Miracle-dz/UniFAR-FTUs huggingface dataset:
Stimulation of Erythrocyte Membrane Blebbing by Naproxen Sodium

Naproxen sodium is a nonsteroidal anti-inflammatory drug (NSAID) having antipyretic and analgesic properties, mainly used for the treatment of rheumatoid arthritis and osteoarthritis. Eryptosis is an alternative term used for suicidal erythrocyte death. In the current study, eryptotic effect of naproxen sodium characterized by membrane blebbing was investigated in erythrocytes after 48 hours of treatment with different concentrations (1-25 µM). The experimental work related to investigation of eryptosis was done by cell size measurement and confirmation of calcium role in the induction of membrane blebbing. As a possible mechanism of eryptosis, oxidative stress induced by naproxen sodium was determined by catalase, glutathione peroxidase, and superoxide dismutase activities. Similarly, hemolytic effect of naproxen sodium was also determined by hemolysis measurement. Results of our study illustrated that the therapeutic doses (10-25 µM) of naproxen sodium induce oxidative stress, confirmed by significant decrease in superoxide dismutase, catalase, and glutathione peroxidase activities that lead to the triggering of cell death by eryptosis and hemolysis.
Design and Characterization of Cyclosporine A-Loaded Nanofibers for Enhanced Drug Dissolution

Despite widespread use as an immunosuppressant, the therapeutic efficacy of the undecapeptide cyclosporine A (CyA) is compromised when given by the oral route because of the innate hydrophobicity of the drug molecule, potentially leading to poor aqueous solubility and bioavailability. The aim of this study was to develop and characterize nanofibers based on the water-miscible polymer polyvinylpyrrolidone (PVP), incorporating CyA preloaded into polymeric surfactants so as to promote micelle formation on hydration; therefore, this approach represents the novel combination of three dissolution enhancement methodologies, namely solid dispersion technology, micellar systems, and nanofibers with enhanced surface area. The preparation of the nanofibers was performed in two steps. First, mixed micelles composed of the water-soluble vitamin E derivative d-α-tocopheryl poly(ethylene glycol) 1000 succinate and the amphiphilic triblock polymer Pluronic F127 (Poloxamer 407) were prepared. The micelles were characterized in terms of size, surface charge, drug loading, and encapsulation efficiency using transmission electron microscopy, dynamic light scattering, Fourier-transform infrared spectroscopy, high-performance liquid chromatography, and scanning electron and atomic force microscopy analysis. Nanofibers composed of PVP and the drug-loaded surfactant system were then prepared via electrospinning, with accompanying thermal, spectroscopic, and surface topological analysis. Dissolution studies indicated an extremely rapid dissolution profile for the fibers compared to the drug alone, while wettability studies also indicated a marked decrease in contact angle compared to the drug alone. Overall, the new approach appears to offer a viable means for considerably improving the dissolution of the hydrophobic peptide CyA, with associated implications for improved oral bioavailability.
Effects of high-intensity interval training on vascular function and maximum oxygen uptake in young sedentary females

Objective: Sedentary behavior is one of the risk factors for cardiometabolic diseases, including cardiovascular diseases, diabetes mellitus, and metabolic syndrome. High-intensity interval training (HIIT) is one effective way to reduce the risk of cardiometabolic diseases. This research studies the effects of cycling-based HIIT on vascular function and cardiorespiratory fitness in sedentary people. Methods: Twenty-two female participants were separated into two groups, including HIIT group who receive intervention and control group who did not receive the intervention. Each of the participants was interviewed to collect and record their medical history, and medical parameters including cardio-ankle vascular index (CAVI), flow-mediated dilation (FMD), and maximal oxygen consumption (VO2max) were measured as a baseline pre-test. The intervention was a cycling-based HIIT lasting 6 weeks, with three sessions per week. During each session, the participant completed a set protocol consisting of 1 min on a cycle ergometer, cycling at 80–85% maximal heart rate, followed by a 1-min rest period. This sequence was repeated for a total of 5 times. Results: After 6 weeks of intervention, results showed that the HIIT group had significant improvements in CAVI (6.39 ± 0.76 vs. 5.91 ± 0.58), FMD (9.26 ± 6.5 vs. 14.01 ± 4.3%), and VO2max (20.10 ± 4.31 vs. 24.34 ± 5.71 ml/kg/min) values compared to the pre-test (P < 0.05). In addition, HIIT increased endothelial function as measured by FMD compared to the control group (14.01 ± 4.3 vs. 9.15 ± 4.16 %, P < 0.05). Conclusion: Six weeks of HIIT were found to improve vascular function and cardiorespiratory fitness in sedentary people and demonstrated the benefits of HIIT as a time-efficient exercise strategy.
case report

