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Background: Diabetic retinopathy (DR) screening using colour retinal photographs is cost-effective and time-efficient. In real-world clinical settings, DR severity is frequently graded by individuals of different expertise levels. We aim to determine the agreement in DR severity grading between human graders of varying expertise and an automated deep learning DR screening software (ADLS). Methods: Using the International Clinical DR Disease Severity Scale, two hundred macula-centred fundus photographs were graded by retinal specialists, ophthalmology residents, family medicine physicians, medical students, and the ADLS. Based on referral urgency, referral grading was divided into no referral, non-urgent referral, and urgent referral to an ophthalmologist. Inter-observer and intra-group variations were analysed using Gwet’s agreement coefficient, and the performance of ADLS was evaluated using sensitivity and specificity. Results: The agreement coefficient for inter-observer and intra-group variability ranged from fair to very good, and moderate to good, respectively. The ADLS showed a high area under curve of 0.879, 0.714, and 0.836 for non-referable DR, non-urgent referable DR, and urgent referable DR, respectively, with varying sensitivity and specificity values. Conclusion: Inter-observer and intra-group agreements among human graders vary widely, but ADLS is a reliable and reasonably sensitive tool for mass screening to detect referable DR and urgent referable DR.

The main goal of the present work was to synthesize a composite consisting of h-BN particles coated with a γ-Al2O3 nanolayer. A method was proposed for applying nanocrystalline γ-Al2O3 to h-BN particles using a sol–gel technique, which ensures the chemical homogeneity of the composite at the nano level. It has been determined that during crystallization on the h-BN surface, the proportion of spinel in alumina decreases from 40 wt.% in pure γ-Al2O3 to 30 wt.% as a result of the involvement of the B3+ ions from the surface nitride monolayers into the transition complex. For comparison, nano-alumina was synthesized from the same sol under the same conditions as the composite. The characterization of the obtained nanostructured powders was carried out using TEM and XRD. A mechanism is proposed for the formation of a nanostructured γ-Al2O3@h-BN composite during the interaction of Al-containing sol and h-BN suspension in aqueous organic media. The resulting composite is a promising model of powdered raw materials for the development of fine-grained ceramic materials for a wide range of applications.

Machining is an indispensable manufacturing process for a wide range of engineering materials, such as metals, ceramics, and composite materials, in which the tool wear is a serious problem, which affects not only the costs and productivity but also the quality of the machined components. Thus, the modification of the cutting tool surface by application of textures on their surfaces is proposed as a very promising method for improving tool life. Surface texturing is a relatively new surface engineering technology, where microscale or nanoscale surface textures are generated on the cutting tool through a variety of techniques in order to improve tribological properties of cutting tool surfaces by reducing the coefficient of friction and increasing wear resistance. In this paper, the studies carried out to date on the texturing of ceramic and superhard cutting tools have been reviewed. Furthermore, the most common methods for creating textures on the surfaces of different materials have been summarized. Moreover, the parameters that are generally used in surface texturing, which should be indicated in all future studies of textured cutting tools in order to have a better understanding of its effects in the cutting process, are described. In addition, this paper proposes a way in which to classify the texture surfaces used in the cutting tools according to their geometric parameters. This paper highlights the effect of ceramic and superhard textured cutting tools in improving the machining performance of difficult-to-cut materials, such as coefficient of friction, tool wear, cutting forces, cutting temperature, and machined workpiece roughness. Finally, a conclusion of the analyzed papers is given.

Spray drying is a widely used method of converting liquid material (aqueous or organic solutions, emulsions and suspensions) into a dry powder. Good flowability, narrow size distribution, and controllable morphology are inherent in powders produced by spray drying. This review considers the granulation factors that influence the final properties of the silicon nitride dried powders. The first group includes the types of atomizers, manifolds, and drying chamber configurations. The process parameters fall into the second group and include the following: inlet temperature, atomizing air flow, feed flow rate, drying gas flow rate, outlet temperature, and drying time. Finally, the last group, feedstock parameters, includes many factors such as feed surface tension, feed viscosity, solvent type, solid particle concentration, and additives. Given the large number of factors affecting morphology, particle size and moisture, optimizing the spray drying process is usually achieved by the “trial and error” approach. Nevertheless, some factors such as the effect of a solvent, dispersant, binder, and sintering additives considered in the literature that affect the Si3N4 granulation process were reviewed in the work. By summarizing the data available on silicon nitride powder production, the authors attempt to tackle the problem of its emerging demand in science and industry.

