Tag: statistics

Sci Rep. 2021 Jul 9;11(1):14180. doi: 10.1038/s41598-021-92964-9.

ABSTRACT

High resistance towards traditional antibiotics has urged the development of new, natural therapeutics against methicillin-resistant Staphylococcus aureus (MRSA). Prenylated (iso)flavonoids, present mainly in the Fabaceae, can serve as promising candidates. Herein, the anti-MRSA properties of 23 prenylated (iso)flavonoids were assessed in-vitro. The di-prenylated (iso)flavonoids, glabrol (flavanone) and 6,8-diprenyl genistein (isoflavone), together with the mono-prenylated, 4′-O-methyl glabridin (isoflavan), were the most active anti-MRSA compounds (Minimum Inhibitory Concentrations (MIC) ≤ 10 µg/mL, 30 µM). The in-house activity data was complemented with literature data to yield an extended, curated dataset of 67 molecules for the development of robust in-silico prediction models. A QSAR model having a good fit (R²_adj 0.61), low average prediction errors and a good predictive power (Q²) for the training (4% and Q²_LOO 0.57, respectively) and the test set (5% and Q²_test 0.75, respectively) was obtained. Furthermore, the model predicted well the activity of an external validation set (on average 5% prediction errors), as well as the level of activity (low, moderate, high) of prenylated (iso)flavonoids against other Gram-positive bacteria. For the first time, the importance of formal charge, besides hydrophobic volume and hydrogen-bonding, in the anti-MRSA activity was highlighted, thereby suggesting potentially different modes of action of the different prenylated (iso)flavonoids.

PMID:34244528 | DOI:10.1038/s41598-021-92964-9

Sci Rep. 2021 Jul 9;11(1):14229. doi: 10.1038/s41598-021-93503-2.

ABSTRACT

Recent studies suggested that cerebrovascular micro-occlusions, i.e. microstokes, could lead to ischemic tissue infarctions and cognitive deficits. Due to their small size, identifying measurable biomarkers of these microvascular lesions remains a major challenge. This work aims to simulate potential MRI signatures combining arterial spin labeling (ASL) and multi-directional diffusion-weighted imaging (DWI). Driving our hypothesis are recent observations demonstrating a radial reorientation of microvasculature around the micro-infarction locus during recovery in mice. Synthetic capillary beds, randomly- and radially-oriented, and optical coherence tomography (OCT) angiograms, acquired in the barrel cortex of mice (n = 5) before and after inducing targeted photothrombosis, were analyzed. Computational vascular graphs combined with a 3D Monte-Carlo simulator were used to characterize the magnetic resonance (MR) response, encompassing the effects of magnetic field perturbations caused by deoxyhemoglobin, and the advection and diffusion of the nuclear spins. We quantified the minimal intravoxel signal loss ratio when applying multiple gradient directions, at varying sequence parameters with and without ASL. With ASL, our results demonstrate a significant difference (p < 0.05) between the signal-ratios computed at baseline and 3 weeks after photothrombosis. The statistical power further increased (p < 0.005) using angiograms measured at week 4. Without ASL, no reliable signal change was found. We found that higher ratios, and accordingly improved significance, were achieved at lower magnetic field strengths (e.g., B0 = 3T) and shorter echo time TE (< 16 ms). Our simulations suggest that microstrokes might be characterized through ASL-DWI sequence, providing necessary insights for posterior experimental validations, and ultimately, future translational trials.

PMID:34244549 | DOI:10.1038/s41598-021-93503-2

RMD Open. 2021 Jul;7(2):e001724. doi: 10.1136/rmdopen-2021-001724.

ABSTRACT

AIM: The objective was to examine the prevalence of atherosclerotic cardiovascular disease (ASCVD) and its risk factors among patients with RA with diabetes mellitus (RA-DM) and patients with RA without diabetes mellitus (RAwoDM), and to evaluate lipid and blood pressure (BP) goal attainment in RA-DM and RAwoDM in primary and secondary prevention.

