Miracle-dz/UniFAR-FTUs huggingface dataset:
Cigarette Smoke Extract Produces Superoxide in Aqueous Media by Reacting with Bicarbonate

The toxicity of cigarette smoke (CS) is largely attributed to its ability to generate reactive oxygen species (ROS). Reportedly, CS generates superoxide in cell culture systems by stimulating the cells to produce superoxide and through direct chemical reactions with components of the culture media. In this study, we investigated CS-induced superoxide formation in biocompatible aqueous media and its characteristics. Cigarette smoke extract (CSE) and total particulate matter (TPM) were prepared from the mainstream smoke of 3R4F reference cigarettes. CSE and TPM generated superoxide in Hank’s balanced salt solution (HBSS), Dulbecco’s modified Eagle media (DMEM), and blood plasma, but not in distilled water and phosphate-buffered saline. Each constituent of HBSS in solution was tested, and bicarbonate was found to be responsible for the superoxide generation. More than half of the superoxide formation was abolished by pretreating CSE or TPM with peroxidase, indicating that the substrates of peroxidase, presumably peroxides and peroxy acids, mainly contributed to the superoxide production. In conclusion, the presence of bicarbonate in experimental conditions should be considered carefully in studies of the biological activity of CS. Furthermore, the local amount of bicarbonate in exposed tissues may be a determinant of tissue sensitivity to oxidative damage by CS.
Evaluation of whole-genome sequence data analysis approaches for short- and long-read sequencing of Mycobacterium tuberculosis

Whole-genome sequencing (WGS) of Mycobacterium tuberculosis (MTB) isolates can be used to get an accurate diagnosis, to guide clinical decision making, to control tuberculosis (TB) and for outbreak investigations. We evaluated the performance of long-read (LR) and/or short-read (SR) sequencing for anti-TB drug-resistance prediction using the TBProfiler and Mykrobe tools, the fraction of genome recovery, assembly accuracies and the robustness of two typing approaches based on core-genome SNP (cgSNP) typing and core-genome multi-locus sequence typing (cgMLST). Most of the discrepancies between phenotypic drug-susceptibility testing (DST) and drug-resistance prediction were observed for the first-line drugs rifampicin, isoniazid, pyrazinamide and ethambutol, mainly with LR sequence data. Resistance prediction to second-line drugs made by both TBProfiler and Mykrobe tools with SR- and LR-sequence data were in complete agreement with phenotypic DST except for one isolate. The SR assemblies were more accurate than the LR assemblies, having significantly (P<0.05) fewer indels and mismatches per 100 kbp. However, the hybrid and LR assemblies had slightly higher genome fractions. For LR assemblies, Canu followed by Racon, and Medaka polishing was the most accurate approach. The cgSNP approach, based on either reads or assemblies, was more robust than the cgMLST approach, especially for LR sequence data. In conclusion, anti-TB drug-resistance prediction, particularly with only LR sequence data, remains challenging, especially for first-line drugs. In addition, SR assemblies appear more accurate than LR ones, and reproducible phylogeny can be achieved using cgSNP approaches.
Structural elucidation, anti-radical and immunomodulatory activities of polysaccharides from the roots of Glehnia littoralis

Abstract This study investigated the structural elucidation, anti-radical and immunomodulatory activities of polysaccharides from the roots of Glehnia littoralis. A crude polysaccharide was extracted from the roots of G. littoralis through the ultrasonic-assisted extraction and further purified by DEAE-52 cellulose and Sephadex G-100 gel column, a major polysaccharide fraction named GLP80-1 was obtained. The chemical properties and structure of GLP and GLP80-1 were characterized by acid hydrolysis, methylation analysis, along with high performance gel permeation chromatography, Fourier transform infrared, nuclear magnetic resonance, scanning electron microscope, thermogravimetric analysis and X-ray diffraction. The molecular weight distributions of GLP were determined as 1.89 × 106 and 1.26 × 104 Da. The monosaccharide composition of GLP was glucose, glucuronic acid, galactose and arabinose with molar ratios of 0.91:0.04:0.03:0.02, respectively. The average molecular weight of GLP80-1 was determined as 1.63 × 104 Da. The structure of GLP80-1 was deduced to be a homogenous glucan, comprised a main chain of (1→4)-linked-α-D-Glcp with a single α-D-Glcp branch substituted at C-6. The results of biological activities in vitro showed that GLP and GLP80-1 exhibited free radical scavenging effects, and displayed promotion for the proliferation of mouse spleen lymphocytes and RAW264.7 cells. The data indicated that GLP and GLP80-1 had the potential to be explored as novel natural antioxidant and immunomodulator for application in functional food. Graphical Abstract
Urinary metabotype of severe asthma evidences decreased carnitine metabolism independent of oral corticosteroid treatment in the U-BIOPRED study

