancer development. Circular RNAs (circRNAs) have been reported to sponge miRNAs to regulate target gene expression and play an essential role in tumorigenesis and progression. This study is aimed at identifying whether circRNAs could be used as the diagnostic biomarkers for NSCLC. Methods. The heterogeneity of samples in this study was assessed by principal component analysis (PCA). Furthermore, the Gene Expression Omnibus (GEO) database was normalized by the affy R package. We further screened the differentially expressed genes (DEGs) and differentially expressed circular RNAs (DEcircRNAs) using the DEseq2 R package. Moreover, we analyzed the Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment of DEGs using the cluster profile R package. Besides, the Gene Set Enrichment Analysis (GSEA) was used to identify the biological function of DEGs. The interaction between DEGs and the competing endogenous RNAs (ceRNA) network was detected using STRING and visualized using Cytoscape. Starbase predicted the miRNAs of target hub genes, and miRanda predicted the target miRNAs of circRNAs. The RNA-seq profiler and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Then, the variables were assessed by the univariate and multivariate Cox proportional hazard regression models. Significant variables in the univariate Cox proportional hazard regression model were included in the multivariate Cox proportional hazard regression model to analyze the association between the variables of clinical features. Furthermore, the overall survival of variables was determined by the Kaplan-Meier survival curve, and the time-dependent receiver operating characteristic (ROC) curve analysis was used to calculate and validate the risk score in NSCLC patients. Moreover, predictive nomograms were constructed and used to predict the prognostic features between the high-risk and low-risk score groups. Results. We screened a total of 2039 DEGs, including 1293 upregulated DEGs and 746 downregulated DEGs in hypoxia-treated A549 cells. A549 cells treated with hypoxia had a total of 70 DEcircRNAs, including 21 upregulated and 49 downregulated DEcircRNAs, compared to A549 cells treated with normoxia. The upregulated genes were significantly enriched in 284 GO terms and 42 KEGG pathways, while the downregulated genes were significantly enriched in 184 GO terms and 25 KEGG pathways. Moreover, the function analysis by GSEA showed enrichment in the enzyme-linked receptor protein signaling pathway, hypoxia-inducible factor- (HIF-) 1 signaling pathway, and G protein-coupled receptor (GPCR) downstream signaling. Furthermore, six hub modules and 10 hub genes, CDC45, EXO1, PLK1, RFC4, CCNB1, CDC6, MCM10, DLGAP5, AURKA, and POLE2, were identified. The ceRNA network was constructed, and it consisted of 4 circRNAs, 14 miRNAs, and 38 mRNAs. The ROC curve was constructed and calculated. The area under the curve (AUC) value was 0.62, and the optimal threshold was 0.28. Based on the optimal threshold, the patients were divided into the high-risk score and low-risk score groups. The survival rate in the high-risk score group was lower than that in the low-risk score group. The expression of SERPINE1, STC2, and LPCAT1; clinical stage; and age of the patient were significantly correlated with the high-risk score. Moreover, nomograms were established based on the risk factors in multivariate analysis, and the median survival time, 3-year survival probability, and 5-year survival were possibly predicted according to nomograms. Conclusion. The ceRNA network associated with NSCLC was identified, and the hub genes, circRNAs, might act as the potential biomarkers for NSCLC.

The space division multiplexing system is helpful to break through the transmission limitations of traditional optical communication systems. Inter-fiber separation and the number of alternating dielectric layers of Bragg fibers array (BFA) are considered with view to applying BFA to space division multiplexing system. The simulation results indicate that BFA with improper inter-fiber separation will result in topological edge state, thus leading to strong crosstalk and high confinement loss, and its crosstalk is hard to decrease with the increase of alternating dielectric layers. The confinement loss of each Bragg fiber in BFA with proper inter-fiber separation is greatly lower than that of traditional Bragg fiber with the same parameters. Our optimized BFA can be realized with low crosstalk of below −30 dB for 55.4 km propagation. In addition, the arrangement analysis of BFA in this paper provides some constructive suggestions for the application of traditional Bragg fiber in optical devices design such as BFA laser and omnidirectional emitting laser.

