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ObjectiveNarcolepsy, a rare neurological disorder believed to have an autoimmune etiology, necessitates lifelong management. This study aimed to provide evidence supporting the safety of pharmacological treatment for narcolepsy.MethodsFive-year data on pitolisant, sodium oxybate, solriamfetol, and modafinil were extracted from the FDA Adverse Event Reporting System (FAERS) self-reporting database for the period spanning from 2019 to 2023. Various statistical methods, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network analysis (BCPNN), and multi-item gamma Poisson shrinker (MGPS), were employed to quantify the signals. Finally, a comparative analysis was conducted between demographic data, outcomes, and inherent associations among the medications and the signals.ResultsAfter data analysis, we obtained 50 signals (a cumulative count of 762 cases) for pitolisant, 640 signals (corresponding to 46,962 cases) for sodium oxybate, 40 signals (equivalent to 1,228 cases) for solriamfetol, and finally, 72 signals (representing 632 cases) for modafinil. The majority of these patients were female. Psychiatric and nervous system disorders were identified as the predominant adverse drug events (ADEs). For sodium oxybate, it is crucial to consider psychiatric disorders (such as suicidal ideation), respiratory disorders (including sleep apnea syndrome and respiratory depression), and signs of pregnancy and congenital familial diseases. For solriamfetol, noteworthy new ADEs include drug inefficacy, suicidal ideation, restless legs syndrome, and somnambulism. Furthermore, a relationship has been observed between modafinil use and restricted fetal growth, spontaneous abortion, cognitive disorders, and drug inefficacy and abuse.ConclusionThe majority of observed adverse reactions in this study were consistent with those listed in the product instructions. However, potential novel or notable ADE signals were identified through real-world pharmacovigilance analysis. It is anticipated that this paper will offer additional information regarding safe and rational medication for narcolepsy.

This paper studies the expectile regression with error-in-variables to reduce the data error and describe the overall data distribution. Specifically, the asymptotic normality of the proposed estimator is thoroughly investigated, and an IRWLS algorithm based on orthogonal distance expectile regression (ODER) is proposed to estimate the parameters. Extensive simulation studies and real data applications evaluate our method’s capabilities in reducing the measurement error bias, demonstrating our model’s parameter estimation effectiveness, and its capability in reducing the simulation error compared with linear and quantile regression schemes.

Swertia mussotii is the most authentic raw material used in Tibetan medicine in China for its various bioactivities. This natural medicine resource is at risk of being exhausted due to the double interference of climate change and anthropogenic over-collection. Little is known about habitat characteristics and the crucial environmental factors that influence the levels of active ingredients. The goal of this study is to understand the variability in the bioactive compound content of a wide range of wild S. mussotii as it adapts to changing environmental conditions. The target compound content of the whole plant material was analyzed with the environmental explanatory variables of the field sample sites using a constrained ordination method for their correlation analysis. The results show that 16.3 percent of the sampled wild S. mussotii populations with the highest bioactive content can be grouped into the elite type. The most prominent environmental variables affecting the content of major bioactive products include altitude, aspect, soil TK content, Fe content, and C/N and N/P ratios. Altitude and aspect put indirect effects that are mediated by plant height and density, N/P ratio puts a direct effect, while soil TK content, Fe content and C/N ratio have both direct and indirect effects on the bioactivity of S. mussotii. In addition to the total negative effects of altitude and C/N ratio, the remaining factors play a driving role. These findings demonstrate variation by geographical conditions across S. mussotii accessions for physiologic responses and secondary compounds in wild populations. The knowledge gained from this study can be used for environmental and plant physiology research, efficient collection of naturally active compounds, and conservation strategies for rare natural plant resources.

Abstract Objective Percutaneous vertebroplasty (PVP) and kyphoplasty (PKP) have been widely used to treat osteoporotic vertebral compression fractures (OVCF), but the risk of vertebral re-fracture after PVP/PKP remains controversial. This study aims to investigate the incidence and risk factors of vertebral re-fracture after PVP/PKP. Methods Relevant literatures published up to November 2021 were collected from PubMed, Embase and Web of Science. A meta-analysis was performed to extract data associated with risk factors of SVCF following the PRISMA guidelines. Also, pooled odds ratio (OR) or weighted mean difference (WMD) with 95% confidence interval (CI) was calculated. Results A total of 23 studies, encompassing 9372 patients with OVCF, met the inclusion criteria. 1255 patients (13.39%) suffered re-fracture after PVP/PKP surgery. A total of 22 studies were from Eastern Asia and only 1 study was from Europe. Female sex (OR = 1.34, 95%CI 1.09–1.64, P = 0.006), older age (WMD = 2.04, 95%CI 0.84–3.24, P = 0.001), lower bone mineral density (BMD, WMD = − 0.38, 95%CI − 0.49–0.26, P