Introduction Asthma is a heterogeneous disease with poorly defined phenotypes. Patients with severe asthma often receive multiple treatments including oral corticosteroids (OCS). Treatment may modify the observed metabotype, rendering it challenging to investigate underlying disease mechanisms. Here, we aimed to identify dysregulated metabolic processes in relation to asthma severity and medication. Methods Baseline urine was collected prospectively from healthy participants (n=100), patients with mild-to-moderate asthma (n=87) and patients with severe asthma (n=418) in the cross-sectional U-BIOPRED cohort; 12–18-month longitudinal samples were collected from patients with severe asthma (n=305). Metabolomics data were acquired using high-resolution mass spectrometry and analysed using univariate and multivariate methods. Results A total of 90 metabolites were identified, with 40 significantly altered (p<0.05, false discovery rate <0.05) in severe asthma and 23 by OCS use. Multivariate modelling showed that observed metabotypes in healthy participants and patients with mild-to-moderate asthma differed significantly from those in patients with severe asthma (p=2.6×10−20), OCS-treated asthmatic patients differed significantly from non-treated patients (p=9.5×10−4), and longitudinal metabotypes demonstrated temporal stability. Carnitine levels evidenced the strongest OCS-independent decrease in severe asthma. Reduced carnitine levels were associated with mitochondrial dysfunction via decreases in pathway enrichment scores of fatty acid metabolism and reduced expression of the carnitine transporter SLC22A5 in sputum and bronchial brushings. Conclusions This is the first large-scale study to delineate disease- and OCS-associated metabolic differences in asthma. The widespread associations with different therapies upon the observed metabotypes demonstrate the need to evaluate potential modulating effects on a treatment- and metabolite-specific basis. Altered carnitine metabolism is a potentially actionable therapeutic target that is independent of OCS treatment, highlighting the role of mitochondrial dysfunction in severe asthma. Metabolomics identified a urinary metabotype of asthma driven by lower carnitine levels in an oral corticosteroid-independent manner. The carnitine transporter SLC22A5 was also decreased, suggesting carnitine metabolism as a potential therapeutic target. https://bit.ly/3BJfvT0
Performance characterization of digital transmission systems with cochannel interference

This paper presents a general methodology for performance characterization of digital transmission systems in the presence of cochannel interference, as a function of the actual number of interferers (ranging from zero to infinity). The bit error probability in time-invariant channels and outage probability in time-varying quasi-stationary channels are discussed. More precisely, a general approach to an outage probability definition based on the concept of the outage domain is introduced. This allows the discussion of the relation to the other definitions which have appeared in the literature and the proposal of some new more accurate methods for the evaluation of outage probability. A suitable comparison between exact evaluation, the well-known Gaussian approximation, and the other new approaches proposed in this paper, is carried out to evaluate performance, bit error probability is suitably obtained for linearly modulated signals by adopting a semianalytical approach, and for nonlinear (e.g., continuous phase) modulation signals, by means of simulation. Finally, as an example, the different approaches to derive performance discussed in the paper have been applied to a linear microcellular scenario.
Comparison of simulated power system dynamics applying various load models with actual recorded data

