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The efficacy of additional water-soluble additives was studied relative to the physical and mechanical properties of particleboards produced from oil palm empty fruit bunch (OPEFB). Polyethylene glycol, acrylamide, and acrylic resin were selected as water-soluble additives for use in the OPEFB particleboard production process. The effects of the three additives at two different concentrations (2% and 4% of dry OPEFB mass) on the particleboard properties were evaluated. Addition of water-soluble additives increased the performance of the OPEFB particleboard. The additive concentration has a significant effect on the properties of the particleboard. With the increase of additive concentration, the internal bonding and modulus of rupture value increased while the thickness swelling and water absorption decreased. Particleboards with an additional 4% of acrylamide or polyethylene glycol achieved the highest modulus of rupture (22 MPa), highest internal bonding strength (1 N/mm2), and lowest thickness swelling (9%). All the particleboards produced with 4% of water-soluble additive achieved the standard requirements of JIS A 5908:2003 for physical and mechanical properties.

Social media posts expressing mental illness such as depression are trending in today's society. The aesthetics of dark and depressing posts are highlighted in blogs or social media accounts of young individuals. Consequently, this study investigated why young people use mental illness as an aesthetic on social media. On top of that, this study contributes to the limited body of research on this subject. This study applied a method known as netnography, an analysis of social interactions online. Furthermore, the actor-network theory (ANT) was employed as an analytical tool to explore insights and draw conclusions. Seven mediators were identified as possible causes that prompted mental illness aesthetic use, including Tumblr, media, attention seekers, coping mechanism, victimhood, emo culture, and mental health awareness. These findings provided insights into developing interventions and systematic methods to discuss mental illness properly. This study also identified current challenges in social media research regarding mental illness detection.

Conventional cancer chemotherapies are not fully efficacious and do not target tumors, leading to significant treatment-related morbidities. A number of genetically attenuated cancer-targeting bacteria are being developed to safely target tumors in vivo. Here we report the toxicological, tumor-targeting, and efficacy profiles of Salmonella enterica serovar Typhimurium CRC2631 in a syngeneic and autochthonous TRAMP model of aggressive prostate cancer. CRC2631 preferentially colonize primary and metastatic tumors in the TRAMP animals. In addition, longitudinal whole genome sequencing studies of CRC2631 recovered from prostate tumor tissues demonstrate that CRC2631 is genetically stable. Moreover, tumor-targeted CRC2631 generates an anti-tumor immune response. Combination of CRC2631 with checkpoint blockade reduces metastasis burden. Collectively, these findings demonstrate a potential for CRC2631 in cancer immunotherapy strategies.

The discovery of new methods to control porosity and microarchitecture may lead to the refinement of carbon materials from lignocellulose as advanced functional materials. However, the high ash content on the surface of lignocellulosic biomass reduces the surface area and adsorption properties of the activated carbon. This study presents a novel approach, using a deashing post-treatment as the pore generator, to increase the quality of the activated carbon. The micropore capacity was improved by deashing post-treatment with distilled water, where 80% of the total pore ratio of the activated carbon was occupied with micropores. Ultrasonic treatment was able to penetrate deeper into the structure of coconut shell activated carbon, creating cavities and pores, thus increasing the surface area. Understanding the effects of these new controlling methods on pore refinement can elucidate the microporous fabrication of other activated carbons from high ash-content lignocellulosic biomass.

Summary Background Deep learning is a novel machine learning technique that has been shown to be as effective as human graders in detecting diabetic retinopathy from fundus photographs. We used a cost-minimisation analysis to evaluate the potential savings of two deep learning approaches as compared with the current human assessment: a semi-automated deep learning model as a triage filter before secondary human assessment; and a fully automated deep learning model without human assessment. Methods In this economic analysis modelling study, using 39 006 consecutive patients with diabetes in a national diabetic retinopathy screening programme in Singapore in 2015, we used a decision tree model and TreeAge Pro to compare the actual cost of screening this cohort with human graders against the simulated cost for semi-automated and fully automated screening models. Model parameters included diabetic retinopathy prevalence rates, diabetic retinopathy screening costs under each screening model, cost of medical consultation, and diagnostic performance (ie, sensitivity and specificity). The primary outcome was total cost for each screening model. Deterministic sensitivity analyses were done to gauge the sensitivity of the results to key model assumptions. Findings From the health system perspective, the semi-automated screening model was the least expensive of the three models, at US$62 per patient per year. The fully automated model was $66 per patient per year, and the human assessment model was $77 per patient per year. The savings to the Singapore health system associated with switching to the semi-automated model are estimated to be $489 000, which is roughly 20% of the current annual screening cost. By 2050, Singapore is projected to have 1 million people with diabetes; at this time, the estimated annual savings would be $15 million. Interpretation This study provides a strong economic rationale for using deep learning systems as an assistive tool to screen for diabetic retinopathy. Funding Ministry of Health, Singapore.