SiC-TiB2-TiC composites with matrices consisting of semiconductor material (SiC), conductive materials (TiB2-TiC), or their combination were fabricated by spark plasma sintering (SPS) at 2000 °C in a vacuum under a pressure of 80 MPa for 3 min. The composition and microstructure of the obtained composites were studied by X-ray diffraction and a scanning electron microscope equipped with an energy-dispersive detector. The flexural strength, Vickers hardness, and fracture toughness of SPSed samples were determined. Based on the observations in this work, three variations of the sintering process were proposed with different matrix compositions. The dense (99.7%) 60SiC-25TiB2-15TiC vol.% sintered ceramic composites exhibited the highest strength and hardness values of the studied composites, as well as a fracture toughness of 6.2 MPa·m1/2.

Introduction Ageing is associated with a multitude of healthcare issues including dementia, depression, frailty, morbidity associated with chronic disease and high healthcare utilisation. With Singapore’s population projected to age significantly over the next two decades, it has become increasingly important to understand the disease burden and etiological process among older adults. The Community Health and Intergenerational study aims to holistically examine ageing in place by investigating the resilience and vulnerability factors of the ageing process in the biological, psychological and social domains within the environment.Methods and analysis Using a cohort multiple randomised controlled trial design, comprehensive health profiles of community-dwelling older adults will be collected. The objective is to recruit 1000 participants (aged 60–99 years) living in the western region of Singapore within a period of 3 years (2018–2020). Assessments include basic sociodemographic, physical health and function (cardiac, oral and blood profiles and visual function), cognitive functioning, daily functioning, physical fitness, emotional state, free-flowing speech, sleep quality, social connectedness, caregiver burden, intergenerational communication, quality of life, life satisfaction, attitudes to ageing and gratitude and compassion. Results from the cohort will enable future studies to identify at-risk groups and develop interventions to improve the physical and mental health and quality of life of older adults.Ethics and dissemination Approval of the cohort study by the National University of Singapore Institutional Review Board (NUS-IRB Reference code: H-17-047) was obtained on 12 October 2017. Written consent will be obtained from all participants. Findings from the cohort study will be disseminated by publication of peer-reviewed manuscripts, presentations at scientific meetings and conferences with local stakeholders.

Purpose. To identify systemic factors that may influence the response to anti-VEGF therapy in patients with diabetic macular edema (DME). Methods. 35 patients undergoing anti-VEGF injections for centre-involving DME were studied in this prospective observational study. The primary outcome was change in macular thickness one month after treatment, measured using spectral-domain optical coherence tomography (OCT). At baseline, information on various systemic factors was collected including glycosylated hemoglobin (HbA1c), serum VEGF levels, lipid profile and markers of renal function, and blood pressure. Thirty-three of the 35 patients were included in this study. Nonparametric statistical tests were used for the analysis of the data in view of the nonnormal distribution of the outcome variables. Multivariate analysis was performed using logistic regression. Stata 12.1 software was used for the analysis. Main Outcome Measures. Reduction in macular central subfield thickness (on spectral-domain OCT) and change in logMAR visual acuity at one month after injection. Results. Lower HbA1c levels (7% or less) were significantly associated with greater reduction in central macular subfield thickness at one month after injection of bevacizumab or ranibizumab on both univariate analysis (p=0.012) and multivariate analysis (p=0.042). Conclusions. Better glycemic control is associated with a greater reduction in central macular thickness after the first injection of bevacizumab or ranibizumab in diabetic macular edema. Patients with high levels of HbA1c and poor response to anti-VEGF may benefit from strict control of their blood glucose.

Heavy metal and metalloid contaminations are among the most concerning types of pollutant in the environment. Consequently, it is important to investigate the molecular mechanisms of cellular responses and detoxification pathways for these compounds in living organisms. To date, a number of genes have been linked to the detoxification process. The expression of these genes can be controlled at both transcriptional and translational levels. In baker's yeast, Saccharomyces cerevisiae, resistance to a wide range of toxic metals is regulated by glutathione S-transferases. Yeast URE2 encodes for a protein that has glutathione peroxidase activity and is homologous to mammalian glutathione S-transferases. The URE2 expression is critical to cell survival under heavy metal stress. Here, we report on the finding of two genes, ITT1, an inhibitor of translation termination, and RPS1A, a small ribosomal protein, that when deleted yeast cells exhibit similar metal sensitivity phenotypes to gene deletion strain for URE2. Neither of these genes were previously linked to metal toxicity. Our gene expression analysis illustrates that these two genes affect URE2 mRNA expression at the level of translation.

