An Algorithm for Idle-State Detection in Motor-Imagery-Based Brain-Computer Interface

For a robust brain-computer interface (BCI) system based on motor imagery (MI), it should be able to tell when the subject is not concentrating on MI tasks (the “idle state”) so that real MI tasks could be extracted accurately. Moreover, because of the diversity of idle state, detecting idle state without training samples is as important as classifying MI tasks. In this paper, we propose an algorithm for solving this problem. A three-class classifier was constructed by combining two two-class classifiers, one specified for idle-state detection and the other for these two MI tasks. Common spatial subspace decomposition (CSSD) was used to extract the features of event-related desynchronization (ERD) in two motor imagery tasks. Then Fisher discriminant analysis (FDA) was employed in the design of two two-class classifiers for completion of detecting each task, respectively. The algorithm successfully provided a way to solve the problem of “idle-state detection without training samples.” The algorithm was applied to the dataset IVc from BCI competition III. A final result with mean square error of 0.30 was obtained on the testing set. This is the winning algorithm in BCI competition III. In addition, the algorithm was also validated by applying to the EEG data of an MI experiment including “idle” task

Exogenous High-Mobility Group Box 1 Protein Injection Improves Cardiac Function after Myocardial Infarction: Involvement of Wnt Signaling Activation

Exogenous high-mobility group box 1 protein (HMGB1) injection could prevent left ventricular remodeling and enhance left ventricular function during myocardial infarction (MI). However, the mechanism remains unclear. This paper was to investigate in the mechanism of cardioprotection of HMGB1 during MI in rats. Anesthetized male rats were treated once with HMGB1 (200 ng) 4 h after MI and then executed after 7 and 28 days, respectively. Cardiac function, collagen deposition, and dishevelled-1 and β-catenin protein expression were measured. After MI 7 days or 28 days, the left ventricular ejection fraction (LVEF) was significantly decreased compared to that of sham-operated control group (P < 0.05). However, the LVEF HMGB1-treated groups were significantly higher compared to those of the MI group in both 7 days and 28 days (P < 0.05). The collagen volume fraction was significantly reduced in the HMGB1-treated group in infarcted border zone. HMGB1 could activate the expression of dishevelled-1 and β-catenin proteins (P < 0.05). Our study suggested that exogenous high-mobility group box 1 protein injection improves cardiac function after MI, which may be involved in Wnt/β-catenin signaling activation

Effects of coarse particulate matter on emergency hospital admissions for respiratory diseases: A time-series analysis in Hong Kong

Background: Many epidemiological studies have linked daily counts of hospital admissions to particulate matter (PM) with an aerodynamic diameter ≤ 10 μm (PM 10) and ≤ 2.5 μm (PM 2.5), but relatively few have investigated the relationship of hospital admissions with coarse PM (PM c; 2.5-10 μm aerodynamic diameter). Objectives: We conducted this study to estimate the health effects of PM c on emergency hospital admissions for respiratory diseases in Hong Kong after controlling for PM 2.5 and gaseous pollutants. Methods: We conducted a time-series analysis of associations between daily emergency hospital admissions for respiratory diseases in Hong Kong from January 2000 to December 2005 and daily PM 2.5 and PM c concentrations. We estimated PMc concentrations by subtracting PM 2.5 from PM 10 measurements. We used generalized additive models to examine the relationship between PM c (single- and multiday lagged exposures) and hospital admissions adjusted for time trends, weather conditions, influenza outbreaks, PM 2.5, and gaseous pollutants (nitrogen dioxide, sulfur dioxide, and ozone). Results: A 10.9-μg/m 3 (interquartile range) increase in the 4-day moving average concentration of PM c was associated with a 1.94% (95% confidence interval: 1.24%, 2.64%) increase in emergency hospital admissions for respiratory diseases that was attenuated but still significant after controlling for PM 2.5. Adjusting for gaseous pollutants and altering models assumptions had little influence on PM c effect estimates. Conclusion: PM c was associated with emergency hospital admissions for respiratory diseases in Hong Kong independent of PM 2.5 and gaseous pollutants. Further research is needed to evaluate health effects of different components of PM c.published_or_final_versio

Exendin-4 attenuates myocardial ischemia and reperfusion injury by inhibiting high mobility group box 1 protein expression

Background: High mobility group box 1 protein (HMGB1) plays an important role in myocardial ischemia and reperfusion (I/R) injury. Exendin-4 (Ex-4), glucagon-like peptide-1 receptor agonist, has been reported to attenuate myocardial I/R injury. This study was to investigate the potential mechanism by which Ex-4 attenuates myocardial I/R injury in rats.Methods: Anesthetized male rats were once treated with Ex-4 (5 μg/kg, i.v.) 1 h before ischemiain the absence and/or presence of exendin (9-39) (an antagonist for glucagon-like peptide-1receptor, 5 μg/kg, i.v.), and then subjected to ischemia for 30 min followed by reperfusion for 4 h. Lactate dehydrogenase (LDH), creatine kinase (CK), malondialdehyde (MDA), superoxide dismutase (SOD) activity and infarct size were measured. HMGB1 expression was assessed by immunoblotting.Results: The results showed that pretreatment of Ex-4 could significantly decrease the infarct size and the levels of LDH and CK after 4 h reperfusion (all p &lt; 0.05). Ex-4 could also significantly inhibit the increase of the MDA level, the decrease of the SOD level (both p &lt; 0.05). Meanwhile, Ex-4 could signifi cantly inhibit HMGB1 expression induced by I/R. Administration of exendin (9-39) could abolish the protective effect of Ex-4 (all p &lt; 0.05).Conclusions: The present study suggested that Ex-4 could attenuate myocardial I/R injury which may be associated with inhibiting HMGB1 expression

