Tag: statistics

Int Endod J. 2021 Mar 12. doi: 10.1111/iej.13513. Online ahead of print.

ABSTRACT

AIM: To explore the proliferation, adhesion and differentiation response and the underlying mechanisms that occur in LPS-induced inflamed dental pulp cells in contact with Biodentine and MTA.

METHODOLOGY: The dental pulp cells (DPCs) were isolated from three healthy donors and named DPC-H1 to DPC-H3. The DPCs were pre-cultured with 2 or 5 ug/mL lipopolysaccharide (LPS) for 24 h to induce inflammation. The expression of inflammation marker-miR-146a was detected by q-PCR. The normal and LPS-induced DPCs were further treated with 0.14 mg/mL Biodentine or 0.13mg/mL MTA for 24 h. MTT assay and adhesion assay were used to analyze the changes of cell phenotypes. DSPP, AKT and ERK expression were detected by western blotting. The data were analyzed by Mann-Whitney test or two-way ANOVA. Differences were considered statistically significant when p < 0.05.

RESULTS: In LPS-induced DPCs, Biodentine and MTA treatment neither induced nor aggravated LPS-induced inflammation, but their presence did increase the expression of the odontogenic differentiation marker DSPP. Under 2or 5 μg/mL LPS-induced inflammation, Biodentine and MTA promoted the proliferation of DPC cells, and significantly in DPC-H2 (p < 0.0001 for both reagents). With the treatment of 2 μg/mL LPS, the cell adhesion of DPCs on the fibronectin-coated culture plates was increased significantly by Biodentine (p = 0.0413) and MTA (p < 0.0001). Biodentine and MTA regulated cell adhesion on the fibronectin-coated culture plates (p < 0.0001 for both reagents) and proliferation (p < 0.0001 for both reagents) via the AKT pathway. However, the AKT pathway was not involved in the expression of DSPP induced by Biodentine and MTA.

CONCLUSION: Biodentine and MTA enhanced the proliferation, adhesion and differentiation of LPS-induced dental pulp cells. The proliferation and adhesion process induced by Biodentine and MTA is via the AKT pathway. However, the cellular differentiation process might not use the same pathway, and this needs to be explored in future studies.

PMID:33711171 | DOI:10.1111/iej.13513

Aliment Pharmacol Ther. 2021 Mar 12. doi: 10.1111/apt.16304. Online ahead of print.

ABSTRACT

BACKGROUND: Gastroparesis is defined by delayed gastric emptying with associated symptoms in the absence of mechanical obstruction.

AIM: To evaluate pharmacokinetics and pharmacodynamics of felcisetrag, a highly selective 5-HT₄ receptor agonist, on total gut transit in patients with documented delayed gastric emptying of solids.

METHODS: Single-centre, placebo-controlled study of 36 participants receiving placebo, 0.1mg, 0.3mg or 1.0mg of felcisetrag I.V. infusion, daily, for 3 days. At baseline, each participant completed a 4h, ^99m Tc-egg meal (300 kcal, 30% fat) gastric emptying test. Following infusion (Day 2), gastric, small bowel and colonic transit of solids were measured over 48h (same meal plus ¹¹¹ In-charcoal delivered in methacrylate-coated capsule). Samples were collected for pharmacokinetics. The primary endpoint was gastric emptying T_1/2 . Statistical analysis used baseline parameters as covariates (ANCOVA).

RESULTS: Patients (22 idiopathic, 14 diabetic gastroparesis) were randomised to felcisetrag (0.1 mg, n = 10; 0.3 mg, n = 9; 1.0 mg, n = 7) or placebo (n = 10). Compared to placebo, felcisetrag significantly accelerated gastric emptying T_1/2 , colonic filling at 6h, and 10% small bowel transit time (overall P < 0.01; all three doses individually Bonferroni corrected P < 0.05) for all three measurements. Ascending colon emptying (T_1/2 ) was significantly accelerated (all doses), and colonic transit at 48 hours was accelerated with 0.1 mg and 0.3 mg felcisetrag compared to placebo. Pharmacokinetic results were dose proportional. Felcisetrag was well tolerated with no clinically significant findings from clinical laboratory, vital signs or ECG.