Although deep learning for Diabetic Retinopathy (DR) screening has shown great success in achieving clinically acceptable accuracy for referable versus non-referable DR, there remains a need to provide more fine-grained grading of the DR severity level as well as automated segmentation of lesions (if any) in the retina images. We observe that the DR severity level of an image is dependent on the presence of different types of lesions and their prevalence. In this work, we adopt a multi-task learning approach to perform the DR grading and lesion segmentation tasks. In light of the lack of lesion segmentation mask ground-truths, we further propose a semi-supervised learning process to obtain the segmentation masks for the various datasets. Experiments results on publicly available datasets and a real world dataset obtained from population screening demonstrate the effectiveness of the multi-task solution over state-of-the-art networks.

Myriad neuropsychiatric disorders are due to dopamine dysfunction. However, understanding these disorders is limited by our ability to measure dopamine storage and release. Fluorescent false neurotransmitters (FFNs), small-molecule dyes that co-transit through the synaptic vesicle cycle, have allowed us to image dopamine in cell culture and acute brain slice, but in vivo microscopy is constrained by the biopenetrance of light. Here, we adapt FFNs into magnetic resonance false neurotransmitters (MFNs). The design principles guiding MFNs are (1) the molecule is a valid false neurotransmitter and (2) it has a 19F-substituent near a pH-sensing functional group, which (3) has pKa close to 6 so that the probe within vesicles is protonated. We demonstrate that MFN103 meets these criteria. While a magnetic resonance spectroscopy (MRS) signal was too low for measurement in vivo with the current technology, in principle, MFNs can quantify neurotransmitters within and without synaptic vesicles, which may underlie noninvasive in vivo analysis of dopamine neurotransmission.

Deep learning-based models are developed to automatically detect if a retina image is `referable' in diabetic retinopathy (DR) screening. However, their classification accuracy degrades as the input images distributionally shift from their training distribution. Further, even if the input is not a retina image, a standard DR classifier produces a high confident prediction that the image is `referable'. Our paper presents a Dirichlet Prior Network-based framework to address this issue. It utilizes an out-of-distribution (OOD) detector model and a DR classification model to improve generalizability by identifying OOD images. Experiments on real-world datasets indicate that the proposed framework can eliminate the unknown non-retina images and identify the distributionally shifted retina images for human intervention., Accepted at IEEE ICIP 2021

The aim of this study was to select the optimal conditions for the carbonization process followed by surface modification treatment with sodium hydroxide (NaOH) to obtain a highly microporous activated carbon structure derived from palm kernel shells (PKS) and coconut shells (CS). The effects of the carbonization temperature and NaOH concentration on the physiochemical properties, adsorption capability, specific surface area, surface morphology, and surface chemistry of PKS and CS were evaluated in this study. The results show that surface-modified activated carbons presented higher surface area values (CS: 356.87 m2 g−1, PKS: 427.64 m2 g−1), smaller pore size (CS: 2.24 nm, PKS: 1.99 nm), and larger pore volume (CS: 0.34 cm3 g−1, PKS: 0.30 cm3 g−1) than the untreated activated carbon, demonstrating that the NaOH surface modification was efficient enough to improve the surface characteristics of the activated carbon. Moreover, surface modification via 25% NaOH greatly increases the active functional group of activated carbon, thereby directly increasing the adsorption capability of activated carbon (CS: 527.44 mg g−1, PKS: 627.03 mg g−1). By applying the NaOH post-treatment as the ultimate surface modification technique to the activated carbon derived from PKS and CS, a highly microporous structure was produced.

Unproductive young rubber trees (15 years old) with smaller diameters (15 to 18 cm) compared to conventional rubber logs, harvested at the age of 25 years old, were selected for the production of laminated panels. Spindleless rotary veneer peeling was applied to logs from short-rotation rubber forest plantations to produce veneers for structural purposes. This raises questions about the utilization of these small-diameter logs with respect to its effect on the quality of veneer and laminated panels produced. This study examines the effect of the glue spread rates on the physical and mechanical properties of rubberwood laminated veneer lumber (LVL). Analysis of variance shows that the application of a 280 g/m2 glue spread rate significantly improved the density, water absorption and dimensional stability of rubberwood LVL. The mechanical properties of rubberwood LVL produced with a 200 g/m2 glue spread rate met the minimum requirement for the 2.1E-3100F stress class, 91.05 MPa for the modulus of rupture in the flatwise direction and 50.23 MPa for compressive strength parallel to the longitudinal axis. The modulus of elasticity in the flatwise direction of 11,189.55 MPa reached the minimum requirement for the 1.5E-2250F stress class.

Interventions engaging community health workers (CHW) for diabetes management aim to improve diabetes care and self-management behaviors among patients. We evaluated the effects of nonsurgical periodontal treatment (NSPT) with the CHW strategy on oral self-care behaviors, periodontal status and oral health-related quality of life (OHQoL) in patients with type 2 diabetes mellitus (T2DM). The participants were randomly assigned to experimental (EG, n = 35) and control (CG, n = 33) groups. All participants received NSPT, whereas the patients in the EG also received one-on-one 30 min lessons from a CHW over 4 weeks. The EG exhibited greater improvement in the probing pocket depth (β = −0.2, effect size [ES] = 0.61) and clinical attachment level (β = −0.2, ES = 0.59) at 1-month follow-up than the CG did. The ES increased over the 1-, 3- and 6-month follow-ups, indicating an increase in OHQoL (ES = 0.19, 0.60, and 0.62, respectively) in the EG. The patients in the EG were more likely to change their oral self-care behaviors than patients in the CG were. The NSPT with CHW strategy had a positive effect on 1-month periodontal treatment outcomes, long-term OHQoL and oral self-care behaviors in patients with T2DM.

