The image quality of deep-learning image reconstruction of chest CT images on a mediastinal window setting.

AIM: To assess the image quality of deep-learning image reconstruction (DLIR) of chest computed tomography (CT) images on a mediastinal window setting in comparison to an adaptive statistical iterative reconstruction (ASiR-V). MATERIALS AND METHODS: Thirty-six patients were evaluated retrospectively. All patients underwent contrast-enhanced chest CT and thin-section images were reconstructed using filtered back projection (FBP); ASiR-V (60% and 100% blending setting); and DLIR (low, medium, and high settings). Image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were evaluated objectively. Two independent radiologists evaluated ASiR-V 60% and DLIR subjectively, in comparison with FBP, on a five-point scale in terms of noise, streak artefact, lymph nodes, small vessels, and overall image quality on a mediastinal window setting (width 400 HU, level 60 HU). In addition, image texture of ASiR-Vs (60% and 100%) and DLIR-high was analysed subjectively. RESULTS: Compared with ASiR-V 60%, DLIR-med and DLIR-high showed significantly less noise, higher SNR, and higher CNR (p<0.0001). DLIR-high and ASiR-V 100% were not significantly different regarding noise (p=0.2918) and CNR (p=0.0642). At a higher DLIR setting, noise was lower and SNR and CNR were higher (p<0.0001). DLIR-high showed the best subjective scores for noise, streak artefact, and overall image quality (p<0.0001). Compared with ASiR-V 60%, DLIR-med and DLIR-high scored worse in the assessment of small vessels (p<0.0001). The image texture of DLIR-high was significantly finer than that of ASIR-Vs (p<0.0001). CONCLUSIONS: DLIR-high improved the objective parameters and subjective image quality by reducing noise and streak artefacts and providing finer image texture.

Influence of the MCT1-T1470A polymorphism (rs1049434) on repeated sprint ability and blood lactate accumulation in elite football players: a pilot study.

PURPOSE: The aim of this study is to investigate the influence of the MCT1 T1470A polymorphism (rs1049434) on repeated sprint ability (RSA) and lactate accumulation after RSA testing. METHODS: Twenty-six elite Italian male football players (age: 17.7 ± 0.78 years; height: 179.2 ± 7.40 cm; weight: 72.1 ± 5.38 kg) performed RSA testing (6 × 30-m sprints with an active recovery between sprints), and lactate measurements were obtained at 1, 3, 5, 7, and 10 min post-exercise. Genotyping for the MCT1 T1470A polymorphism was performed using PCR. RESULTS: Genotype distributions were in Hardy-Weinberg equilibrium, being 42% wildtype (A/A), 46% heterozygotes (T/A), and 12% mutated homozygotes (T/T). Significant differences between genotypic groups were found in the two final sprint times of the RSA test. Under a dominant model, carriers of the major A-allele (Glu-490) in the dominant model showed a significantly lower sprint time compared to footballers with the T/T (Asp/Asp) genotype (5th Sprint time: A/A + T/A = 4.60 s vs TT = 4.97 s, 95% CI 0.07-0.67, p = 0.022; 6th Sprint: A/A + T/A = 4.56 s vs T/T = 4.87 s, 95% CI 0.05-0.57, p = 0.033). CONCLUSIONS: The T1470A (Glu490Asp) polymorphism of MCT1 was associated with RSA. Our findings suggest that the presence of the major A-allele (Glu-490) is favourable for RSA in football players.

Low prevalence of maternal microchimerism in peripheral blood of Japanese children with type 1 diabetes.

AIM: To clarify the prevalence and degree of maternal microchimerism in Japanese children with type 1 diabetes, as well as its effect on phenotypic variation. METHODS: We studied 153 Japanese children with type 1 diabetes, including 124 children positive for ß-cell autoantibodies, and their 71 unaffected siblings. The number of circulating microchimeric cells per 105 host cells was estimated by the use of quantitative-polymerase chain reaction targeting non-transmitted maternal human leukocyte antigen alleles. The results were compared to previous data from white European people. Phenotypic comparison was performed between maternal microchimerism carriers and non-carriers with diabetes. RESULTS: Maternal microchimerism was detected in 15% of children with autoantibody-positive type 1 diabetes, 28% of children with autoantibody-negative type 1 diabetes, and 16% of unaffected siblings. There were no differences in the prevalence or levels of maternal microchimerism among the three groups or between the children with type 1 diabetes and their unaffected siblings. Furthermore, maternal microchimerism carriers and non-carriers exhibited similar phenotypes. CONCLUSIONS: Maternal microchimerism appears to be less common in Japanese children with type 1 diabetes than in white European people. Our data indicate that maternal microchimerism is unlikely to be a major trigger or a phenotypic determinant of type 1 diabetes in Japanese children and that the biological significance of maternal microchimerism in type 1 diabetes may differ among ethnic groups.