A 45&#8208;year&#8208;old woman developed pulmonary veno&#8208;occlusive disease (PVOD) following treatment with cyclophosphamide for nodular lymphocyte predominant Hodgkin lymphoma. The woman, who had nodular lymphocyte predominant Hodgkin lymphoma, was treated with RCHOP regimen consisting of cyclophosphamide, rituximab, doxorubicin, vincristine and prednisone [ dosage and route not stated ]. After 1 month, she presented with worsening dyspnoea and was admitted. High&#8208;resolution chest CT scan revealed interlobular septal thickening and ground&#8208;glass opacities. Dyspnoea was associated with hypoxaemia. Diffusion capacity of the lung for carbon monoxide (DLCO) was found to be severely reduced to 55% predicted. Open lung biopsy showed significant intimal and medial thickening of the pulmonary arterioles, capillary proliferation and sclerosis of pulmonary veins with focal occlusion associated with dilated lymphatics. Special stain with movat pentachrome revealed intra&#8208;alveolar haemosiderin and septal thickening with collagen deposition associated with veno&#8208;occlusive changes in pulmonary veins with fibrosis and sclerosis along with capillary proliferation and arterial changes. These changes were diffusely noted in pulmonary arterioles with associated changes suggestive of pulmonary capillary haemangiomatosis. A diagnosis of PVOD was suspected and he was transferred to pulmonary vascular diseases centre. Ventilation-perfusion lung scan was abnormal with multiple perfusion defects. Right heart catheterisation (RHC) revealed mean right atrial pressure of 4mm Hg, mean pulmonary artery wedge pressure of 7mm Hg, mean pulmonary artery pressure of 19mm Hg, preserved cardiac output (4.8 L/min) and PVR of 2.5 Wood units (WU). A 6&#8208;min walk test revealed walk distance of 388m with oxygen desaturation to 75%. Based on these findings, a diagnosis of PVOD induced by cyclophosphamide was made. The woman was then treated with off-label prednisone 60mg daily with significant improvement in the symptoms. The steroid dose was slowly tapered over a year with close monitoring of DLCO, echocardiograms and arterial blood gases. Progression was noticed over the first 2&#8208;years following the diagnosis. RHC in October 2020 revealed haemodynamically confirmed pulmonary hypertension. She then received off-label treatment with sildenafil and macitentan on two separate occasions. However, these treatments required immediate discontinuation after single dose due to worsening of hypoxaemia. In the previous 1 year, she was tapered-off prednisone, while receiving supplemental oxygen and was clinically stable. Further, the genetic testing revealed heterozygous EIF2AK4 mutation c.744&#8208;11 T > G.
Effects of Pregnancy on the Pharmacokinetics of Metformin