Background Clinical trials have demonstrated that initiating oral anti-diabetic drugs (OADs) significantly reduce glycated hemoglobin (HbA1c) levels. However, variability in lifestyle modifications and OAD adherence impact on their actual effect on glycemic control. Furthermore, evidence on dose adjustments and discontinuation of OAD on HbA1c is lacking. This study aims to use real-world data to determine the effect of OAD initiation, up-titration, down-titration, and discontinuation on HbA1c levels, among Asian patients managed in primary care. Methods A retrospective cohort study over a 5-year period, from Jan 2015 to Dec 2019 was conducted on a cohort of multi-ethnic adult Asian patients with clinical diagnosis of type 2 diabetes mellitus (T2DM) managed by a network of primary care clinics in Singapore. Nine OADs from five different classes (biguanides, sulphonyurea, dipeptidyl peptidase-4 [DPP-4] inhibitors, sodium-glucose cotransporter-2 [SGLT-2] inhibitors, and alpha-glucosidase inhibitors) were evaluated. Patients were grouped into “No OAD”, “Non-titrators,” and “Titrators” cohorts based on prescribing patterns. For the “Titrators” cohort, the various OAD titrations were identified. Subsequently, a descriptive analysis of HbA1c values before and after each titration was performed to compute a mean difference for each unique titration identified. Results Among the cohort of 57,910 patients, 43,338 of them had at least one OAD titration, with a total of 76,990 pairs of HbA1c values associated with an OAD titration. There were a total of 206 unique OAD titrations. Overall, initiation of OADs resulted in a reduction of HbA1c by 3 to 12 mmol/mol (0.3 to 1.1%), respectively. These results were slightly lower than those reported in clinical trials of 6 to 14 mmol/mol (0.5 to 1.25%). The change of HbA1c levels due to up-titration, down-titration, and discontinuation were −1 to −8 mmol/mol (−0.1 to −0.7%), +1 to 7 mmol/mol (+0.1 to +0.6%), and +2 to 11 mmol/mol (+0.2 to +1.0%), respectively. The HbA1c lowering effect of initiating newer OADs, namely DPP-4 inhibitors and SGLT-2 inhibitors was 8 to 11 mmol/mol (0.7 to 0.9%) and 7 to 11 mmol/mol (0.6 to 1.0%), respectively. Conclusion The real-world data on Asians with T2DM in this study show that the magnitudes of OAD initiation and dose titration are marginally lower than the results from clinical trials. During shared decision-making in selecting treatment options, the results enable physicians to communicate realistic expectation of the effect of oral medications on the glycemic control of their patients in primary care.

Patient similarity analytics has emerged as an essential tool to identify cohorts of patients who have similar clinical characteristics to some specific patient of interest. In this study, we propose a patient similarity measure called D3K that incorporates domain knowledge and data-driven insights. Using the electronic health records (EHRs) of 169,434 patients with either diabetes, hypertension or dyslipidaemia (DHL), we construct patient feature vectors containing demographics, vital signs, laboratory test results, and prescribed medications. We discretize the variables of interest into various bins based on domain knowledge and make the patient similarity computation to be aligned with clinical guidelines. Key findings from this study are: (1) D3K outperforms baseline approaches in all seven sub-cohorts, (2) our domain knowledge-based binning strategy outperformed the traditional percentile-based binning in all seven sub-cohorts, (3) there is substantial agreement between D3K and physicians (κ = 0.746), indicating that D3K can be applied to facilitate shared decision making. This is the first study to use patient similarity analytics on a cardiometabolic syndrome-related dataset sourced from medical institutions in Singapore. We consider patient similarity among patient cohorts with the same medical conditions to develop localized models for personalized decision support to improve the outcomes of a target patient.

Background Aortic dissection is a life-threatening syndrome that sometimes requires emergency intervention, and endovascular aortic aneurysm repair (EVAR) is a treatment option. Long-term image follow-up is also required for patients after EVAR due to possible complications. Case presentation We present the case of a 73-year-old male with underlying chronic renal disease diagnosed with a type A aortic dissection who underwent EVAR. Four-dimensional (three spatial dimensions combined with time) phase-contrast magnetic resonance imaging (4D PC-MRI) was performed during regular follow-up in preference to contrast-enhanced computed tomography or simple MRI while taking his poor renal function into consideration. Conclusions We considered this preferable given his issues with renal function.

Ischemic stroke is a leading cause of death and long-term disability that is difficult to predict reliably. Retinal fundus photography has been proposed for stroke risk assessment, due to its non-invasiveness and the similarity between retinal and cerebral microcirculations, with past studies claiming a correlation between venular caliber and stroke risk. However, it may be that other retinal features are more appropriate. In this paper, extensive experiments with deep learning on six retinal datasets are described. Feature isolation involving segmented vascular tree images is applied to establish the effectiveness of vessel caliber and shape alone for stroke classification, and dataset ablation is applied to investigate model generalizability on unseen sources. The results suggest that vessel caliber and shape could be indicative of ischemic stroke, and sourcespecific features could influence model performance.