Estimation of glycaemic control in the past month using ratio of glycated albumin to HbA1c.

AIMS: To evaluate comprehensively the use of the glycated albumin to HbA1c ratio for estimation of glycaemic control in the previous month. METHODS: A total of 306 children with Type 1 diabetes mellitus underwent ≥10 simultaneous measurements of glycated albumin and HbA1c . Correlation and concordance rates were examined between HbA1c measurements taken 1 month apart (ΔHbA1c ) and glycated albumin/HbA1c ratio fluctuations were calculated as Z-scores from the cohort value at enrolment of this study cohort (method A) or the percent difference from the individual mean over time (method B). RESULTS: Fluctuations in glycated albumin/HbA1c ratio (using both methods) were weakly but significantly correlated with ΔHbA1c , whereas concordance rates were significant for glycaemic deterioration but not for glycaemic improvement. Concordance rates were higher using method B than method A. CONCLUSIONS: The glycated albumin/HbA1c ratio was able to estimate glycaemic deterioration in the previous month, while estimation of glycaemic improvement in the preceding month was limited. Because method B provided a better estimate of recent glycaemic control than method A, the individual mean of several measurements of the glycated albumin/HbA1c ratio over time may also identify individuals with high or low haemoglobin glycation phenotypes in a given population, such as Japanese children with Type 1 diabetes, thereby allowing more effective diabetes management.

Protein-altering variants of PTPN2 in childhood-onset Type 1A diabetes.

AIM: To examine the contribution of PTPN2 coding variants to the risk of childhood-onset Type 1A diabetes. METHODS: PTPN2 mutation analysis was carried out for 169 unrelated Japanese people with childhood-onset Type 1A diabetes. We searched for coding variants that were absent or extremely rare in the general population and were scored as damaging by multiple in silico programs. We performed mRNA analysis and three-dimensional structural prediction of the detected variants, when possible. We also examined possible physical links between these variants and previously reported risk SNPs as well as clinical information from variant-positive children. RESULTS: One frameshift variant (p.Q286Yfs*24) and two probably damaging missense substitutions (p.C232W and p.R350Q) were identified in one child each. Of these, p.Q286Yfs*24 and p.C232W were hitherto unreported, while p.R350Q accounted for 2/121,122 alleles of the exome datasets. The p.Q286Yfs*24 variant did not encode stable mRNA, and p.C232W appeared to affect the structure of the tyrosine-protein phosphatase domain. The three variants were physically unrelated to known risk SNPs. The variant-positive children manifested Type 1A diabetes without additional clinical features and invariably carried risk human leukocyte antigen alleles. CONCLUSIONS: The results provide the first indication that PTPN2 variants contribute to the risk of Type 1A diabetes, independently of known risk SNPs. PTPN2 coding variants possibly induce non-specific Type 1A diabetes phenotypes in individuals with human leukocyte antigen-mediated disease susceptibility. Our findings warrant further validation.

Heritability estimates of endurance-related phenotypes: A systematic review and meta-analysis.

