Category: Statistics

Mol Immunol. 2021 Apr 16;135:62-72. doi: 10.1016/j.molimm.2021.04.006. Online ahead of print.

ABSTRACT

The occurrence of asthma is closely related to environmental factors such as cigarette smoke (CS), one of the common risk factors. Environmental stimuli have the potential to activate transient receptor potential ankyrin 1 (TRPA1) and cause or aggravate asthma. The destruction of tight junctions (TJs) between airway epithelial cells by environmental stimuli in asthma has been researched. It is worth exploring whether CS can injury TJs and aggravate asthma by activating TRPA1. The objective of this study was to investigate the aggravation of CS on ovalbumin (OVA)-induced asthma related phenotypes and TJs expression in mice, and to explore the relationship between TRPA1 and the expression of TJs protein. Female wild type (WT) C57BL/6 mice, induced by OVA, CS and OVA plus CS (OVA + CS) respectively, were used to establish a 42-day asthma model, and mice with TRPA1 knockout (TRPA1^-/-) were treated in the same way. This study detected the number of inflammatory cells in peripheral blood and bronchoalveolar lavage fluid (BALF), the levels of IL-4, IL-5, IL-13 in BALF, enhanced pause (Penh) of lung function, pathological changes and the gene and protein expressions of TRPA1 and TJs (including ZO-1, Occludin and Claudin-2) in lung tissues. Compared with normal saline (NS) group, WT mice in the OVA group and OVA + CS group were significantly higher in asthma related phenotypes. The WT-OVA + CS group also showed higher Penh value, levels of IL-5 and IL-13 in BALF and lung tissue injury scores when compared with the WT-OVA group and WT-CS group. However, WT-OVA + CS group mice had significantly larger number of neutrophils in BALF than the WT-OVA group, and had larger number of eosinophils in peripheral blood and higher levels of IL-4 in BALF than the WT-CS group. Meanwhile, compared with the WT-NS group, the expressions of TRPA1 and Claudin-2 in lung tissues increased in other three groups while their expressions of ZO-1 and Occludin decreased, among which, the WT-OVA + CS group showed more remarkable changes. Compared with the WT-OVA + CS group, mice in the TRPA1^-/--OVA + CS showed a significant decrease in the number of inflammatory cells, levels of IL-4, IL-5 and IL-13 in BALF, Penh value and lung tissue injury score, and a downregulation of Claudin-2 expression while an upregulation of ZO-1 and Occludin expressions. In addition, the airway inflammation and injury, and the expressions of ZO-1, Occluding and Claudin-2 expressions were found with no statistic differences between TRPA1^-/--OVA group and TRPA1^-/--OVA + CS group. These results suggest that CS has aggravated the airway inflammation, pathological damage and destruction of TJs in airway epithelium of OVA-induced asthmatic mice, the processes of which are related to the increase of TRPA1 expression.

PMID:33873095 | DOI:10.1016/j.molimm.2021.04.006

Comput Biol Med. 2021 Apr 16;133:104396. doi: 10.1016/j.compbiomed.2021.104396. Online ahead of print.

ABSTRACT

BACKGROUND: Pacing artifacts must be excluded from the analysis of paced ECG waveform. This study aimed to develop and validate an algorithm to identify and remove the pacing artifacts on ECG and vectorcardiogram (VCG).

METHODS: We developed a semi-automatic algorithm that identifies the onset and offset of a pacing artifact based on the VCG signal slope steepness and designed a graphical user interface that permits quality control and fine-tuning the constraining threshold values. We used 1054 ECGs from the retrospective, multicenter cohort study “Global Electrical Heterogeneity and Clinical Outcomes,” including 3825 atrial and 10,031 ventricular pacing artifacts for the algorithm development and 22 ECGs including 108 atrial and 241 ventricular pacing artifacts for validation. Validation was performed per digital sample. We used the kappa-statistic of interrater agreement between manually labeled sample (ground-truth) and automated detection.

RESULTS: The constraining parameter values were for onset threshold 13.06 ± 6.21 μV/ms, offset threshold 34.77 ± 17.80 μV/ms, and maximum window size 27.23 ± 3.53 ms. The automated algorithm detected a digital sample belonging to pacing artifact with a sensitivity of 74.5% and specificity of 99.6% and classified correctly 98.8% of digital samples (ROC AUC 0.871; 95%CI 0.853-0.878). The kappa-statistic was 0.785, indicating substantial agreement. The agreement was on 98.81% digital samples, significantly (P < 0.00001) larger than the random agreement on 94.43% of digital samples.