Objective: To determine the prevalence and risk factors of Giardia (G.) lamblia infections among the aboriginal community during the wet and dry seasons. Methods: A total of 473 stool samples from the aborigines in Temerloh, Pahang, Malaysia were collected during wet (n=256) and dry seasons (n=217). Smear of all the PVA-preserved stool samples were subjected to Trichrome staining and microscopic examination under 1 000 x magnification (Nikon eclipse E100) for the detection of G. lamblia. Positivity was recorded based on the presence of G. lamblia in trophozoite and/or cyst forms. Results: The prevalence of giardiasis was 12.10% and 8.29% during the wet and dry season, respectively. Age of less or equal to 15 years old and presence of other family members with G. lamblia infection were found to be the significant risk factors to acquire G. lamblia infections during both seasons. Untreated water supply was the significant risk factor of giardiasis during the dry season. This study highlighted the possibility of anthroponotic transmission of G. lamblia during both seasons and waterborne transmission during the dry season in the aboriginal community. Conclusions: This study suggests that seasonal variation plays an important role in the prevalence and risk factor of G. lamblia infection in the aboriginal community. Therefore, close contact with Giardia-infected family members and water-related activities or usage of untreated water must be avoided to reduce the burden of G. lamblia infection in this community.

The success of microbial termiticides in controlling termites depends on the ability of microbes to grow in different media and the functionality of the microbes as a resistant barrier or toxic bait. This study was conducted to understand the mortality rate and behaviour changes of the subterranean termite Coptotermes curvignathus Holmgren introduced with different concentrations of Serratia marcescens strain LGMS 1 and Pseudomonas aeruginosa strain LGMS 3 using wood and soil as bacterial transfer medium. In general, higher concentration of bacteria in soil caused a reduction in tunnelling activity and wood consumption and an increase in mortality. However, application on wood revealed a different outcome. Wood treated with S. marcescens of 10 6 CFU ml −1 concentration proved to be more efficient as bait than higher concentration applications as it caused a high mortality rate while still highly palatable for termites. Wood or soil treated with S. marcescens concentration higher than 10 9 CFU ml −1 creates a high toxicity and repellent barrier for termites. Pseudomonas aeruginosa of 10 9 CFU ml −1 concentrations applied on wood served as a slow-acting toxic bait. However, the ability for S. marcescens and P. aeruginosa to survive on wood is low, which made the bait unable to retain a useful level of toxicity for a long period of time and frequent reapplication is needed.

Background Sepsis causes death and morbidity in young infants. Globally, an estimated 1.3 – 3.9 million young infants experience sepsis and 400,000 – 700,000 die from sepsis-related conditions annually. Even though there have been significant progress over the past twenty years in reducing young infant mortality, sepsis currently accounts for up to 15% of all young infant deaths. A thorough understanding of young infant sepsis can inform strategies that span prevention, diagnosis and intervention for young infant sepsis. Objectives We aimed to perform a systematic review and meta-analysis to investigate the case fatality rates (CFRs) among young infants less than 90 days with sepsis globally. Methods We used the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 2009 guidelines. We searched PubMed, Cochrane Central, Embase and Web of Science for randomized clinical trials and observational studies in English language, published between 2010 to 2019. Studies involving young infants less than 90 days old with sepsis and reported CFRs were included. We obtained pooled CFRs estimates using the random effects model. Additional stratifications by gestation, birth weight, onset of sepsis (early onset was defined as Results Among 6314 articles screened, 240 studies with a total of 437,796 patients met the inclusion criteria and were included in our analysis. 99 came from high income countries, 44 from upper middle income countries, 82 from lower middle income countries, 6 from low income countries and 9 were conducted in multiple countries. Overall, the pooled CFR was 0.18 (95% CI, 0.17–0.19). The CFR was the highest in low income countries (0.25 [95% CI, 0.07–0.43]), followed by lower middle (0.24 [95% CI, 0.21–0.26]), upper middle (0.21 [95% CI, 0.18–0.24]) and lastly high income countries (0.12 [95% CI, 0.11–0.13]). Other factors associated with higher CFRs included prematurity (0.23 [95% CI, 0.19–0.26] vs term CFR 0.10 [95% CI, 0.08–0.13]), low birth weight (0.21 [95% CI, 0.19–0.24] vs normal birth weight 0.19 [95% CI, 0.18–0.20]), early onset sepsis (0.20 [95% CI, 0.17–0.24] vs combined (0.16 [95% CI, 0.14–0.18]) and hospital acquired infection (0.23 [95% CI, 0.17–0.30] vs community acquired infections 0.21 [95% CI, 0.10–0.33]). Time trend analysis showed higher CFRs in the low income countries than the middle and high income countries. A decreasing trend in CFRs over time was observed in high and upper middle income countries, as compared to an increasing trend in lower middle and low income countries. Conclusions While we saw a declining trend of young infant sepsis CFRs among high and upper middle income countries across the years, the increasing trend amongst lower middle and low income countries highlights a disparity in infant sepsis outcomes based on resource availability. We highlight specific vulnerable patient populations that should be further studied in order to reduce the global burden of young infant sepsis.