This study’s primary objective was to fully characterize the pharmacokinetics of metformin in pregnant women with gestational diabetes mellitus (GDM) versus nonpregnant controls. Steady-state oral metformin pharmacokinetics in pregnant women with GDM receiving either metformin monotherapy (n = 24) or a combination with glyburide (n = 30) as well as in nonpregnant women with type 2 diabetes mellitus (T2DM) (n = 24) were determined utilizing noncompartmental techniques. Maternal and umbilical cord blood samples were collected at delivery from 38 women. With both 500- and 1000-mg doses, metformin bioavailability, volume of distribution beta (Vβ), clearance, and renal clearance were significantly increased during pregnancy. In addition, in the women receiving metformin 500 mg, significantly higher metformin apparent oral clearance (CL/F) (27%), weight-adjusted renal secretion clearance (64%), and apparent oral volume of distribution beta (Vβ/F) (33%) were seen during pregnancy. Creatinine clearance was significantly higher during pregnancy. Increasing metformin dose from 500 to 1000 mg orally twice daily significantly increased Vβ/F by 28%, weight-adjusted Vβ/F by 32% and CL/F by 25%, and weight-adjusted CL/F by 28% during pregnancy. Mean metformin umbilical cord arterial-to-venous plasma concentration ratio was 1.0 ± 0.1, venous umbilical cord-to-maternal concentration ratio was 1.4 ± 0.5, and arterial umbilical cord-to-maternal concentration ratio was 1.5 ± 0.5. Systemic exposure after a 500-mg dose of metformin was lower during pregnancy compared with the nonpregnant women with T2DM. However, in patients receiving metformin 1000 mg, changes in estimated bioavailability during pregnancy offset the changes in clearance leading to no significant change in CL/F with the higher dose. SIGNIFICANCE STATEMENT Gestational diabetes mellitus complicates 5%–13% of pregnancies and is often treated with metformin. Pregnant women undergo physiological changes that alter drug disposition. Preliminary data suggest that pregnancy lowers metformin concentrations, potentially affecting efficacy and safety. This study definitively describes pregnancy’s effects on metformin pharmacokinetics and expands the mechanistic understanding of pharmacokinetic changes across the dosage range. Here we report the nonlinearity of metformin pharmacokinetics and the increase in bioavailability, clearance, renal clearance, and volume of distribution during pregnancy.
Frequently Consumed Foods and Energy Contributions among Food Secure and Insecure U.S. Children and Adolescents

Food insecurity is associated with nutritional risk in children. This study identified and compared the most frequently consumed foods, beverages, and food groups and their contributions to energy intake among U.S. children and adolescents (6–11, 12–17 years) by food security status. Dietary intake from the day-1, 24-h dietary recall, and household child food security status were analyzed in the 2007–2014 National Health and Nutrition Examination Survey (n = 8123). Foods and beverages were classified into food categories, ranked, and compared by weighted proportional frequency and energy contribution for food security groups by age. Significant differences between household child food security groups were determined using the Rao-Scott modified chi-square statistic. The weighted proportional frequency of beverages (including diet, sweetened, juice, coffee, and tea) and their energy was significantly higher among food insecure compared with food secure while the reverse was true for water frequency among 12–17 years. Beverage and mixed dish frequency were higher among food insecure compared with food secure 6–11 years while the reverse was true for frequency and energy from snacks. Frequency-differentiated intake patterns for beverages and snacks by food security across age groups may inform dietary recommendations, population-specific dietary assessment tools, interventions, and policy for food insecure children.
A Novel Coronavirus from Patients with Pneumonia in China, 2019

Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)
Lean back and wait for the alarm? Testing an automated alarm system for nosocomial outbreaks to provide support for infection control professionals

Introduction Outbreaks of communicable diseases in hospitals need to be quickly detected in order to enable immediate control. The increasing digitalization of hospital data processing offers potential solutions for automated outbreak detection systems (AODS). Our goal was to assess a newly developed AODS. Methods Our AODS was based on the diagnostic results of routine clinical microbiological examinations. The system prospectively counted detections per bacterial pathogen over time for the years 2016 and 2017. The baseline data covers data from 2013–2015. The comparative analysis was based on six different mathematical algorithms (normal/Poisson and score prediction intervals, the early aberration reporting system, negative binomial CUSUMs, and the Farrington algorithm). The clusters automatically detected were then compared with the results of our manual outbreak detection system. Results During the analysis period, 14 different hospital outbreaks were detected as a result of conventional manual outbreak detection. Based on the pathogens’ overall incidence, outbreaks were divided into two categories: outbreaks with rarely detected pathogens (sporadic) and outbreaks with often detected pathogens (endemic). For outbreaks with sporadic pathogens, the detection rate of our AODS ranged from 83% to 100%. Every algorithm detected 6 of 7 outbreaks with a sporadic pathogen. The AODS identified outbreaks with an endemic pathogen were at a detection rate of 33% to 100%. For endemic pathogens, the results varied based on the epidemiological characteristics of each outbreak and pathogen. Conclusion AODS for hospitals based on routine microbiological data is feasible and can provide relevant benefits for infection control teams. It offers in-time automated notification of suspected pathogen clusters especially for sporadically occurring pathogens. However, outbreaks of endemically detected pathogens need further individual pathogen-specific and setting-specific adjustments.
Spatial Variation and Source of Dissolved Heavy Metals in the Lancangjiang River, Southwest China