CONCLUSIONS: The semi-automated algorithm can detect and remove ECG pacing artifacts with high accuracy and provide a user-friendly interface for quality control.

PMID:33872969 | DOI:10.1016/j.compbiomed.2021.104396

Comput Biol Med. 2021 Apr 15;133:104380. doi: 10.1016/j.compbiomed.2021.104380. Online ahead of print.

ABSTRACT

Immune evasion is one of the unique characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attributed to its ORF8 protein. This protein modulates the adaptive host immunity through down-regulation of MHC-1 (Major Histocompatibility Complex) molecules and innate immune responses by surpassing the host’s interferon-mediated antiviral response. To understand the host’s immune perspective concerning the ORF8 protein, a comprehensive study of the ORF8 protein and mutations possessed by it have been performed. Chemical and structural properties of ORF8 proteins from different hosts, such as human, bat, and pangolin, suggest that the ORF8 of SARS-CoV-2 is much closer to ORF8 of Bat RaTG13-CoV than to that of Pangolin-CoV. Eighty-seven mutations across unique variants of ORF8 in SARS-CoV-2 can be grouped into four classes based on their predicted effects (Hussain et al., 2021) [1]. Based on the geo-locations and timescale of sample collection, a possible flow of mutations was built. Furthermore, conclusive flows of amalgamation of mutations were found upon sequence similarity analyses and consideration of the amino acid conservation phylogenies. Therefore, this study seeks to highlight the uniqueness of the rapidly evolving SARS-CoV-2 through the ORF8.

PMID:33872970 | DOI:10.1016/j.compbiomed.2021.104380

Parkinsonism Relat Disord. 2021 Apr 11;86:74-77. doi: 10.1016/j.parkreldis.2021.04.003. Online ahead of print.

ABSTRACT

OBJECTIVE: To study the association between impulse control disorders (ICDs) in Parkinson’s disease (PD) and genetic risk scores (GRS) for 40 known or putative risk factors (e.g. depression, personality traits).

BACKGROUND: In absence of published genome-wide association studies (GWAS), little is known about the genetics of ICDs in PD. GRS of related phenotypes, for which large GWAS are available, may help shed light on the genetic contributors of ICDs in PD.

METHODS: We searched for GWAS on European ancestry populations with summary statistics publicly available for a broad range of phenotypes, including other psychiatric disorders, personality traits, and simple phenotypes. We separately tested their predictive ability in two of the largest PD cohorts with clinical and genetic available: the Parkinson’s Progression Markers Initiative database (N = 368, 33% female, age range = [33-84]) and the Drug Interaction With Genes in Parkinson’s Disease study (N = 373, 40% female, age range = [29-85]).

RESULTS: We considered 40 known or putative risk factors for ICDs in PD for which large GWAS had been published. After Bonferroni correction for multiple comparisons, no GRS or the combination of the 40 GRS were significantly associated with ICDs from the analyses in each cohort separately and from the meta-analysis.

CONCLUSION: Albeit unsuccessful, our approach will gain power in the coming years with increasing availability of genotypes in clinical cohorts of PD, but also from future increase in GWAS sample sizes of the phenotypes we considered. Our approach may be applied to other complex disorders, for which GWAS are not available or limited.

PMID:33872999 | DOI:10.1016/j.parkreldis.2021.04.003

Int J Food Microbiol. 2021 Mar 26;347:109171. doi: 10.1016/j.ijfoodmicro.2021.109171. Online ahead of print.

ABSTRACT

Potatoes contain several nutrients essential for fungal growth, making them an excellent component of media such as the popular Potato Dextrose Agar (PDA) medium. Commercially, PDA is available from multiple retailers offering virtually the same product. These media, however, could contain small differences in composition of nutrients affecting the expression of secondary metabolites. This study aims to investigate the use of four PDA media from different manufacturers (Fluka, Oxoid, Sigma, and VWR) and their effect on the metabolite profile of four species of Fusarium (F. fujikuroi, F. graminearum, F. pseudograminearum and F. avenaceum). Secondary metabolites were analysed using HPLC-HRMS, from which statistically significant differences in intensities were observed for 9 out of 10 metabolites.