Introduction: Although collagen is widely used in various forms as a functional ingredient in skin care products, the effect of oral supplementation of collagen tripeptides (CTPs) on human skin is unclear. Moreover, the majority of the positive outcomes of CTP reported so far have not considered the effect of weather conditions. Therefore, we tested the effect of CTP and adjusting for climate change on skin properties in middle-aged women.Materials and Methods: A randomized controlled trial was conducted with 84 women between 40 and 60 years of age. Participants were randomized to receive placebo or 1,000 mg CTP daily for 12 weeks. CTP was prepared from the skin of Nile Tilapia by the digestion method using collagenase from non-pathogenic bacteria of the genus Bacillus. Skin hydration, wrinkling, and elasticity were assessed at baseline and after 6 and 12 weeks with adjustments for temperature, humidity, and ultraviolet A exposure during the evaluation time using weather data from the regional meteorological office.Results: Of the 82 participants, 74 completed the trial without adverse effects. Compared with the control group, trans-epidermal water loss was reduced more in the CTP group after 12 weeks (P < 0.05). At 12 weeks, even after adjustment for humidity, temperature, and UVA in the region, the difference of the two groups in TEWL remained statistically significant (adjusted for humidity and temperature, P = 0.024; adjusted for UVA, P = 0.032; adjusted for temperature, high temperature, and ultraviolet A, P = 0.031). In terms of skin hydration, more improvement was evident in the CTP group than in the control group. In the subgroup analysis, subjects under 50 years of age showed a significant improvement in total score and moisture in the subjective skin improvement questionnaire after taking CTP for 12 weeks. Application of CTP was well-tolerated, and no notable adverse effect was reported from both groups.Discussion: Our findings suggest that oral ingestion of CTP from the Skin of Nile Tilapia (Oreochromis niloticus) is well-tolerated and helps reduce water loss in in middle-aged women.Clinical Trial Registration:www.clinicaltrials.gov/, Identifier: NCT03505684.

Background Clinical trials have demonstrated that either initiating or up-titrating a statin dose substantially reduce Low-Density Lipoprotein-Cholesterol (LDL-C) levels. However, statin adherence in actual practice tends to be suboptimal, leading to diminished effectiveness. This study aims to use real-world data to determine the effect on LDL-C levels and LDL-C goal attainment rates, when selected statins are titrated in Asian patients. Methods A retrospective cohort study over a 5-year period, from April 2014 to March 2019 was conducted on a cohort of multi-ethnic adult Asian patients with clinical diagnosis of Dyslipidaemia in a primary care clinic in Singapore. The statins were classified into low-intensity (LI), moderate-intensity (MI) and high-intensity (HI) groups according to the 2018 American College of Cardiology and American Heart Association (ACC/AHA) Blood Cholesterol Guidelines. Patients were grouped into “No statin”, “Non-titrators” and “Titrators” cohorts based on prescribing patterns. For the “Titrators” cohort, the mean percentage change in LDL-C and absolute change in LDL-C goal attainment rates were computed for each permutation of statin intensity titration. Results Among the cohort of 11,499 patients, with a total of 266,762 visits, there were 1962 pairs of LDL-C values associated with a statin titration. Initiation of LI, MI and HI statin resulted in a lowering of LDL-C by 21.6% (95%CI = 18.9–24.3%), 28.9% (95%CI = 25.0–32.7%) and 25.2% (95%CI = 12.8–37.7%) respectively. These were comparatively lower than results from clinical trials (30 to 63%). The change of LDL-C levels due to up-titration, down-titration, and discontinuation were − 12.4% to − 28.9%, + 13.2% to + 24.6%, and + 18.1% to + 32.1% respectively. The improvement in LDL-C goal attainment ranged from 26.5% to 47.1% when statin intensity was up-titrated. Conclusion In this study based on real-world data of Asian patients in primary care, it was shown that although statin titration substantially affected LDL-C levels and LDL-C goal attainment rates, the magnitude was lower than results reported from clinical trials. These results should be taken into consideration and provide further insight to clinicians when making statin adjustment recommendations in order to achieve LDL-C targets in clinical practice, particularly for Asian populations.

Background There is increasing evidence supporting coronavirus disease 2019 (COVID-19)-related coagulopathy. In the available literature, only 2 cases of superior mesenteric vein thrombosis have been described. Methods We present a peculiar case of high-grade small bowel obstruction in a patient with COVID-19 infection. Results Exploratory laparotomy revealed a congenital adhesion band with associated focal bowel ischemia contributed by superior mesenteric vein thrombosis and positive lupus anticoagulant. Conclusions It is important to consider the rare differential of mesenteric vein thrombosis and its related sequelae of mesenteric ischemia in a patient with COVID-19 who presents with abdominal pain.