Hypomethylation of CYP2E1 and DUSP22 Promoters Associated With Disease Activity and Erosive Disease Among Rheumatoid Arthritis Patients.

OBJECTIVE:Epigenetic modifications have previously been associated with rheumatoid arthritis (RA). In this study, we aimed to determine whether differential DNA methylation in peripheral blood cell subpopulations is associated with any of 4 clinical outcomes among RA patients. METHODS:Peripheral blood samples were obtained from 63 patients in the University of California, San Francisco RA cohort (all satisfied the American College of Rheumatology classification criteria; 57 were seropositive for rheumatoid factor and/or anti-cyclic citrullinated protein). Fluorescence-activated cell sorting was used to separate the cells into 4 immune cell subpopulations (CD14+ monocytes, CD19+ B cells, CD4+ naive T cells, and CD4+ memory T cells) per individual, and 229 epigenome-wide DNA methylation profiles were generated using Illumina HumanMethylation450 BeadChips. Differentially methylated positions and regions associated with the Clinical Disease Activity Index score, erosive disease, RA Articular Damage score, Sharp score, medication at time of blood draw, smoking status, and disease duration were identified using robust regression models and empirical Bayes variance estimators. RESULTS:Differential methylation of CpG sites associated with clinical outcomes was observed in all 4 cell types. Hypomethylated regions in the CYP2E1 and DUSP22 gene promoters were associated with active and erosive disease, respectively. Pathway analyses suggested that the biologic mechanisms underlying each clinical outcome are cell type-specific. Evidence of independent effects on DNA methylation from smoking, medication use, and disease duration were also identified. CONCLUSION:Methylation signatures specific to RA clinical outcomes may have utility as biomarkers or predictors of exposure, disease progression, and disease severity

Real-world efficacy and safety of pyrotinib in patients with HER2-positive metastatic breast cancer: A prospective real-world study

Background: Pyrotinib, a novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor, shows encouraging anticancer activity and acceptable tolerability in multiple phase II and phase III randomized clinical trials, but the real-world data of pyrotinib, especially the outcomes in HER2-positive metastatic breast cancer, have been rarely reported. Here, we evaluated the treatment outcomes of pyrotinib in real-world practice in patients with HER2-positive metastatic breast cancer (MBC).Methods: This was a prospective, real-world, observational cohort study. Through the Breast Cancer Information Management System, HER-2 positive MBC patients treated with pyrotinib between 2017/06 and 2020/09 were included. Provider-reported objective response rate, progression-free survival (PFS), and overall survival (OS) were considered in the assessment of treatment outcomes. Tumor responses to pyrotinib treatment were calculated using RECIST 1.1. Adverse events were evaluated using clinical records.Results: The trial involved 113 individuals who were receiving pyrotinib treatment, with an average age of 51 years. Complete response, partial response and stable disease were observed in 9 (8.0%), 66 (58.4%), and 17 (15.0%) patients, respectively, while progressive disease was recorded in 20 (17.7%) patients. After a median follow-up of 17.2 months, the median PFS was 14.1. The most common adverse events of any grade were diarrhea (87.6%), vomiting (31.9%), and palmar-plantar erythrodysesthesia (26.6%). Among the patients with brain metastases, the median PFS and OS were 15.2 and 19.8 months, respectively. In addition, pyrotinib has similar efficacy in various subtypes of HER2-positive MBC patients, as shown by the lack of a significant difference of PFS and OS among pyrotinib-treated patients with or without brain metastases, or patients using pyrotinib as first-line, second-line, third-line or beyond therapies.Conclusion: Our real-world results demonstrated equivalent clinical efficacy in HER-2 positive MBC patients compared to phase II and phase III clinical trials with pyrotinib, and promising outcomes in patients with brain metastases

Monitoring and analysis of STEC in cow manure from a dairy farm and retail fresh beef around Chengdu City