Time domain stability simulation results using derived load models were compared with corresponding data obtained from transient disturbance recorders to validate the accuracy of the load models. Observations of real and reactive power load responses at primary substations and real and reactive power flows on major trunk lines indicated that using a composite (dynamic and static) load model provides a more accurate representation than other models, and closely matches the actual recorded values from the Taipower System. A severe fault, during which enormous voltage and frequency excursions occurred in the system, was extensively examined considering load rejection due to large voltage drops. >
Short Observation Period and Aggressive Discharge of Patients With Head Injury and Serial CT Scans

Background: Many patients undergo two head computed tomography (CT) scans after mild traumatic brain injury (TBI). Radiographic progression without clinical deterioration does not usually alter management. Evidence-based guidelines offer potential for limited repeat imaging and safe discharge. This study characterizes patients who had two head CTs in the Emergency Department (ED), determines the change between initial and repeat CTs, and describes timing of repeat scans. Methods: This retrospective series includes all patients with head CTs during the same ED visit at an urban trauma center between May 1st, 2016 and April 30th, 2018. Radiographic interpretation was coded as positive, negative, or equivocal. Results: Of 241 subjects, the number of positive, negative, and equivocal initial CT results were 154, 50, and 37, respectively. On repeat CT, 190 (78.8%) interpretations were congruent with the original scan. Out of the 21.2% of repeat scans that diverged from the original read, 14 (5.8%) showed positive to negative conversion, 1 (.4%) showed positive to equivocal conversion, 2 (.88%) showed negative to positive conversion, 20 (8.3%) showed equivocal to negative conversion, and 14 (5.8%) showed equivocal to positive conversion. Average time between scans was 4.4 hours, and median length of stay was 10.2 hours. Conclusions: In this retrospective review, most repeat CT scans had no new findings. A small percentage converted to positive, rarely altering clinical management. This study demonstrates the need for continued prospective research to update clinical guidelines that could reduce admission and serial CT scanning for mild TBI.
A descriptive study of mental health and burnout among Nigerian medical students

Background: Increasing attention is being paid to medical students’ mental wellbeing globally due in part to their exposure to stressors inherent in medical education and the numerous reports of elevated rates of mental health conditions in this population. Aims: This study aimed to identify stressors and determine prevalence rates of psychiatric morbidity, substance use and burnout in a sample of Nigerian medical students. Methods: In a cross-sectional online survey, 505 medical students from 25 Nigerian medical schools completed a socio-demographic questionnaire, short version of the General Health Questionnaire (GHQ-12), the CAGE questionnaire and the Oldenburg Burnout Inventory (OLBI). Result: The most commonly reported sources of stress were study (75.6%), money (52.3%) and relationships (30.1%). Nine students (1.8%) had received a mental health diagnosis prior to medical school but this number had increased to 29 (5.7%) whilst in medical school, with the majority being cases of anxiety and depressive disorders. The prevalence of psychological distress was 54.5%, but <5% of affected students had received any help for their mental health conditions. Twenty five students (5%) met criteria for problematic alcohol use and 6% had used cannabis. The proportions of students who met criteria for disengagement and exhaustion domains of the OLBI were 84.6% and 77.0% respectively. Conclusion: The prevalence of psychological distress and burnout is high among medical students. Interventions for medical students’ well-being should be tailored to their needs and should target risk factors related to personal, organisational and medical school academic structure attributes.
Sources of Cognitive Conflict and Their Relevance to Theory-of-Mind Proficiency in Healthy Aging: A Preregistered Study

Age-related decline in theory of mind (ToM) may be due to waning executive control, which is necessary for resolving conflict when reasoning about other individuals’ mental states. We assessed how older (n = 50) and younger (n = 50) adults were affected by three theoretically relevant sources of conflict within ToM: competing self-other perspectives, competing cued locations, and outcome knowledge. We examined which best accounted for age-related difficulty with ToM. Our data show unexpected similarity between age groups when people are representing a belief incongruent with their own. Individual differences in attention and response speed best explained the degree of conflict experienced through incompatible self-other perspectives. However, older adults were disproportionately affected by managing conflict between cued locations. Age and spatial working memory were most relevant for predicting the magnitude of conflict elicited by conflicting cued locations. We suggest that previous studies may have underestimated older adults’ ToM proficiency by including unnecessary conflict in ToM tasks.
Renal outcomes of diabetic patients treated with combination therapy of ACE inhibitors plus either thiazide diuretics or calcium channel blockers: comparative retrospective cohort study in Northwestern Ethiopia