Glioblastoma (GBM) is a uniformly lethal disease driven by glioma stem cells (GSCs). Here, we use a chemical biology approach to unveil previously unknown GBM dependencies. By studying sulconazole (SN) with anti-GSC properties, we find that SN disrupts biotin distribution to the carboxylases and histones. Transcriptomic and metabolomic analyses of SN-treated GSCs reveal metabolic alterations that are characteristic of biotin-deficient cells, including intracellular cholesterol depletion, impairment of oxidative phosphorylation, and energetic crisis. Furthermore, SN treatment reduces histone biotinylation, histone acetylation, and expression of superenhancer-associated GSC critical genes, which are also observed when biotin distribution is genetically disrupted by holocarboxylase synthetase (HLCS) depletion. HLCS silencing impaired GSC tumorigenicity in an orthotopic xenograft brain tumor model. In GBM, high HLCS expression robustly indicates a poor prognosis. Thus, the dependency of GBM on biotin distribution suggests that the rational cotargeting of biotin-dependent metabolism and epigenetic pathways may be explored for GSC eradication. National Research Foundation (NRF) National University of Singapore (NUS), Temasek Laboratories Published version This work was supported by the National Research Foundation Fellowship NRF-NRFF2017-01 (D.S.T.O.), National University of Singapore (NUS) start-up grant (D.S.T.O. and M.J.K.), NUS President’s Assistant Professorship (D.S.T.O.), and NUS Research Scholarships (M.J.Y.A., B.W.L.L., Y.H.C., and R.T.M.). S.K. and C.S.V. thank A*STAR and NSCC for support.

Background: South-East Asia has seen a dramatic increase in type 2 diabetes (T2D). Risk prediction models for Major adverse cardiovascular events (MACE) identify patients who may benefit most from intensive prevention strategies. Existing risk prediction models for T2D were developed mainly in Caucasian populations, limiting their generalizability to Asian populations. We developed a Lasso-Cox regression model to predict the 5-year risk of incident MACE in Asian patients with T2DM using data from the largest diabetes registry in Singapore. Methodology: The diabetes registry contained public healthcare data from 9 primary healthcare centers, 4 hospitals and 3 national specialty centers. Data from 120,131 T2D subjects without MACE at baseline, from 2008 to 2018, were used for model development and validation. Patients with less than 5 years of follow-up data were excluded. Lasso-Cox, a semi-parametric variant of the Cox Proportional Hazard Model with l1-regularization, was used to predict individual survival distribution of incident MACE. A total of 69 features within electronic health records, including demographic data, vital signs, laboratory tests, and prescriptions for blood pressure, lipid and glucose-lowering medication were supplied to the model. Regression shrinkage and selection via the lasso method was used to identify variables associated with incident MACE. Identified variables were used to generate individual survival probability curves. Incident MACE was defined as the first occurrence of nonfatal myocardial infarction, nonfatal stroke, and CV disease-related death. Results: A total of 12,535 (10.4%) subjects developed MACE between 2008 and 2018. Model performance was evaluated by time-dependent concordance index and Brier score at 1, 2 and 5 years. The results of 5-fold cross validation shows that the model displayed good discrimination, achieving time-dependent C-statistics of 0.746±0.005, 0.742±0.003 and 0.738±0.002 at 1, 2 and 5 years respectively. The model demonstrated low Brier scores of 0.0355±0.0004, 0.0601±0.0011, 0.104±0.004 at 1, 2 and 5 years respectively, indicating good calibration. Factors most predictive of MACE were age and a history of hypertension and hyperlipidemia. Conclusions: We have developed a risk prediction model for MACE in Asian T2D using a large Singaporean T2D cohort, which can be used to support clinical decision-making. The individual survival probability estimates achieve an average C-statistics of 0.742 and are well-calibrated at 1, 2 and 5 years.

Microbial pathogens continue to attract a great deal of attention to manage the termite population. Every bacterium has its own mode of action and in fact, the mechanisms used by bacteria to attack termites remain elusive at the moment. Hence, the objective of this study was to evaluate the susceptibility of subterranean termites Coptotermes curvignathus to opportunistic pathogens using culturable aerobic bacteria isolated from the termite gut and its foraging pathways. Bacterial suspensions were prepared in concentrations of 10 3 , 10 6 and 10 9 colony-forming units (CFU) ml −1 and introduced to the termites via oral-contact and physical contact treatment. The data show that contact method acted slower and gave lower mortality, compared to the oral-contact method. Coptotermes curvignathus were highly susceptible to Serratia marcescens and Pseudomonas aeruginosa . Serratia marcescens showed the highest mortality percentage of 68% and 54% at bacterial concentration of 10 9 CFU ml −1 via oral-contact and contact method, respectively. Serratia marcescens was also defined as the bacteria with the highest ability to induce the high mortality of C. curvignathus with the lowest concentration of bacterial suspension at a given time under laboratory condition. The results of this study indicate that P. aeruginosa and S. marcescens in particular may be attractive candidates worth further examination as a possible biocontrol agent against C. curvignathus in the field and to evaluate environmental and ecological risks of the biocontrol.

