Genome-Wide Association Study in Asian Populations Identifies Variants in ETS1 and WDFY4 Associated with Systemic Lupus Erythematosus

Systemic lupus erythematosus is a complex and potentially fatal autoimmune disease, characterized by autoantibody production and multi-organ damage. By a genome-wide association study (320 patients and 1,500 controls) and subsequent replication altogether involving a total of 3,300 Asian SLE patients from Hong Kong, Mainland China, and Thailand, as well as 4,200 ethnically and geographically matched controls, genetic variants in ETS1 and WDFY4 were found to be associated with SLE (ETS1: rs1128334, P = 2.33×10−11, OR = 1.29; WDFY4: rs7097397, P = 8.15×10−12, OR = 1.30). ETS1 encodes for a transcription factor known to be involved in a wide range of immune functions, including Th17 cell development and terminal differentiation of B lymphocytes. SNP rs1128334 is located in the 3′-UTR of ETS1, and allelic expression analysis from peripheral blood mononuclear cells showed significantly lower expression level from the risk allele. WDFY4 is a conserved protein with unknown function, but is predominantly expressed in primary and secondary immune tissues, and rs7097397 in WDFY4 changes an arginine residue to glutamine (R1816Q) in this protein. Our study also confirmed association of the HLA locus, STAT4, TNFSF4, BLK, BANK1, IRF5, and TNFAIP3 with SLE in Asians. These new genetic findings may help us to gain a better understanding of the disease and the functions of the genes involved

Real-time modelling of observation filter in the remote microphone technique for an active noise control application

The remote microphone technique (RMT) is often used in active noise control (ANC) applications to overcome design constraints in microphone placements by estimating the acoustic pressure at inconvenient locations using a pre-calibrated observation filter (OF), albeit limited to stationary primary acoustic fields. While the OF estimation in varying primary fields can be significantly improved through the recently proposed source decomposition technique, it requires knowledge of the relative source strengths between incoherent primary noise sources. This paper proposes a method for combining the RMT with a new source-localization technique to estimate the source ratio parameter. Unlike traditional source-localization techniques, the proposed method is capable of being implemented in a real-time RMT application. Simulations with measured responses from an open-aperture ANC application showed a good estimation of the source ratio parameter, which allows the observation filter to be modelled in real-time.Ministry of National Development (MND)National Research Foundation (NRF)Submitted/Accepted versionThis research is supported by the Singapore Ministry of National Development and the National Research Foundation, Prime Minister’s Office under the Cities of Tomorrow Research Programme (Award No. COT-V4-2019-1)

MOV-modified-FxLMS algorithm with variable penalty factor in a practical power output constrained active control system

Practical Active Noise Control (ANC) systems typically require a restriction in their maximum output power, to prevent overdriving the loudspeaker and causing system instability. Recently, the minimum output variance filtered-reference least mean square (MOV-FxLMS) algorithm was shown to have optimal control under output constraint with an analytically formulated penalty factor, but it needs offline knowledge of disturbance power and secondary path gain. The constant penalty factor in MOV-FxLMS is also susceptible to variations in disturbance power that could cause output power constraint violations. This letter presents a new variable penalty factor that utilizes the estimated disturbance in the established Modified-FxLMS (MFxLMS) algorithm, resulting in a computationally efficient MOV-MFxLMS algorithm that can adapt to changes in disturbance levels in real-time. Numerical simulation with real noise and plant response showed that the variable penalty factor always manages to meet its maximum power output constraint despite sudden changes in disturbance power, whereas the fixed penalty factor has suffered from a constraint mismatch.Published versio

Clevudine therapy for 24 weeks further reduced serum hepatitis B virus DNA levels and increased ALT normalization rates without emergence of viral breakthrough than 12 weeks of clevudine therapy

