Metformin hydrochloride (Met.HCl) is widely used for the management of type 2 diabetes mellitus (T2DM); however, conventional dosage forms can be inconvenient for individuals with dysphagia. This study aimed to develop orally disintegrating tablets (ODT) that rapidly disintegrate upon contact with saliva, thereby improving patient compliance. Met.HCl was spray-dried with selected excipients to enhance compressibility and mask its bitterness. A D-optimal design of experiments (DOE) was employed to optimize excipient ratios and compression parameters. The resulting Met.HCl ODT were evaluated for hardness, disintegration time, tensile strength, dissolution performance, and stability. The D-optimal DOE successfully predicted the optimal factors and responses with model validation confirming its reliability. The optimized Met.HCl ODT, formulated with spray-dried Met.HCl, exhibited excellent hardness (70 N), rapid disintegration (< 30 s), complete drug release within 5 min and maintained its physical stability over 6 months of accelerated storage. This study demonstrates that D-optimal DOE-based formulation optimization, combined with spray-dried Met.HCl, allows the development of ODT that balance fast disintegration and robust mechanical performance. The optimized Met.HCl ODT provides a patient-friendly alternative for individuals with swallowing difficulties while maintaining effective drug delivery.
Single-nucleotide polymorphisms (SNPs) influence disease susceptibility, making it essential to identify harmful variants. The vitamin D receptor (VDR) and bone morphogenetic protein 2 (BMP2) genes, which regulate bone metabolism, calcium balance, and immune function, are implicated in ankylosing spondylitis (AS). Deleterious non-synonymous SNPs (nsSNPs) in VDR and BMP2 genes, which were identified using various computational tools, such as Polyphen-2, SIFT, Mutation Assessor, Meta-SNP, PhD-SNP, PROVEAN, PANTHER, SNAP-2, and SNPs GO. Predicted nsSNPs were further analyzed for protein stability (I-Mutant, MUpro, ) evolutionary conservation (ConSurf), protein interaction (GeneMANIA, STRING). and structural impact (Project HOPE) analysis. Fourteen missense SNPs in VDR and ten missense SNPs in the BMP2 gene were predicted to be deleterious. Stability analysis indicated that these SNPs altered protein stability, while ConSurf showed that SNPs were located in conserved regions. Project HOPE analysis revealed significant effects on residue physicochemical properties and protein structure. The identified deleterious nsSNPs in the VDR and BMP2 genes may contribute to AS susceptibility by affecting protein structure and function. These findings highlight the potential contribution of these nsSNPs in AS susceptibility and could be utilized in future experimental studies. The predicted nsSNPs may also serve as molecular targets for diagnostic and therapeutic applications.
This article examines the relationship between green resources, digital technology capabilities, and firm performance within the Malaysian automotive industry. Despite growing attention to sustainability, the industry continues to operate under a linear “take-make-dispose” model. Consequently, contributes substantially to greenhouse gas emissions through material and energy consumption. This conceptual article draws from the underpinning theories, the Resource-Based View (RBV) and the Dynamic Capabilities View (DCV). The green resources encompassing eco-friendly materials, waste recovery, water and energy conservation, green technology, and skilled personnel represent valuable, rare, inimitable, and non-substitutable (VRIN) characteristics. However, their potential to enhance firm performance remains partially absent without suitable activation mechanisms. We argue that digital technology capabilities (sensing, learning, integrating, and coordinating) serve as a mediating enabler that transforms static green resources into dynamic performance outcomes. A framework and four testable hypotheses are developed and contribute to the sustainability literature by bridging the RBV and DCV in an emerging economy context. This study offers practical insights for managers and policymakers seeking to align digital transformation with circular economy goals.
Private higher education institutions in Malaysia play a vital role in producing digitally skilled workers that can support the Malaysia Education Blueprint, Malaysian Qualifications Framework, Industry4WRD and MyDIGITA, while also achieving the outcomes of the Sustainable Development Goals. However, these institutions face several significant issues including not developing 21st century skillsets (e.g., critical thinking, self-regulation and responsible use of technology) consistently among their students. This conceptual paper reconceptualises academic performance as being determined mostly by demonstrable employability skills/competencies and not by academic results. This research will then consider how well constructs such as digital well-being, digital self-control, satisfaction with life, digital homo-ignorance, and social anxiety can predict students’ success at private higher education institutions (HEIs). Using Social Cognitive Theory (SCT) as a theoretical foundation, the proposed conceptual framework will delineate how there are reciprocal relationships among personal factors, digital environments, and self-regulatory behaviours of students, with self-efficacy being the primary mechanism for achieving lifelong success. The research has the potential to contribute to academia by providing a performance discourse which is inclusive of both the digital and the socio-psychological dimensions while also providing valuable information for policymakers and HEIs to assist in reframing their curricula, digital hygiene, information literacy and student well-being interventions. The research helps mitigate urgent gaps in employability, improves the competitiveness of institutions, to underpin Malaysia's aspirations as a leading education hub. This paper is limited in its conceptual nature, thus potential research is warranted to empirically test this framework, encompassing broader student populations, advanced quantitative methods and longitudinal designs. Ultimately, the framework demonstrates that HEIs need to develop holistic graduates that are digitally balanced, with cognitive expertise, emotional robustness, and future preparedness.
Summary: Background: The drivers of mortality and their associated risk factors evolve throughout the course of life. Understanding these transitions is essential for effective, equitable, and age-appropriate health interventions. Methods: As part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, we examined life expectancy and the probability of death from birth to age 70 years (70q0) from 1990 to 2023 for each Association of Southeast Asian Nations (ASEAN) member state. In addition, we assessed causes of death and risk factor by age and sex across different life stages. Life expectancy was estimated from age-specific mortality rates with standard demographic techniques, and 70q0 from mortality and GBD life tables. Cause-specific mortality was estimated using the Cause of Death Ensemble model, and risk-attributable mortality using the comparative risk assessment framework. Findings: In 2023, regional life expectancy was 70·1 years (95% uncertainty interval 69·6–70·7) for males and 76·2 years (75·7–76·7) for females, ranging from 87·5 years (87·3–87·8) for females in Singapore to 62·1 years (60·8–63·5) for males in Myanmar. Correspondingly, all-cause 70q0 was higher for males than for females. Neonatal disorders were the leading cause of mortality among infants younger than 1 year. Road injuries were the primary driver of mortality among males from adolescence through to early adulthood, accounting for 25·0% (17·0–31·0) of total mortality (8230 [5740–10 800] deaths) in males aged 15–19 years, with mortality rates varying from 3·0 per 100 000 population (2·3–3·7) to 49·0 per 100 000 population (25·0–67·1) between countries. Among females, maternal disorders were the leading cause of death in ages 25–34 years. In mid-adulthood, non-communicable diseases such as ischaemic heart disease and stroke emerged as major causes. Tobacco use was the dominant risk factor across most of adulthood in males, whereas high blood pressure was the prevailing risk factor among adult females. Interpretation: Although the leading causes of death have converged across countries, the outcomes of these causes remain divergent, reflecting persistent inequalities across the region. These patterns present a strategic opportunity for multilateral action to mobilise collective resources and achieve regional health equity. Funding: Gates Foundation.