In recent years, imidacloprid and fipronil have been reported to harm beneficial insects, such as honey bees, and to potentially pose risks to mammals, including humans. Considering their widespread use and potential minimum toxic range from 10 ppb to 1 ppm (species dependent), a simple, rapid, sensitive, and reliable method for screening and detection is urgently needed. Here, we present a surface plasmon resonance (SPR)-based nanoplasmonic chip integrated with a multichannel spectral imaging system to detect ecosystem-harming pesticides. The pre-modification of the designed mercapto-haptens reduced detection time to 2.5 h. Moreover, owing to the multichannel configuration, it was possible to introduce an internal standard analytical method to effectively reduce matrix interference in real samples; thus, the concentration of the target pesticide could be determined more precisely. The strong linearity of the spiked sample test results indicated high accuracy in quantifying target pesticides. Considering the limit of detection (~10 ppb), the cutoffs for detection and quantification were set at 15 and 45 ppb, respectively, and were used as the detection criteria. The detection results of the blind tests of real samples were also compared with those of liquid chromatography electrospray ionization tandem mass spectrometry (standard method) and were highly consistent. The custom-made integrated SPR system allows much simpler, label-free, high-throughput, and reliable on-site identification and quantification of imidacloprid and fipronil. All test results validated the platform's capability in the on-site rapid screening and detection of pesticide residues at the parts per billion and parts per million levels.

Deep learning (DL) has been shown to be effective in developing diabetic retinopathy (DR) algorithms, possibly tackling financial and manpower challenges hindering implementation of DR screening. However, our systematic review of the literature reveals few studies studied the impact of different factors on these DL algorithms, that are important for clinical deployment in real-world settings. Using 455,491 retinal images, we evaluated two technical and three image-related factors in detection of referable DR. For technical factors, the performances of four DL models (VGGNet, ResNet, DenseNet, Ensemble) and two computational frameworks (Caffe, TensorFlow) were evaluated while for image-related factors, we evaluated image compression levels (reducing image size, 350, 300, 250, 200, 150 KB), number of fields (7-field, 2-field, 1-field) and media clarity (pseudophakic vs phakic). In detection of referable DR, four DL models showed comparable diagnostic performance (AUC 0.936-0.944). To develop the VGGNet model, two computational frameworks had similar AUC (0.936). The DL performance dropped when image size decreased below 250 KB (AUC 0.936, 0.900, p p p

Summary Background Screening for chronic kidney disease is a challenge in community and primary care settings, even in high-income countries. We developed an artificial intelligence deep learning algorithm (DLA) to detect chronic kidney disease from retinal images, which could add to existing chronic kidney disease screening strategies. Methods We used data from three population-based, multiethnic, cross-sectional studies in Singapore and China. The Singapore Epidemiology of Eye Diseases study (SEED, patients aged ≥40 years) was used to develop (5188 patients) and validate (1297 patients) the DLA. External testing was done on two independent datasets: the Singapore Prospective Study Program (SP2, 3735 patients aged ≥25 years) and the Beijing Eye Study (BES, 1538 patients aged ≥40 years). Chronic kidney disease was defined as estimated glomerular filtration rate less than 60 mL/min per 1·73m2. Three models were trained: 1) image DLA; 2) risk factors (RF) including age, sex, ethnicity, diabetes, and hypertension; and 3) hybrid DLA combining image and RF. Model performances were evaluated using the area under the receiver operating characteristic curve (AUC). Findings In the SEED validation dataset, the AUC was 0·911 for image DLA (95% CI 0·886 −0·936), 0·916 for RF (0·891–0·941), and 0·938 for hybrid DLA (0·917–0·959). Corresponding estimates in the SP2 testing dataset were 0·733 for image DLA (95% CI 0·696–0·770), 0·829 for RF (0·797–0·861), and 0·810 for hybrid DLA (0·776–0·844); and in the BES testing dataset estimates were 0·835 for image DLA (0·767–0·903), 0·887 for RF (0·828–0·946), and 0·858 for hybrid DLA (0·794–0·922). AUC estimates were similar in subgroups of people with diabetes (image DLA 0·889 [95% CI 0·850–0·928], RF 0·899 [0·862–0·936], hybrid 0·925 [0·893–0·957]) and hypertension (image DLA 0·889 [95% CI 0·860–0·918], RF 0·889 [0·860–0·918], hybrid 0·918 [0·893–0·943]). Interpretation A retinal image DLA shows good performance for estimating chronic kidney disease, underlying the feasibility of using retinal photography as an adjunctive or opportunistic screening tool for chronic kidney disease in community populations. Funding National Medical Research Council, Singapore.