The prediction of mechanical properties of hot rolled strips can be used for on-line dynamic control of product properties and optimal design of new steel grade. Tensile strength is an important index of the mechanical properties for hot rolled strips. The influencing factors of tensile strength include alloy elements, microstructure, and production process parameters. It is very crucial to establish a reliable prediction model of steel tensile strength based on these factors to improve the mechanical properties. This paper proposes a prediction model which combines a generalized radial basis function neural network and composite expectile regression to solve nonlinear problems and data heterogeneity problems in modeling. At the same time, CS algorithm (Cuckoo Search) was applied to develop an estimation procedure, which overcomes the shortcoming of traditional gradient descent algorithm by avoiding to fall into local optimum. Because expectile regression can describe the conditional distribution, and neural network has strong non-linear interpretation ability, the proposed model enables us to explore potential nonlinear relationships among variables. Based on the measured data collected from a hot rolling production process, the experimental results show that the model proposed in this paper has better prediction accuracy, the mean absolute percentage error (MAPE) and root mean square error (RMSE) are 2.49

BackgroundWith the widespread application of platinum drugs in antitumor therapy, the incidence of platinum drug adverse events (ADEs) is always severe. This study aimed to explore the adverse event signals of Cisplatin, Carboplatin and Oxaliplatin, three widely used platinum-containing drugs, and to provide a reference for rational individualized clinical drug use.MethodsThe adverse event report data of the three platinum drugs from the first quarter of 2017 to the fourth quarter of 2021 were extracted from the FAERS database, and the data mining and risk factors for the relevant reports were carried out using the reporting odds ratio (ROR) method the proportional reporting ratio (PRR)and the comprehensive criteria (MHRA) method.ResultsA total of 1853 effective adverse event signals were obtained for the three platinum agents, including 558 effective signals for Cisplatin, 896 effective signals for Carboplatin, and 399 effective signals for Oxaliplatin. The signals involve 23 effective different system organs (SOCs). The adverse events of Cisplatin are mainly fixed on blood and lymphatic system diseases, gastrointestinal diseases, systemic diseases and various reactions at the administration site. The adverse events of Carboplatin are mainly focused on blood and lymphatic system diseases, respiratory system, thoracic and mediastinal diseases, while the adverse events of Oxaliplatin are mainly concentrated in respiratory system, thoracic and mediastinal diseases, various nervous system diseases, and gastrointestinal system diseases.ConclusionIt was found that the main systems involved in common adverse events of platinum drugs are different, and the correlation strength of platinum drugs with the certain adverse events of each system is different.

A purified polysaccharide, designated as SE-WGPI, was isolated from wheat germ modified by steam explosion. The primary structure characteristics were determined by HPGPC, GC, periodate oxidation-Smith degradation, methylation analysis, FT-IR, NMR and Congo red test. The results showed that SE-WGPI was a homogeneous hetero-polysaccharide with the average molecular weight of 5.6 × 103 Da. The monosaccharide composition mainly consisted of glucose, arabinose and xylose with a molar ratio of 59.51: 20.71: 19.77. The main backbone of SE-WGPI consisted of →4,6)-α-D-Glcp(1→6)-α-D-Glcp(1→3)-β-D-Xylp(1→5)-α-L-Araf(1→ and the side chain was α-D-Glcp(1→ linked at the C4-position of →4,6)-α-D-Glcp(1→. SE-WGPI likely has a complex netted structure with triple helix conformation and good thermal stability. In addition, SE-WGPI had valid in vitro radical scavenging activities on DPPH and hydroxyl radicals. This study may provide structural information of SE-WGPI for its promising application in the fields of functional foods or medicines.