PMID:33872940 | DOI:10.1016/j.ijfoodmicro.2021.109171

Spectrochim Acta A Mol Biomol Spectrosc. 2021 Apr 1;257:119763. doi: 10.1016/j.saa.2021.119763. Online ahead of print.

ABSTRACT

Achieving good glycemic control in patients with type II diabetes mellitus is essential for preventing both microvascular and macrovascular complications. Combination therapy represents the principle strategy for successful long term control of type II diabetes mellitus with minimal complications. Two sensitive, precise and non-destructive spectroscopic methods were developed for the simultaneous estimation of two new co-formulated hypoglycemic drugs; canagliflozin/metformin (CAG/MEF) and empagliflozin/linagliptin (EMG/LIG) in tablets with no need of previous separation. The first method was amplitude modulation (a normalized spectra-based UV spectrophotometric method) for the analysis of (CAG/MEF) binary mixture. The amplitude of the constant at the plateau region at (264-310 nm) on the ratio spectrum was measured and used for the determination of CAG concentration in the mixture. On the other hand, MEF was estimated by subtracting the previously obtained amplitude from the total amplitude of CAG and MEF at the isosbestic point (λ_iso) at 250 nm. The second method was chemometric-assisted FTIR spectrophotometric method for the determination of (EMG/LIG) binary mixture. (EMG/LIG) mixture in chloroform was analyzed using FTIR in the region 4000-400 cm^-1. The spectral region 3900-2900 cm^-1 was selected for (EMG/LIG) determination using principal component regression and partial least squares chemometric methods. The methods were validated according to ICH guidelines. The studied drugs were successfully determined in tablets applying the developed methods. Validation parameters were in agreement with acceptance limits, ensuring methods accuracy and selectivity. Besides, no significant difference was obtained by statistically comparing the obtained results with the reported one.

PMID:33872950 | DOI:10.1016/j.saa.2021.119763

Spectrochim Acta A Mol Biomol Spectrosc. 2021 Mar 24;257:119741. doi: 10.1016/j.saa.2021.119741. Online ahead of print.

ABSTRACT

When our liver does not work well, it can induce damage to other organs causing their dysfunction. With this background, we aim to study the effect of liver fibrosis on other organs such as heart, lungs, kidney and spleen by assessing the variations in the inherent emission property of the tissue, using fluorescence spectroscopy. Fluorescence emission spectra from excised organs of liver fibrosis induced rats were collected at excitation wavelengths 320 and 410 nm. Optical redox ratio derived from the spectral data supported by multivariate statistical analysis, principal component analysis followed by linear discriminant analysis (PCA-LDA) distinguished between control and fibrosis induced groups. The two different excitation wavelength provided variations in the endogenous flurophores collagen, nicotinamide adenine dinucleotide (NADH), flavin adenine dinucleotide (FAD), lipopigments and porphyrins. Additionally, evaluation of redox ratio provided variations in tissue metabolic activity of different organs. The PCA-LDA modelling yielded a sensitivity of 85 to 97% and specificity of 80 to 96% on 320 nm excitation and a sensitivity of 72 to 100% and specificity of 59 to 100% on 410 nm excitation. Fluorescence emission spectral study along with multivariate analysis paved way to identify the biochemical alterations caused to other organs due to the development of liver fibrosis, which could lead to their damage and dysfunction.

PMID:33872953 | DOI:10.1016/j.saa.2021.119741

J Mech Behav Biomed Mater. 2021 Apr 16;119:104510. doi: 10.1016/j.jmbbm.2021.104510. Online ahead of print.

ABSTRACT

The present study elucidates the impact of detergent-based chemical decellularization on the micro-mechanical properties of porcine and rabbit corneas for the purpose of extracellular matrix (ECM) derived scaffolds. Aiming to optimize the decellularization process, different concentrations of Sodium Dodecyl Sulfate (SDS), Triton X-100 and CHAPS detergents were assessed on their ability to decellularize corneas from both bio-models at incubation periods of 12 and 24h. We evaluated the effect of decellularization on corneal ECM Young’s Modulus and various area’s roughness parameters (topography features) at a microscale by using Atomic Force Microscopy (AFM). Only SDS presented adequate decellularization properties at the selected concentrations (0.2, 0.5 and 1%) and incubation periods. All topography features displayed by native corneas were preserved after SDS treatments, while no statistically significant differences were identified for the average value of Young’s Modulus between the control samples and those treated with 0.2% SDS (rabbit corneas) and 0.5% SDS (porcine corneas) after 12h. In this sense, cornea decellularization procedures can be improved by simultaneously reducing SDS concentration and incubation period. AFM is a useful tool to perform biomechanical analysis of the effect of decellularization on scaffold micro-mechanics. Evaluation of the scaffold mechanical behavior at a microscale could help in understanding cell-scaffold interactions in terms of mechanotransduction, complementing macroscale techniques (e.g. tensile tests) relevant for tissue engineering quality control and decision-making.