Ischemia-reperfusion (I/R) injury contributes to the morbidity and mortality of ischemic strokes. As an in vitro model, oxygen-glucose deprivation and reperfusion (OGD/R) exposure induces neuronal injury. Low-dose ethanol preconditioning (EtOH-PC) was reported to alleviate neuronal apoptosis during OGD/R. However, whether the mitochondrial BKCa (mitoBKCa) channel is involved in the neuroprotective effect of EtOH-PC during OGD/R is not clearly defined. This study attempts to explore the mediation of the mitoBKCa channel in the neuroprotective effect of EtOH-PC on OGD/R-induced neuronal apoptosis and the underlying mechanisms. OGD/R model was established using primary cortical neurons that were preincubated with ethanol. Subsequently, the cell viability was measured by CCK-8 assay, and the apoptotic cells were determined by TUNEL assay. Annexin V/7-AAD staining and mitochondrial membrane potential using JC-10 were detected by flow cytometry. Western blot analysis was performed to check the apoptosis-related proteins. In the mixed primary culture, 95% neurofilament-positive cells were cortical neurons. Low-dose EtOH-PC (10 mmol/L) for 24 h significantly attenuated the OGD2h/R24h-induced neuronal apoptosis through activating the BKCa channel. Further investigations suggested that ethanol pretreatment increased the mitochondrial membrane potential (MMP) and downregulated the production of cleaved caspase 3 in OGD/R-injured neurons by activating the mitoBKCa channel. Low-dose ethanol pretreatment significantly attenuated the OGD/R-induced neuronal apoptosis mediated by the mitoBKCa channel which modulated the mitochondrial function by impeding the uncontrolled opening of mitochondrial permeability transition pore (MPTP).

The transmission characteristics of the Bessel-Gaussian (BG) beam propagation in free space and turbulence atmosphere after passing through the Cassegrain antenna system are researched in this paper. The research results show that the half-cone angles of the beam and parameters of the optical system can be used to control the propagation trajectory and the cross-talk among different orbital angular momentum (OAM) modes of the BG beam. The BG beam has a focusing property when propagating in free space after passing through the collimating optical system. The trend of cross-talk among different OAM modes is different for focused BG beam and non-focused beam, and the focusing beam can potentially reduce cross-talk among different OAM modes at the receiver plane.

ObjectiveTo examine the clinical characteristics of autoimmune encephalitis associated with the contactin-associated protein-2 (CASPR2) antibody.Materials and MethodsMedical records of all patients diagnosed with CASPR2 antibody-associated encephalitis were retrospectively analysed. Data regarding demographic features, neurological symptoms and signs, laboratory tests, imaging results, treatments, and prognosis were collected.ResultsA total of 25 patients aged from 3 to 79 years old were enrolled in this study, with a median age of 43. Eight of 25 (32%) were female, and 17 of 25 (68%) were male. The median age of symptom onset was 42 years old with the course of disease from onset to hospital admission ranging from 2 days to 6 months (median was 17 days). Six patients (6/25) had fever as an onset symptom. During the course of disease, cognitive disturbance was the most common symptom, which was observed in 17 patients (17/25) in total. Eight patients (8/25) met the criteria for limbic encephalitis. Epileptic seizure occurred in six of these eight patients. Four patients (4/25) were diagnosed as Morvan syndrome. All patients were positive for anti-CASPR2 antibody in the serum (1:10–1:300). In six patients, antibodies were detected both in the blood and CSF (1:32–1:100). White blood cell (WBC) counts in the CSF were elevated in eight patients (8/25). The concentration of proteins in CSF increased in 10 patients (ranging from 480 to 1,337.6 mg/dl), decreased in seven patients (ranging from 23.2 to 130.5 mg/dl) and remained at a normal range in the other eight patients (ranging from 150 to 450 mg/dl). Abnormal electroencephalogram (EEG) activities included slow background activity and epileptic patterns. Abnormal signals in the bilateral hippocampus were detected by magnetic resonance imaging (MRI) in three patients presenting cognitive disturbance. In one patient who had limbic encephalitis, increased metabolism of bilateral basal ganglia and the mesial temporal lobe was revealed by PET-CT. Eleven of 15 patients receiving immunotherapy experienced varying degrees of improvement. Relapse occurred in four of 25 patients (4/25) after 2 months.ConclusionCASPR-antibody-mediated autoimmune encephalitis is characterized by diverse clinical manifestations. The most prominent conclusion revealed by this retrospective analysis is the involvement of both central and peripheral nerve systems, as well as a lower relapse rate, a good response to immunotherapy, and favorable short-term prognosis after treatment was also demonstrated. Besides, additional work is necessary to evaluate the long-term prognosis.

