Unlocking hidden potential: advancements, approaches, and obstacles in repurposing drugs for cancer therapy.

High rates of failure, exorbitant costs, and the sluggish pace of new drug discovery and development have led to a growing interest in repurposing "old" drugs to treat both common and rare diseases, particularly cancer. Cancer, a complex and heterogeneous disease, often necessitates a combination of different treatment modalities to achieve optimal outcomes. The intrinsic polygenicity of cancer, intricate biological signalling networks, and feedback loops make the inhibition of a single target frequently insufficient for achieving the desired therapeutic impact. As a result, addressing these complex or "smart" malignancies demands equally sophisticated treatment strategies. Combinatory treatments that target the multifaceted oncogenic signalling network hold immense promise. Repurposed drugs offer a potential solution to this challenge, harnessing known compounds for new indications. By avoiding the prohibitive costs and long development timelines associated with novel cancer drugs, this approach holds the potential to usher in more effective, efficient, and cost-effective cancer treatments. The pursuit of combinatory therapies through drug repurposing may hold the key to achieving superior outcomes for cancer patients. However, drug repurposing faces significant commercial, technological and regulatory challenges that need to be addressed. This review explores the diverse approaches employed in drug repurposing, delves into the challenges faced by the drug repurposing community, and presents innovative solutions to overcome these obstacles. By emphasising the significance of combinatory treatments within the context of drug repurposing, we aim to unlock the full potential of this approach for enhancing cancer therapy. The positive aspects of drug repurposing in oncology are underscored here; encompassing personalized treatment, accelerated development, market opportunities for shelved drugs, cancer prevention, expanded patient reach, improved patient access, multi-partner collaborations, increased likelihood of approval, reduced costs, and enhanced combination therapy.

Multifunctional Sandwich-Structured Super-Hygroscopic Zinc-Based MOF-Overlayed Cooling Wearables for Special Personal Thermal Management.

Personal protective equipment pays attention exclusively to external safety protection and ignores the internal thermoregulation of physiological state in association with sweating. Herein, a super-hygroscopic calcium-doped poly(sodium 4-styrenesulfonate) and superhydrophobic metal-organic-framework-overlayed wearables (Ca-PSS/MOF) integrated cooling wearable is proposed for special personal thermal management (PTM). Compared to the pristine fabric, the superhydrophobic MOF wearables exhibit anti-fouling and antibacterial capabilities, and the antibacterial efficiency is up to 99.99% and 98.99% against E. coli and S. aureus, respectively. More importantly, Ca-PSS/MOF demonstrate significant heat index changes up to 25.5 °C by reducing relative humidity dramatically from 91.0% to 60.0% and temperature from 36.5 to 31.6 °C during the running test. The practical feasibility of the Ca-PSS/MOF cooling wearables is well proved with the protective suit of the fireman. Owing to these multifunctional merits, the sandwich-structured cooling Ca-PSS/MOF are expected to provide new insights for designing the next-generation multifunctional apparel for PTM.

Recent Advances in Understanding the Molecular Basis of Infantile Haemangioma Development.

Infantile haemangioma (IH), the most common vascular tumour of infancy, is comprised of diverse cell types including endothelial cells, pericytes, fibroblasts and immune cells. IH is characterized by rapid proliferation followed by slow involution over 1 - 10 years. Most lesions regress spontaneously, but up to 10% can be disfiguring with complications that require further medical treatment. Recent research has revealed the biological characteristics of IH, highlighting the involvement of angiogenesis and vasculogenesis during tumour formation. Gene expression profiling has provided vital insights into these underlying biological processes, with some of the key IH-related pathways identified, including VEGF, RAAS, HIF-1α, Notch, PDGF, PI3K/Akt/mTOR, JAK/STAT, FGF, PPARγ, IGF. Further evidence suggests extracellular matrix factors and hormone receptors regulate IH progression. In this review, we explore the molecular mechanisms involved in the proliferating, plateau and involuting phases of IH. This involves identifying differentially expressed genes, targeted proteins, and key signalling pathways. This knowledge will increase the broader understanding of vascular development, tissue remodelling and angiogenesis.

Artificial Intelligence (AI)-driven dental education: Exploring the role of chatbots in a clinical learning environment.

