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An efficient one-pot approach for the synthesis of diaryl sulfoxides and diaryl sulfones using aryl thiols and aryl diazonium salts was developed. The use of a visible-light-driven silver catalysis and the subsequent singlet-oxygen-induced oxidation enabled selective synthesis of sulfoxides and sulfones in the absence of a photocatalyst. The reactions were carried out under mild reaction conditions; the desired products were obtained under air atmosphere at room temperature.

This corrects the article DOI: 10.1038/sdata.2017.179.

Background: Given that YKL-40 is a known marker of inflammation, we sought to determine its association with urinary tract infection (UTI) in febrile children., Methods: In total, 44 children aged 0 to 24 months with febrile UTI and 35 age- and sex-matched controls with fever from other causes were enrolled in the study. ELISA was performed to determine the level of YKL-40 in urine collected from each child., Results: The ratio of urinary YKL-40 to creatinine (Cr) was higher in the children with a UTI than in the controls (P<0.001). The area under the ROC curve for detecting UTI was 0.88 for the urinary YKL-40/Cr ratio, 0.86 for pyuria, and 0.71 for positive nitrite on urinalysis. We applied a cut-off value of 125.23 pg/mg to urinary YKL-40/Cr for detecting UTI. Eight of nine children in the control group with pyuria had urinary YKL-40/Cr levels lower than 125.23 pg/mg, and the one child in the UTI group without pyuria or positive nitrite had a urinary YKL-40/Cr level greater than 125.23 pg/mg., Conclusions: Determining the levels of urinary YKL-40/Cr may help identify true cases of UTI in febrile young children, especially when they have pyuria but not nitrite, or have neither pyuria nor nitrite in the urine., Competing Interests: The authors declare that they have no conflict of interest., (© The Korean Society for Laboratory Medicine)

The purpose of this study was to evaluate the effect of a forest environment on salivary cortisol concentration, particularly on the characteristics of its distribution. The participants were 348 young male subjects. The experimental sites were 34 forests and 34 urban areas across Japan. The subjects viewed the landscape (forest or urban environment) for a period of 15 min while sitting in a chair. Saliva was sampled from the participants at the end of this 15-min period and then analyzed for cortisol concentration. Differences in the skewness and kurtosis of the distributions between the two environments were tested by performing a permutation test. The cortisol concentrations exhibited larger skewness (0.76) and kurtosis (3.23) in a forest environment than in an urban environment (skewness = 0.49; kurtosis = 2.47), and these differences were statistically significant. The cortisol distribution exhibited a more peaked and longer right-tailed curve in a forest environment than in an urban environment., Competing Interests: The authors declare no conflict of interest.

To mitigate the negative effects of modern cities on health, scientists are focusing on the diverse benefits of natural environments; a conceptual approach to use gardens for promoting human health is being attempted. In this study, the effects of the visual landscape of a traditional garden on psychological and physiological activities were investigated. Eighteen male and female adults participated in this indoor experiment (mean age, 26.7 years). Twelve different landscape images for city and garden were presented continuously for 90 s. In the time series changes of oxygenated hemoglobin (O₂Hb), different patterns of changes were observed between the city and garden. The mean O₂Hb values increased for the city landscapes, whereas they decreased for the garden landscapes both in the left and right prefrontal cortices. Significant differences in the negative psychological states of tension, fatigue, confusion, and anxiety were observed between the city and garden landscapes. Important differences in the physiological and psychological responses to the two different landscapes were also detected between male and female participants, providing valuable clues to individual differences in the health benefits of natural landscapes. To validate the use of gardens as a resource for promoting health in urban dwellers, further scientific evidence, active communication, and collaboration among experts in the relevant field are necessary., Competing Interests: The author declares no conflict of interest.

Differential methylations of the HIF3A (hypoxia-inducible factor 3a) gene have been linked to body mass index (BMI). To explore the association of these methylations to childhood obesity, we measured 5 CpG methylation sites (cg27146050, cg46801562, cg22891070, cg16672562 and cg46801675) in intron 1 of the HIF3A gene by pyrosequencing, in the Korean population (mean age: 13.9 yrs, 305 obese cases and 387 controls). Two CpG methylations, cg46801562 and cg16672562, had statistically significant association with childhood obesity ( P = 2.09E-9 and 1.66E-7, respectively). Notably, in the case of cg16672562, all correlations were significantly positive with BMI ( beta = 0.285, P = 1.652E-13), waist-hip ratio ( beta = 0.0028, P = 1.42E-15) and fasting plasma glucose level ( beta = 0.0645, P = 2.61E-4), when analyzed by linear regression, with age and sex as covariates. We investigated any genetic effect of cg16672562 methylation by using 14 single nucleotide polymorphisms (SNP) identified by exome sequencing of the HIF3A locus cg16672562 methylation showed no statistically significant changes due to the 14 polymorphisms. In this study, we show that cg16672562 is the most significant blood DNA methylation marker for childhood obesity in the Korean population, and might be independent of any underlying HIF3A genetic background., Competing Interests: CONFLICTS OF INTEREST These authors declare no conflicts of interest.