Post-traumatic epilepsy (PTE) is one of the consequences after traumatic brain injury (TBI), which increases the morbidity and mortality of survivors. About 20% of patients with TBI will develop PTE, and at least one-third of them are resistant to conventional antiepileptic drugs (AEDs). Therefore, it is of utmost importance to explore the mechanisms underlying PTE from a new perspective. More recently, neuroinflammation has been proposed to play a significant role in epileptogenesis. This review focuses particularly on glial cells activation, peripheral leukocytes infiltration, inflammatory cytokines release and chronic neuroinflammation occurrence post-TBI. Although the immune response to TBI appears to be primarily pro-epileptogenic, further research is needed to clarify the causal relationships. A better understanding of how neuroinflammation contributes to the development of PTE is of vital importance. Novel prevention and treatment strategies based on the neuroinflammatory mechanisms underlying epileptogenesis are evidently needed.Search StrategySearch MeSH Terms in pubmed: “[“Epilepsy”(Mesh)] AND “Brain Injuries, Traumatic”[Mesh]”. Published in last 30 years. 160 results were founded. Full text available:145 results. Record screened manually related to Neuroinflammation and Post-traumatic epilepsy. Then finally 123 records were included.

Our previous study revealed that miR-184 expression is significantly altered in the brain following ischemic stroke in rats. However, it is unknown whether this alteration in miR-184 expression contributes to brain injury after ischemic stroke. Here, we aim to address the potential of miR-184 to impact nerve injury following ischemia and reperfusion. Rats received ICV injection of miR-184 adenovirus or empty vector and were subjected to right middle cerebral artery occlusion (MCAO) to establish an ischemic stroke model. We cultured SH-SY5Y cells under oxygen-glucose deprivation/reoxygenation (OGD/R) and transfected them with miR-184 lentivirus to explore the primary mechanisms. To evaluate miR-184 expression, neurological function deficits, the cerebral infarct volume, cell viability, and apoptosis, qRT-PCR analysis of miR-184 expression, the modified neurological severity score (mNSS) system, TTC staining, the CCK-8 assay, flow cytometry, and dual-luciferase reporter assays were utilized. We found that miR-184 expression was downregulated and that the cerebral infarct volume and mNSSs were increased following ischemic stroke; however, increasing the level of miR-184 alleviated brain damage. Overexpression of miR-184 resulted in increased viability and reduced apoptosis of SH-SY5Y cells following OGD/R in vitro. We identified the phosphatidic acid phosphatase type 2B (PPAP2B) gene as a direct target gene of miR-184. In summary, our results reveal that attenuation of miR-184 levels in ischemic stroke contributes to ischemic injury through targeting PPAP2B mRNA-mediated apoptosis, which may be a promising therapeutic target for ischemic stroke.

