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Article ; Online: Multidisciplinary Effort to Drive Precision-Medicine for the Future

Dewei Kong / Haojie Yu / Xueling Sim / Kevin White / E. Shyong Tai / Markus Wenk / Adrian Kee Keong Teo

Frontiers in Digital Health, Vol

2022 Volume 4

Abstract: In the past one or two decades, countries across the world have successively implemented different precision medicine (PM) programs, and also cooperated to implement international PM programs. We are now in the era of PM. Singapore's National Precision ... ...

Abstract	In the past one or two decades, countries across the world have successively implemented different precision medicine (PM) programs, and also cooperated to implement international PM programs. We are now in the era of PM. Singapore's National Precision Medicine (NPM) program, initiated in 2017, is now entering its second phase to generate a large genomic database for Asians. The National University of Singapore (NUS) also launched its own PM translational research program (TRP) in 2021, aimed at consolidating multidisciplinary expertise within the Yong Loo Lin School of Medicine to develop collaborative projects that can help to identify and validate novel therapeutic targets for the realization of PM. To achieve this, appropriate data collection, data processing, and results interpretation must be taken into consideration. There may be some difficulties during these processes, but with the improvement of relevant rules and the continuous development of omics-based technologies, we will be able to solve these problems, eventually achieving precise prediction, diagnosis, treatment, or even prevention of diseases.
Keywords	precision medicine ; big data ; omics technologies ; data collection ; data processing ; results interpretation ; Medicine ; R ; Public aspects of medicine ; RA1-1270 ; Electronic computers. Computer science ; QA75.5-76.95
Subject code	006
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Women’s Usage Behavior and Perceived Usefulness with Using a Mobile Health Application for Gestational Diabetes Mellitus

Shilpa Surendran / Chang Siang Lim / Gerald Choon Huat Koh / Tong Wei Yew / E Shyong Tai / Pin Sym Foong

International Journal of Environmental Research and Public Health, Vol 18, Iss 6670, p

Mixed-Methods Study

2021 Volume 6670

Abstract: The prevalence of gestational diabetes mellitus (GDM) is increasing, and only a few mobile health (mHealth) applications are specifically designed to manage GDM. In this mixed-methods study, a follow-up study of a randomized controlled trial (RCT) ... ...

Abstract	The prevalence of gestational diabetes mellitus (GDM) is increasing, and only a few mobile health (mHealth) applications are specifically designed to manage GDM. In this mixed-methods study, a follow-up study of a randomized controlled trial (RCT) analyzed a largely automated mHealth application-based lifestyle coaching program to (a) measure the application’s usage behavior and (b) explore users’ perceptions of its usefulness in GDM management. Quantitative data were collected from the 170 application users who had participated in the intervention arm of the RCT. Semi-structured interviews (n = 14) captured users’ experiences when using the application. Data were collected from June 2019 to January 2020. Quantitative data were analyzed descriptively, and interviews were analyzed thematically. Only 57/170 users (34%) logged at least one meal, and only 35 meals on average were logged for eight weeks because of the incorrectly worded food items and limited food database. On the contrary, an average of 1.85 (SD = 1.60) weight values were logged per week since the weight tracking component was easy to use. Many users (6/14 (43%)) mentioned that the automatic coach messages created an immediate sense of self-awareness in food choices and motivated behavior. The findings suggest that for GDM management, a largely automated mHealth application has the potential to promote self-awareness of healthy lifestyle choices, reducing the need for intensive human resources. Additionally, several gaps in the application’s design were identified which need to be addressed in future works.
Keywords	diabetes ; gestational ; follow-up studies ; mentoring ; mobile applications ; telemedicine ; Medicine ; R
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Multifactorial e- and mHealth interventions for cardiovascular disease primary prevention

Artur Direito / Jonathan Rawstorn / Jacqueline Mair / Reza Daryabeygi-Khotbehsara / Ralph Maddison / E Shyong Tai

Digital Health, Vol

Protocol for a systematic review and meta-analysis of randomised controlled trials

2019 Volume 5

Abstract: Objective Cardiovascular diseases (CVD) are a leading cause of mortality and disease burden. Preventative interventions to augment the population-level adoption of health lifestyle behaviours that reduce CVD risk are a priority. Face-to-face ... ...