CONCLUSION: I.V. felcisetrag significantly accelerated gastric, small bowel and colonic transit in patients with gastroparesis, and should be further evaluated for short-term treatment of gastric and intestinal motility disorders. ClinicalTrials.gov #NCT03281577.

PMID:33711180 | DOI:10.1111/apt.16304

Orthod Craniofac Res. 2021 Mar 12. doi: 10.1111/ocr.12482. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to quantify the 3D asymmetry of the maxilla in patients with unilateral cleft lip and palate (UCP) and investigate the defect factors responsible for the variability of the maxilla on the cleft side using a deep learning-based CBCT image segmentation protocol. Setting and Sample Population CBCT images of 60 patients with UCP were acquired. The samples in this study consisted of 39 males and 21 females, with a mean age of 11.52 years (SD=3.27 years; range of 8-18 years).

MATERIALS AND METHODS: The deep learning-based protocol was used to segment the maxilla and defect initially, followed by manual refinement. Paired t-tests were performed to characterize the maxillary asymmetry. A multiple linear regression was carried out to investigate the relationship between the defect parameters and those of the cleft side of the maxilla.

RESULTS: The cleft side of the maxilla demonstrated a significant decrease in maxillary volume and length as well as alveolar length, anterior width, posterior width, anterior height, and posterior height. A significant increase in maxillary anterior width was demonstrated on the cleft side of the maxilla. There was a close relationship between the defect parameters and those of the cleft side of the maxilla.

CONCLUSIONS: Based on the 3D volumetric segmentations, significant hypoplasia of the maxilla on the cleft side existed in the pyriform aperture and alveolar crest area near the defect. The defect structures appeared to contribute to the variability of the maxilla on the cleft side.

PMID:33711187 | DOI:10.1111/ocr.12482

Br J Surg. 2021 Mar 12;108(2):e83. doi: 10.1093/bjs/znaa015.

NO ABSTRACT

PMID:33711110 | DOI:10.1093/bjs/znaa015

Br J Surg. 2021 Mar 12;108(2):138-144. doi: 10.1093/bjs/znaa049.

ABSTRACT

BACKGROUND: There is a shortage of high-quality studies regarding choice of mesh in open anterior inguinal hernia repair in relation to long-term chronic pain. The authors hypothesized that heavyweight compared with lightweight mesh causes increased postoperative pain.

METHODS: An RCT was undertaken between 2007 and 2009 at two sites in Sweden. Men aged 25 years or older with an inguinal hernia evaluated in the outpatient clinic were randomized in an unblinded fashion to heavyweight or lightweight mesh for open anterior inguinal hernia repair. Data on pain affecting daily activities, as measured by the Short-Form Inguinal Pain Questionnaire 9-12 years after surgery, were collected as the primary outcome. Differences between groups were evaluated by generalized odds and numbers needed to treat.

RESULTS: A total of 412 patients were randomized; 363 were analysed with 320 questionnaires sent out. A total of 271 questionnaires (84.7 per cent) were returned; of these, 121 and 150 patients were in the heavyweight and lightweight mesh groups respectively. Pain affecting daily activities was more pronounced in patients randomized to heavyweight versus lightweight mesh (generalized odds 1.33, 95 per cent c.i. 1.10 to 1.61). This translated into a number needed to treat of 7.06 (95 per cent c.i. 4.28 to 21.44). Two reoperations for recurrence were noted in the heavyweight mesh group, and one in the lightweight mesh group.

CONCLUSION: A large-pore lightweight mesh causes significantly less pain affecting daily activities a decade after open anterior inguinal hernia repair. Registration number: NCT00451893 (http://www.clinicaltrials.gov).

PMID:33711123 | DOI:10.1093/bjs/znaa049

Br J Surg. 2021 Mar 12;108(2):e81-e82. doi: 10.1093/bjs/znaa124.

NO ABSTRACT

PMID:33711133 | DOI:10.1093/bjs/znaa124

JMIRx Med. 2020 Oct 19;1(1):e23582. doi: 10.2196/23582. eCollection 2020 Jan-Dec.

ABSTRACT

BACKGROUND: Approximately 80% of those infected with COVID-19 are immune. They are asymptomatic unknown carriers who can still infect those with whom they come into contact. Understanding what makes them immune could inform public health policies as to who needs to be protected and why, and possibly lead to a novel treatment for those who cannot, or will not, be vaccinated once a vaccine is available.

OBJECTIVE: The primary objectives of this study were to learn if machine learning could identify patterns in the pathogen-host immune relationship that differentiate or predict COVID-19 symptom immunity and, if so, which ones and at what levels. The secondary objective was to learn if machine learning could take such differentiators to build a model that could predict COVID-19 immunity with clinical accuracy. The tertiary purpose was to learn about the relevance of other immune factors.

METHODS: This was a comparative effectiveness research study on 53 common immunological factors using machine learning on clinical data from 74 similarly grouped Chinese COVID-19-positive patients, 37 of whom were symptomatic and 37 asymptomatic. The setting was a single-center primary care hospital in the Wanzhou District of China. Immunological factors were measured in patients who were diagnosed as SARS-CoV-2 positive by reverse transcriptase-polymerase chain reaction (RT-PCR) in the 14 days before observations were recorded. The median age of the 37 asymptomatic patients was 41 years (range 8-75 years); 22 were female, 15 were male. For comparison, 37 RT-PCR test-positive patients were selected and matched to the asymptomatic group by age, comorbidities, and sex. Machine learning models were trained and compared to understand the pathogen-immune relationship and predict who was immune to COVID-19 and why, using the statistical programming language R.

RESULTS: When stem cell growth factor-beta (SCGF-β) was included in the machine learning analysis, a decision tree and extreme gradient boosting algorithms classified and predicted COVID-19 symptom immunity with 100% accuracy. When SCGF-β was excluded, a random-forest algorithm classified and predicted asymptomatic and symptomatic cases of COVID-19 with 94.8% AUROC (area under the receiver operating characteristic) curve accuracy (95% CI 90.17%-100%). In total, 34 common immune factors have statistically significant associations with COVID-19 symptoms (all c<.05), and 19 immune factors appear to have no statistically significant association.

CONCLUSIONS: The primary outcome was that asymptomatic patients with COVID-19 could be identified by three distinct immunological factors and levels: SCGF-β (>127,637), interleukin-16 (IL-16) (>45), and macrophage colony-stimulating factor (M-CSF) (>57). The secondary study outcome was the suggestion that stem-cell therapy with SCGF-β may be a novel treatment for COVID-19. Individuals with an SCGF-β level >127,637, or an IL-16 level >45 and an M-CSF level >57, appear to be predictively immune to COVID-19 100% and 94.8% (AUROC) of the time, respectively. Testing levels of these three immunological factors may be a valuable tool at the point of care for managing and preventing outbreaks. Further, stem-cell therapy via SCGF-β and M-CSF appear to be promising novel therapeutics for patients with COVID-19.

PMID:33711083 | PMC:PMC7924715 | DOI:10.2196/23582

Phys Chem Chem Phys. 2021 Mar 12. doi: 10.1039/d0cp06002j. Online ahead of print.

ABSTRACT

The formation of native point defects in semiconductors and their behaviors play a crucial role in material properties. Although the native defects of V2O5 include vacancies, self-interstitials, and antisites, only oxygen vacancies have been extensively explored. In this work, we carried out first-principles calculations to systematically study the properties of possible native defects in V2O5. The electronic structure and the formation energy of each defect were calculated using the DFT+U method. Defect concentrations were estimated using a statistical model with a constraint of charge neutrality. We found that the vanadyl vacancy is a shallow acceptor that could supply holes to the system. However, the intrinsic p-type doping in V2O5 hardly occurred because the vanadyl vacancy could be readily compensated by the more stable donor, i.e., the oxygen vacancy and oxygen interstitial, instead of holes. The oxygen vacancy is the most dominant defect under oxygen-deficient conditions. However, under extreme O-rich conditions, a deep donor of oxygen interstitial becomes the major defect species. The dominant oxygen vacancy under synthesized conditions plays an important role in determining the electronic conductivity of V2O5. It induces the formation of compensating electron polarons. The polarons are trapped at V centers close to the vacancy site with the effective escaping barriers of around 0.6 eV. Such barriers are higher than that of the isolated polaron hopping (0.2 eV). The estimated polaron mobilities obtained from kinetic Monte Carlo simulations confirmed that oxygen vacancies act as polaron-trapping sites, which diminishes the polaron mobility by 4 orders of magnitude. Nevertheless, when the sample is synthesized at elevated temperatures, a number of thermally activated polarons in samples are quite high due to the high concentrations of oxygen vacancies. These polarons can contribute as charge carriers of intrinsic n-type semiconducting V2O5.

PMID:33711089 | DOI:10.1039/d0cp06002j

J Bras Nefrol. 2021 Mar 12:S0101-28002021005027301. doi: 10.1590/2175-8239-JBN-2020-0225. Online ahead of print.

ABSTRACT

INTRODUCTION: In this study, we aimed to detect the cytokine that is involved in the early stage of chronic kidney disease and associated with cardiovascular disease.

METHODS: We included 50 patients who were diagnosed with predialytic chronic kidney disease and 30 healthy pediatric patients in Ege University Medical Faculty Pediatric Clinic, İzmir/Turkey. Interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-13 (IL-13), and transforming grow factor-β1 (TGF-β1) levels (pg/mL) were measured by ELISA. Carotid-femoral pulse wave velocity (PWV), augmentation index (Aix), carotid intima media thickness (cIMT), and left ventricular mass index (LVMI) were evaluated as markers of cardiovascular disease. The presence of a cardiovascular disease marker was defined as an abnormality in any of the parameters (cIMT, PWV, Aix, and left ventricular mass index (SVKI)). The patient group was divided into two groups as with and without cardiovascular disease.

RESULTS: Mean Aix and PWV values were higher in CKD patients than controls (Aix: CKD 32.8±11.11%, healthy subjects: 6.74±6.58%, PWV CKD: 7.31±4.34m/s, healthy subjects: 3.42±3.01m/s, respectively; p=0.02, p=0.03). The serum IL-8 levels of CKD were significantly higher than of healthy subjects 568.48±487.35pg/mL, 33.67±47.47pg/mL, respectively (p<0.001). There was no statistically significant difference between IL-8, IL-10, IL-13, TGF-1, in CKD patients with and without cardiovascular disease (p> 0.05).

DISCUSSION: IL-8 is the sole cytokine that increases in pediatric patients with chronic kidney disease among other cytokines (IL-10, IL-13 and TGF-β1). However, we did not show that IL-8 is related to the presence of cardiovascular disease.

PMID:33711092 | DOI:10.1590/2175-8239-JBN-2020-0225

PLoS One. 2021 Mar 12;16(3):e0248337. doi: 10.1371/journal.pone.0248337. eCollection 2021.

ABSTRACT

Despite many attempts to introduce evolutionary models that permit substitutions to instantly alter more than one nucleotide in a codon, the prevailing wisdom remains that such changes are rare and generally negligible or are reflective of non-biological artifacts, such as alignment errors. Codon models continue to posit that only single nucleotide change have non-zero rates. Here, we develop and test a simple hierarchy of codon-substitution models with non-zero evolutionary rates for only one-nucleotide (1H), one- and two-nucleotide (2H), or any (3H) codon substitutions. Using over 42, 000 empirical alignments, we find widespread statistical support for multiple hits: 61% of alignments prefer models with 2H allowed, and 23%-with 3H allowed. Analyses of simulated data suggest that these results are not likely to be due to simple artifacts such as model misspecification or alignment errors. Further modeling reveals that synonymous codon island jumping among codons encoding serine, especially along short branches, contributes significantly to this 3H signal. While serine codons were prominently involved in multiple-hit substitutions, there were other common exchanges contributing to better model fit. It appears that a small subset of sites in most alignments have unusual evolutionary dynamics not well explained by existing model formalisms, and that commonly estimated quantities, such as dN/dS ratios may be biased by model misspecification. Our findings highlight the need for continued evaluation of assumptions underlying workhorse evolutionary models and subsequent evolutionary inference techniques. We provide a software implementation for evolutionary biologists to assess the potential impact of extra base hits in their data in the HyPhy package and in the Datamonkey.org server.

PMID:33711070 | DOI:10.1371/journal.pone.0248337