Objective The study determined the comparative renal functions on patients with diabetes treated with ACE inhibitors (ACEIs) plus either thiazide diuretics or calcium channel blockers (CCBs) in Northwestern Ethiopia. Design Retrospective cohort study design was employed to collect the data from medical records of patients with diabetes followed for 1–5 years (N=404). Setting The medical records of patients in chronic diabetic follow-up clinics of the hospital. Participants All the patients with diabetes medical records in Northwestern Ethiopian specialised hospital. Main outcome measures Exposures were ACEIs plus thiazide diuretics or CCBs collected from March to June 2020. Outcomes were defined as declining in estimated glomerular filtration rate (eGFR) values by ≥30% from the baseline recorded from 2015 to 2019. Descriptive and analytical statistics were illustrated to compare the study groups. Kaplan-Meier with log- rank test was used to plot the survival analyses curve. Potential factors substantially associated to renal events were examined using cox proportional hazards model. Result About 20% of patients developed renal events and significant numbers were from hydrochlorothiazide (HCT) users. The mean eGFR levels were significantly higher in patients on CCBs users over the follow-up years compared with HCT-based users. The CCBs users had an 18.8 mL/min/1.73 m2 higher in eGFR levels at the end of the follow-up period than HCT users (p<0.001). HCT users had shorter survival probability overtime to develop the outcomes compared with CCBs users (p=0.003). The CCBs-based regimen prevented risks of declining in renal function by 56.4% than HCT (p=0.001). Hazards of declining in eGFR levels were 93% higher for the patients with initial systolic blood pressure (SBP) levels were more than 150 mm Hg (p=0.006). Conclusion Compared with HCT, patients on CCBs had significantly prevented risks of renal events. However, both groups appeared with the same cardiovascular events. HCT-based regimen and higher initial SBP levels were significantly associated with eGFR reductions.
Adopting a Mediterranean-style eating pattern with low, but not moderate, unprocessed, lean red meat intake reduces fasting serum trimethylamine N-oxide (TMAO) in adults who are overweight or obese

Abstract A Mediterranean-style eating pattern (MED-EP) may include moderate red meat intake. However, it is unknown if the pro-atherogenic metabolite trimethylamine N-oxide (TMAO) is affected by the amount of red meat consumed with a MED-EP. The results presented are from a secondary, retrospective objective of an investigator-blinded, randomised, crossover, controlled feeding trial (two 5-week interventions separated by a 4-week washout) to determine if a MED-EP with 200 g unprocessed lean red meat/week (MED-CONTROL) reduces circulating TMAO concentrations compared to a MED-EP with 500 g unprocessed lean red meat/week (MED-RED). Participants were seventy-seven women and twelve men (n 39 total) who were either overweight or obese (BMI: mean (30·5) (sem 0·3) kg/m2). Serum samples were obtained following an overnight fast both before (pre) and after (post) each intervention. Fasting serum TMAO, choline, carnitine and betaine concentrations were measured using a targeted liquid chromatography-MS. Data were analysed to assess if (a) TMAO and related metabolites differed by intervention and (b) if changes in TMAO were associated with changes in Framingham 10-year risk score. Serum TMAO was lower post-intervention following MED-CONTROL compared with MED-RED intervention (post-MED-CONTROL 3·1 (sem 0·2) µm v. post-MED-RED 5·0 (sem 0·5) µm, P < 0·001), and decreased following MED-CONTROL (pre- v. post-MED-CONTROL, P = 0·025). Exploratory analysis using mixed model ANCOVA identified a positive association between changes in TMAO and changes in homoeostatic model assessment of insulin resistance (P = 0·036). These results suggest that lower amounts of red meat intake lead to lower TMAO concentrations in the context of a MED-EP.
Public opinion in vaccine allocation priority: who comes first?