OBJECTIVES: The objectives of the study were to evaluate the safety and antiviral activity of 24-week treatment with clevudine 30 mg in HBeAg(+) chronic hepatitis B patients. Biochemical and serological responses were also assessed. METHOD: Twenty-one patients received clevudine 30 mg for 24 weeks and were followed up for another 24 weeks off therapy. RESULTS: Median decreases from baseline in HBV DNA were 4.65 and 1.96 log(10) copies/ml at week 24 (end of treatment) and week 48 (24 weeks off therapy), respectively. Analysis of individual data showed that HBV DNA levels were below the lower limit of detection (300 copies/ml) by Amplicor PCR assay in 19, 57, 19 and 0% at week 12, 24, 34 and 48, respectively. The proportion of patients with normal ALT were 67, 81 and 75% at week 24 (end of treatment), 34 and 48 (24 weeks off therapy), respectively. The rates of HBeAg loss were 24 and 20% at week 24 and 48, respectively. No viral breakthrough during treatment was observed. CONCLUSION: Clevudine 30 mg treatment for 24 weeks was well tolerated and exhibited more potent antiviral activity and a higher ALT normalization rate than 12-week treatment with durable efficacy at week 24 off therapy

Association of anxiety, depression and resilience with overall health and functioning in axial spondyloarthritis (axSpA): a cross-sectional study

Objectives To evaluate the association between anxiety, depression and resilience with overall health and functioning in axial spondyloarthritis (axSpA).Design Cross-sectional evaluation of baseline data from a prospective cohort study, with recruitment from January 2018 to March 2021.Setting Outpatient clinic in a tertiary hospital in Singapore.Participants Patients aged 21 years and above who were diagnosed with axSpA.Outcome measures The Hospital Anxiety and Depression Scale (HADS) was used for assessing anxiety and depression, 10-item Connor Davidson Resilience Scale (CD-RISC-10) for resilience, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for disease activity, Bath Ankylosing Spondylitis Functional Index (BASFI) for functional limitation and Assessment of SpondyloArthritis International Society Health Index (ASAS HI) for overall health and functioning. Univariable and multivariable linear regression analyses were performed to assess the association between anxiety, depression and resilience with health and functioning.Results We included 296 patients in this study. The median (IQR) score for HADS-Anxiety was 5.0 (2.0–8.0), with 13.5% and 13.9% having borderline abnormal and abnormal anxiety, respectively. The median (IQR) score for HADS-Depression was 3.0 (1.0–7.0), with 12.8% and 8.4% having borderline abnormal and abnormal depression, respectively. The median (IQR) CD-RISC-10 score was 29.0 (23.0–32.0) while the median (IQR) ASAS HI score was 4.0 (2.0–7.0). Apart from BASDAI, BASFI and disease duration, anxiety and depression were associated with overall health and functioning (β: 0.12, 95% CI 0.03, 0.20; β: 0.20, 95% CI 0.09, 0.31) in the multivariable linear regression. Level of resilience was not associated with health and functioning.Conclusion Anxiety and depression, but not resilience, were associated with poorer health and functioning. Clinicians could consider routinely screening for anxiety and depression in their patients, especially in patients with more severe symptoms

A 12-week clevudine therapy showed potent and durable antiviral activity in HBeAg-positive chronic hepatitis B

Clevudine is a nucleoside analog with an unnatural beta-L configuration. In a phase I/II clinical trial, once daily doses ranging from 10 to 200 mg for 28 days were well tolerated, and produced significant antiviral activity. The present study was conducted to assess the degree and durability of the antiviral response to 12 weeks of clevudine treatment, and to investigate its safety and tolerability. A total of 98 patients with HBeAg-positive chronic hepatitis B were randomized to placebo (n=32), 30-mg clevudine (n=32), and 50-mg clevudine (n=34) groups. Patients were followed up after 12 weeks of treatment for a further 24 weeks off-therapy. Median serum hepatitis B virus DNA reductions from baseline at week 12 were 0.20, 4.49, and 4.45 log10 copies/mL in the placebo, 30-mg clevudine, and 50-mg clevudine groups, respectively (P < .0001). Posttreatment antiviral activities were sustained, with 3.32 and 2.99 log10 reductions at week 12 off-therapy and 2.28 and 1.40 log10 reductions at week 24 off-therapies in the 30- and 50-mg clevudine groups, respectively. Median serum alanine aminotransferase (ALT) levels decreased markedly from baseline during clevudine treatment and were maintained below the upper limit of normal throughout the 24 weeks off-therapy in the two clevudine-treated groups. The incidences of adverse events and treatment-emergent grade 3 or 4 laboratory abnormalities were similar for the three groups. In conclusion, clevudine showed potent antiviral activity during therapy and induced a sustained posttreatment antiviral effect for 6 months after a 12-week treatment period, and this was associated with a sustained normalization of ALT levels