The aim of this study was to clarify heritability estimates for endurance-related phenotypes and the underlying factors affecting these estimates. A systematic literature search was conducted for studies reporting heritability estimates of endurance-related phenotypes using the PubMed database (up to 30 September 2016). Studies that estimated the heritability of maximal oxygen uptake (V˙O2max), submaximal endurance phenotypes, and endurance performance were selected. The weighted mean heritability for endurance-related phenotypes was calculated using a random-effects model. A total of 15 studies were selected via a systematic review. Meta-analysis revealed that the weighted means of the heritability of V˙O2max absolute values and those adjusted for body weight and for fat-free mass were 0.68 (95% CI: 0.59-0.77), 0.56 (95% CI: 0.47-0.65), and 0.44 (95% CI: 0.13-0.75), respectively. There was a significant difference in the weighted means of the heritability of V˙O2max across these different adjustment methods (P < .05). Moreover, there was evidence of statistical heterogeneity in the heritability estimates among studies. Meta-regression analysis revealed that sex could partially explain the heterogeneity in the V˙O2max heritability estimates adjusted by body weight. For submaximal endurance phenotypes and endurance performance, the weighted mean heritabilities were 0.49 (95% CI: 0.33-0.65) and 0.53 (95% CI: 0.27-0.78), respectively. There was statistically significant heterogeneity in the heritability estimates reported among the studies, and we could not identify the specific factors explaining the heterogeneity. Although existing studies indicate that genetic factors account for 44%-68% of the variability in endurance-related phenotypes, further studies are necessary to clarify these values.

FUT2 non-secretor status is associated with Type 1 diabetes susceptibility in Japanese children.

AIM: To examine the contribution of the FUT2 gene and ABO blood type to the development of Type 1 diabetes in Japanese children. METHODS: We analysed FUT2 variants and ABO genotypes in a total of 531 Japanese children diagnosed with Type 1 diabetes and 448 control subjects. The possible association of FUT2 variants and ABO genotypes with the onset of Type 1 diabetes was statistically examined. RESULTS: The se2 genotype (c.385A>T) of the FUT2 gene was found to confer susceptibility to Type 1A diabetes in a recessive effects model [odds ratio for se2/se2, 1.68 (95% CI 1.20-2.35); corrected P value = 0.0075]. CONCLUSIONS: The FUT2 gene contributed to the development of Type 1 diabetes in the present cohort of Japanese children.

Heritability estimates of muscle strength-related phenotypes: A systematic review and meta-analysis.

The purpose of this study was to clarify the heritability estimates of human muscle strength-related phenotypes (H2 -msp). A systematic literature search was conducted using PubMed (through August 22, 2016). Studies reporting the H2 -msp for healthy subjects in a sedentary state were included. Random-effects models were used to calculate the weighted mean heritability estimates. Moreover, subgroup analyses were performed based on phenotypic categories (eg, grip strength, isotonic strength, jumping ability). Sensitivity analyses were also conducted to investigate potential sources of heterogeneity of H2 -msp, which included age and sex. Twenty-four articles including 58 measurements were included in the meta-analysis. The weighted mean H2 -msp for all 58 measurements was 0.52 (95% confidence intervals [CI]: 0.48-0.56), with high heterogeneity (I2 =91.0%, P<.001). Subgroup analysis showed that the heritability of isometric grip strength, other isometric strength, isotonic strength, isokinetic strength, jumping ability, and other power measurements was 0.56 (95% CI: 0.46-0.67), 0.49 (0.47-0.52), 0.49 (0.32-0.67), 0.49 (0.37-0.61), 0.55 (0.45-0.65), and 0.51 (0.31-0.70), respectively. The H2 -msp decreased with age (P<.05). In conclusion, our results indicate that the influence of genetic and environmental factors on muscle strength-related phenotypes is comparable. Moreover, the role of environmental factors increased with age. These findings may contribute toward an understanding of muscle strength-related phenotypes.

The Association Between MCT1 T1470A Polymorphism and Power-Oriented Athletic Performance.

The purpose of this study was to investigate the effects of the MCT1 T1470A polymorphism (rs1049434) on power-oriented performance and lactate concentration during or after cycling sprints in Japanese wrestlers. Participants (199 wrestlers and 649 controls) were genotyped for the MCT1 T1470A genotype (rs1049434) using the TaqMan® Assay. All wrestlers were international (n=77) or national (n=122) level athletes. Among them, 46 wrestlers performed 2 anaerobic performance tests, a 30-s Wingate Anaerobic test (WAnT) and a series of 10 maximal effort 10-s sprints on a cycle ergometer. Blood lactate levels were measured before, during, and after the tests. In the A-allele recessive model (AA vs. TA+TT), the frequency of the AA genotype was significantly higher in all wrestlers than in controls (p=0.037). Wrestlers with AA genotype had lower blood lactate concentrations than those with TA+TT genotype at 10 min after the WAnT and following the 5th and the final set of repeated cycling sprints (p<0.05). The AA genotype of the MCT1 T1470A polymorphism is over-represented in wrestlers compared with controls and is associated with lower blood lactate concentrations after 30-s WAnT and during intermittent sprint tests in Japanese wrestlers.

