Miracle-dz/UniFAR-FTUs huggingface dataset:
Lower Tear Meniscus Height Measurements Using Keratography and Swept-Source Optical Coherence Tomography and Effect of Fluorescein Instillation Methods

ABSTRACT Purpose: The first aim of this study was to compare inferior tear meniscus height (TMH) measured by keratography and swept-source optical coherence tomography (OCT). Effect of locations of fluorescein instillation and subjects’ subjective sensation, and the TMH results were also investigated. Methods: Forty-one eyes from 41 healthy adults had TMH randomly measured by keratography (K5M, Oculus, Germany) and swept-source OCT (Casia SS-1000, Tomey Corp, Japan) at baseline, followed by touching either the inferior bulbar or inferior palpebral conjunctiva, randomly assigned, with a moistened fluorescein strip. Two-way analysis of variance (ANOVA) was used to compare TMH obtained from the two devices and three measurement conditions. Subjective sensation of conjunctival touch was obtained through a 4-point scale with zero representing no sensation, and one to three representing ocular sensation in an ascending order. Results: Two-way ANOVA revealed no significant difference in TMH between keratography and swept-source OCT (Factor (devices): F = 0.579, p = . 451) while there was a significant difference among fluorescein instillations (Factor (conditions): F = 10.146, p < . 001). Baseline TMH was around 0.25 mm, and increased to around 0.28 mm after instillation of fluorescein sodium. Ocular sensation was similar between the two conjunctival touch, and TMH was not significantly associated with ocular sensation. Conclusions: Keratography and swept-source OCT provided similar TMH results. Applying fluorescein sodium through moistened fluorescein strip could over-estimate TMH by around 0.03 mm. Applying moistened fluorescein strip at bulbar or palpebral conjunctival led to similar subjective sensations and did not affect TMH measurement. Graphical Abstract
Sodium‐glucose co‐transporter inhibitors, their role in type 1 diabetes treatment and a risk mitigation strategy for preventing diabetic ketoacidosis: The STOP DKA Protocol

Recent phase 3 clinical trials have evaluated the impact of adding sodium‐glucose co‐transporter (SGLT) inhibitors to the type 1 diabetes armamentarium. These trials studied SGLT2 inhibitors (dapagliflozin and empagliflozin) and a dual SGLT1 and SGLT2 inhibitor (sotagliflozin), and demonstrated that these oral non‐insulin antihyperglycaemic medications are able not only to improve glycaemic control, but also to reduce body weight and extend time in range without increasing rates of hypoglycaemia in type 1 diabetes. Diabetic ketoacidosis (DKA) is a feature of type 1 diabetes and the risk is increased when SGLT inhibitors are used in type 1 diabetes. To minimize the risk of DKA and still gain the multiple benefits, we developed the “STOP DKA Protocol “, an easily accessible and practical tool, that provides a risk mitigation strategy for reducing DKA in patients with type 1 diabetes being treated with SGLT inhibitors.
Metformin prevents murine ovarian aging

A number of studies have shown that metformin can delay aging process and extend healthy lifespan in animals. However, its role in female reproductive lifespan is unclear. This study was aimed to explore the potential anti-aging effect of metformin on the ovary and its possible mechanisms. Female C57BL/6 mice of 27-week old were divided into two groups, the control group (CON) and metformin-treated group (MET). CON mice were fed ad libitum, while MET mice were fed on chows supplied with 100mg/kg metformin for half a year. Ovarian reserve and function were assessed by ovarian follicle counts, estrous cycle and sex hormones levels. The expressions of oxidized metabolites, such as 8-hydroxy-2´-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE), nitrotyrosine (NTY), and ovarian aging associated proteins P16, SIRT1, p-rpS6 and Bcl2 were examined. The MET mice exhibited increased level of serum E2 hormone and higher percentage of regular estrous cycles after 6 months' feeding, compared to the CON mice. The amount of primordial and primary follicles and the expression of SIRT1 were significantly increased, but the levels of P16, 8-OHdG, 4-HNE and p-rpS6 were decreased in the MET mice. These results indicate that metformin can delay ovarian aging process, probably by inducing the expression of SIRT1 and reducing the oxidative damage.
Effect of Nutrient and Micronutrient Intake on Chylomicron Production and Postprandial Lipemia

