Publications by authors named "Foo R"

Focal adhesions (FAs) are force-bearing multiprotein complexes, whose nanoscale organization and signaling are essential for cell growth and differentiation. However, the specific organization of FA components to exert spatiotemporal activation of FA proteins for force sensing and transduction remains unclear. In this study, we unveil the intricacies of FA protein nanoarchitecture and that its dynamics are coordinated by a molecular scaffold protein, BNIP-2, to initiate downstream signal transduction for cardiomyoblast differentiation.

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There is a new awareness of the widespread nature of metabolic dysfunction-associated steatotic liver disease (MASLD) and its connection to cardiovascular disease (CVD). This has catalyzed collaboration between cardiologists, hepatologists, endocrinologists, and the wider multidisciplinary team to address the need for earlier identification of those with MASLD who are at increased risk for CVD. The overlap in the pathophysiologic processes and parallel prevalence of CVD, metabolic syndrome, and MASLD highlight the multisystem consequences of poor cardiovascular-liver-metabolic health.

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To date, over 40 epigenetic and 300 epitranscriptomic modifications have been identified. However, current short-read sequencing-based experimental methods can detect <10% of these modifications. Integrating long-read sequencing technologies with advanced computational approaches, including statistical analysis and machine learning, offers a promising new frontier to address this challenge.

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  • The study connects genetic variants linked to coronary artery disease (CAD) with cellular and molecular traits by analyzing chromatin accessibility and gene expression in human coronary arteries.
  • Through single-cell analysis, researchers identified thousands of specific chromatin accessibility loci (caQTLs) and found that smooth muscle cells (SMCs) are particularly susceptible to genetic risks associated with CAD.
  • They developed a comprehensive mapping approach to trace disease variants to potential causal genes across different cell types and confirmed their findings using advanced techniques like genome-wide Hi-C and CRISPR interference.
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Heart failure is a clinical syndrome with rising global incidence and poor prognosis despite improvements in medical therapy. There is increasing research interest in epigenetic therapies for heart failure. Pathological cardiac remodelling may be driven by stress-activated cardiac signalling cascades, and emerging research has shown the involvement of epigenetic signals that regulate transcriptional changes leading to heart failure.

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Background & Aims: Plant sterols (PS) have been shown to lower blood lipid-lipoproteins concentrations and may serve as a potential functional ingredient for cardiovascular disease (CVD) risk management. However, there are limited studies examining this effect in individuals with metabolic syndrome (MetS). The aim of this study was to evaluate the effects of PS-enriched food consumption as part of a healthy dietary pattern (HDP) on blood pressure and endothelial function in Singaporean adults with MetS.

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  • - The study aimed to determine how long it takes for intensive lipid-lowering therapy to reduce major adverse cardiovascular events (MACE) in people with established cardiovascular disease (CVD), particularly before and after 2010 when new treatments like PCSK9 inhibitors and ezetimibe were introduced.
  • - Researchers reviewed seven randomized controlled trials involving over 92,000 adults and found that it takes about 19.6 months of intensive therapy to prevent one MACE per 100 patients, with variations based on the treatment used.
  • - Results showed that before 2010, high-intensity statin therapy required a TTB of 15.2 months, while PCSK9i and ezetimibe therapies had longer TTB
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Rationale: Cardiac-expressed long noncoding RNAs (lncRNAs) are important for cardiomyocyte (CM) differentiation and function. Several lncRNAs have been identified and characterized for early CM lineage commitment, however those in later CM lineage specification and maturation remain less well studied. Moreover, unique atrial / ventricular lncRNA expression has never been studied in detail.

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Background: Heart failure (HF) is a leading cause of morbidity and mortality worldwide, with over 18 million deaths annually. Despite extensive research, genetic and environmental factors contributing to HF remain complex and poorly understood. Recent studies suggest that epigenetic modifications, such as DNA methylation, may play a crucial role in regulating HF-associated phenotypes.

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Introduction: This study addresses the rising cardiovascular disease (CVD) rates in the United Arab Emirates (UAE) by investigating the occurrence and impact of genetic variants in CVD-related genes.

Methods: We collected all genes linked to heritable CVD from public and diagnostic databases and mapped them to their corresponding biological processes and molecular pathways. We then evaluated the types and burden of genetic variants within these genes in 343 individuals from the Emirati Mendelian Study Cohort and 3,007 national electronic health records.

