Clusters of tumor cells are often observed in the blood of cancer patients. These structures have been described as malignant entities for more than 50 years, although their comprehensive ...characterization is lacking. Contrary to current consensus, we demonstrate that a discrete population of circulating cell clusters isolated from the blood of colorectal cancer patients are not cancerous but consist of tumor-derived endothelial cells. These clusters express both epithelial and mesenchymal markers, consistent with previous reports on circulating tumor cell (CTC) phenotyping. However, unlike CTCs, they do not mirror the genetic variations of matched tumors. Transcriptomic analysis of single clusters revealed that these structures exhibit an endothelial phenotype and can be traced back to the tumor endothelium. Further results show that tumor-derived endothelial clusters do not form by coagulation or by outgrowth of single circulating endothelial cells, supporting a direct release of clusters from the tumor vasculature. The isolation and enumeration of these benign clusters distinguished healthy volunteers from treatment-naïve as well as pathological early-stage (≤IIA) colorectal cancer patients with high accuracy, suggesting that tumor-derived circulating endothelial cell clusters could be used as a means of noninvasive screening for colorectal cancer. In contrast to CTCs, tumor-derived endothelial cell clusters may also provide important information about the underlying tumor vasculature at the time of diagnosis, during treatment, and throughout the course of the disease.
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.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In early 2020, coronavirus disease (COVID-19) emerged and spread by community and nosocomial transmission. Effective contact tracing of potentially exposed health care workers is crucial for the ...prevention and control of infectious disease outbreaks in the health care setting.
This study aimed to evaluate the comparative effectiveness of contact tracing during the COVID-19 pandemic through the real-time locating system (RTLS) and review of the electronic medical record (EMR) at the designated hospital for COVID-19 response in Singapore.
Over a 2-day study period, all admitted patients with COVID-19, their ward locations, and the health care workers rostered to each ward were identified to determine the total number of potential contacts between patients with COVID-19 and health care workers. The numbers of staff-patient contacts determined by EMR reviews, RTLS-based contact tracing, and a combination of both methods were evaluated. The use of EMR-based and RTLS-based contact tracing methods was further validated by comparing their sensitivity and specificity against self-reported staff-patient contacts by health care workers.
Of 796 potential staff-patient contacts (between 17 patients and 162 staff members), 104 (13.1%) were identified by both the RTLS and EMR, 54 (6.8%) by the RTLS alone, and 99 (12.4%) by the EMR alone; 539 (67.7%) were not identified through either method. Compared to self-reported contacts, EMR reviews had a sensitivity of 47.2% and a specificity of 77.9%, while the RTLS had a sensitivity of 72.2% and a specificity of 87.7%. The highest sensitivity was obtained by including all contacts identified by either the RTLS or the EMR (sensitivity 77.8%, specificity 73.4%).
RTLS-based contact tracing showed higher sensitivity and specificity than EMR review. Integration of both methods provided the best performance for rapid contact tracing, although technical adjustments to the RTLS and increasing user compliance with wearing of RTLS tags remain necessary.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The Singapore Integrative Omics Study provides valuable insights on establishing population reference measurement in 364 Chinese, Malay, and Indian individuals. These measurements include > 2.5 ...millions genetic variants, 21,649 transcripts expression, 282 lipid species quantification, and 284 clinical, lifestyle, and dietary variables. This concept paper introduces the depth of the data resource, and investigates the extent of ethnic variation at these omics and non-omics biomarkers. It is evident that there are specific biomarkers in each of these platforms to differentiate between the ethnicities, and intra-population analyses suggest that Chinese and Indians are the most biologically homogeneous and heterogeneous, respectively, of the three groups. Consistent patterns of correlations between lipid species also suggest the possibility of lipid tagging to simplify future lipidomics assays. The Singapore Integrative Omics Study is expected to allow the characterization of intra-omic and inter-omic correlations within and across all three ethnic groups through a systems biology approach.The Singapore Genome Variation projects characterized the genetics of Singapore's Chinese, Malay, and Indian populations. The Singapore Integrative Omics Study introduced here goes further in providing multi-omic measurements in individuals from these populations, including genetic, transcriptome, lipidome, and lifestyle data, and will facilitate the study of common diseases in Asian communities.