METHODS: The cohort was derived from the Survey of Cardiovascular Disease Risk Factors in Patients with Rheumatoid Arthritis from 53 centres/19 countries/3 continents during 2014-2019. We evaluated the prevalence of cardiovascular disease (CVD) among RA-DM and RAwoDM. The study population was divided into those with and without ASCVD, and within these groups we compared risk factors and CVD preventive treatment between RA-DM and RAwoDM.

RESULTS: The study population comprised of 10 543 patients with RA, of whom 1381 (13%) had DM. ASCVD was present in 26.7% in RA-DM compared with 11.6% RAwoDM (p<0.001). The proportion of patients with a diagnosis of hypertension, hyperlipidaemia and use of lipid-lowering or antihypertensive agents was higher among RA-DM than RAwoDM (p<0.001 for all). The majority of patients with ASCVD did not reach the lipid goal of low-density lipoprotein cholesterol <1.8 mmol/L. The lipid goal attainment was statistically and clinically significantly higher in RA-DM compared with RAwoDM both for patients with and without ASCVD. The systolic BP target of <140 mm Hg was reached by the majority of patients, and there were no statistically nor clinically significant differences in attainment of BP targets between RA-DM and RAwoDM.

CONCLUSION: CVD preventive medication use and prevalence of ASCVD were higher in RA-DM than in RAwoDM, and lipid goals were also more frequently obtained in RA-DM. Lessons may be learnt from CVD prevention programmes in DM to clinically benefit patients with RA .

PMID:34244381 | DOI:10.1136/rmdopen-2021-001724

Aging (Albany NY). 2021 Jul 9;13. doi: 10.18632/aging.203252. Online ahead of print.

ABSTRACT

Previous studies have provided limited evidence for the effect of tomato intake on bladder cancer incidence. This study aimed to evaluate the association between dietary tomato or lycopene consumption and bladder cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression model adjusting for confounders. After a median of 12.5 years of follow-up, 774 incident bladder cancer cases were identified. We found no statistically significant association between dietary intake of raw tomatoes and bladder cancer risk (Adjusted model: HR_{Q5 VS Q1} = 1.20, 95% CI: 0.95-1.52; P for trend = 0.243). Dietary intakes of tomato catsup, tomato salsa and tomato juice were also not associated with the risk of bladder cancer (all P for trend > 0.05). There was no statistically significant association between dietary consumption of lycopene and bladder cancer risk (Adjusted model: HR_{Q5 vs. Q1} = 1.04, 95% CI 0.82-1.33; P for trend = 0.590). In summary, analysis of the PLCO study suggested that dietary consumption of tomato or lycopene was not associated with the risk of bladder cancer.

PMID:34244460 | DOI:10.18632/aging.203252

Sci Rep. 2021 Jul 9;11(1):14206. doi: 10.1038/s41598-021-93091-1.

ABSTRACT

We consider a velocity field with linear viscous interactions defined on a one dimensional lattice. Brownian baths with different parameters can be coupled to the boundary sites and to the bulk sites, determining different kinds of non-equilibrium steady states or free-cooling dynamics. Analytical results for spatial and temporal correlations are provided by analytical diagonalisation of the system’s equations in the infinite size limit. We demonstrate that spatial correlations are scale-free and time-scales become exceedingly long when the system is driven only at the boundaries. On the contrary, in the case a bath is coupled to the bulk sites too, an exponential correlation decay is found with a finite characteristic length. This is also true in the free cooling regime, but in this case the correlation length grows diffusively in time. We discuss the crucial role of boundary driving for long-range correlations and slow time-scales, proposing an analogy between this simplified dynamical model and dense vibro-fluidized granular materials. Several generalizations and connections with the statistical physics of active matter are also suggested.

PMID:34244527 | DOI:10.1038/s41598-021-93091-1

BMJ Mil Health. 2021 Jul 9:bmjmilitary-2021-001791. doi: 10.1136/bmjmilitary-2021-001791. Online ahead of print.