Postprandial lipemia, which is one of the main characteristics of the atherogenic dyslipidemia with fasting plasma hypertriglyceridemia, low high-density lipoprotein cholesterol and an increase of small and dense low-density lipoproteins is now considered a causal risk factor for atherosclerotic cardiovascular disease and all-cause mortality. Postprandial lipemia, which is mainly related to the increase in chylomicron production, is frequently elevated in individuals at high cardiovascular risk such as obese or overweight patients, type 2 diabetic patients and subjects with a metabolic syndrome who share an insulin resistant state. It is now well known that chylomicron production and thus postprandial lipemia is highly regulated by many factors such as endogenous factors: circulating factors such as hormones or free fatty acids, genetic variants, circadian rhythms, or exogenous factors: food components, dietary supplements and prescription drugs. In this review, we focused on the effect of nutrients, micronutrients and phytochemicals but also on food structure on chylomicron production and postprandial lipemia.
Challenging behaviours: Views and preferences of people with intellectual disabilities

Abstract Background Challenging behaviour is a common problem among people with ID and in services for people with ID. This paper aims to provide an overview of the views and preferences of people with ID on challenging behaviour. Method Semi‐structured interviews were conducted with thirteen adults with mild to moderate ID and seven proxies (family or close associates of adults with ID who were unable to communicate and/or with severe or profound ID) in the Netherlands. The interviews were audio‐recorded, transcribed and analysed thematically. Results People with ID and (a history of) challenging behaviour have clear views and preferences on factors related to challenging behaviour, assessments, non‐pharmacological and pharmacological interventions and health professionals’ approach. Conclusions The identified views and preferences of people with ID are not always in accordance with current procedures and treatments for challenging behaviour and should be included in future care processes and research.
Surface Modification by Polyzwitterions of the Sulfabetaine-Type, and Their Resistance to Biofouling

Films of zwitterionic polymers are increasingly explored for conferring fouling resistance to materials. Yet, the structural diversity of polyzwitterions is rather limited so far, and clear structure-property relationships are missing. Therefore, we synthesized a series of new polyzwitterions combining ammonium and sulfate groups in their betaine moieties, so-called poly(sulfabetaine)s. Their chemical structures were varied systematically, the monomers carrying methacrylate, methacrylamide, or styrene moieties as polymerizable groups. High molar mass homopolymers were obtained by free radical polymerization. Although their solubilities in most solvents were very low, brine and lower fluorinated alcohols were effective solvents in most cases. A set of sulfabetaine copolymers containing about 1 mol % (based on the repeat units) of reactive benzophenone methacrylate was prepared, spin-coated onto solid substrates, and photo-cured. The resistance of these films against the nonspecific adsorption by two model proteins (bovine serum albumin—BSA, fibrinogen) was explored, and directly compared with a set of references. The various polyzwitterions reduced protein adsorption strongly compared to films of poly(n-butyl methacrylate) that were used as a negative control. The poly(sulfabetaine)s showed generally even somewhat higher anti-fouling activity than their poly(sulfobetaine) analogues, though detailed efficacies depended on the individual polymer–protein pairs. Best samples approach the excellent performance of a poly(oligo(ethylene oxide) methacrylate) reference.
Time‐Dependent Myocardial Necrosis in Patients With ST‐Segment–Elevation Myocardial Infarction Without Angiographic Collateral Flow Visualized by Cardiac Magnetic Resonance Imaging: Results From the Multicenter STEMI‐SCAR Project

Background Acute complete occlusion of a coronary artery results in progressive ischemia, moving from the endocardium to the epicardium (ie, wavefront). Dependent on time to reperfusion and collateral flow, myocardial infarction (MI) will manifest, with transmural MI portending poor prognosis. Late gadolinium enhancement cardiac magnetic resonance imaging can detect MI with high diagnostic accuracy. Primary percutaneous coronary intervention is the preferred reperfusion strategy in patients with ST‐segment–elevation MI with <12 hours of symptom onset. We sought to visualize time‐dependent necrosis in a population with ST‐segment–elevation MI by using late gadolinium enhancement cardiac magnetic resonance imaging (STEMI‐SCAR project). Methods and Results ST‐segment–elevation MI patients with single‐vessel disease, complete occlusion with TIMI (Thrombolysis in Myocardial Infarction) score 0, absence of collateral flow (Rentrop score 0), and symptom onset <12 hours were consecutively enrolled. Using late gadolinium enhancement cardiac magnetic resonance imaging, the area at risk and infarct size, myocardial salvage index, transmurality index, and transmurality grade (0–50%, 51–75%, 76–100%) were determined. In total, 164 patients (aged 54±11 years, 80% male) were included. A receiver operating characteristic curve (area under the curve: 0.81) indicating transmural necrosis revealed the best diagnostic cutoff for a symptom‐to‐balloon time of 121 minutes: patients with >121 minutes demonstrated increased infarct size, transmurality index, and transmurality grade (all P<0.01) and decreased myocardial salvage index (P<0.001) versus patients with symptom‐to‐balloon times ≤121 minutes. Conclusions In MI with no residual antegrade and no collateral flow, immediate reperfusion is vital. A symptom‐to‐balloon time of >121 minutes causes a high grade of transmural necrosis. In this pure ST‐segment–elevation MI population, time to reperfusion to salvage myocardium was less than suggested by current guidelines.
Comparisons of Outcomes of Real-World Patients With Advanced Pancreatic Cancer Treated With FOLFIRINOX Versus Gemcitabine and Nab-Paclitaxel: A Population-Based Cohort Study.

OBJECTIVES The aim of this study was to compare the efficacy and safety of FOLFIRINOX (5-FU/leucovorin, irinotecan, and oxaliplatin) and gemcitabine/nab-paclitaxel (GnP) in patients with advanced pancreatic cancer. METHODS Patients with newly diagnosed advanced pancreatic cancer in Saskatchewan, Canada, from 2011 to 2016, who received FOLFIRINOX or GnP were assessed. A Cox proportional multivariate analysis was performed to evaluate prognostic variables. RESULTS One hundred nineteen eligible patients with median age of 61 years and men/women ratio of 70:49 were identified. Seventy-seven percent had metastatic disease. Of 119 patients, 86 (72%) received FOLFIRINOX and 33 (28%) were treated with GnP. Median progression-free survival of the FOLFIRINOX group was 6.0 months [95% confidence interval (CI), 4.5-7.5] versus 4.0 months (95% CI, 2.9-5.1) with GnP (P = 0.39). The median overall survival of the FOLFIRINOX group was 9.0 months (95% CI, 7-11) compared with 9.0 months (95% CI, 4.2-13.8) with GnP (P = 0.88). On multivariate analysis, albumin [hazard ratio (HR), 0.63; 95% CI, 0.41-0.97], male sex (HR, 0.65; 95% CI, 0.43-0.97), and second-line therapy (HR, 0.50; 95% CI, 0.28-0.86) were correlated with survival. CONCLUSIONS Our results showed that real-world patients with advanced pancreatic cancer treated with FOLFIIRNOX or GnP had comparable survival with different safety profile.
Emerging Novel GII.P16 Noroviruses Associated with Multiple Capsid Genotypes

Noroviruses evolve by antigenic drift and recombination, which occurs most frequently at the junction between the non-structural and structural protein coding genomic regions. In 2015, a novel GII.P16-GII.4 Sydney recombinant strain emerged, replacing the predominance of GII.Pe-GII.4 Sydney among US outbreaks. Distinct from GII.P16 polymerases detected since 2010, this novel GII.P16 was subsequently detected among GII.1, GII.2, GII.3, GII.10 and GII.12 viruses, prompting an investigation on the unique characteristics of these viruses. Norovirus positive samples (n = 1807) were dual-typed, of which a subset (n = 124) was sequenced to yield near-complete genomes. CaliciNet and National Outbreak Reporting System (NORS) records were matched to link outbreak characteristics and case outcomes to molecular data and GenBank was mined for contextualization. Recombination with the novel GII.P16 polymerase extended GII.4 Sydney predominance and increased the number of GII.2 outbreaks in the US. Introduction of the novel GII.P16 noroviruses occurred without unique amino acid changes in VP1, more severe case outcomes, or differences in affected population. However, unique changes were found among NS1/2, NS4 and VP2 proteins, which have immune antagonistic functions, and the RdRp. Multiple polymerase-capsid combinations were detected among GII viruses including 11 involving GII.P16. Molecular surveillance of protein sequences from norovirus genomes can inform the functional importance of amino acid changes in emerging recombinant viruses and aid in vaccine and antiviral formulation.
Comparison of the Effect of Native 1,4-Naphthoquinones Plumbagin, Menadione, and Lawsone on Viability, Redox Status, and Mitochondrial Functions of C6 Glioblastoma Cells

Background: 1,4-naphthoquinones, especially juglone, are known for their anticancer activity. However, plumbagin, lawsone, and menadione have been less investigated for these properties. Therefore, we aimed to determine the effects of plumbagin, lawsone, and menadione on C6 glioblastoma cell viability, ROS production, and mitochondrial function. Methods: Cell viability was assessed spectrophotometrically using metabolic activity method, and by fluorescent Hoechst/propidium iodide nuclear staining. ROS generation was measured fluorometrically using DCFH-DA. Oxygen uptake rates were recorded by the high-resolution respirometer Oxygraph-2k. Results: Plumbagin and menadione displayed highly cytotoxic activity on C6 cells (IC50 is 7.7 ± 0.28 μM and 9.6 ± 0.75 μM, respectively) and caused cell death by necrosis. Additionally, they increased the amount of intracellular ROS in a concentration-dependent manner. Moreover, even at very small concentrations (1–3 µM), these compounds significantly uncoupled mitochondrial oxidation from phosphorylation impairing energy production in cells. Lawsone had significantly lower viability decreasing and mitochondria-uncoupling effect, and exerted strong antioxidant activity. Conclusions: Plumbagin and menadione exhibit strong prooxidant, mitochondrial oxidative phosphorylation uncoupling and cytotoxic activity. In contrast, lawsone demonstrates a moderate effect on C6 cell viability and mitochondrial functions, and possesses strong antioxidant properties.
Proinsulin misfolding is an early event in the progression to type 2 diabetes

Biosynthesis of insulin – critical to metabolic homeostasis – begins with folding of the proinsulin precursor, including formation of three evolutionarily conserved intramolecular disulfide bonds. Remarkably, normal pancreatic islets contain a subset of proinsulin molecules bearing at least one free cysteine thiol. In human (or rodent) islets with a perturbed endoplasmic reticulum folding environment, non-native proinsulin enters intermolecular disulfide-linked complexes. In genetically obese mice with otherwise wild-type islets, disulfide-linked complexes of proinsulin are more abundant, and leptin receptor-deficient mice, the further increase of such complexes tracks with the onset of islet insulin deficiency and diabetes. Proinsulin-Cys(B19) and Cys(A20) are necessary and sufficient for the formation of proinsulin disulfide-linked complexes; indeed, proinsulin Cys(B19)-Cys(B19) covalent homodimers resist reductive dissociation, highlighting a structural basis for aberrant proinsulin complex formation. We conclude that increased proinsulin misfolding via disulfide-linked complexes is an early event associated with prediabetes that worsens with ß-cell dysfunction in type two diabetes.
Posterior staphylomas and scleral curvature in highly myopic children and adolescents investigated by ultra-widefield optical coherence tomography

Purpose To determine the early signs of posterior staphylomas in highly myopic eyes of younger subjects by swept-source ultra-widefield optical coherence tomography (WF-OCT). Methods This was an observational case series study. Highly myopic subjects younger than 20 years old who were examined consecutively by prototype WF-OCT were studied. High myopia was defined according to the Ministry of Health and Welfare, Japan classification. A posterior displacement of the sclera and two OCT features indicating the staphyloma edges were used as markers of a staphyloma. Results Fifty-five eyes of 30 patients with the mean age of 12.3 years, and the mean axial length of 27.9 mm were studied. Seven of the 55 eyes (12.7%) had a posterior displacement of the sclera and were diagnosed as having a staphyloma. Among the two OCT features of the staphyloma edges, a gradual thinning of the choroid toward the staphyloma edge and gradual re-thickening of choroid from the staphyloma edge toward the posterior pole were found in these 7 eyes. However, the other feature of an inward protrusion of the sclera at the staphyloma edge, was obvious in only 2 eyes. The subfoveal choroid and choroid nasal to the optic disc were significantly thinner in eyes with a staphyloma than those without it. Conclusions The changes of the choroidal thickness toward the staphyloma edge with the posterior displacement of the sclera were considered an early sign which precedes an inward protrusion of sclera at the staphyloma edge.
Understanding of Nanophase Separation and Hydrophilic Morphology in Nafion and SPEEK Membranes: A Combined Experimental and Theoretical Studies