Background: Severe bronchopulmonary dysplasia often leads to prolonged mechanical ventilation lasting several months. Cyanotic episodes frequently occur in these patients, necessitating long-term sedation and/or intermittent muscle paralysis. Neurally adjusted ventilatory assist (NAVA) might provide precisely the amount of support that these patients need without sedation., Methods: We reviewed the medical records of preterm infants who underwent tracheostomy and required mechanical ventilation for >6 months during a period of 6 years. We compared two groups of patients: those supported with NAVA for ≥2 months versus those supported by pneumatically triggered assist methods. We also evaluated any change after NAVA use in the NAVA group., Results: Among 14 prematurely born patients who received prolonged ventilation, nine were supported with NAVA and five were supported using other ventilator modes. Duration of continuous sedation was significantly shorter and the bolus use of sedatives was also significantly lower in the NAVA group than in the pneumatically triggered assist group. In addition, the NAVA group received a lower dose of dexamethasone than the pneumatically triggered assist group. Compared with before NAVA, the frequency of cyanotic episodes and of the bolus sedatives was significantly decreased after implementation of NAVA., Conclusions: For infants on prolonged mechanical ventilation, NAVA could reduce cyanotic episodes and the need for sedatives and dexamethasone. NAVA may be superior to pneumatically triggered modes in terms of the minimization of patient-ventilator dyssynchrony while delivering appropriate respiratory support in premature infants with tracheostomy., (© 2017 Japan Pediatric Society.)

To what extent the risks of neonatal morbidities are directly related to premature birth or to biological mechanisms of preterm birth remains uncertain. We aimed to examine the effect of exposure to amniotic fluid (AF) infection and elevated cytokine levels on the mortality and pulmonary, intestinal, and neurologic outcomes of preterm infants, and whether these associations persist after adjustment for gestational age at birth. This retrospective cohort study included 152 premature singleton infants who were born at ≤ 32 weeks. AF obtained by amniocentesis was cultured; and interleukin-6 (IL-6) and IL-8 levels in AF were determined. The primary outcome was adverse perinatal outcome defined as the presence of one or more of the followings: stillbirth, neonatal death, bronchopulmonary dysplasia, necrotizing enterocolitis, intraventricular hemorrhage, and periventricular leukomalacia. Logistic regression analysis was adjusted for gestational age at birth and other potential confounders. In bivariate analyses, elevated AF IL-6 and IL-8 levels were significantly associated with adverse perinatal outcome. These results were not changed after adjusting for potential confounders, such as low Apgar scores, mechanical ventilation, and surfactant application. However, the independent effect of elevated cytokine levels in AF disappeared when additionally adjusted for low gestational age at birth; consequently, low gestational age remained strongly associated with the risk of adverse perinatal outcome. In conclusion, elevated levels of pro-inflammatory cytokines in AF are associated with increased risk of adverse perinatal outcomes, but this risk is not independent of low gestational age at birth. Culture-proven AF infection is not associated with this risk., Competing Interests: The authors have no potential conflicts of interest to disclose.

Brain MRI atlases may be used to characterize brain structural changes across the life course. Atlases have important applications in research, e.g., as registration and segmentation targets to underpin image analysis in population imaging studies, and potentially in future in clinical practice, e.g., as templates for identifying brain structural changes out with normal limits, and increasingly for use in surgical planning. However, there are several caveats and limitations which must be considered before successfully applying brain MRI atlases to research and clinical problems. For example, the influential Talairach and Tournoux atlas was derived from a single fixed cadaveric brain from an elderly female with limited clinical information, yet is the basis of many modern atlases and is often used to report locations of functional activation. We systematically review currently available whole brain structural MRI atlases with particular reference to the implications for population imaging through to emerging clinical practice. We found 66 whole brain structural MRI atlases world-wide. The vast majority were based on T1, T2, and/or proton density (PD) structural sequences, had been derived using parametric statistics (inappropriate for brain volume distributions), had limited supporting clinical or cognitive data, and included few younger (>5 and <18 years) or older (>60 years) subjects. To successfully characterize brain structural features and their changes across different stages of life, we conclude that whole brain structural MRI atlases should include: more subjects at the upper and lower extremes of age; additional structural sequences, including fluid attenuation inversion recovery (FLAIR) and T2 * sequences; a range of appropriate statistics, e.g., rank-based or non-parametric; and detailed cognitive and clinical profiles of the included subjects in order to increase the relevance and utility of these atlases.