PMID:33872923 | DOI:10.1016/j.jmbbm.2021.104510

Transbound Emerg Dis. 2021 Apr 19. doi: 10.1111/tbed.14108. Online ahead of print.

ABSTRACT

Bovine tuberculosis (TB) is a chronic disease caused mainly by Mycobacterium bovis, a zoonotic pathogen that has a worldwide distribution causing serious economic losses for milk and meat producers. In Chile the disease in dairy cattle has a heterogeneous distribution, where the Metropolitan Region concentrates the highest animal prevalence and the main challenge for the national control and eradication program. In this epidemiological context, vaccination with the M. bovis Bacillus Calmette-Guerin (BCG) vaccine might be a useful strategy for disease prevention and control. The objective of this study was to assess the efficacy and impacts on productivity and fertility of vaccination with the BCG Russia strain in 11-month-old heifers from a dairy farm, under a natural transmission condition. Sixty-two animals were vaccinated via the subcutaneous route with the equivalent of 1 human dose of BCG and 60 control animals received saline. Subsequently, blood sampling was performed at 3, 6, 9, 12, 15 and 18 months post inoculation, and infection status was determined using the IFNγ release assay (IGRA)with the DIVA (Differentiate Infected from Vaccinated Animals) antigens ESAT-6, CFP-10 and Rv3615c. Efficacy was calculated as the percentage of reduction in the incidence of infection attributable to vaccination, which showed a statistically significant level of overall protection of 66.5%. No adverse effects on fertility and production were recorded. In contrast, we observed beneficial effects of vaccination on several milk production parameters, with the milk yield in the first 100 days after calving in the BCG group significantly higher compared to unvaccinated heifers( p <0.05).These results suggest that BCG vaccination of heifers in a natural transmission setting might result in both sanitary and productive benefits, supporting its implementation as a new strategy for TB prevention in a high prevalence area of Chile.

PMID:33872473 | DOI:10.1111/tbed.14108

Pain Pract. 2021 Apr 19. doi: 10.1111/papr.13018. Online ahead of print.

ABSTRACT

BACKGROUND: SNRB was shown to effectively control radiating pain and reduce the need for surgical intervention. However, repetitive injections may trigger corticosteroid-induced side effects (hypercorticism, hyperglycemia, or fluid retention). This study aims to compare the potency of hyaluronic acid-carboxymethylcellulose (HA-CMC) solution versus that of corticosteroids regarding lower leg radiating pain (LLRP) improvement and functional outcome.

METHODS: Among 128 patients, 44 patients who complain LLRP due to lumbar spinal stenosis and do not have neurological symptoms requiring surgery were enrolled for this study. Group A with 22 patients injected with cocktail A (local anesthetics, corticosteroid) and group B with 22 patients injected with cocktail B (local anesthetics, HA-CMC). Outcome measures were the visual analog scale (VAS), Oswestry Disability Index (ODI), and short form -36 (SF-36). All patients were asked to fill in the questionnaires during the follow-up assessment period at 3 days, 7 days, 2 weeks, 6 weeks, and 12 weeks.

RESULTS: In all time periods, there were no statistical differences between the two groups for VAS scores and VAS improvement over time, ODI scores and ODI improvement over time, and SF-36 PCS scores and SF-36 MCS scores. Additionally, the 95% confidence interval of the difference in VAS score improvement between the two groups in all time periods was within VAS 5.0, which is the minimum clinically relevant difference.

CONCLUSIONS: Considering the adverse effects of corticosteroids, and the similar LLRP improvements, functional outcome, and quality of life, the HA-CMC solution may be an alternative option to corticosteroid in SNRB.

PMID:33872462 | DOI:10.1111/papr.13018