Objective: The epidemiological characteristics of patients with antibody-medicated autoimmune encephalitis in China remain unclear, and a large-scale epidemiological survey is necessary.Methods: A multiple-center retrospective study was performed. We collected 1,047 patients with suspected autoimmune encephalitis and ultimately enrolled 778 defined patients across centers in China. All patients were positive for serum [or cerebrospinal fluid (CSF)] antibodies. Demographic information and clinical data from January 2014 to January 2019 from 22 centers in China were reviewed.Results: A total of 778 patients with autoimmune encephalitis were enrolled in the study. In general, the ratio of males to females was ~1.2:1. The main subtypes of autoimmune encephalitis were NMDAR-AE (61.35%), LGI-1-AE (20.61%), and GABAbR-AE (12.40%). According to the characteristics of age of onset, the incidence of autoimmune encephalitis showed a “double peak” distribution entailing a 20-year-old age group and a 60-year-old age group. We next analyzed the proportion of patients with tumors in this cohort. More specifically, there were 34 patients with tumors and 85 with tumor marker positivity. Relapse occurred in 81 patients within at least 1 year's follow up study: 52 with NMDAR-AE (18.2%); 19 with LGI-1-AE (16.8%); 5 with GABAbR-AE (9%); and 3 with CASPR2-AE.Interpretation: Due to the vast differences in demographic features, the incidence of cancer and the genetic characteristics between the populations in China and Western countries, the demographics, sex distribution, concomitant tumor rate, clinical features, and relapse characteristics associated with autoimmune encephalitis in China shows a similar profile with Western countries with some minor differences.

To clarify the different regional brain electroencephalogram (EEG) activities and biochemical responses in seizure and epilepsy models, we assessed the EEG and c-Fos immunolabeling characteristics in a lithium-pilocarpine-induced status epilepticus (SE) model and pentylenetetrazol (PTZ)-induced seizure model. The regional brain activities were evaluated by EEG and c-Fos immunolabeling. ZnT3 immunostaining was performed to observe hippocampal mossy fiber sprouting (MFS) within 7 days after the induction of SE in the lithium-pilocarpine model. The EEG recordings showed distinctive features of activation in different brain areas. With the aggravation of the behavioral manifestations of the seizures, the frequency and amplitude of the discharges on EEG gradually increased. SE was eventually induced and sustained. The labeling of c-Fos was enhanced in the cortex and hippocampal CA1, CA3, and dentate gyrus (DG); however, compared to the PTZ-induced seizure model, c-Fos staining could only be observed in the striatum and thalamus in the lithium-pilocarpine-induced epilepsy model. In each brain region, prominent c-Fos labeling was observed 2 h and 4 h after the induction of SE or seizures and diminished at 24 h. During the lithium-pilocarpine-induced chronic epilepsy phase after SE induction, MFS was observed 7 days after SE and was accompanied by the dynamic evolution of epileptic EEG activities. These findings validated the lithium-pilocarpine-induced SE model as an epilepsy model with a specific spatial-temporal profile of neural activation. The EEG characteristics and c-Fos expression patterns differ from those presented in a previous study using a PTZ-induced seizure model. Hippocampal mossy fiber spouting might be associated with spontaneous seizures during the chronic phase and can be detected at least within 1 week by ZnT3 staining after stimulation.

There is growing evidence that ketone bodies, which are derived from fatty acid oxidation and usually produced in fasting state or on high-fat diets have broad neuroprotective effects. Although the mechanisms underlying the neuroprotective effects of ketone bodies have not yet been fully elucidated, studies in recent years provided abundant shreds of evidence that ketone bodies exert neuroprotective effects through possible mechanisms of anti-oxidative stress, maintaining energy supply, modulating the activity of deacetylation and inflammatory responses. Based on the neuroprotective effects, the ketogenic diet has been used in the treatment of several neurological diseases such as refractory epilepsy, Parkinson's disease, Alzheimer's disease, and traumatic brain injury. The ketogenic diet has great potential clinically, which should be further explored in future studies. It is necessary to specify the roles of components in ketone bodies and their therapeutic targets and related pathways to optimize the strategy and efficacy of ketogenic diet therapy in the future.