In this work, steam explosion (SE) was exploited as a potential hydrothermal-humification process of vegetable wastes to deconstruct their structure and accelerate their decomposition to prepare humified substances. Results indicated that the SE process led to the removal of hemicellulose, re-condensation of lignin, degradation of the cellulosic amorphous region, and the enhancement of thermal stability of broccoli wastes, which provided transformable substrates and a thermal-acidic reaction environment for humification. After SE treatment, total humic substances (HS), humic acids (HAs), and fulvic acids (FAs) contents of broccoli samples accounted for up to 198.3 g/kg, 42.3 g/kg, and 166.6 g/kg, and their purification were also facilitated. With the increment of SE severity, structural characteristics of HAs presented the loss of aliphatic compounds, carbohydrates, and carboxylic acids and the enrichment of aromatic structures and N-containing groups. Lignin substructures were proved to be the predominant aromatic structures and gluconoxylans were the main carbohydrates associated with lignin in HAs, both of their signals were enhanced by SE. Above results suggested that SE could promote the decomposition of easily biodegradable matters and further polycondensation, aromatization, and nitrogen-fixation reactions during humification, which were conducive to the formation of HAs.

The aim of this study was to perform an exposure assessment of PM2.5 (particulate matter less than 2.5μm in aerodynamic diameter) among children and to explore the potential sources of exposure from both indoor and outdoor environments.In terms of real-time exposure measurements of PM2.5, we collected data from 57 children aged 8-12 years (9.64 ± 0.93 years) in two schools in Shanghai, China. Simultaneously, questionnaire surveys and time-activity diaries were used to estimate the environment at home and daily time-activity patterns in order to estimate the exposure dose of PM2.5 in these children. Principle component regression analysis was used to explore the influence of potential sources of PM2.5 exposure.All the median personal exposure and microenvironment PM2.5 concentrations greatly exceeded the daily 24-h PM2.5 Ambient Air Quality Standards of China, the USA, and the World Health Organization (WHO). The median Etotal (the sum of the PM2.5 exposure levels in different microenvironment and fractional time) of all students was 3014.13 (μg.h)/m3. The concentration of time-weighted average (TWA) exposure of all students was 137.01 μg/m3. The median TWA exposure level during the on-campus period (135.81 μg/m3) was significantly higher than the off-campus period (115.50 μg/m3, P = 0.013 < 0.05). Besides ambient air pollution and meteorological conditions, storey height of the classroom and mode of transportation to school were significantly correlated with children's daily PM2.5 exposure.Children in the two selected schools were exposed to high concentrations of PM2.5 in winter of 2013 in Shanghai. Their personal PM2.5 exposure was mainly associated with ambient air conditions, storey height of the classroom, and children's transportation mode to school.

Climatic changes and heat stress have become a great challenge in the livestock industry, negatively affecting, in particular, poultry feed intake and intestinal barrier malfunction. Recently, phytogenic feed additives were applied to reduce heat stress effects on animal farming. Here, we investigated the effects of ginseng extract using various in vitro and in vivo experiments. Quantitative real-time PCR, transepithelial electrical resistance measurements and survival assays under heat stress conditions were carried out in various model systems, including Caco-2 cells, Caenorhabditis elegans and jejunum samples of broilers. Under heat stress conditions, ginseng treatment lowered the expression of HSPA1A (Caco-2) and the heat shock protein genes hsp-1 and hsp-16.2 (both in C. elegans), while all three of the tested genes encoding tight junction proteins, CLDN3, OCLN and CLDN1 (Caco-2), were upregulated. In addition, we observed prolonged survival under heat stress in Caenorhabditis elegans, and a better performance of growing ginseng-fed broilers by the increased gene expression of selected heat shock and tight junction proteins. The presence of ginseng extract resulted in a reduced decrease in transepithelial resistance under heat shock conditions. Finally, LC-MS analysis was performed to quantitate the most prominent ginsenosides in the extract used for this study, being Re, Rg1, Rc, Rb2 and Rd. In conclusion, ginseng extract was found to be a suitable feed additive in animal nutrition to reduce the negative physiological effects caused by heat stress.

This paper is concerned with a PDE-based approach to the horizontally quasiconvex (h-quasiconvex, for short) envelope of a given continuous function in the Heisenberg group. We provide a characterization for upper semicontinuous, h-quasiconvex functions in terms of the viscosity subsolution to a first-order nonlocal Hamilton-Jacobi equation. We also construct the corresponding envelope of a continuous function by iterating the nonlocal operator. One important step in our arguments is to prove the uniqueness and existence of viscosity solutions to the Dirichlet boundary problem for the nonlocal Hamilton-Jacobi equation. Applications of our approach to the h-convex hull of a given set in the Heisenberg group are discussed as well. [ABSTRACT FROM AUTHOR]