© 2020 Elsevier Ltd Background: Observational studies have suggested that accelerated surgery is associated with improved outcomes in patients with a hip fracture. The HIP ATTACK trial assessed whether accelerated surgery could reduce mortality and major complications. Methods: HIP ATTACK was an international, randomised, controlled trial done at 69 hospitals in 17 countries. Patients with a hip fracture that required surgery and were aged 45 years or older were eligible. Research personnel randomly assigned patients (1:1) through a central computerised randomisation system using randomly varying block sizes to either accelerated surgery (goal of surgery within 6 h of diagnosis) or standard care. The coprimary outcomes were mortality and a composite of major complications (ie, mortality and non-fatal myocardial infarction, stroke, venous thromboembolism, sepsis, pneumonia, life-threatening bleeding, and major bleeding) at 90 days after randomisation. Patients, health-care providers, and study staff were aware of treatment assignment, but outcome adjudicators were masked to treatment allocation. Patients were analysed according to the intention-to-treat principle. This study is registered at ClinicalTrials.gov (NCT02027896). Findings: Between March 14, 2014, and May 24, 2019, 27 701 patients were screened, of whom 7780 were eligible. 2970 of these were enrolled and randomly assigned to receive accelerated surgery (n=1487) or standard care (n=1483). The median time from hip fracture diagnosis to surgery was 6 h (IQR 4–9) in the accelerated-surgery group and 24 h (10–42) in the standard-care group (p

Pleural empyema is an inflammatory condition characterized by accumulation of pus inside the pleural cavity, which is usually followed by bacterial pneumonia. During the disease process, the pro-inflammatory and pro-fibrotic cytokines in the purulent pleural effusion cause proliferation of fibroblasts and deposition of extracellular matrix, which lead to fibrin deposition and fibrothorax. Urokinase instillation therapy through a chest drainage tube is frequently used for fibrinolysis in patients with empyema. However, urokinase treatment requires multiple instillation (2-3 times per day, for 4-8 days) and easily flows out from the chest drainage tube due to its high water solubility. In this in vitro study, we developed a thermo-responsive hydrogel based on poloxamer 407 (P407) combined with hyaluronic acid (HA) for optimal loading and release of urokinase. Our results show that the addition of HA to poloxamer gels provides a significantly more compact microstructure, with smaller pore sizes (**p < 0.001). The differential scanning calorimetry (DSC) profile revealed no influence on the micellization intensity of poloxamer gel by HA. The 25% poloxamer-based gel was significantly superior to the 23% poloxamer-based gel, with slower gel erosion when comparing the 16th hour residual gel weight of both gels (*p < 0.05; **p < 0.001). The 25% poloxamer-HA gel also exhibited a superior urokinase release profile and longer release time. A Fourier-transform infrared spectroscopy (FT-IR) study of the P407/HA hydrogel showed no chemical interactions between P407 and HA in the hydrogel system. The thermoresponsive P407/HA hydrogel may have a promising potential in the loading and delivery of hydrophilic drugs. On top of that, in vitro toxicity test of this combination demonstrates a lower toxicity.

Microscopy-based technique has been widely used in the detection of Blastocystis sp. This study was conducted to compare the techniques used for screening of Blastocystis sp., namely in vitro cultivation of stool specimens in Jones’ medium (IVC) followed by Wheatley Trichrome staining and direct examination of stool samples preserved with polyvinyl alcohol (PVA) followed by Wheatley Trichrome staining with single-round polymerase chain reaction (PCR) as the reference technique. The study was performed on 466 stool samples obtained from the aboriginal community in Pahang, Malaysia. IVC showed higher detection rate of Blastocystis sp. (35.6%) than PVA (20.0%). Single-round PCR detected Blastocystis sp. in 41.0% of the stool specimens. The sensitivity and specificity of PVA and IVC in comparison to the reference technique were 75.3% (95% CI: 65.2-83.6) and 68.5% (CI: 63.7-73.3) and 88.6% (CI: 82.7-93.0) and 86.3% (CI: 81.9-90.0), respectively. The agreement between the reference technique and PVA showed statistically significant fair agreement by Cohen Kappa statistics of (K=0.318, p

Pleural empyema is an inflammatory condition characterized by accumulation of pus inside the pleural cavity, which is usually followed by bacterial pneumonia. During the disease process, the pro-inflammatory and pro-fibrotic cytokines in the purulent pleural effusion cause proliferation of fibroblasts and deposition of extracellular matrix, which lead to fibrin deposition and fibrothorax. Urokinase instillation therapy through a chest drainage tube is frequently used for fibrinolysis in patients with empyema. However, urokinase treatment requires multiple instillation (2-3 times per day, for 4-8 days) and easily flows out from the chest drainage tube due to its high water solubility. In this in vitro study, we developed a thermo-responsive hydrogel based on poloxamer 407 (P407) combined with hyaluronic acid (HA) for optimal loading and release of urokinase. Our results show that the addition of HA to poloxamer gels provides a significantly more compact microstructure, with smaller pore sizes (**p < 0.001). The differential scanning calorimetry (DSC) profile revealed no influence on the micellization intensity of poloxamer gel by HA. The 25% poloxamer-based gel was significantly superior to the 23% poloxamer-based gel, with slower gel erosion when comparing the 16th hour residual gel weight of both gels (*p < 0.05; **p < 0.001). The 25% poloxamer-HA gel also exhibited a superior urokinase release profile and longer release time. A Fourier-transform infrared spectroscopy (FT-IR) study of the P407/HA hydrogel showed no chemical interactions between P407 and HA in the hydrogel system. The thermoresponsive P407/HA hydrogel may have a promising potential in the loading and delivery of hydrophilic drugs. On top of that, in vitro toxicity test of this combination demonstrates a lower toxicity.