Dissolved heavy metals are not only the essential micronutrients, but also the toxic elements for human bodies. To investigate the heavy metal sources and assess the water quality of the Lancangjiang River, dissolved Cr, Ni, Cu, Zn, Mo, and Pb were detected in this study. The results show that dissolved Ni and Mo, Cr and Pb, and Cu and Zn were similarly distributed within the drainage basin. The correlation analysis exhibited that dissolved Ni and Mo had correlation with water parameter, and dissolved Cu was weakly correlated with Ni, indicating that they might be affected by natural processes. The principal component analysis explained 68.342% of the total variance for three principal components, of which dissolved Ni, Mo, and Cu were controlled by natural inputs; dissolved Cu and Cr were affected by anthropogenic activities; and dissolved Zn was influenced by agricultural activities in the downstream. The water quality showed that the water in upstream was worse than in midstream and downstream, and the whole drainage basin had water of excellent quality. Water within the drainage basin poses no risks to human bodies via daily diets and dermal routes. Dissolved Zn, Cu, and Mo occupied the major proportion of heavy metals transporting into the Mekong River. The agricultural inputs of dissolved Zn might pose potential risks to the Mekong River.
Evaluation of a 68Ga-Labeled DOTA-Tetrazine as a PET Alternative to 111In-SPECT Pretargeted Imaging

The bioorthogonal reaction between a tetrazine and strained trans-cyclooctene (TCO) has garnered success in pretargeted imaging. This reaction was first validated in nuclear imaging using an 111In-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-linked bispyridyl tetrazine (Tz) ([111In]In-DOTA-PEG11-Tz) and a TCO functionalized CC49 antibody. Given the initial success of this Tz, it has been paired with TCO functionalized small molecules, diabodies, and affibodies for in vivo pretargeted studies. Furthermore, the single photon emission tomography (SPECT) radionuclide, 111In, has been replaced with the β-emitter, 177Lu and α-emitter, 212Pb, both yielding the opportunity for targeted radiotherapy. Despite use of the ‘universal chelator’, DOTA, there is yet to be an analogue suitable for positron emission tomography (PET) using a widely available radionuclide. Here, a 68Ga-labeled variant ([68Ga]Ga-DOTA-PEG11-Tz) was developed and evaluated using two different in vivo pretargeting systems (Aln-TCO and TCO-CC49). Small animal imaging and ex vivo biodistribution studies were performed and revealed target specific uptake of [68Ga]Ga-DOTA-PEG11-Tz in the bone (3.7 %ID/g, knee) in mice pretreated with Aln-TCO and tumor specific uptake (5.8 %ID/g) with TCO-CC49 in mice bearing LS174 xenografts. Given the results of this study, [68Ga]Ga-DOTA-PEG11-Tz can serve as an alternative to [111In]In-DOTA-PEG11-Tz.
Receiver operating characteristic curve analysis of clinical signs for screening of convergence insufficiency in young adults

Convergence insufficiency (CI) is a dysfunction of binocular vision that is associated with various signs and symptoms in near work. However, CI screening is performed less frequently in adults than in children. We aimed to evaluate the ability of screening tests to discriminate CI from other binocular vision anomalies and normal binocular vision in young adults. One hundred eighty-four university students (age, 18–28 years) who underwent an eye examination due to ocular discomfort were included. Near point of convergence (NPC), phoria, accommodative amplitude, fusional vergence, the ratio of accommodative convergence to accommodation, relative accommodation, binocular accommodative facility, vergence facility, and the values corresponding to Sheard’s and Percival’s criteria were evaluated. Receiver operating characteristic (ROC) curve analysis for each test was also performed. The prevalence of CI ranged from 10.3% to 21.2%, depending on the signs and the presence of CI associated with accommodative disorders. Assessments based on NPC, Sheard’s criterion, and Percival’s criterion showed high discriminative ability, with the ability being higher between the CI and normal binocular vision groups than between the CI and non-CI groups. Sheard’s criterion showed the highest diagnostic performance in discriminating CI with three signs from the non-CI group. The cut-off values were 7.2 cm for NPC, -0.23 to 1.00 for Sheard’s criterion, and -4.00 to -2.33 for Percival’s criterion. Our results suggest that the use of Sheard’s criterion with NPC shows high performance for screening of CI.
The effect of intravenous magnesium on postoperative morphine consumption in noncardiac surgery: A systematic review and meta-analysis with trial sequential analysis.