Variants associated with autoimmune Type 1 diabetes in Japanese children: implications for age-specific effects of cis-regulatory haplotypes at 17q12-q21.

AIMS: The aim of this study was to clarify the significance of previously reported susceptibility variants in the development of autoimmune Type 1 diabetes in non-white children. Tested variants included rs2290400, which has been linked to Type 1 diabetes only in one study on white people. Haplotypes at 17q12-q21 encompassing rs2290400 are known to determine the susceptibility of early-onset asthma by affecting the expression of flanking genes. METHODS: We genotyped 63 variants in 428 Japanese people with childhood-onset autoimmune Type 1 diabetes and 457 individuals without diabetes. Possible association between variants and age at diabetes onset was examined using age-specific quantitative trait locus analysis and ordered-subset regression analysis. RESULTS: Ten variants, including rs2290400 in GSDMB, were more frequent among the people with Type 1 diabetes than those without diabetes. Of these, rs689 in INS and rs231775 in CTLA4 yielded particularly high odds ratios of 5.58 (corrected P value 0.001; 95% CI 2.15-14.47) and 1.64 (corrected P value 5.3 × 10-5 ; 95% CI 1.34-2.01), respectively. Age-specific effects on diabetes susceptibility were suggested for rs2290400; heterozygosity of the risk alleles was associated with relatively early onset of diabetes, and the allele was linked to the phenotype exclusively in the subgroup of age at onset ≤ 5.0 years. CONCLUSIONS: The results indicate that rs2290400 in GSDMB and polymorphisms in INS and CTLA4 are associated with the risk of Type 1 diabetes in Japanese children. Importantly, cis-regulatory haplotypes at 17q12-q21 encompassing rs2290400 probably determine the risk of autoimmune Type 1 diabetes predominantly in early childhood.

Blockade of cysteinyl leukotriene-1 receptors suppresses airway remodelling in mice overexpressing GATA-3.

BACKGROUND: We demonstrated previously that GATA-3 overexpression markedly enhanced allergen-induced airway inflammation and airway remodelling, including subepithelial fibrosis, and smooth muscle cell hyperplasia, in transgenic mice. OBJECTIVE: Because cysteinyl leukotrienes (cysLTs) have been shown to be involved in such structural changes, the effects of a specific cysLT1 receptor antagonist, montelukast, were evaluated in a mouse model of chronic asthma. METHODS: GATA-3-overexpressing mice and wild-type Balb/c mice were sensitized and repeatedly challenged by ovalbumin (OVA) or saline. The effects of montelukast on the development of airway remodelling were compared between the two mouse genotypes. RESULTS: CysLTs in the lung were increased after repeated allergen challenges, and significantly enhanced in GATA-3-overexpressing mice. The enhanced cysLT levels were accompanied by the development of eosinophilia, smooth muscle cell hyperplasia, and increased stromal cell-derived factor-1 gene expression with a small increase in pro-collagen gene expression in OVA-challenged GATA-3-overexpressing mice, but not in wild-type mice. Montelukast significantly decreased lung cysLT levels and inhibited the GATA-3-overexpression-related airway remodelling, potently preventing smooth muscle cell hyperplasia, but partially suppressed the increased pro-collagen gene expression and eosinophilic inflammation. Increases in the levels of IL-4, IL-5, IL-13, and eotaxin in bronchial lavage and TGF-ß gene expression in the lungs were induced by OVA in both mouse genotypes. Montelukast treatment also significantly reduced these levels to the levels seen after saline challenges in GATA-3-overexpressing mice. CONCLUSION: Montelukast efficaciously prevented airway inflammation and remodelling in a GATA-3-overexpression antigen challenge mouse model by decreasing the cysLT-driven Th2 cytokine cycle of amplification of airway pathologies.

Thermally induced switching field distribution of a single CoPt dot in a large array.