As part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Li et al., 2015), that described how we intended to replicate selected experiments from the paper ‘The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44’ (Liu et al., 2011). Here we report the results. We found the microRNA, miR-34a, was expressed at twice the level in CD44+ prostate cancer cells purified from xenograft tumors (LAPC4 cells) compared to CD44- LAPC4 cells, whereas the original study reported miR-34a was underexpressed in CD44+ LAPC4 cells (Figure 1B; Liu et al., 2011). When LAPC4 cells engineered to express miR-34a were injected into mice, we did not observe changes in tumor growth or CD44 expression; however, unexpectedly miR-34a expression was lost in vivo. In the original study, LAPC4 cells expressing miR-34a had a statistically significant reduction in tumor regeneration and reduced CD44 expression compared to control (Figure 4A and Supplemental Figures 4A,B and 5C; Liu et al., 2011). Furthermore, when we tested if miR-34a regulated CD44 through binding sites in the 3’UTR we did not find a statistically significant difference, whereas the original study reported miR-34a decreased CD44 expression that was partially abrogated by mutation of the binding sites in the CD44 3’UTR (Figure 4D; Liu et al., 2011). Finally, where possible, we report meta-analyses for each result.

OBJECTIVE: The aim of this study was to assess the association between non-high-density-lipoprotein-cholesterol (non-HDL-C) and the prevalence of asymptomatic intracranial arterial stenosis (ICAS). METHODS AND RESULTS: The Asymptomatic Polyvascular Abnormalities Community (APAC) study is a prospective cohort study based on the Kailuan district (China) population. A total of 5351 eligible subjects, aged ≥40, and without history of stroke or myocardial infarction, were enrolled in this study. Transcranial Doppler Ultrasonography (TCD) was performed on all enrolled subjects for the evaluation of ICAS presence. Out of 5351 patients, 698 subjects showed evidence of ICAS (prevalence of 13.04%). Multivariate analysis showed that non-HDL-C is an independent indicator for the presence of ICAS (OR = 1.15, 95%CI: 1.08 - 1.23), but with a gender difference (P for interaction

We demonstrated negative refraction effects of light propagating in two-dimensional square and hexagonal-lattice silicon photonic crystals (PhCs). The plane wave expansion method was used to solve the complex eigenvalue problems, as well as to find dispersion curves and equal-frequency contour (EFC). The finite-difference time-domain (FDTD) method was used to simulate and visualize electromagnetic wave propagation and scattering in the PhCs. Theoretical analyses and numerical simulations are presented. Two different kinds of negative refractions, namely, all-angle negative refraction (AANR) without a negative index and negative refraction with effective negative index, have been verified and compared.

Aims: This study aims to investigate the safety, tolerability, efficacy, and pharmacokinetics of Pynegabine as an add‐on therapy in the treatment of focal epilepsy. Methodology: This is a protocol phase‐IIa, randomized, double‐blinded, placebo‐controlled, multicenter study in patients with focal epilepsy from multiple centers in China who have been treated with at least 2 ASMs without effective control. The study involves an 8‐week run‐in period with stable use of previous medications. Patients are then randomized to receive either Pynegabine or a placebo. Sentinel administration is performed initially, and subsequent patients are randomized based on safety assessments. Three dose cohorts (15, 20, and 25 mg/d) are established. Efficacy is assessed through various measures, including seizure frequency, CGI score, PGI score, HAMA score, HAMD score, MoCA scale score, QOLIE‐31 scale score, and 12 h‐EEG score. Safety evaluations, PK blood samples, concomitant medications, and adverse events are also recorded. Conclusion: Data from the study will be used to evaluate the safety, tolerability, efficacy, and pharmacokinetics of Pynegabine tablets as add‐on therapy for focal epilepsy. [ABSTRACT FROM AUTHOR]