STATEMENT OF PROBLEM: Despite their widespread use in various educational contexts, the integration of chatbots into dental clinical education has not been thoroughly investigated. The noted discrepancy signifies a lack of understanding of how chatbots could enhance the personalized and interactive learning experiences of predoctoral dental students. PURPOSE: The purpose of this study was to evaluate the awareness and perceptions of artificial intelligence (AI) technology, interaction experiences, and concerns about a custom-developed chatbot (CB) intervention in the clinical education of predoctoral dental students at the University of Illinois Chicago, College of Dentistry (UIC-COD) compared with the traditional Blackboard (BB) online platform. MATERIAL AND METHODS: Eligible participants (n=86) providing verbal consent were allocated via the random block method into BB (n=43) and CB (n=43) groups and asked to engage with their designated platforms for 10 to 15 minutes by focusing on clinical inquiries in a predoctoral implant clinic and supported by a list of 35 typical questions. After the interaction, participants responded on a 5-point Likert scale to a 19-item survey probing AI awareness, platform engagement, and technological concerns. Survey data were anonymized and analyzed using descriptive, inferential statistics and nonparametric Mann-Whitney U tests to compare interventions. The Bonferroni correction for multiple comparisons was performed (α=.0045). RESULTS: Neither the BB or CB group showed any difference in their awareness and perception of AI technology. The CB group demonstrated improved timeliness (P<.001), more interaction (P<.001), reduced faculty workload (P=.001), enhanced receptiveness (P=.002), and less anxiety (P<.001) and was more satisfied (P<.001) when compared with the BB group. However, concerns regarding the potential for incorrect information (P=.003) were more pronounced in the CB group. CONCLUSIONS: The integration of chatbot technology into dental clinical education significantly enhanced learning and student engagement, highlighting the potential for future technological enrichment of the educational landscape.

Wood Lamella-Inspired Photothermal Stearic Acid-Eutectic Gallium-Indium-Based Phase Change Aerogel for Thermal Management and Infrared Stealth.

Eutectic Gallium-Indium (EGaIn) liquid metal is an emerging phase change metal material, but its low phase transition enthalpy and low light absorption limit its application in photothermal phase change energy storage materials (PCMs) field. Here, based on the dipole layer mechanism, stearic acid (STA)-EGaIn-based PCMs which exhibit extraordinary solar-thermal performance and phase change enthalpy are fabricated by ball milling method. The wood lamella-inspired cellulose-derived aerogel and molybdenum disulfide (MoS2 ) are used to support the PCMs by the capillary force and decrease the interfacial thermal resistance. The resulted PCMs achieved excellent photothermal conversion performance and leakage proof. They  have excellent thermal conductivity of 0.31 W m-1 K-1 (this is increased by 138% as compared with pure STA), and high phase change enthalpy of187.50 J g-1 , which is higher than the most of the reported PCMs. Additionally, the thermal management system and infrared stealth materials based on the PCMs are developed. This work provides a new way to fabricate smart EGaIn-based PCMs for energy storage device thermal management and infrared stealth.

Reversible Hydration Composite Films for Evaporative Perspiration Control and Heat Stress Management.

Donning of personal protective equipment (PPE) in the healthcare sector has been intensified by the on-going COVID-19 pandemic around the globe. While extensive PPE provides protection, it typically limits moisture permeability and severely hinders the sweat evaporation process, resulting in greater heat stress on the personnel. Herein, a zinc-poly(vinyl alcohol) (Zn-PVA) composite film is fabricated by embedding a super-hygroscopic zinc-ethanolamine complex (Zn-complex) in the PVA matrix. By attaching the Zn-PVA composite film, the relative humidity (RH) inside the protective suit decreases from 91.0% to 48.2%. The reduced RH level, in turn, enhances evaporative cooling, hence bringing down the heat index from 64.6 to 40.0 °C at an air temperature of 35 °C, remarkably lowering the likelihood of heat stroke. The American Society for Testing and Materials tests conducted on a sweating manikin have also proven that the Zn-PVA composite films can significantly reduce the evaporative resistance of the protective suit by 90%. The low material cost, facile fabrication process, and reusability allow the Zn-PVA composition films to be readily available for healthcare workers worldwide. This application can be further extended to other occupations that are facing severe thermal discomfort and heat stress.

Proteomic analysis of low- and high-grade human colon adenocarcinoma tissues and tissue-derived primary cell lines reveals unique biological functions of tumours and new protein biomarker candidates.

BACKGROUND: Colon cancer is the third most common cancer and second highest cause of cancer deaths worldwide. The aim of the study was to find new biomarkers for diagnosis, prognosis and therapeutic drug targets for this disease. METHODS: Four low-grade and four high-grade human colon adenocarcinoma tumours with patient-matched normal colon tissues were analysed. Additionally, tissue-derived primary cell lines were established from each tumour tissue. The cell lines were validated using DNA sequencing to confirm that they are a suitable in vitro model for colon adenocarcinoma based on conserved gene mutations. Label-free quantitation proteomics was performed to compare the proteomes of colon adenocarcinoma samples to normal colon samples, and of colon adenocarcinoma tissues to tissue-derived cell lines to find significantly differentially abundant proteins. The functions enriched within the differentially expressed proteins were assessed using STRING. Proteomics data was validated by Western blotting. RESULTS: A total of 4767 proteins were identified across all tissues, and 4711 across primary tissue-derived cell lines. Of these, 3302 proteins were detected in both the tissues and the cell lines. On average, primary cell lines shared about 70% of proteins with their parent tissue, and they retained mutations to key colon adenocarcinoma-related genes and did not diverge far genetically from their parent tissues. Colon adenocarcinoma tissues displayed upregulation of RNA processing, steroid biosynthesis and detoxification, and downregulation of cytoskeletal organisation and loss of normal muscle function. Tissue-derived cell lines exhibited increased interferon-gamma signalling and aberrant ferroptosis. Overall, 318 proteins were significantly up-regulated and 362 proteins significantly down-regulated by comparisons of high-grade with low-grade tumours and low-grade tumour with normal colon tissues from both sample types. CONCLUSIONS: The differences exhibited between tissues and cell lines highlight the additional information that can be obtained from patient-derived primary cell lines. DNA sequencing and proteomics confirmed that these cell lines can be considered suitable in vitro models of the parent tumours. Various potential biomarkers for colon adenocarcinoma initiation and progression and drug targets were identified and discussed, including seven novel markers: ACSL4, ANK2, AMER3, EXOSC1, EXOSC6, GCLM, and TFRC.

Addressing cellular heterogeneity in tumor and circulation for refined prognostication.

Despite pronounced genomic and transcriptomic heterogeneity in non-small-cell lung cancer (NSCLC) not only between tumors, but also within a tumor, validation of clinically relevant gene signatures for prognostication has relied upon single-tissue samples, including 2 commercially available multigene tests (MGTs). Here we report an unanticipated impact of intratumor heterogeneity (ITH) on risk prediction of recurrence in NSCLC, underscoring the need for a better genomic strategy to refine prognostication. By leveraging label-free, inertial-focusing microfluidic approaches in retrieving circulating tumor cells (CTCs) at single-cell resolution, we further identified specific gene signatures with distinct expression profiles in CTCs from patients with differing metastatic potential. Notably, a refined prognostic risk model that reconciles the level of ITH and CTC-derived gene expression data outperformed the initial classifier in predicting recurrence-free survival (RFS). We propose tailored approaches to providing reliable risk estimates while accounting for ITH-driven variance in NSCLC.

Beyond fitness tracking: The use of consumer-grade wearable data from normal volunteers in cardiovascular and lipidomics research.

The use of consumer-grade wearables for purposes beyond fitness tracking has not been comprehensively explored. We generated and analyzed multidimensional data from 233 normal volunteers, integrating wearable data, lifestyle questionnaires, cardiac imaging, sphingolipid profiling, and multiple clinical-grade cardiovascular and metabolic disease markers. We show that subjects can be stratified into distinct clusters based on daily activity patterns and that these clusters are marked by distinct demographic and behavioral patterns. While resting heart rates (RHRs) performed better than step counts in being associated with cardiovascular and metabolic disease markers, step counts identified relationships between physical activity and cardiac remodeling, suggesting that wearable data may play a role in reducing overdiagnosis of cardiac hypertrophy or dilatation in active individuals. Wearable-derived activity levels can be used to identify known and novel activity-modulated sphingolipids that are in turn associated with insulin sensitivity. Our findings demonstrate the potential for wearables in biomedical research and personalized health.

Knowledge of Heart Disease, Preventive Behavior and Source of Information in a Multi-ethnic Asian Population: A Population-Based Survey.

Several population-based studies have been conducted to better understand the public knowledge of cardiovascular disease (CVD) and behavior. However, most studies have predominantly focused on Western populations. This study aimed to investigate heart disease knowledge, preventive behavior and source of information on heart disease in a multi-ethnic Asian population. We conducted a nation-wide population-based survey of 1000 participants of three ethnic groups (Chinese, Malay, Indian) in Singapore. A structured questionnaire was used to collect sociodemographics, knowledge on CVD risk factors, symptoms, emergency action, preventive health behaviors and sources of information on heart disease. Univariate and multivariate analyses were conducted to identify factors associated with the CVD knowledge and behavior. Knowledge on CVD risk factors was generally high. Knowledge on emergency actions was low particularly in younger people. More than 60% did not meet the recommended levels of physical activity, and this was more evident for individuals of overweight/obese status, lower education and workforce. Chinese were less likely to be obese/overweight compared to the Malays and Indians. Malays were less likely to seek information from internet and social media compared to their ethnic counterparts. This study highlighted heterogeneity in the levels of knowledge and health behavior across population segments, suggesting the need for a tailored approach to heart health interventions and optimal channels for information dissemination. Our findings will form the basis for contextually and culturally appropriate interventions to combat the growing CVD burden and prevent its toll on a rapidly ageing population.

Bilateral Mastoid Process Hypertrophy Associated With Severe Trismus.

ABSTRACT: The mastoid process, a pneumatized prominence of the temporal bone with air-filled air cells, grows with age. We present here a series of 4 patients with bilateral mastoid hypertrophy associated with severe trismus from different etiologies, and discuss the possible explanation of this observation.

Novel Conformal Skin Patch with Embedded Thin-Film Electrodes for Early Detection of Extravasation.

Extravasation is a complication of intravenous (IV) cannulation in which vesicant drugs leak from a vein into the surrounding subcutaneous tissue. The severity of extravasation depends on the type, concentration, and volume of drugs that accumulate in the subcutaneous tissue. Rapid detection of extravasation can facilitate prompt medical intervention, minimizing tissue damage, and preventing adverse events. In this study, we present two portable sensor patches, namely gold- and carbon-based sensing patches, for early detection of extravasation. The gold-based sensor patch detected extravasated fluid of volume as low as 2 mL in in vivo animal models and human clinical trials; the patch exhibited a resistance change of 41%. The carbon-based sensor patch exhibited a resistance change of 51% for 2 mL of extravasated fluid, and fabrication throughput and cost-effectiveness are superior for this patch compared with the gold-based sensing patch.

Ultrathin Two-Dimensional Membranes Assembled by Ionic Covalent Organic Nanosheets with Reduced Apertures for Gas Separation.

Covalent organic frameworks (COFs) are a promising category of porous materials possessing extensive chemical tunability, high porosity, ordered arrangements at a molecular level, and considerable chemical stability. Despite these advantages, the application of COFs as membrane materials for gas separation is limited by their relatively large pore apertures (typically >0.5 nm), which exceed the sieving requirements for most gases whose kinetic diameters are less than 0.4 nm. Herein, we report the fabrication of ultrathin two-dimensional (2D) membranes through layer-by-layer (LbL) assembly of two kinds of ionic covalent organic nanosheets (iCONs) with different pore sizes and opposite charges. Because of the staggered packing of iCONs with strong electrostatic interactions, the resultant membranes exhibit features of reduced aperture size, optimized stacking pattern, and compact dense structure without sacrificing thickness control, which are suitable for molecular sieving gas separation. One of the hybrid membranes, TpEBr@TpPa-SO3Na with a thickness of 41 nm, shows a H2 permeance of 2566 gas permeation units (GPUs) and a H2/CO2 separation factor of 22.6 at 423 K, surpassing the recent Robeson upper bound along with long-term hydrothermal stability. This strategy provides not only a high-performance H2 separation membrane candidate but also an inspiration for pore engineering of COF or 2D porous polymer membranes.

Quantification of effects of mean blood pressure and left ventricular mass on noninvasive fast fractional flow reserve.

Proper inlet boundary conditions are essential for accurate computational fluid dynamics (CFD) modeling. We developed methodology to derive noninvasive FFRB using CFD and computed tomography coronary angiography (CTCA) images. This study aims to assess the influence of brachial mean blood pressure (MBP) and total coronary inflow on FFRB computation. Twenty-two patients underwent both CTCA and FFR measurements. Total coronary flow was computed from left ventricular mass (LVM) measured from CTCA. A total of 286 CFD simulations were run by varying MBP and LVM at 70, 80, 90, 100, 110, 120, and 130% of the measured values. FFRB increased with incrementally higher input values of MBP: 0.78 ± 0.12, 0.80 ± 0.11, 0.82 ± 0.10, 0.84 ± 0.09, 0.85 ± 0.08, 0.86 ± 0.08, and 0.87 ± 0.07, respectively. Conversely, FFRB decreased with incrementally higher inputs value of LVM: 0.86 ± 0.08, 0.85 ± 0.08, 0.84 ± 0.09, 0.84 ± 0.09, 0.83 ± 0.10, 0.83 ± 0.10, and 0.82 ± 0.10, respectively. Noninvasive FFRB calculated using measured MBP and LVM on a total of 30 vessels was 0.84 ± 0.09 and correlated well with invasive FFR (0.83 ± 0.09) (r = 0.92, P < 0.001). Positive association was observed between FFRB and MBP input values (mmHg) and negative association between FFRB and LVM values (g). Respective slopes were 0.0016 and -0.005, respectively, suggesting potential application of FFRB in a clinical setting. Inaccurate MBP and LVM inputs differing from patient-specific values could result in misclassification of borderline ischemic lesions.NEW & NOTEWORTHY While brachial mean blood pressure (MBP) and left ventricular mass (LVM) measured from CTCA are the two CFD simulation input parameters, their effects on noninvasive fractional flow reserve (FFRB) have not been systematically investigated. We demonstrate that inaccurate MBP and LVM inputs differing from patient-specific values could result in misclassification of borderline ischemic lesions. This is important in the clinical application of noninvasive FFR in coronary artery disease diagnosis.

Hydro-Assisted Self-Regenerating Brominated N-Alkylated Thiophene Diketopyrrolopyrrole Dye Nanofibers-A Sustainable Synthesis Route for Renewable Air Filter Materials.

With rising global concerns over the alarming levels of particulate pollution, a sustainable air quality management is the need of the hour. Air filtration research has gained momentum in recent years. However, the research perspective is still blinkered toward formulating new fiber systems for the energy-intensive electrospinning process to fabricate high quality factor air filters. A holistic approach on sustainable air filtration models is still lacking. The air filter model presented in this work uses a simple process involving water-induced self-organization and self-regeneration of nanofibers, and an easy recycling route after the filter life that not only facilitates reuse of the microfibrous scaffold holding the nanofibers but also allows renewal of nanofibers. Three generations of air filters are fabricated and tested, all having high particulate matter (PM)-adsorbing tendency, high filtration efficiency (>95%), and high Young's modulus (≈5 GPa). The renewable air filters offer a sustainable alternative to the present cost-intensive electrospun air filters.

Cystic Adventitial Disease of the Common Femoral Vein Successfully Treated with Resection, Synthetic Graft Reconstruction, and Fistula Creation.

Cystic adventitial disease (CAD) is a rare, benign disease of blood vessels which most commonly affects the popliteal artery. Less than 50 cases of CAD affecting veins have ever been described in the literature to date. We report the case of a 56-year-old woman who presented with unilateral lower extremity swelling and varicosities due to CAD of her common femoral vein. Resection and reconstruction with a venous interposition graft, employing a polytetrafluoroethylene graft and arteriovenous fistula in order to maintain venous bypass patency, were performed successfully. The patient recovered well without any evidence of recurrence or postoperative complications.

Patient Preferences for Coronary CT Angiography with Stress Perfusion, SPECT, or Invasive Coronary Angiography.

Background Patient preference is pivotal for widespread adoption of tests in clinical practice. Patient preferences for invasive versus other noninvasive tests for coronary artery disease are not known. Purpose To compare patient acceptance and preferences for noninvasive and invasive cardiac imaging in North and South America, Asia, and Europe. Materials and Methods This was a prospective 16-center trial in 381 study participants undergoing coronary CT angiography with stress perfusion, SPECT, and invasive coronary angiography (ICA). Patient preferences were collected by using a previously validated questionnaire translated into eight languages. Responses were converted to ordinal scales and were modeled with generalized linear mixed models. Results In patients in whom at least one test was associated with pain, CT and SPECT showed reduced median pain levels, reported on 0-100 visual analog scales, from 20 for ICA (interquartile range [IQR], 4-50) to 6 for CT (IQR, 0-27.5) and 5 for SPECT (IQR, 0-25) (P < .001). Patients from Asia reported significantly more pain than patients from other continents for ICA (median, 25; IQR, 10-50; P = .01), CT (median, 10; IQR, 0-30; P = .02), and SPECT (median, 7; IQR, 0-28; P = .03). Satisfaction with preparation differed by continent and test (P = .01), with patients from Asia reporting generally lower ratings. Patients from North America had greater percentages of "very high" or "high" satisfaction than patients from other continents for ICA (96% vs 82%, respectively; P < .001) and SPECT (95% vs 79%, respectively; P = .04) but not for CT (89% vs 86%, respectively; P = .70). Among all patients, CT was preferred by 54% of patients, compared with 18% for SPECT and 28% for ICA (P < .001). Conclusion For cardiac imaging, patients generally favored CT angiography with stress perfusion, while study participants from Asia generally reported lowest satisfaction. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Woodard and Nguyen in this issue.