The understanding of the relationship between the chemical structure and the hydrophilic structure is crucial for the designing of high-performance PEMs. Comparative studies in typical Nafion and sulfonated poly (ether ether ketone) (SPEEK) were performed using a combined experimental and theoretical method. SPEEK showed suppressed fuel crossover and good mechanical property but low water uptake, weak phase separation, and inadequate proton conductivity. Molecular dynamics (MD) simulation approaches were employed to get a molecular-level understanding of the structure–property relationship of SPEEK and Nafion membranes. In SPEEK membranes, the local aggregation of hydrophilic clusters is worse, and much stronger electrostatic interaction between Os–Hh was verified, resulting in less delocalized free H3O+ and much lower DH3O+. In addition, the probability of H2O–H3O+ association varied with water content. Particularly, SPEEK exhibited much lower H9O4+ probability at various relative water contents, leading to lower structural diffusivity than Nafion. Eventually, SPEEK possessed low vehicular and structural diffusivities, which resulted in a low proton conductivity. The results indicated that the structure of hydrated hydronium complexes would deform to adapt the confining hydrophilic channels. The confinement effect on diffusion of H2O and H3O+ is influenced by the water content and the hydrophilic morphologies. This study provided a new insight into the exploration of high-performance membranes in fuel cell.
Spatio-temporal distribution of outbreaks of highly pathogenic avian influenza virus subtype H5N1 in Vietnam, 2015- 2018.

Despite strong commitments of the central and provincial veterinary authorities in Vietnam to control highly pathogenic avian influenza H5N1 (HPAI-H5N1) in poultry and to diminish the risk of human infection, outbreaks continue to occur in poultry. This study describes the spatio-temporal distribution of HPAI-H5N1 outbreaks in Vietnam for the period December 2014-April 2018 using the space-time K-function and the space-time scan statistic. The space-time K-function analyses showed statistically significant spatio-temporal clustering of HPAI-H5N1 outbreaks in poultry during the study period of up to 50 days and 60 kilometres. The space-time scan statistic test identified three statistically significant space-time clusters of HPAI-H5N1 in the south of the country where the incidence of HPAI-H5N1 outbreaks was greater than that expected if outbreaks were randomly distributed in space and time. The analyses indicated shortfalls in the effectiveness of control measures used to control HPAI-H5N1 throughout the study period. Development of a better understanding of the relative impact of HPAI-H5N1 control measures (depopulation of infected flocks, vaccination, movement restrictions) on space-time interaction would allow animal health authorities to focus their efforts on control measures shown to have the greatest relative effect.
Communication between healthcare professionals and relatives of patients approaching the end-of-life: A systematic review of qualitative evidence

Background: Effective communication between healthcare professionals and relatives of patients approaching the end-of-life is vital to ensure patients have a ‘good death’. To improve communication, it is important to first identify how this is currently being accomplished. Aim: To review qualitative evidence concerning characteristics of communication about prognosis and end-of-life care between healthcare professionals and relatives of patients approaching the end-of-life. Design: Qualitative systematic review (PROSPERO registration CRD42017065560) using thematic synthesis. Peer-reviewed, English language articles exploring the content of conversations and how participants communicated were included. No date restrictions were applied. Quality of included studies was appraised using the Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research. Data sources: An electronic database search of CINAHL, MEDLINE, PsycINFO and EMBASE was performed. Results: Thirty-one papers were included. Seven themes were identified: highlighting deterioration; involvement in decision-making, post-decision interactional work, tailoring, honesty and clarity, specific techniques for information delivery and roles of different healthcare professionals. Varied levels of family involvement in decision-making were reported. Healthcare professionals used strategies to aid understanding and collaborative decision-making, such as highlighting the patient’s deterioration, referring to patient wishes and tailoring information delivery. Doctors were regarded as responsible for discussing prognosis and decision-making, and nurses for providing individualized care. Conclusion: Findings suggest training could provide healthcare professionals with these strategies to improve communication. Interventions such as question prompt lists could help relatives overcome barriers to involvement in decision-making. Further research is needed to understand communication with relatives in different settings and with different healthcare professionals.