ABSTRACT

INTRODUCTION: Military studies have investigated acute injuries associated with parachute jumps, but the literature does not address paratroopers’ cumulative microtraumatic (CMT) injury risk, nor does it compare injury risks between paratroopers and the rest of the military population. This study determined whether US active duty Army paratroopers experienced greater injury risks than their non-paratrooper soldier counterparts and whether their injuries cost more to treat suggesting greater injury severity.

METHODS: This retrospective study evaluated electronic medical records (2016-2018) for 31 621 paratroopers and a randomly selected comparison group of 170 715 non-paratrooper soldiers. Analyses included univariate and multivariate regression to quantify odds of injuries associated with risk variables and additional descriptive statistics.

RESULTS: Paratroopers had a 57% increase in the odds of experiencing one or more injuries (OR=1.57, 95% CI: 1.52 to 1.62) after controlling for sex, race and age, with a greater proportion of acute injuries (OR=1.38, 95% CI: 1.34 to 1.42), relative to comparison group soldiers. Injury types proportionally higher among paratroopers included head trauma and shoulder injuries. Average injury cost among paratroopers was 13% lower than for non-paratroopers ($2470 vs $2830 per injury). Among both populations, acute injury costs were notably higher than for CMT injuries (paratroopers, $1710/$630; non-paratroopers, $1860/$880 per injury).

CONCLUSIONS: Paratroopers were more likely to incur injury, especially an acute injury, than non-paratroopers. However, paratroopers’ average injury costs were less. This may be due to higher return-to-duty motivations, fitness levels, and/or facility-specific cost of care. Future studies should investigate causes of injuries found to be proportionally higher among paratroopers.

PMID:34244378 | DOI:10.1136/bmjmilitary-2021-001791

Liver Int. 2021 Jul 9. doi: 10.1111/liv.15009. Online ahead of print.

ABSTRACT

BACKGROUND&AIMS: Sustained virologic response (SVR) to direct-acting antivirals (DAA) ameliorates portal hypertension, improves hepatic function and may reverse the procoagulant state observed in patients with cirrhosis. However, an unexpected incidence of portal vein thrombosis (PVT) immediately after antiviral therapy has recently been reported. Therefore, we analyzed the long-term impact of SVR on the development of non-tumoral-PVT.

METHODS: Our study comprised two well-characterized prospective cohorts (‘HCV-Cured’:n=354/’HCV-Active’:n=179) of patients with HCV-cirrhosis who underwent standardized ultrasound surveillance. In the main analysis, the event of interest was de novo non-tumoral-PVT and events known to modify its natural history (OLT, TIPS, death, tumoral-PVT and anticoagulation) were considered as competing risk. Adjusted models were built using propensity scores for baseline covariates. Moreover, predictive factors were investigated by conventional multivariate analysis.

RESULTS: Ten (2.8%) patients in the ‘HCV-Cured’-cohort developed a non-tumoral-PVT during a median follow-up of 37.1 months, while 8 (4.5%) patients in the ‘HCV-Active’-cohort were diagnosed with non-tumoral-PVT during a median follow-up of 42.2 months. High Child-Pugh score was the only independent risk factor for non-tumoral-PVT-development and stage A patients were at low risk. Importantly, HCV-cure did not decrease the risk of non-tumoral-PVT in inverse probability of treatment-weighted (IPTW) analysis (subdistribution hazard ratio (sHR): 1.31(95% confidence interval (95%CI): 0.43-3.97); P=0.635). In contrast, SVR was associated with a substantial reduction in mortality (IPTW-adjusted sHR: 0.453 (95%CI: 0.287-0.715); P<0.001).

CONCLUSIONS: The risk of non-tumoral-PVT persists after HCV-cure in patients with cirrhosis, despite improving survival. Even after etiological cure, severity of liver disease remains the main determinant of non-tumoral-PVT-development.

PMID:34242479 | DOI:10.1111/liv.15009

Liver Int. 2021 Jul 9. doi: 10.1111/liv.15011. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: Aspirin and statins have been suggested to prevent hepatocellular carcinoma (HCC). However, the combined effects of aspirin and statins on HCC risk in patients with chronic hepatitis B (CHB) is not clear.

