Lymphoplasmapheresis versus plasma exchange in severe myasthenia gravis: a retrospective cohort study

BackgroundLymphoplasmapheresis (LPE) is a new therapy developed on the basis of traditional plasma exchange (PE) in combination with leukapheresis. Currently, it remains unclear whether PE and LPE show differences in efficacy for severe MG.MethodsA retrospective analysis was conducted on 198 MG patients, 75 in the PE group and 123 in the LPE group, and the patients’ Myasthenia Gravis Foundation of America (MGFA) Clinical Classification was Class IV. The treatment outcome was the change in Quantitative Myasthenia Gravis Score (QMGS) from baseline to the end of treatment. Propensity score matching (PSM) was applied for the balance of confounders between the two groups.ResultsIn this study cohort, the safety profile of LPE and PE was good and no serious adverse events were observed. Based on PSM, 62 patients treated with LPE and 62 patients treated with PE were entered into a comparative efficacy analysis. In the PE group, patients underwent a total of 232 replacements, with a mean of 3.74. PE significantly improved the patients’ QMGS performance, with the mean QMGS decreasing from 22.98 ± 4.03 points at baseline to 18.34 ± 5.03 points after treatment, a decrease of 4.68 ± 4.04 points (p < 0.001). A decrease of ≥3 points in QMGS was considered a significant improvement, with a treatment response rate of 67.7% in the PE group. In the LPE group, patients received a total of 117 replacements, with a mean of 1.89. The patients’ mean QMGS was 23.19 ± 4.11 points at baseline and was 16.94 ± 5.78 points after treatment, a decrease of 6.26 ± 4.39 points (p < 0.001). The improvement in QMGS was more significant in patients treated with LPE compared to the PE group (p = 0.039). The treatment response rate in the LPE group was 79%, which was not significantly different compared to the PE group (p = 0.16). The LEP group had a shorter mean length of stay compared to the PE group (10.86 ± 3.96 vs. 12.14 ± 4.14 days), but the difference was not statistically significant (p = 0.13). During the 2-month follow-up period, LPE may be associated with better functional outcomes for patients, with lower QMG score and relapse rate. LPE and PE were both effective in reducing the levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) and AChR-Ab. Compared to PE, LPE was superior in the reduction of AChR-Ab titer.ConclusionIn severe MG, LPE may be a more preferred treatment option than PE. It achieves treatment outcomes that are not inferior to or even better than PE with fewer replacements. This study provides further evidence to support the application of LPE as a new treatment option for MG

Extensive Crosstalk between O-GlcNAcylation and Phosphorylation Regulates Akt Signaling

O-linked N-acetylglucosamine glycosylations (O-GlcNAc) and O-linked phosphorylations (O-phosphate), as two important types of post-translational modifications, often occur on the same protein and bear a reciprocal relationship. In addition to the well documented phosphorylations that control Akt activity, Akt also undergoes O-GlcNAcylation, but the interplay between these two modifications and the biological significance remain unclear, largely due to the technique challenges. Here, we applied a two-step analytic approach composed of the O-GlcNAc immunoenrichment and subsequent O-phosphate immunodetection. Such an easy method enabled us to visualize endogenous glycosylated and phosphorylated Akt subpopulations in parallel and observed the inhibitory effect of Akt O-GlcNAcylations on its phosphorylation. Further studies utilizing mass spectrometry and mutagenesis approaches showed that O-GlcNAcylations at Thr 305 and Thr 312 inhibited Akt phosphorylation at Thr 308 via disrupting the interaction between Akt and PDK1. The impaired Akt activation in turn resulted in the compromised biological functions of Akt, as evidenced by suppressed cell proliferation and migration capabilities. Together, this study revealed an extensive crosstalk between O-GlcNAcylations and phosphorylations of Akt and demonstrated O-GlcNAcylation as a new regulatory modification for Akt signaling

The Effects of Topology on Throughput Capacity of Large Scale Wireless Networks

In this paper, we jointly consider the inhomogeneity and spatial dimension in large scale wireless networks. We study the effects of topology on the throughput capacity. This problem is inherently difficult since it is complex to handle the interference caused by simultaneous transmission. To solve this problem, we, according to the inhomogeneity of topology, divide the transmission into intra-cluster transmission and inter-cluster transmission. For the intra-cluster transmission, a spheroidal percolation model is constructed. The spheroidal percolation model guarantees a constant rate when a power control strategy is adopted. We also propose a cube percolation mode for the inter-cluster transmission. Different from the spheroidal percolation model, a constant transmission rate can be achieved without power control. For both transmissions, we propose a routing scheme with five phases. By comparing the achievable rate of each phase, we get the rate bottleneck, which is the throughput capacity of the network

Study on the relationship between intracellular metabolites and astaxanthin accumulation during Phaffia rhodozyma fermentation