Abstract	Objective Cardiovascular diseases (CVD) are a leading cause of mortality and disease burden. Preventative interventions to augment the population-level adoption of health lifestyle behaviours that reduce CVD risk are a priority. Face-to-face interventions afford individualisation and are effective for improving health-related behaviours and outcomes, but they are costly and resource intensive. Electronic and mobile health (e- and mHealth) approaches aimed at modifying lifestyle risk factors may be an effective and scalable approach to reach many individuals while preserving individualisation. This systematic review aims to (a) determine the effectiveness of multifactorial e- and mHealth interventions on CVD risk and on lifestyle-related cardiometabolic risk factors and self-management behaviours among adults without CVD; and (b) describe the evidence on adverse events and on the cost-effectiveness of these interventions. Methods Methods were detailed prior to the start of the review in order to improve conduct and prevent inconsistent decision making throughout the review. This protocol was prepared following the PRISMA-P 2015 statement. MEDLINE, CINAHL, Embase, PsycINFO, Web of Science, Cochrane Public Health Group Specialised Register and CENTRAL electronic databases will be searched between 1991 and September 2019. Eligibility criteria are: (a) population: community-dwelling adults; (b) intervention/comparison: randomised controlled trials comparing e- or mHealth CVD risk preventative interventions with usual care; and (c) outcomes: modifiable CVD risk factors. Selection of study reports will involve two authors independently screening titles and abstracts, followed by a full-text review of potentially eligible reports. Two authors will independently undertake data extraction and assess risk of bias. Where appropriate, meta-analysis of outcome data will be performed. Discussion This protocol describes the pre-specified methods for a systematic review that will provide quantitative and narrative syntheses of ...
Keywords	Computer applications to medicine. Medical informatics ; R858-859.7
Subject code	610 ; 306
Language	English
Publishing date	2019-11-01T00:00:00Z
Publisher	SAGE Publishing
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Retinal microvascular signs and risk of diabetic kidney disease in asian and white populations

Simon Nusinovici / Charumathi Sabanayagam / Kristine E. Lee / Liang Zhang / Carol Y. Cheung / E. Shyong Tai / Gavin S. W. Tan / Ching Yu Cheng / Barbara E. K. Klein / Tien Yin Wong

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 8

Abstract: Abstract The objective was to examine prospectively the association between retinal microvascular signs and development of diabetic kidney disease (DKD) in Asian and White populations. We analysed two population-based cohorts, composing of 1,221 Asians ( ... ...

Abstract	Abstract The objective was to examine prospectively the association between retinal microvascular signs and development of diabetic kidney disease (DKD) in Asian and White populations. We analysed two population-based cohorts, composing of 1,221 Asians (SEED) and 703 White (WESDR) adults with diabetes. Retinal microvascular signs at baseline included vascular caliber (arteriolar—CRAE, and venular—CRVE) and diabetic retinopathy (DR). Incident cases of DKD were identified after ~ 6-year. Incident cases were defined based on eGFR in SEED and proteinuria or history of renal dialysis in WESDR. The incidence of DKD were 11.8% in SEED and 14.0% in WESDR. Wider CRAE in SEED (OR = 1.58 [1.02, 2.45]) and wider CRVE (OR = 1.69 [1.02, 2.80)) in WESDR were associated with increased risk of DKD. Presence of DR was associated with an increased risk of DKD in both cohorts (SEED: OR = 1.91 [1.21, 3.01] in SEED, WESDR: OR = 1.99 [1.18, 3.35]). Adding DR and retinal vascular calibers in the model beyond traditional risk factors led to an improvement of predictive performance of DKD risk between 1.1 and 2.4%; and improved classification (NRI 3 between 9%). Microvascular changes in the retina are longitudinally associated with risk of DKD.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: PAX4 loss of function increases diabetes risk by altering human pancreatic endocrine cell development

Nature Communications, Vol 14, Iss 1, Pp 1-

2023 Volume 19

Abstract: Abstract The coding variant (p.Arg192His) in the transcription factor PAX4 is associated with an altered risk for type 2 diabetes (T2D) in East Asian populations. In mice, Pax4 is essential for beta cell formation but its role on human beta cell ... ...

