Advancing Personalized Medicine Through the Application of Whole Exome Sequencing and Big Data Analytics

There is a growing attention toward personalized medicine. This is led by a fundamental shift from the ‘one size fits all’ paradigm for treatment of patients with conditions or predisposition to diseases, to one that embraces novel approaches, such as tailored target therapies, to achieve the best possible outcomes. Driven by these, several national and international genome projects have been initiated to reap the benefits of personalized medicine. Exome and targeted sequencing provide a balance between cost and benefit, in contrast to whole genome sequencing (WGS). Whole exome sequencing (WES) targets approximately 3% of the whole genome, which is the basis for protein-coding genes. Nonetheless, it has the characteristics of big data in large deployment. Herein, the application of WES and its relevance in advancing personalized medicine is reviewed. WES is mapped to Big Data “10 Vs” and the resulting challenges discussed. Application of existing biological databases and bioinformatics tools to address the bottleneck in data processing and analysis are presented, including the need for new generation big data analytics for the multi-omics challenges of personalized medicine. This includes the incorporation of artificial intelligence (AI) in the clinical utility landscape of genomic information, and future consideration to create a new frontier toward advancing the field of personalized medicine

The relationship between corporate governance attributes and environmental disclosure quality of Malaysian public listed companies

This study aims to assess the effects of corporate governance attributes consists of proportion of independent directors, non-duality of Chief Executive Officer (CEO), board size and managerial ownership on environmental disclosure quality of Malaysian public listed companies. Besides good financial returns, companies today are also expected by its stakeholders to contribute back to the society in terms of sustainability activities despite Malaysia is still in the midst of improving the corporate governance. The composition of corporate board assistances in improving corporate performance remains as an issue. Environmental improvement and contribution commonly made through environmental disclosure, however, besides complying with regulations and being voluntary in reporting on environmental, the quality of the environmental disclosure is still unclear. This study is carried out in Malaysia among companies in environmentally sensitive industry as the operations of environmentally sensitive industry are considered to be more detrimental to the environment. Data are extracted from companies’ annual reports over five years’ duration, namely year 2012 to 2016. The data collected is being analyzed using panel data analysis. The proportion of independent directors and non-duality of CEO are significant in improving the environmental disclosure quality of Malaysian listed companies

Acute decompensated heart failure in a non cardiology tertiary referral centre, Sarawak General Hospital (SGH‑HF)

Abstract Background: Data on clinical characteristics of acute decompensated heart failure (ADHF) in Malaysia especially in East Malaysia is lacking. Methods: This is a prospective observational study in Sarawak General Hospital, Medical Department, from October 2017 to September 2018. Patients with primary admission diagnosis of ADHF were recruited and followed up for 90 days. Data on patient’s characteristics, precipitating factors, medications and short-term clinical outcomes were recorded. Results: Majority of the patients were classified in lower socioeconomic group and the mean age was 59 years old. Hypertension, diabetes mellitus and dyslipidaemia were the common underlying comorbidities. Heart failure with ischemic aetiology was the commonest ADHF admission precipitating factor. 48.6% of patients were having preserved ejection fraction HF and the median NT-ProBNP level was 4230 pg/mL. Prescription rate of the evidencebased heart failure medication was low. The in-patient mortality and the average length of hospital stay were 7.5% and 5 days respectively. 43% of patients required either ICU care or advanced cardiopulmonary support. The 30-day, 90-day mortality and readmission rate were 13.1%, 11.2%, 16.8% and 14% respectively. Conclusion: Comparing with the HF data from West and Asia Pacific, the short-term mortality and readmission rate were high among the ADHF patients in our study cohort. Maladaptation to evidence-based HF prescription and the higher prevalence of cardiovascular risk factors in younger patients were among the possible issues to be addressed to improve the HF outcome in regions with similar socioeconomic background. Keywords: Acute decompensated heart failure, Epidemiology, Sarawak, Southeast Asia, Malaysi

Clinical Outcome Predictor using Killip Scoring in Acute Decompensated Heart Failure (ADHF): A Non-Cardiac Centre Pilot Experience