We report the ALMA Cycle 2 observations of the Class I binary protostellar system L1551 NE in the 0.9 mm continuum, C18O (3-2), 13CO (3-2), SO (78-67), and CS (7-6) emission. At 0 18 (=25 au) ...resolution, ∼4 times higher than that of our Cycle 0 observations, the circumbinary disk (CBD) as seen in the 0.9 mm emission is shown to be composed of a northern and a southern spiral arm, with the southern arm connecting to the circumstellar disk (CSD) around Source B. The western parts of the spiral arms are brighter than the eastern parts, suggesting the presence of an m = 1 spiral mode. In the C18O emission, the infall gas motions in the interarm regions and the outward gas motions in the arms are identified. These observed features are well reproduced with our numerical simulations, where gravitational torques from the binary system impart angular momenta to the spiral-arm regions and extract angular momenta from the interarm regions. Chemical differentiation of the CBD is seen in the four molecular species. Our Cycle 2 observations have also resolved the CSDs around the individual protostars, and the beam-deconvolved sizes are 0 29 × 0 19 (=40 × 26 au) (P.A. = 144°) and 0 26 × 0 20 (=36 × 27 au) (P.A. = 147°) for Sources A and B, respectively. The position and inclination angles of these CSDs are misaligned with those of the CBD. The C18O emission traces the Keplerian rotation of the misaligned disk around Source A.
Background and objective
Limited data exist on the prevalence variation in sleep‐disordered breathing (SDB) across different Asian ethnicities. This population study aimed to estimate the prevalence ...of SDB in Singapore, a multiethnic nation, and to quantify the prevalence variation among Chinese, Malays and Indians.
Methods
The Singapore Health Study 2012 was a cross‐sectional population study conducted on adults aged 21–79 years. Among 2329 participants who completed baseline examination, a sample of 242 subjects completed home‐based sleep testing with an Embletta device (type 3 monitor). Moderate‐to‐severe SDB, defined as an apnoea–hypopnoea index (AHI) of ≥15 events/h, was used to estimate prevalence.
Results
The weighted estimates of the population prevalence of moderate‐to‐severe SDB and sleep apnoea syndrome were 30.5% and 18.1%, respectively. Of subjects with AHI ≥15, 91.0% were previously undiagnosed. Moderate‐to‐severe SDB prevalence varied across the Chinese (32.1%), Malays (33.8%) and Indians (16.5%). The mean body mass index (BMI) was lowest in Chinese (23.3 kg/m2) and highest among Malays (26.0 kg/m2) and Indians (25.4 kg/m2). Compared with Chinese, Indians had lower odds of moderate‐to‐severe SDB after adjustment for age, sex and BMI (odds ratio 0.82, 95% CI: 0.70–0.96, P = 0.02).
Conclusion
Sleep‐disordered breathing is prevalent but mostly undiagnosed among Asians in Singapore. There was a lower prevalence of SDB among Indians compared with Chinese that remained after adjustment for age, sex and BMI. Strategies are needed to optimize diagnosis and recognize ethnic differences in SDB prevalence.
We found an estimated population prevalence of moderate‐severe SDB of 30.5% in Singapore. Ninety‐one percent of subjects with moderate‐to‐severe SDB were previously undiagnosed. Moderate‐to‐severe SDB prevalence varied across Chinese, Malay and Indian people. Indian people had lower odds of moderate‐to‐severe SDB compared to Chinese people after adjustment for BMI, age and sex.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Historically, diabetes is diagnosed by measuring fasting (FPG) and two-hour post oral glucose load (OGTT) plasma concentration and interpreting it against recommended clinical thresholds of the ...patient. More recently, glycated haemoglobin A1c (HbA1c) has been included as a diagnostic criterion. Within-individual biological variation (CVi), analytical variation (CVa) and analytical bias of a test can impact on the accuracy and reproducibility of the classification of a disease. A test with large biological and analytical variation increases the likelihood of erroneous classification of the underlying disease state of a patient. Through numerical simulations based on the laboratory results generated from a large population health survey, we examined the impact of CVi, CVa and bias on the classification of diabetes using fasting plasma glucose (FPG), oral glucose tolerance test (OGTT) and HbA1c. From the results of the simulations, HbA1c has comparable performance to FPG and is better than OGTT in classifying subjects with diabetes, particularly when laboratory methods with smaller CVa are used. The use of the average of the results of the repeat laboratory tests has the effect of ameliorating the combined (analytical and biological) variation. The averaged result improves the consistency of the disease classification.