Background: To study the relationship between intracellular anabolism and astaxanthin production, the influence of intracellular protein and fatty acids on astaxanthin production by four mutant Phaffia rhodozyma strains and their variations was investigated in this research. Results: First, the content of astaxanthin in cells showed a reverse fluctuation in contrast to that of protein during the whole fermentation process. Moreover, compared with the three other strains, the astaxanthin-overproducing mutant strain of the yeast P. rhodozyma, called JMU-MVP14, had the highest specific productivity of astaxanthin as 6.8 mg/g, whereas its intracellular protein and fatty acid contents were the lowest. In addition, as a kind of sugar metabolic product, ethanol was only produced by P. rhodozyma JMU-VDL668 and JMU-7B12 during fermentation. Conclusions: The results indicated that the accumulation of ethanol, intracellular protein, and fatty acids had competition effects on astaxanthin synthesis. This condition may explain why the P. rhodozyma strains JMU-VDL668 and JMU-7B12 achieved relatively lower astaxanthin production (1.7 and 1.2 mg/L) than the other two strains JMU-MVP14 and JMU-17W (20.4 and 3.9 mg/L)

Landslide Susceptibility Mapping Based on Deep Learning Algorithms Using Information Value Analysis Optimization

Selecting samples with non-landslide attributes significantly impacts the deep-learning modeling of landslide susceptibility mapping. This study presents a method of information value analysis in order to optimize the selection of negative samples used for machine learning. Recurrent neural network (RNN) has a memory function, so when using an RNN for landslide susceptibility mapping purposes, the input order of the landslide-influencing factors affects the resulting quality of the model. The information value analysis calculates the landslide-influencing factors, determines the input order of data based on the importance of any specific factor in determining the landslide susceptibility, and improves the prediction potential of recurrent neural networks. The simple recurrent unit (SRU), a newly proposed variant of the recurrent neural network, is characterized by possessing a faster processing speed and currently has less application history in landslide susceptibility mapping. This study used recurrent neural networks optimized by information value analysis for landslide susceptibility mapping in Xinhui District, Jiangmen City, Guangdong Province, China. Four models were constructed: the RNN model with optimized negative sample selection, the SRU model with optimized negative sample selection, the RNN model, and the SRU model. The results show that the RNN model with optimized negative sample selection has the best performance in terms of AUC value (0.9280), followed by the SRU model with optimized negative sample selection (0.9057), the RNN model (0.7277), and the SRU model (0.6355). In addition, several objective measures of accuracy (0.8598), recall (0.8302), F1 score (0.8544), Matthews correlation coefficient (0.7206), and the receiver operating characteristic also show that the RNN model performs the best. Therefore, the information value analysis can be used to optimize negative sample selection in landslide sensitivity mapping in order to improve the model’s performance; second, SRU is a weaker method than RNN in terms of model performance

IL23R gene confers susceptibility to ankylosing spondylitis concomitant with uveitis in a Han Chinese population.

PURPOSE: The interleukin-23 receptor (IL-23R) has been shown to be associated with ankylosing spondylitis (AS) in many different populations. This study examined whether IL-23R polymorphisms were associated with susceptibility to this disease in a Chinese Han population. METHODS: Three single-nucleotide polymorphisms (SNP), rs7517847, rs11209032, and rs17375018, were genotyped in 291 AS patients and 312 age-, sex-, and ethnically matched healthy controls using a polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) assay. RESULTS: The genotype and allele frequencies of rs17375018, rs7517847, and rs11209032 were not different between the patients with AS and the healthy controls. On the one hand, stratification analysis indicated that the rs17375018 GG genotype and the G allele were increased in AS patients who were HLA-B27 positive (corrected p = 0.024, odds ratio [OR] 2.35, 95% CI 1.30-4.24; p c = 0.006, OR 1.98, 95% CI 1.28-3.07, respectively). On the other hand, the analysis according to clinical characteristics showed a significantly increased prevalence of the homozygous rs17375018 GG genotype and the G allele in patients with AS and uveitis compared with the controls (p c = 0.024 and p c = 0.024, respectively). In addition, haplotype analysis performed with the SHEsis platform revealed no significant difference concerning the haplotypes between AS patients and healthy controls. CONCLUSIONS: In this study, the results suggested that the rs17375018 of IL23R was positively associated with HLA-B27-positive AS and that the rs17375018 GG of IL-23R was associated with AS concomitant with uveitis. We found no evidence for an association between the other two SNPs of IL-23R and AS

A Novel Simulation Model for Nonstationary Rice Fading Channels

In this paper, we propose a new simulator for nonstationary Rice fading channels under nonisotropic scattering scenarios, as well as the improved computation method of simulation parameters. The new simulator can also be applied on generating Rayleigh fading channels by adjusting parameters. The proposed simulator takes into account the smooth transition of fading phases between the adjacent channel states. The time-variant statistical properties of the proposed simulator, that is, the probability density functions (PDFs) of envelope and phase, autocorrelation function (ACF), and Doppler power spectrum density (DPSD), are also analyzed and derived. Simulation results have demonstrated that our proposed simulator provides good approximation on the statistical properties with the corresponding theoretical ones, which indicates its usefulness for the performance evaluation and validation of the wireless communication systems under nonstationary and nonisotropic scenarios