Abstract	Abstract The coding variant (p.Arg192His) in the transcription factor PAX4 is associated with an altered risk for type 2 diabetes (T2D) in East Asian populations. In mice, Pax4 is essential for beta cell formation but its role on human beta cell development and/or function is unknown. Participants carrying the PAX4 p.His192 allele exhibited decreased pancreatic beta cell function compared to homozygotes for the p.192Arg allele in a cross-sectional study in which we carried out an intravenous glucose tolerance test and an oral glucose tolerance test. In a pedigree of a patient with young onset diabetes, several members carry a newly identified p.Tyr186X allele. In the human beta cell model, EndoC-βH1, PAX4 knockdown led to impaired insulin secretion, reduced total insulin content, and altered hormone gene expression. Deletion of PAX4 in human induced pluripotent stem cell (hiPSC)-derived islet-like cells resulted in derepression of alpha cell gene expression. In vitro differentiation of hiPSCs carrying PAX4 p.His192 and p.X186 risk alleles exhibited increased polyhormonal endocrine cell formation and reduced insulin content that can be reversed with gene correction. Together, we demonstrate the role of PAX4 in human endocrine cell development, beta cell function, and its contribution to T2D-risk.
Keywords	Science ; Q
Subject code	571
Language	English
Publishing date	2023-09-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Trust and Trade-Offs in Sharing Data for Precision Medicine

Tamra Lysaght / Angela Ballantyne / Hui Jin Toh / Andrew Lau / Serene Ong / Owen Schaefer / Makoto Shiraishi / Willem van den Boom / Vicki Xafis / E Shyong Tai

Journal of Personalized Medicine, Vol 11, Iss 921, p

A National Survey of Singapore

2021 Volume 921

Abstract: Background: Precision medicine (PM) programs typically use broad consent. This approach requires maintenance of the social license and public trust. The ultimate success of PM programs will thus likely be contingent upon understanding public expectations ...

Abstract	Background: Precision medicine (PM) programs typically use broad consent. This approach requires maintenance of the social license and public trust. The ultimate success of PM programs will thus likely be contingent upon understanding public expectations about data sharing and establishing appropriate governance structures. There is a lack of data on public attitudes towards PM in Asia. Methods: The aim of the research was to measure the priorities and preferences of Singaporeans for sharing health-related data for PM. We used adaptive choice-based conjoint analysis (ACBC) with four attributes: uses, users, data sensitivity and consent. We recruited a representative sample of n = 1000 respondents for an in-person household survey. Results: Of the 1000 respondents, 52% were female and majority were in the age range of 40–59 years (40%), followed by 21–39 years (33%) and 60 years and above (27%). A total of 64% were generally willing to share de-identified health data for IRB-approved research without re-consent for each study. Government agencies and public institutions were the most trusted users of data. The importance of the four attributes on respondents’ willingness to share data were: users (39.5%), uses (28.5%), data sensitivity (19.5%), consent (12.6%). Most respondents found it acceptable for government agencies and hospitals to use de-identified data for health research with broad consent. Our sample was consistent with official government data on the target population with 52% being female and majority in the age range of 40–59 years (40%), followed by 21–39 years (33%) and 60 years and above (27%). Conclusions: While a significant body of prior research focuses on preferences for consent, our conjoint analysis found consent was the least important attribute for sharing data. Our findings suggest the social license for PM data sharing in Singapore currently supports linking health and genomic data, sharing with public institutions for health research and quality improvement; but does not support ...
Keywords	Precision medicine ; bioethics ; trust ; data sharing ; survey ; Singapore ; Medicine ; R
Subject code	310
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Screening for diabetes with HbA1c

Wei-Yen Lim / Stefan Ma / Derrick Heng / E. Shyong Tai / Chin Meng Khoo / Tze Ping Loh

Scientific Reports, Vol 8, Iss 1, Pp 1-

Test performance of HbA1c compared to fasting plasma glucose among Chinese, Malay and Indian community residents in Singapore

2018 Volume 9

Abstract: Abstract The prevalence of diabetes in Singapore is high. Screening to facilitate early detection and intervention has been shown to be cost-effective. Current clinical practice guidelines in Singapore recommend screening with fasting plasma glucose (FPG) ...