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Previous reports suggested that female breast cancer is associated with earlier ages at onset among Asian than Western populations. However, most studies utilized cross-sectional analyses that may be ...confounded by calendar-period and/or birth cohort effects. We, therefore, considered a longitudinal (forward-looking) approach adjusted for calendar-period changes and conditioned upon birth cohort.
Invasive female breast cancer data (1988-2009) were obtained from cancer registries in China, Hong Kong, South Korea, Taiwan, Singapore, and the United States. Age-period-cohort models were used to extrapolate longitudinal age-specific incidence rates for the 1920, 1944, and 1970 birth cohorts.
Cross-sectional age-specific incidence rates rose continuously until age 80 years among US white women, but plateaued or decreased after age 50 years among Asian women. In contrast, longitudinal age-specific rates were proportional (similar) among all Asian countries and the United States with incidence rates rising continuously until age 80 years. The extrapolated estimates for the most recent cohorts in some Asian countries actually showed later ages at onset than in the United States. Additionally, over successive birth cohorts, the incidence rate ratios (IRRs) for the longitudinal curves converged (narrowed) between Asian and US white women.
Similar longitudinal age-specific incidence rates along with converging IRRs indicate that the age effects for invasive breast cancer are more similar among Asian and Western populations than might be expected from a solely cross-sectional analysis. Indeed, the Asian breast cancer rates in recent generations are even surpassing the historically high rates in the United States, highlighting an urgent need for efficient prevention and treatment strategies among Asian populations.
Biofuel production by oleaginous microalgae is a promising alternative to the conventional fossil fuels. Many microalgae species have been investigated and deemed as potential renewable sources for ...the production of biofuel, biogas, food supplements and other products. Oleaginous microalgae, named for their ability to produce oil, are reported to store 30–70% of lipid content due to its metabolic properties under nutrient starvation conditions. This review presents the assortment of the research studies focused on biofuel production from oleaginous microalgae. The new methods and technologies developed for oleaginous microalgae cultivation to improve their biomass content and lipid accumulation capacity were reviewed. The production of renewable, carbon neutral, bio-based or microalgae-based transport fuels are necessary for environmental protection and economic sustainability. Microalgae are a significant source of renewable biodiesel because of their ability to produce oils in the presence of sunlight more efficiently than that of crop oils. This review will provide the background to understanding the bottlenecks and the need for improvement in the cultivation or harvesting process for oleaginous microalgae.
In recent decades, several Western countries have reported an increase in oropharyngeal and anal cancers caused by human papillomavirus (HPV). Trends in HPV-associated cancers in Asia have not been ...as well described. We describe the epidemiology of potentially HPV-related cancers reported to the Singapore Cancer Registry from 1968-2012. Analysis included 998 oropharyngeal squamous cell carcinoma (OPSCC), 183 anal squamous cell carcinoma (ASCC) and 8,019 invasive cervical cancer (ICC) cases. Additionally, 368 anal non-squamous cell carcinoma (ANSCC) and 2,018 non-oropharyngeal head and neck carcinoma (non-OP HNC) cases were included as comparators. Age-standardized incidence rates (ASR) were determined by gender and ethnicity (Chinese, Malay and Indian). Joinpoint regression was used to evaluate annual percentage change (APC) in incidence. OPSCC incidence increased in both genders (men 1993-2012, APC = 1.9%, p<0.001; women 1968-2012, APC = 2.0%, p = 0.01) and was 5 times higher in men than women. In contrast, non-OP HNC incidence declined between 1968-2012 among men (APC = -1.6%, p<0.001) and women (APC = -0.4%, p = 0.06). ASCC and ANSCC were rare (ASR = 0.2 and 0.7 per 100,000 person-years, respectively) and did not change significantly over time except for increasing ANSCCs in men (APC = 2.8%, p<0.001). ICC was the most common HPV-associated cancer (ASR = 19.9 per 100,000 person-years) but declined significantly between 1968-2012 (APC = -2.4%). Incidence of each cancer varied across ethnicities. Similar to trends in Western countries, OPSCC incidence increased in recent years, while non-OP HNC decreased. ICC remains the most common HPV-related cancer in Singapore, but Pap screening programs have led to consistently decreasing incidence.
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