METHODS: A nationwide nested case-control study was performed with data from the National Health Insurance Service gathered between 2005 and 2015 in Korea. In a cohort of 538,135 treatment-naïve, non-cirrhotic patients with CHB, 6,539 HCC cases were matched to 26,156 controls and were analyzed by conditional logistic regression. Separate historical cohort studies for each drug were analyzed by time-dependent Cox regression as a sensitivity analysis.

RESULTS: In the nested case-control study, statins (OR 0.34; 95% CI 0.32-0.37) and aspirin (OR 0.92; 95% CI 0.85-0.99) were significantly associated with a HCC risk reduction. However, dose-dependent risk reduction was observed only with statins. By sensitivity analysis in the historical cohorts, statin users (n = 244,455; HR 0.67; 95% CI 0.66-0.68) and aspirin users (n = 288,777; HR 0.81; 95% CI 0.80-0.82) had significantly lower HCC risk. In the drug-stratified analyses, statins were associated with significantly reduced risk of HCC regardless of aspirin, whereas aspirin did not show such associations.

CONCLUSIONS: In this nationwide population-based study of patients with CHB, statin use was consistently associated with a significant and dose-dependent reduction in HCC risk. In contrast, the association between aspirin use and HCC risk reduction was not dose-dependent and was suggested to be confounded by statins.

PMID:34242482 | DOI:10.1111/liv.15011

Curr Protoc. 2021 Jul;1(7):e194. doi: 10.1002/cpz1.194.

ABSTRACT

Candida albicans biofilm formation in the presence of drugs can be examined through time-lapse microscopy. In many cases, the images are used qualitatively, which limits their utility for hypothesis testing. We employed a machine-learning algorithm implemented in the Orbit Image Analysis program to detect the percent area covered by cells from each image. This is combined with custom R scripts to determine the growth rate, growth asymptote, and time to reach the asymptote as quantitative proxies for biofilm formation. We describe step-by-step protocols that go from sample preparation for time-lapse microscopy through image analysis parameterization and visualization of the model fit. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Sample preparation Basic Protocol 2: Time-lapse microscopy: Evos protocol Basic Protocol 3: Batch file renaming Basic Protocol 4: Machine learning analysis of Evos images with Orbit Basic Protocol 5: Parametrization of Orbit output in R Basic Protocol 6: Visualization of logistic fits in R.

PMID:34242490 | DOI:10.1002/cpz1.194

Eur J Pain. 2021 Jul 9. doi: 10.1002/ejp.1836. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic pain is a significant health problem worldwide and requires a biopsychosocial treatment approach. Access to traditional pain medicine specialist services is limited and innovative treatment models are required to support patients in tertiary care. The study evaluated the clinical effectiveness and safety of the Treatment Access Pathway (TAP), an allied health expanded scope model of care which included innovative group assessment and collaboration with patients to create individualised treatment plans.

METHODS: One hundred and eighty-one patients referred to a tertiary level chronic pain service were randomly allocated to either the TAP or the waitlist study groups. Primary (pain interference) and secondary outcome measures were collected at recruitment and again at 6 months. Per-protocol analyses were utilised due to high participant attrition (46% across groups).

RESULTS: The TAP group reported greater reductions in pain interference at 6-months than waitlist group (0.9, 95% CI: 0.2 to 1.6), with more than half of the TAP group (52%) reporting clinically significant improvement. In addition, statistically significant differences between the TAP and waitlist groups were observed for objective measurements of walking endurance (5.4 meters, 95% CI: 1.7 to 9.1); and global impressions of change (1.4 unit decrease, 95% CI: 1 to 1.9). Nil adverse events were recorded.

CONCLUSIONS: The study suggests that an expanded scope allied health model of care prioritising patient choice and group-based interventions, provides modest benefits for tertiary-referral chronic pain patients. TAP warrants further investigation as a potentially viable alternative for tertiary healthcare where traditional pain services are unavailable or have long waiting lists.

PMID:34242463 | DOI:10.1002/ejp.1836