The presence of acetic acid during industrial alcohol fermentation reduces the yield of fermentation by imposing additional stress on the yeast cells. The biology of cellular responses to stress has been a subject of vigorous investigations. Although much has been learned, details of some of these responses remain poorly understood. Members of heat shock chaperone HSP proteins have been linked to acetic acid and heat shock stress responses in yeast. Both acetic acid and heat shock have been identified to trigger different cellular responses including reduction of global protein synthesis and induction of programmed cell death. Yeast HSC82 and HSP82 code for two important heat shock proteins that together account for 1–2% of total cellular proteins. Both proteins have been linked to responses to acetic acid and heat shock. In contrast to the overall rate of protein synthesis which is reduced, the expression of HSC82 and HSP82 is induced in response to acetic acid stress. In the current study we identified two yeast genes DOM34 and RPL36A that are linked to acetic acid and heat shock sensitivity. We investigated the influence of these genes on the expression of HSP proteins. Our observations suggest that Dom34 and RPL36A influence translation in a CAP-independent manner.

The rising demand for powerful oncolytic virotherapy agents has led to the identification of Maraba virus, one of the most potent oncolytic viruses from Rhabdoviridae family which displays high selectivity for killing malignant cells and low cytotoxicity in normal cells. Although the virus is readied to be used for clinical trials, the interactions between the virus and the host cells is still unclear. Using a newly developed interferon-sensitive mutant Maraba virus (MG1), we have identified two key regulators of global translation (4E-BP1 and eIF2α) as being involved in the regulation of protein synthesis in the infected cells. Despite the translational arrest upon viral stress, we showed an up-regulation of anti-apoptotic Bcl-xL protein that provides a survival benefit for the host cell, yet facilitates effective viral propagation. Given the fact that eIF5B canonically regulates 60S ribosome subunit end joining and is able to replace the role of eIF2 in delivering initiator tRNA to the 40S ribosome subunit upon the phosphorylation of eIF2α we have tested whether eIF5B mediates the translation of target mRNAs during MG1 infection. Our results show that the inhibition of eIF5B significantly down-regulates the level of Bcl-xL steady-state mRNA, thus indirectly attenuates viral propagation.

Scavenger receptor class B type I (SR-BI) has an established role in mediating the selective uptake of cholesterol from HDL in hepatocytes, steroidogenic cells, and other tissues. SR-BI is present on the plasma membrane but also localizes to stable intracellular compartments of unknown function. Using indirect immunofluorescence and subcellular fractionation, we have investigated the subcellular distribution of SR-BI. We report that red fluorescent protein-tagged mouse SR-BI (RFP-mSR-BI) colocalizes with the late endosomal and lysosomal markers, Rab7, LBPA, and Rab9. In addition, endogenous SR-BI is also found on lysosomes and colocalizes with LAMP-2 in primary hepatocytes. Furthermore, we demonstrate that the trafficking of SR-BI through these compartments is Rab7 dependent. Interestingly, filipin staining indicates accumulation of lysosomal cholesterol in SR-BI-deficient (−/−) as compared with wild-type hepatocytes. In addition to its role as a plasma membrane receptor, SR-BI may function in cholesterol trafficking from late endosomes/lysosomes.

The influence of WEDM parameters (Spark gap voltage, Pulse-on time, Spark frequency, and Wire speed) on the recast layer thickness and surface roughness of Spark Plasma Sintered SiC-TiB2-TiC ceramic composite was investigated. For this, an orthogonal L9 Taguchi design was used, and grey relational analysis was carried out for multi-response WEDM parameter optimization in order to determine the minimum RLT and SR. It was noticed that for RLT, the Pulse-on time was observed as the most significant process parameter, followed by Spark gap voltage. On the other hand, Spark frequency and Wire speed had no significance for RLT. Moreover, Spark frequency was observed as the most significant process parameter, followed by Pulse-on time and Spark gap voltage, while Wire speed had a negligible effect on SR. It was found that at optimal process parameters (U = 48V; Ton = 1.0 µs; f = 10 kHz; q = 8 m/min), we obtained an RLT of 3.16 µm and an SR of Ra = 0.847 µm. The confirmation test showed a decrease in RLT and SR by 43.67% and 7.12%, respectively, in comparison to the initial machining conditions. [ABSTRACT FROM AUTHOR]

A nitroreductase (NTR) responsive fluorescent probe with long wavelength fluorescence emission was used to determine the NTR activity of a selection of bacterial species under a range of different bacterial growth conditions ensuring applicability under multiple complex clinical environments, where sensitivity, reaction time, and the detection accuracy were suitable for planktonic cultures and biofilms. [ABSTRACT FROM AUTHOR]