BACKGROUND Several studies suggest that systemic magnesium reduces postoperative opioid consumption and the intensity of pain, but others report conflicting results. The efficacy and safety profile of intravenous magnesium in noncardiac surgery remain uncertain. OBJECTIVES The aim of this review was to investigate the effect of intravenous magnesium on the consumption of postoperative morphine in the first 24 h in adults undergoing noncardiac surgery. DESIGN Systematic review and meta-analysis with trial sequential analysis. DATA SOURCES MEDLINE, EMBASE, CENTRAL from their inception until January 2019. ELIGIBILITY CRITERIA All randomised clinical trials comparing intravenous magnesium versus placebo in noncardiac surgery were systematically searched in the databases. Observational studies, case reports, case series and nonsystematic reviews were excluded. RESULTS Fifty-one trials (n=3311) were included for quantitative meta-analysis. In comparison with placebo, postoperative morphine consumption at 24-h was significantly reduced in the magnesium group, with a mean difference [95% confidence interval (CI)] of -5.6 mg (-7.54 to -3.66, P < 0.001, I = 92%, level of evidence low). The trial sequential analysis for the effect of magnesium on postoperative morphine consumption was conclusive. Patients who received magnesium had a longer time to the first analgesia request [143 (103 to 183) min, P < 0.001, I = 99%, level of evidence low] and a lower incidence of shivering [0.26 (0.15 to 0.44), P < 0.001, I = 35%, level of evidence very low]. However, no significance differences were demonstrated in postoperative pain scores in the first 24 h (mean difference, 95% CI) -0.30 (-0.69 to 0.09, P = 0.13, I = 91%, level of evidence low), bradycardia (odds ratio, 95% CI) 1.13 (0.43 to 2.98, P = 0.80, I = 35%, level of evidence very low) and postoperative nausea and vomiting (odds ratio, 95% CI) 0.90 (0.67 to 1.22, P = 0.49, I = 25%, level of evidence moderate). CONCLUSION The current meta-analysis demonstrates that the use of intravenous magnesium as part of multimodal analgesia may reduce morphine consumption in the first 24 h after surgery and delay the time to the first request for analgesia in patients undergoing noncardiac surgery. However, the included studies were of low-quality with substantial heterogeneity. TRIAL REGISTRATION CRD42018086846.
Growth Behavior of Listeria monocytogenes in a Traditional Norwegian Fermented Fish Product (Rakfisk), and Its Inhibition through Bacteriophage Addition

Listeria monocytogenes may persist in food production environments and cause listeriosis. In Norway, a product of concern is the traditional and popular fermented fish product “rakfisk”, which is made from freshwater salmonid fish by mild-salting and brine maturation at low temperatures for several months. It is eaten without any heat treatment, and L. monocytogenes, therefore, poses a potential hazard. We investigated the effect of salt and temperature on the growth of L. monocytogenes in rakfisk during the 91 days of maturation. The amounts of organic acids produced during fermentation were too low to inhibit growth of L. monocytogenes. Temperature was clearly the most important parameter for controlling L. monocytogenes. At 7 °C, approximately 2 log growth was observed during the first 14 days of fermentation, and the level of L. monocytogenes thereafter remained constant. At 4 °C, only a little growth potential of the pathogen was recorded. We also investigated the effect of the anti-Listeria bacteriophage P100 on rakfisk with added L. monocytogenes. The phage was introduced to the L. monocytogenes-inoculated fish before fermentation, and an average of 0.9 log reduction was observed throughout the fermentation period. This is the first study of L. monocytogenes behavior in rakfisk and points to possible measures for increasing the product safety.