Abstract	Abstract The prevalence of diabetes in Singapore is high. Screening to facilitate early detection and intervention has been shown to be cost-effective. Current clinical practice guidelines in Singapore recommend screening with fasting plasma glucose (FPG), followed by an oral glucose tolerance test (OGTT) in those with FPG 6.1-6.9 mmol/L. Glycated haemoglobin A1c (HbA1c) has robust stability at ambient temperature, and can be performed on non-fasted capillary blood samples, making it an attractive potential alternative for screening. However, limitations of HbA1c include differential performance in different races, and its performance as a screening test has not been well characterized in Asian populations. This study compares HbA1c and FPG as diabetes screening modalities in 3540 community-dwelling Singapore residents of Chinese, Malay and Indian race to detect diabetes mellitus diagnosed based on blood glucose (FPG ≥ 7.0 mmol/L, 2 hr OGTT ≥ 11.1 mmol/L). The area under the receiver-operating-characteristic curve (AUC) was higher for FPG compared to HbA1c in the overall population and age, race and age-race strata, but these differences were not statistically significant. HbA1c > = 7.0% identified 95% of individuals with diabetes mellitus, and the remainder had impaired glucose tolerance (IGT). HbA1c cut-off at 6.1% had better sensitivity (0.825) to FPG at 6.1 mmol/L. The positive predictive value of HbA1c at 6.1% was 40–50% in different age-race combinations with a negative predictive value of about 98%. If follow-up screening with FPG is used, a lower cut-off at 5.6 mmol/L is appropriate in identifying people with pre-diabetes, as about 85% of people with HbA1c 6.1–6.9% and FPG 5.6–6.9 mmol/L had IFG/IGT or diabetes in the study sample. HbA1c is an appropriate alternative to FPG as a first-step screening test, and the combination of Hba1c > = 6.1% and FPG > = 5.6 mmol/L would improve the identification of individuals with diabetes mellitus and prediabetes.
Keywords	Medicine ; R ; Science ; Q
Subject code	571
Language	English
Publishing date	2018-08-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: “Who is watching the watchdog?”

Tamra Lysaght / Angela Ballantyne / Vicki Xafis / Serene Ong / Gerald Owen Schaefer / Jeffrey Min Than Ling / Ainsley J. Newson / Ing Wei Khor / E. Shyong Tai

BMC Medical Ethics, Vol 21, Iss 1, Pp 1-

ethical perspectives of sharing health-related data for precision medicine in Singapore

2020 Volume 11

Abstract: Abstract Background We aimed to examine the ethical concerns Singaporeans have about sharing health-data for precision medicine (PM) and identify suggestions for governance strategies. Just as Asian genomes are under-represented in PM, the views of Asian ...

Abstract	Abstract Background We aimed to examine the ethical concerns Singaporeans have about sharing health-data for precision medicine (PM) and identify suggestions for governance strategies. Just as Asian genomes are under-represented in PM, the views of Asian populations about the risks and benefits of data sharing are under-represented in prior attitudinal research. Methods We conducted seven focus groups with 62 participants in Singapore from May to July 2019. They were conducted in three languages (English, Mandarin and Malay) and analysed with qualitative content and thematic analysis. Results Four key themes emerged: nuanced understandings of data security and data sensitivity; trade-offs between data protection and research benefits; trust (and distrust) in the public and private sectors; and governance and control options. Participants were aware of the inherent risks associated with data sharing for research. Participants expressed conditional support for data sharing, including genomic sequence data and information contained within electronic medical records. This support included sharing data with researchers from universities and healthcare institutions, both in Singapore and overseas. Support was conditional on the perceived social value of the research and appropriate de-identification and data security processes. Participants suggested that a data sharing oversight body would help strengthen public trust and comfort in data research for PM in Singapore. Conclusion Maintenance of public trust in data security systems and governance regimes can enhance participation in PM and data sharing for research. Contrary to themes in much prior research, participants demonstrated a sophisticated understanding of the inherent risks of data sharing, analysed trade-offs between risks and potential benefits of PM, and often adopted an international perspective.
Keywords	Data sharing ; Bioethics ; Governance ; Precision medicine ; Public attitudes ; Public trust ; Medical philosophy. Medical ethics ; R723-726
Subject code	170
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Robust estimation of the effect of an exposure on the change in a continuous outcome

Yilin Ning / Nathalie C. Støer / Peh Joo Ho / Shih Ling Kao / Kee Yuan Ngiam / Eric Yin Hao Khoo / Soo Chin Lee / E-Shyong Tai / Mikael Hartman / Marie Reilly / Chuen Seng Tan

BMC Medical Research Methodology, Vol 20, Iss 1, Pp 1-

2020 Volume 11

Abstract: Abstract Background The change in two measurements of a continuous outcome can be modelled directly with a linear regression model, or indirectly with a random effects model (REM) of the individual measurements. These methods are susceptible to model ... ...