Background: Physicians in tertiary centers face a constant challenge in selecting patient with ADHF to be admitted from district healthcare centre, especially with limited resources. Appropriate risk stratification of patients with ADHF would improve the efficiency of our healthcare delivery system. Objective: We aim to find potential relationship between Killip clinical scoring with clinical outcome of ADHF, including in-patient mortality and requirement of advanced cardiorespiratory support. Methods: 35 consecutive cases with a discharge diagnosis of ADHF and admission creatinine clearance of more than 30 were randomly reviewed. Cases were analyzed retrospectively for their Killip score, in-patient mortality, requirement of advance cardiorespiratory care or ICU admission. Results: There were 21 male patients (60%) and 14 female patients. Mean age was 61±19 years old. Mean duration of ward-stay was 6±4 days. Comorbidities were 14 (40%) with history of coronary artery diseases and 17 (49%) with diabetes mellitus. 15 patients (43%) were on at least a single type of guideline directed medication for heart failure. The cohort was almost evenly distributed between those with a Killip score of 2 and above 2. A Killip score of 3 and above was found to have good positive predictive value (87%) for advanced cardio-respiratory care and negative predictive value of 78%. No in-patient death was observed for the group with Killip 2 while 5 deaths were recorded in the group scoring more than 2. A Killip score of 3 had excellent (100%) negative predictive value for in-patient mortality but poor positive predictive value (33%). Significant relationship (p<0.001) was observed for Killip scoring on both outcomes. Conclusion: Killip scoring may be useful for on-call physician to decide the need on tertiary care among patient with ADHF and mortality outcome. However, more prospective studies and patients should be recruited to validate the study

Prognostic Value of Leucocyte Telomere Length in Acute Myocardial Infarction

Introduction: Leucocyte telomere length (LTL) has been described as a marker of biological age, endothelial dysfunction and atherosclerosis. The association between LTL and clinical characteristics of Asian patients, and their outcomes following acute myocardial infarction (AMI) have been inconclusive. Objective: To investigate the relationship between LTL and developing AMI, the association of LTL with inpatient and 30-day mortality, and the comparison to LTL with established AMI risk scores in predicting these outcomes. Methodology: 100 patients aged 30-70 years admitted with an AMI to a tertiary referral center between May-Oct 2017 were enrolled; these were matched with 100 non-AMI ('healthy') controls for gender and age (+/- 1 year). Clinical data was obtained prospectively; inpatient and 30-day outcomes documented. LTL was reflected by a well described variable called a tis ratio (TSR). The TSR was measured at enrolment using a quantitative PCR-based methods (qPCR) and results blinded to the clinician

Nano-Sampling and Reporter Tools to Study Metabolic Regulation in Zebrafish

In the past years, evidence has emerged that hallmarks of human metabolic disorders can be recapitulated in zebrafish using genetic, pharmacological or dietary interventions. An advantage of modeling metabolic diseases in zebrafish compared to other “lower organisms” is the presence of a vertebrate body plan providing the possibility to study the tissue-intrinsic processes preceding the loss of metabolic homeostasis. While the small size of zebrafish is advantageous in many aspects, it also has shortcomings such as the difficulty to obtain sufficient amounts for biochemical analyses in response to metabolic challenges. A workshop at the European Zebrafish Principal Investigator meeting in Trento, Italy, was dedicated to discuss the advantages and disadvantages of zebrafish to study metabolic disorders. This perspective article by the participants highlights strategies to achieve improved tissue-resolution for read-outs using “nano-sampling” approaches for metabolomics as well as live imaging of zebrafish expressing fluorescent reporter tools that inform on cellular or subcellular metabolic processes. We provide several examples, including the use of reporter tools to study the heterogeneity of pancreatic beta-cells within their tissue environment. While limitations exist, we believe that with the advent of new technologies and more labs developing methods that can be applied to minimal amounts of tissue or single cells, zebrafish will further increase their utility to study energy metabolism

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe