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Abstract This paper aims to develop an automated web application to generate validated daily effective reproduction numbers (Rt) which can be used to examine the effects of super-spreading events due to mass gatherings and the effectiveness of the various Movement Control Order (MCO) stringency levels on the outbreak progression of COVID-19 in Malaysia. The effective reproduction number, Rt, was estimated by adopting and modifying an Rt estimation algorithm using a validated distribution mean of 3.96 and standard deviation of 4.75 with a seven-day sliding window. The Rt values generated were validated using thea moving window SEIR model with a negative binomial likelihood fitted using methods from the Bayesian inferential framework. A Pearson’s correlation between the Rt values estimated by the algorithm and the SEIR model was r = 0.70, p

Abstract This study sought to determine the potential role of HBB haplotypes to predict beta-thalassemia in the Malaysian population. A total of 543 archived samples were selected for this study. Five tagging SNPs in the beta-globin gene (HBB; NG_000007.3) were analyzed for SNP-based and haplotype association using SHEsis online software. Single-SNP-based association analysis showed three SNPs have a statistically significant association with beta-thalassemia. When Bonferroni correction was applied, four SNPs were found statistically significant with beta-thalassemia; IVS2-74T>G (p adj = 0.047), IVS2-16G>C (p adj = 0.017), IVS2-666C>T (p adj = 0.017) and 3’UTR + 314G>A (p adj = 0.002). However, 3'UTR + 233G>C did not yield a significant association with p adj value = 0.076. Further investigation using combined five SNPs for haplotype association analysis revealed three susceptible haplotypes with significant p values of which, haplotypes 1-2-2-1-1 (p = 6.49 × 10−7, OR = 10.371 [3.345–32.148]), 1-2-1-1-1 (p = 0.009, OR = 1.423 [1.095–1.850] and 1-1-1-1-1 (p = 1.39 × 10−4, OR = 10.221 [2.345–44.555]). Three haplotypes showed protective effect with significant p value of which, 2-2-1-1-1 (p = 0.006, OR = 0.668 [0.500–0.893]), 1-1-2-2-1 (p = 0.013, OR = 0.357 [0.153–0.830]) and 1-1-2-1-1 (p = 0.033, OR = 0.745 [0.567–0.977]). This study has identified the potential use of intragenic polymorphic markers in the HBB gene, which were significantly associated with beta-thalassemia. Combining these five SNPs defined a new haplotype model for beta-thalassemia and further evaluation for predicting severity in beta-thalassemia.

Abstract The susceptible-infectious-removed (SIR) model offers the simplest framework to study transmission dynamics of COVID-19, however, it does not factor in its early depleting trend observed during a lockdown. We modified the SIR model to specifically simulate the early depleting transmission dynamics of COVID-19 to better predict its temporal trend in Malaysia. The classical SIR model was fitted to observed total (I total), active (I) and removed (R) cases of COVID-19 before lockdown to estimate the basic reproduction number. Next, the model was modified with a partial time-varying force of infection, given by a proportionally depleting transmission coefficient, $$\beta_{t}$$ β t and a fractional term, z. The modified SIR model was then fitted to observed data over 6 weeks during the lockdown. Model fitting and projection were validated using the mean absolute percent error (MAPE). The transmission dynamics of COVID-19 was interrupted immediately by the lockdown. The modified SIR model projected the depleting temporal trends with lowest MAPE for I total, followed by I, I daily and R. During lockdown, the dynamics of COVID-19 depleted at a rate of 4.7% each day with a decreased capacity of 40%. For 7-day and 14-day projections, the modified SIR model accurately predicted I total, I and R. The depleting transmission dynamics for COVID-19 during lockdown can be accurately captured by time-varying SIR model. Projection generated based on observed data is useful for future planning and control of COVID-19.

Abnormal immune reactivity in patients with beta-thalassemia (beta-thal) major can be associated with poor prognosis. Immunome protein-array analysis represents a powerful approach to identify novel biomarkers. The Sengenics Immunome Protein Array platform was used for high-throughput quantification of autoantibodies in 12 serum samples collected from nine beta-thal major patients and three non-thalassemia controls, which were run together with two pooled normal sera (Sengenics Internal QC samples). To obtain more accurate and reliable results, the evaluation of the biological relevance of the shortlisted biomarkers was analyzed using an Open Target Platform online database. Elevated autoantibodies directed against 23 autoantigens on the immunome array were identified and analyzed using a penetrance fold change-based bioinformatics method. Understanding the autoantibody profile of beta-thal major patients would help to further understand the pathogenesis of the disease. The identified autoantigens may serve as potential biomarkers for the prognosis of beta-thal major.

Background Prospective data on cardiac iron removal are limited beyond one year and longer-term studies are, therefore, important.Design and Methods Seventy-one patients in the EPIC cardiac substudy elected to continue into the 3rd year, allowing cardiac iron removal to be analyzed over three years.Results Mean deferasirox dose during year 3 was 33.6±9.8 mg/kg per day. Myocardial T2*, assessed by cardiovascular magnetic resonance, significantly increased from 12.0 ms ±39.1% at baseline to 17.1 ms ±62.0% at end of study (P

Background The efficacy of cardiac iron chelation in transfusion-dependent patients has been demonstrated in one-year prospective trials. Since normalization of cardiac T2* takes several years, the efficacy and safety of deferasirox was assessed for two years in patients with β-thalassemia major in the cardiac sub-study of the EPIC trial.Design and Methods Eligible patients with myocardial T2* greater than 5 to less than 20 ms received deferasirox, with the primary endpoint being the change in T2* from baseline to two years.Results Baseline myocardial T2* was severe (>5 to