ObjectiveTo understand the carrying status and strain characteristics of STEC strains in cattle and beef in the local area， provide scientific basis for evaluating the STEC pollution status， infection risk， prevention and control strategies in the region， the Shiga toxin producing Escherichia coli （STEC） in the feces of calves and adult cows and feeding environment in a dairy farm around Chengdu， as well as fresh beef from vegetable markets and supermarkets for three years were continuously monitored.MethodsSTEC using fluorescence quantitative PCR method was identified， and drug sensitivity testing using micro broth dilution method was conducted. After sequencing the entire genome of the isolated strain， the MLST type， strain type， serotyping， and virulence gene information were obtained on the EnteroBase database. The stx subtype information was compared using the Abricate software. Perform cgMLST clustering analysis was used by BioNumerics 7.6 software.ResultsFrom 2019 to 2021， a total of 247 cow manure and environmental samples were collected from dairy farms， and 25 STEC strains were isolated， with a detection rate of 10.12%. 294 fresh beef samples were collected and 32 STECs were isolated， with a detection rate of 10.88%. A total of 57 STEC strains were isolated. The STEC strain had the highest resistance rate to ampicillin， reaching 42.11%（24/57）， followed by cefotaxime and cefazolin at 38.60%（22/57）. Multiple resistant strains accounted for 35.09%（20/57）. A total of 30 serotypes were isolated from 57 STEC strains， among which the serotypes that can cause outbreaks include O26：H11， O103：H25， and O145：H12. Through virulence gene analysis， it was found that subtypes with pathogenic risk included stx2a， stx2c， stx2d， stx2e， stx2g， stx2k， as well as eae-STEC and STEC/ETEC heterozygous strains.ConclusionThe pollution of STEC in cow manure from dairy farms and fresh beef from vegetable markets continued to exist from 2019 to 2021. The detection rate of calf feces was 21.43%， which was higher than that of adult cow feces by 0.91%. The STEC detection rate of fresh beef in vegetable markets is significantly higher than that in supermarkets. The drug resistance of strains isolated from cow manure is more severe than that of strains isolated from beef. Some isolated strains have stronger pathogenicity due to carrying strong virulence genes or other pathogenic related genes

Desipramine Pretreatment Improves Sympathetic Remodeling and Ventricular Fibrillation Threshold after Myocardial Ischemia

Abnormal increase in sympathetic nerve sprouting was responsible for the ventricular arrhythmogenesis after myocardial infarction. This study investigated whether the norepinephrine transporter inhibitor, desipramine, can modulate sympathetic remodeling and ventricular fibrillation threshold (VFT) after myocardial ischemia-reperfusion. Rats were administered desipramine (0.8 mg/kg, IV) before or after myocardial ischemia. VFT, infarct size, tyrosine hydroxylase (TH) and growth-associated protein 43 (GAP43)-positive nerve fibers were measured after one week. The VFT of preischemic treatment group was 11.0±2.65 V and significantly higher than that of control ischemic group (7.2±1.30 V, P<0.05). Infarct size in the preischemic treatment group (23.3±2.4%) was significantly lower than that in the control ischemic group (30.8±1.3%, P<0.05) and the delayed application group (27.1±2.6%, P<0.05). The density of TH and GAP43-positive nerve fibers in the control ischemic group was significantly higher than that in the other three groups (P<0.05). The density of nerve fibers improved after desipramine treatment. Moreover, there was a negative correlation between the VFT and both TH and GAP43-positive nerve fiber density in the infarct border zone (P<0.05). Desipramine treatment before acute myocardial ischemia can decrease infarct size, improve sympathetic remodeling, and increase VFT and electrical stability of ischemic hearts. Desipramine appears to cause myocardial ischemic preconditioning

Mendelian randomization shows a causal effect of low vitamin D on multiple sclerosis risk.

ObjectiveWe sought to estimate the causal effect of low serum 25(OH)D on multiple sclerosis (MS) susceptibility that is not confounded by environmental or lifestyle factors or subject to reverse causality.MethodsWe conducted mendelian randomization (MR) analyses using an instrumental variable (IV) comprising 3 single nucleotide polymorphisms found to be associated with serum 25(OH)D levels at genome-wide significance. We analyzed the effect of the IV on MS risk and both age at onset and disease severity in 2 separate populations using logistic regression models that controlled for sex, year of birth, smoking, education, genetic ancestry, body mass index at age 18-20 years or in 20s, a weighted genetic risk score for 110 known MS-associated variants, and the presence of one or more HLA-DRB1*15:01 alleles.ResultsFindings from MR analyses using the IV showed increasing levels of 25(OH)D are associated with a decreased risk of MS in both populations. In white, non-Hispanic members of Kaiser Permanente Northern California (1,056 MS cases and 9,015 controls), the odds ratio (OR) was 0.79 (p = 0.04, 95% confidence interval (CI): 0.64-0.99). In members of a Swedish population from the Epidemiological Investigation of Multiple Sclerosis and Genes and Environment in Multiple Sclerosis MS case-control studies (6,335 cases and 5,762 controls), the OR was 0.86 (p = 0.03, 95% CI: 0.76-0.98). A meta-analysis of the 2 populations gave a combined OR of 0.85 (p = 0.003, 95% CI: 0.76-0.94). No association was observed for age at onset or disease severity.ConclusionsThese results provide strong evidence that low serum 25(OH)D concentration is a cause of MS, independent of established risk factors