Abstract Objective We investigated people’s preferences in COVID-19 vaccine allocation priority, comparing different social categories based on age and occupation. Vaccine allocation preferences were related to perceived health vulnerability and economic backlash (economic negative consequences) endured by the different social groups during the pandemic. In-group favoritism in vaccine allocation preferences was analyzed. Design Data were collected through an online survey in Italy (n = 506) before the start of the vaccination campaign. Main outcome measures Vaccine allocation preferences, health vulnerability, and economic backlash due to COVID-19, measured through ranking tasks. Results The healthcare workers category was placed at the top of the ranking in vaccine allocation priority by 65% of the respondents. Vaccine allocation priority was related to perceived health vulnerability and not economic difficulties. Limited self-preference effects emerged. People who did not consider healthcare workers a priority (1/5 of the sample) had a lower education level, were more worried about COVID-19 infection risk, and did not trust vaccines. Conclusions A consensus emerged on who should be vaccinated first. Governments and policymakers should be aware of these preferences when designing and communicating vaccine allocation plans to predict and foster the public’s acceptance of the COVID-19 vaccination programs created by experts.
Participatory project management for improved disaster resilience

Purpose – Disaster response and recovery is implemented through multiple projects with traditional project management approaches criticised as too time consuming and inflexible in circumstances of high uncertainty, requiring rapid reaction for multiple stakeholders. This research aims to understand the role of project and stakeholder management in the management of disasters as an opening for identifying improved disaster resilience opportunities using participatory project management approaches. Design/methodology/approach – Using the 2011 Queensland floods as a case study, the positioning of project management in disaster management discourse was investigated through summative content analysis. Findings – Results demonstrate that project and stakeholder engagement are poorly positioned in current disaster management discourse, although risk management appears more central, closely associated with disaster response. Research limitations/implications – This is the first stage of more extensive reviews of .
Microglial PD‐1 stimulation by astrocytic PD‐L1 suppresses neuroinflammation and Alzheimer’s disease pathology

Chronic neuroinflammation is a pathogenic component of Alzheimer’s disease (AD) that may limit the ability of the brain to clear amyloid deposits and cellular debris. Tight control of the immune system is therefore key to sustain the ability of the brain to repair itself during homeostasis and disease. The immune‐cell checkpoint receptor/ligand pair PD‐1/PD‐L1, known for their inhibitory immune function, is expressed also in the brain. Here, we report upregulated expression of PD‐L1 and PD‐1 in astrocytes and microglia, respectively, surrounding amyloid plaques in AD patients and in the APP/PS1 AD mouse model. We observed juxtamembrane shedding of PD‐L1 from astrocytes, which may mediate ectodomain signaling to PD‐1‐expressing microglia. Deletion of microglial PD‐1 evoked an inflammatory response and compromised amyloid‐β peptide (Aβ) uptake. APP/PS1 mice deficient for PD‐1 exhibited increased deposition of Aβ, reduced microglial Aβ uptake, and decreased expression of the Aβ receptor CD36 on microglia. Therefore, ineffective immune regulation by the PD‐1/PD‐L1 axis contributes to Aβ plaque deposition during chronic neuroinflammation in AD.
Performance of Geosynthetic-Reinforced Soil Structures at Limit Equilibrium State

Potential failure mechanisms representing various limit equilibrium states of geosynthetic-reinforced soil walls/slopes are employed to study the behavior of reinforced soil walls/slopes. Parametric analyses were conducted to investigate the effects of varying the values of pore water pressure, soil strength, geosynthetic strength, soil-geosynthetic interaction coefficients, vertical spacing of geosynthetic, surcharge load, facing slope, and backslope. In the analyses, geosynthetic-reinforced soil walls/slopes are assumed to have competent foundations. Seepage forces and other dynamic forces such as earthquake forces have not been taken into account. Similarly, the stabilizing effects of facing rigidity and strength are neglected. The results are presented in a nondimensional graphical form. Methods of optimizing the design of geosynthetic-reinforced soil structures are suggested.