Abstract	Abstract Background The change in two measurements of a continuous outcome can be modelled directly with a linear regression model, or indirectly with a random effects model (REM) of the individual measurements. These methods are susceptible to model misspecifications, which are commonly addressed by applying monotonic transformations (e.g., Box-Cox transformation) to the outcomes. However, transforming the outcomes complicates the data analysis, especially when variable selection is involved. We propose a robust alternative through a novel application of the conditional probit (cprobit) model. Methods The cprobit model analyzes the ordered outcomes within each subject, making the estimate invariant to monotonic transformation on the outcome. By scaling the estimate from the cprobit model, we obtain the exposure effect on the change in the observed or Box-Cox transformed outcome, pending the adequacy of the normality assumption on the raw or transformed scale. Results Using simulated data, we demonstrated a similar good performance of the cprobit model and REM with and without transformation, except for some bias from both methods when the Box-Cox transformation was applied to scenarios with small sample size and strong effects. Only the cprobit model was robust to skewed subject-specific intercept terms when a Box-Cox transformation was used. Using two real datasets from the breast cancer and inpatient glycemic variability studies which utilize electronic medical records, we illustrated the application of our proposed robust approach as a seamless three-step workflow that facilitates the use of Box-Cox transformation to address non-normality with a common underlying model. Conclusions The cprobit model provides a seamless and robust inference on the change in continuous outcomes, and its three-step workflow is implemented in an R package for easy accessibility.
Keywords	Box-Cox transformation ; Conditional probit model ; Normal errors ; Random effects model ; Medicine (General) ; R5-920
Subject code	310
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cordyceps inhibits ceramide biosynthesis and improves insulin resistance and hepatic steatosis

Ying Li / Chad Lamar Talbot / Bhawna Chandravanshi / Alec Ksiazek / Ayushi Sood / Kamrul Hasan Chowdhury / J. Alan Maschek / James Cox / Adhini Kuppuswamy Satheesh Babu / Henry A. Paz / Pon Velayutham Anandh Babu / David K. Meyerholz / Umesh D. Wankhade / William Holland / E. Shyong Tai / Scott A. Summers / Bhagirath Chaurasia

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 14

Abstract: Abstract Ectopic ceramide accumulation in insulin-responsive tissues contributes to the development of obesity and impairs insulin sensitivity. Moreover, pharmacological inhibition of serine palmitoyl transferase (SPT), the first enzyme essential for ... ...

Abstract	Abstract Ectopic ceramide accumulation in insulin-responsive tissues contributes to the development of obesity and impairs insulin sensitivity. Moreover, pharmacological inhibition of serine palmitoyl transferase (SPT), the first enzyme essential for ceramide biosynthesis using myriocin in rodents reduces body weight and improves insulin sensitivity and associated metabolic indices. Myriocin was originally extracted from fruiting bodies of the fungus Isaria sinclairii and has been found abundant in a number of closely related fungal species such as the Cordyceps. Myriocin is not approved for human use but extracts from Cordyceps are routinely consumed as part of traditional Chinese medication for the treatment of numerous diseases including diabetes. Herein, we screened commercially available extracts of Cordyceps currently being consumed by humans, to identify Cordyceps containing myriocin and test the efficacy of Cordyceps extract containing myriocin in obese mice to improve energy and glucose homeostasis. We demonstrate that commercially available Cordyceps contain variable amounts of myriocin and treatment of mice with a human equivalent dose of Cordyceps extract containing myriocin, reduces ceramide accrual, increases energy expenditure, prevents diet-induced obesity, improves glucose homeostasis and resolves hepatic steatosis. Mechanistically, these beneficial effects were due to increased adipose tissue browning/beiging, improved brown adipose tissue function and hepatic insulin sensitivity as well as alterations in the abundance of gut microbes such as Clostridium and Bilophila. Collectively, our data provide proof-of-principle that myriocin containing Cordyceps extract inhibit ceramide biosynthesis and attenuate metabolic impairments associated with obesity. Moreover, these studies identify commercially available Cordyceps as a readily available supplement to treat obesity and associated metabolic diseases.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
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