Magnetic dot arrays with perpendicular magnetic anisotropy were fabricated by patterning Co(80)Pt(20)-alloy continuous films by means of laser interference lithography. As commonly seen in large dot arrays, there is a large difference in the switching field between dots. Here we investigate the origin of this large switching field distribution, by using the anomalous Hall effect (AHE). The high sensitivity of the AHE permits us to measure the magnetic reversal of individual dots in an array of 80 dots with a diameter of 180 nm. By taking 1000 hysteresis loops we reveal the thermally induced switching field distribution SFD(T) of individual dots inside the array. The SFD(T) of the first and last switching dots were fitted to an Arrhenius model, and a clear difference in switching volume and magnetic anisotropy was observed between dots switching at low and high fields.

Increase in body mass index category since age 20 years and all-cause mortality: a prospective cohort study (the Ohsaki Study).

BACKGROUND: It is still unclear whether weight gain from early to late adulthood affects longevity. Furthermore, no study has addressed its association with all-cause and cause-specific mortality in an Asian population. METHODS: We prospectively assessed the association between an increase in body mass index (BMI) category since age 20 years and risk of all-cause, cardiovascular disease (CVD) and cancer mortality. Self-reported information pertaining to BMI was collected from 38 080 Japanese men and women aged 40-79 years at study entry in 1994 after exclusion of participants with a BMI of <18.5 kg/m(2) at age 20 years or at study entry. We defined six patterns of increase in BMI category at age 20 years and study entry: stable normal, overweight and obese, normal to overweight or obese, and overweight to obese. RESULTS: During 7 years of follow-up, 2617 participants died. After adjustment for potential confounders, we observed a significantly increased risk of all-cause mortality for the pattern of normal weight at age 20 years and obese at study entry and of stable obese compared with stable normal in BMI category, the multivariate HRs (95% confidence interval (CI)) being 1.42 (1.08-1.88) and 2.26 (1.45-3.51), respectively. For the pattern of overweight at age 20 years and obese at study entry, the multivariate hazard ratio (95% CI) was 1.35 (0.92-1.98). In contrast, we did not observe an increased risk of all-cause mortality for normal weight at age 20 years and overweight at study entry, and stable overweight. For CVD and cancer mortality, these results were consistently observed. CONCLUSION: We observed an increased risk of all-cause mortality both among participants who had been persistently obese since early adulthood and participants who showed an increase in BMI category from normal to obese, compared with participants with a stable normal BMI category.

Magnetic anisotropy of epitaxially grown Co and its alloy thin films.

We have performed a systematic study on the correlation between magnetic anisotropy energy (MAE) and crystal structures, such as lattice parameters, stacking fault densities, lattice strain, and so on, for epitaxially grown Co, Co-Pt, and Co-Pd alloy thin films, and have found that the MAE strongly depends on the axial ratio c/a of the hcp crystal lattice. As the c/a of hcp Co decreases down to ∼1.61 which is smaller than 1.622 for bulk Co, the MAE becomes significantly enhanced up to ∼10(6) J m(-3). Similar trends have also been verified for hcp Co-Pt and -Pd. These results, which are qualitatively consistent with the classic single-ion anisotropy model and the recent first principles calculation, suggest a new effective way to control the MAE of magnetic thin films.

u-SHARE: web-based decision support/risk communication tool for healthcare consumers with unruptured intracranial aneurysms.

PURPOSE: Clinical management for unruptured intracranial aneurysms (UIA) is controversial and requires professional knowledge which is the main reason that patients have difficulty in making decisions. The purpose of this study is to develop a tool that aids healthcare consumers in making optimal shared decisions with decision analysis. METHODS: The decision model and relevant data were derived from published literature. A web-based decision analytic tool was designed to provide a systematic guide for patients to understand favorable treatment options, intrinsic uncertainty, and critical factors for decision making. Twenty-nine testers evaluated content appropriateness, usability and clinical usefulness of the tool. RESULTS: The decision analytic tool has been successfully implemented and evaluated. Testers generally judged the web-based decision analytic tool as functional and useful. Acceptance rate for decision analysis was higher in nonhealthcare professionals than health care professionals. CONCLUSIONS: Our decision analytic tool was well accepted especially by healthcare consumers. The tool enables UIA patients to enhance their knowledge and understanding toward optimal shared decision making and can be an alternative "structured informed consent tool".