Loyalty Card Membership Challenge: A Study on Membership Churn and their Spending Behaviour

Understand member spending behaviour and their loyalty is important in all industries. By gaining loyalty from customers and understand how they spend, companies are able to retain their customers, increase their revenue and plan their marketing strategy to continue grow their business in a competitive business ecosystem. This research investigates member spending behaviour and membership churn for a loyalty card company in Malaysia. This research conducts exploratory analysis on three key partners registered with the company to understand their outlets’ spending activities and patterns. Meanwhile, this research also model membership churn based on the last 24 months membership data to identify factors that influence membership churn so that effective strategy can be formulated to retain active members in the company

A meta-analysis comparing 48-week treatment outcomes of single and multi-tablet antiretroviral regimens for the treatment of people living with HIV

Abstract Objectives To compare outcomes with single tablet regimens (STR) versus multi-tablet regimens (MTR) for human immunodeficiency virus (HIV) treatment using published data. Design Systematic review and random-effects meta-analysis of literature on approved and investigational HIV regimens. Methods The research followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Single or un-blinded studies reporting a direct comparison between STR and MTR were eligible for the meta-analysis. Double-blinded studies were excluded due to lack of difference in pill burden between cohorts. The key outcomes of interest included: adherence rates/proportion meeting target, efficacy, safety/tolerability, non-clinical and economic outcomes. Results After screening 63 full-text articles and posters, 14 studies were eligible for the meta-analysis. The analysis showed that patients taking STR had improved outcomes over those taking MTR. Patients were significantly more adherent regardless of daily dosing frequency (odds ratio [OR]: 1.96, p < 0.001) and were more likely to achieve virological suppression (relative risk [RR]: 1.05, p = 0.002). There was a trend toward a lower discontinuation risk in the STR cohort, together with reported higher therapy satisfaction, better symptom control, improved health status, reduced healthcare resource utilization and demonstrated cost-effectiveness compared to MTR. There were no differences in CD4 cell count increase (at 48 weeks) or safety outcomes. Conclusions The findings of this study confirm previously reported preliminary findings of the advantages of STR over MTR for HIV treatment in adherence, therapy continuation, viral suppression, tolerability, quality of life improvement, cost-effectiveness and healthcare resource utilization

Evaluation of bacteriological quality of locally produced raw and pasteurised milk in Selangor, Malaysia

High demand for milk has been observed amongst the Malaysian public. Hence, research in milk is essential to assure food safety in milk consumption. This study evaluated the quality of locally-produced milk and present of bacterial hazards in cow and goat milk. A total of 120 milk samples including thirty raw cow milk, thirty pasteurized cow milk, thirty raw goat milk and thirty pasteurised goat milk were collected from dairy farms, delivery milkman, marts and markets in Selangor, Malaysia. The bacteriological quality of milk was evaluated for the presence of Escherichia coli, mesophilic, and coliform bacteria. An acceptable standard limit of < 1 x 105 CFU/mL for the total bacterial count was used to indicate good quality of milk. Overall, all type of milk exceeded 100,000 CFU/mL. The pasteurized raw goat milk showed the highest (7.16 log10 CFU/mL) in total plate count while the pasteurized cow milk recorded as the lowest (5.38 log10 CFU/mL) in total plate count. Approximately half of the milk samples were contaminated with coliform bacteria and a proportion has exceeded the acceptable limit of 50 CFU/mL. The presence of E. coli was detected in over 44% of the samples. Milk contaminated with the pathogenic E. coli can cause self-limited, watery to bloody diarrhea including severe diseases like haemolytic uremic syndrome (HUS). Hence, it is important to ensure the quality of milk for public health safety

Discovery of N-trisubstituted Pyrimidine Derivatives as Type-I RET and RET Gatekeeper Mutant Inhibitors with a Novel Kinase Binding Pose

Rearranged during transfection (RET) kinase is an attractive therapeutic target in cancers in which RET gene fusions and point mutations in the kinase domain are reported. Mutation of V804, the RET gatekeeper residue, leads to resistance to several FDA approved inhibitors. In this study, we discovered a series of N-trisubstituted pyrimidine derivatives as potent inhibitors for both wt-RET and RETV804M. Enzyme kinetics indicate that these inhibitors are ATP-competitive. The X-ray structure of a representative inhibitor in complex with RET reveals that the compound binds a unique pose that bifurcates beneath the P-loop; this is the first time that such a binding pose for a kinase inhibitor is described. Moreover, this binding pose explained the ability of N-trisubstituted pyrimidine compounds of targeting RETV804M. A structure activity relationship (SAR) was performed and compound 20 was identified as a lead one, displaying potent inhibition of RET and RETV804M with IC50 of 6.20nM and 18.68nM, respectively. Additionally, compound 20 showed potent anti-proliferative activity in CCDC6-RET driven LC-2/ad lung carcinoma cells. A wound healing assay indicated that compound 20 inhibits migration of RET mutant tumor cells. Analysis of apoptosis and RET phosphorylation indicated that such biological activities were mediated by RET inhibition. Collectively, N-trisubstituted pyrimidine derivatives could serve as scaffolds for the discovery and development of potent type-I RET and its gatekeeper mutant inhibitors for the treatment of RET driven cancers

Targeted Quantification of Phosphorylation Dynamics in the Context of EGFR-MAPK Pathway

Large-scale phosphoproteomics with coverage of over 10,000 sites of phosphorylation have now been routinely achieved with advanced mass spectrometry (MS)-based workflows. However, accurate targeted MS-based quantification of phosphorylation dynamics, an important direction for gaining quantitative understanding of signaling pathways or networks, has been much less investigated. Herein, we report an assessment of the targeted workflow in the context of signal transduction pathways, using the epidermal growth factor receptor (EGFR)–mitogen-activated protein kinase (MAPK) pathway as our model. A total of 43 phosphopeptides from the EGFR–MAPK pathway were selected for the study. The recovery and sensitivity of two commonly used enrichment methods, immobilized metal affinity chromatography (IMAC) and titanium oxide (TiO₂), combined with selected reaction monitoring (SRM)-MS were evaluated. The recovery of phosphopeptides by IMAC and TiO₂ enrichment was quantified to be 38 ± 5% and 58 ± 20%, respectively, based on internal standards. Moreover, both enrichment methods provided comparable sensitivity from 1 to 100 μg starting peptides. Robust quantification was consistently achieved for most targeted phosphopeptides when starting with 25–100 μg peptides. However, the numbers of quantified targets significantly dropped when peptide samples were in the 1–25 μg range. Finally, IMAC-SRM was applied to quantify signaling dynamics of EGFR-MAPK pathway in Hs578T cells following 10 ng/mL EGF treatment. The kinetics of phosphorylation clearly revealed early and late phases of phosphorylation, even for very low abundance proteins. These results demonstrate the feasibility of robust targeted quantification of phosphorylation dynamics for specific pathways, even starting with relatively small amounts of protein