Light Generation in Lead Halide Perovskite Nanocrystals: LEDs, Color Converters, Lasers, and Other Applications.

Facile solution processing lead halide perovskite nanocrystals (LHP-NCs) exhibit superior properties in light generation, including a wide color gamut, a high flexibility for tuning emissive wavelengths, a great defect tolerance and resulting high quantum yield; and intriguing electric feature of ambipolar transport with moderate and comparable mobility. As a result, LHP-NCs have accomplished great achievements in various light generation applications, including color converters for lighting and display, light-emitting diodes, low threshold lasing, X-ray scintillators, and single photon emitters. Herein, the considerable progress that has been made thus far is reviewed along with the current challenges and future prospects in the light generation applications of LHP-NCs.

Expression of (pro)renin receptor and its effect on endothelial cell proliferation in infantile hemangioma.

BACKGROUND: Propranolol is the preferred treatment for problematic proliferating infantile hemangioma (IH) by targeting the renin-angiotensin system (RAS) expressed by IH endothelium. (Pro)renin receptor (PRR) is a major component of the RAS associated with the canonical wnt signaling pathway. We proposed that activation of PRR by renin causes proliferation of IH. METHODS: The expression of PRR in IH tissue samples was investigated using immunohistochemical (IHC) staining and NanoString analysis. NanoString analysis was also used to confirm transcriptional expression of PRR in CD34-sorted proliferating IH-derived primary cell lines. MTT assay was utilized to determine the effect of exogenous renin on the number of viable IH cells. RT-qPCR was used to determine the effect of renin on the stem cell gene expression. RESULTS: NanoString analysis and IHC staining confirmed transcriptional and translational expression of PRR, which was localized to the non-endothelial and the endothelial IH cell populations. MTT assay demonstrated an increased number of viable IH cells by administration of renin and the effect was negated by the wnt receptor blocker dickkopf-1. CONCLUSION: Our results present a model for renin-induced increased proliferation of IH cells through PRR acting via the wnt signaling pathway, which may account for accumulation of cells in IH during the proliferative phase of the tumor.

Harnessing technology and molecular analysis to understand the development of cardiovascular diseases in Asia: a prospective cohort study (SingHEART).

BACKGROUND: Cardiovascular disease (CVD) imposes much mortality and morbidity worldwide. The use of "deep learning", advancements in genomics, metabolomics, proteomics and devices like wearables have the potential to unearth new insights in the field of cardiology. Currently, in Asia, there are no studies that combine the use of conventional clinical information with these advanced technologies. We aim to harness these new technologies to understand the development of cardiovascular disease in Asia. METHODS: Singapore is a multi-ethnic country in Asia with well-represented diverse ethnicities including Chinese, Malays and Indians. The SingHEART study is the first technology driven multi-ethnic prospective population-based study of healthy Asians. Healthy male and female subjects aged 21-69 years old without any prior cardiovascular disease or diabetes mellitus will be recruited from the general population. All subjects are consented to undergo a detailed on-line questionnaire, basic blood investigations, resting and continuous electrocardiogram and blood pressure monitoring, activity and sleep tracking, calcium score, cardiac magnetic resonance imaging, whole genome sequencing and lipidomic analysis. Outcomes studied will include mortality and cause of mortality, myocardial infarction, stroke, malignancy, heart failure, and the development of co-morbidities. DISCUSSION: An initial target of 2500 patients has been set. From October 2015 to May 2017, an initial 683 subjects have been recruited and have completed the initial work-up the SingHEART project is the first contemporary population-based study in Asia that will include whole genome sequencing and deep phenotyping: including advanced imaging and wearable data, to better understand the development of cardiovascular disease across different ethnic groups in Asia.