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  • The study aims to project cardiovascular disease (CVD) mortality trends and risk factors from 2025 to 2050 to aid healthcare planning.
  • Using historical data and Poisson regression, projections indicate a significant increase in CVD prevalence (90%), crude mortality (73.4%), and DALYs (54.7%), with ischaemic heart disease and high blood pressure as major contributors.
  • Despite a stable age-standardized CVD prevalence, the study underscores a concerning rise in crude mortality due to an aging population, prompting the need for effective healthcare strategies.
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  • * Researchers utilized a fine-mapping approach blending data from a diverse genome-wide association study and expression analysis from different ancestry groups to identify 14 potential causal genes linked to AF.
  • * By silencing a major AF-related gene using CRISPR in heart cells, the study revealed disruptions in pathways crucial for heart tissue and conduction system development.
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  • Molecular chaperons, particularly mitochondrial ones like TRAP1, are important for protein folding, tissue health, and may play a role during infections by regulating processes like oxidative phosphorylation and apoptosis.
  • A case study of a healthy Asian female who developed severe respiratory failure linked to CD4 lymphocytopenia revealed two rare mutations in TRAP1, indicating a connection to her vulnerability to opportunistic infections.
  • The study showed that these TRAP1 mutations led to decreased TRAP1 expression, increased activation of certain caspases, and impaired cellular functions like respiration and glycolysis, highlighting the crucial role of TRAP1 in immune response and disease susceptibility.
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Among their many unique biological features, bats are increasingly recognized as a key reservoir of many emerging viruses that cause massive morbidity and mortality in humans. Bats are capable of harboring many of these deadly viruses without any apparent signs of pathology, in a mechanism known as viral disease tolerance. However, the immunological mechanisms behind viral tolerance remain poorly understood.

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  • Researchers studied 472 patients with left ventricular thrombus (LVT) to identify unique clinical profiles using cluster analysis.
  • They found two distinct groups: one made up of younger patients with fewer risk factors linked primarily to recent heart attacks, and another older group with more comorbidities related to ischemic cardiomyopathy.
  • The study revealed that the second group had a lower chance of LVT resolution and a higher risk of mortality, highlighting the importance of tailored treatment approaches for different patient profiles.
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  • A study forecasts a 91.2% increase in crude cardiovascular disease (CVD) mortality in Asia from 2025 to 2050, despite a 23.0% decrease in the age-standardized mortality rate.
  • Ischaemic heart disease and stroke will remain the top causes of mortality, with Central Asia experiencing the highest mortality rates while high systolic blood pressure is identified as the leading risk factor across most of Asia.
  • The research highlights the need for targeted health interventions due to the significant variations in CVD burden across different regions in Asia.
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DNA methylation plays an important role in various biological processes, including cell differentiation, ageing, and cancer development. The most important methylation in mammals is 5-methylcytosine mostly occurring in the context of CpG dinucleotides. Sequencing methods such as whole-genome bisulfite sequencing successfully detect 5-methylcytosine DNA modifications.

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Improved upstream primary prevention of cardiovascular disease (CVD) would enable more individuals to lead lives free of CVD. However, there remain limitations in the current provision of CVD primary prevention, where artificial intelligence (AI) may help to fill the gaps. Using the data informatics capabilities at the National University Health System (NUHS), Singapore, empowered by the Endeavour AI system, and combined large language model (LLM) tools, our team has created a real-time dashboard able to capture and showcase information on cardiovascular risk factors at both individual and geographical level- CardioSight.

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Aim: Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are at increased risk of incident cardiovascular disease. However, the clinical characteristics and prognostic importance of MASLD in patients presenting with acute myocardial infarction (AMI) have yet to be examined.

Methods: This study compared the characteristics and outcomes of patients with and without MASLD presenting with AMI at a tertiary centre in Singapore.

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  • Cardiomyocyte differentiation is regulated by the modulation of BMP/Wnt signaling pathways, with current research focused on understanding how these pathways remove regulatory obstacles during development.* -
  • A genome-wide CRISPR screen identified NF2 as a critical factor for early cardiomyocyte specification, demonstrating that NF2 is essential for maintaining cardiomyocyte identity during differentiation.* -
  • The study revealed that NF2 works with AMOT to inhibit YAP activation during mesendoderm formation, highlighting their joint role in clearing regulatory barriers necessary for proper cardiac lineage development.*
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Background: It is known that gestational diabetes mellitus (GDM)-complicated pregnancies could affect maternal cardiometabolic health after delivery, resulting in hepatic dysfunction and a heightened risk of developing non-alcoholic fatty liver disease (NAFLD). Hence, this study aims to summarise existing literature on the impact of GDM on NAFLD in mothers and investigate the intergenerational impact on NAFLD in offspring.

Methods: Using 4 databases (PubMed, Embase, Web of Science and Scopus) between January 1980 and December 2023, randomized controlled trials and observational studies that assessed the effect of maternal GDM on intergenerational liver outcomes were extracted and analysed using random-effects meta-analysis to investigate the effect of GDM on NAFLD in mothers and offspring.

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  • Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disorder, but existing treatments mainly relieve symptoms rather than address root causes; research on circular RNAs (circRNAs) offers new insights.
  • A specific circRNA, circZFPM2, was found to be significantly upregulated in HCM cardiac tissue and plays a crucial role in regulating heart cell functions, as shown through experiments in different cell models.
  • Delivering circZFPM2 improved heart cell health by reducing hypertrophy and increasing cell survival, suggesting it could be a potential new target for HCM therapies based on its positive effects on heart function and mitochondrial health.
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