Motivation: Recently, many methods have been developed for conducting rare-variant association studies for sequencing data. These methods have primarily been based on gene-level associations but have not been proven to be as effective as expected. Gene-set-level tests have shown great advantages over gene-level tests in terms of power and robustness, because complex diseases are often caused by multiple genes that comprise of biological gene sets., Results: Here, we propose several novel gene-set tests that employ rapid and efficient dimensionality reduction. The performance of these tests was investigated using extensive simulations and application to 1058 whole-exome sequences from a Korean population. We identified some known pathways and novel pathways whose rare or common variants are associated with elevated liver enzymes and replicated the results in an independent cohort., Availability and Implementation: Source R code for our algorithm is freely available at http://statgen.snu.ac.kr/software/QTest, Contact: tspark@stats.snu.ac.kr, Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Rare variants have gathered increasing attention as a possible alternative source of missing heritability. Since next generation sequencing technology is not yet cost-effective for large-scale genomic studies, a widely used alternative approach is imputation. However, the imputation approach may be limited by the low accuracy of the imputed rare variants. To improve imputation accuracy of rare variants, various approaches have been suggested, including increasing the sample size of the reference panel, using sequencing data from study-specific samples (i.e., specific populations), and using local reference panels by genotyping or sequencing a subset of study samples. While these approaches mainly utilize reference panels, imputation accuracy of rare variants can also be increased by using exome chips containing rare variants. The exome chip contains 250 K rare variants selected from the discovered variants of about 12,000 sequenced samples. If exome chip data are available for previously genotyped samples, the combined approach using a genotype panel of merged data, including exome chips and SNP chips, should increase the imputation accuracy of rare variants., Results: In this study, we describe a combined imputation which uses both exome chip and SNP chip data simultaneously as a genotype panel. The effectiveness and performance of the combined approach was demonstrated using a reference panel of 848 samples constructed using exome sequencing data from the T2D-GENES consortium and 5,349 sample genotype panels consisting of an exome chip and SNP chip. As a result, the combined approach increased imputation quality up to 11 %, and genomic coverage for rare variants up to 117.7 % (MAF < 1 %), compared to imputation using the SNP chip alone. Also, we investigated the systematic effect of reference panels on imputation quality using five reference panels and three genotype panels. The best performing approach was the combination of the study specific reference panel and the genotype panel of combined data., Conclusions: Our study demonstrates that combined datasets, including SNP chips and exome chips, enhances both the imputation quality and genomic coverage of rare variants.

Human height is associated with risk of multiple diseases and is profoundly determined by an individual's genetic makeup and shows a high degree of ethnic heterogeneity. Large-scale genome-wide association (GWA) analyses of adult height in Europeans have identified nearly 180 genetic loci. A recent study showed high replicability of results from Europeans-based GWA studies in Asians; however, population-specific loci may exist due to distinct linkage disequilibrium patterns. We carried out a GWA meta-analysis in 93 926 individuals from East Asia. We identified 98 loci, including 17 novel and 81 previously reported loci, associated with height at P < 5 × 10(-8), together explaining 8.89% of phenotypic variance. Among the newly identified variants, 10 are commonly distributed (minor allele frequency, MAF > 5%) in Europeans, with comparable frequencies with in Asians, and 7 single-nucleotide polymorphisms are with low frequency (MAF < 5%) in Europeans. In addition, our data suggest that novel biological pathway such as the protein tyrosine phosphatase family is involved in regulation of height. The findings from this study considerably expand our knowledge of the genetic architecture of human height in Asians., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To provide scientific evidence of the physiological and psychological effects of forest and urban environments on 47 young male adults undergoing stay-in forest therapy., Methods: Field experiments were conducted at four sites in Japan. At each site, 12 subjects participated in the experiment. The experiments were conducted in forest and urban environments, and the subjects' physiological and psychological responses to these environments were compared. On the first day, six subjects were sent to a forest area, and the other six were sent to an urban area as controls. The groups were switched the next day. Heart rate variability and heart rate were measured to assess physiological responses. The semantic differential method for assessing emotions, the reports of "refreshed" feeling, and the Profile of Mood States (POMS) were used to assess psychological responses. The physiological and psychological responses of each subject were recorded during and after walking, and the differences in indices were compared between the two environments., Results: The forest environment was associated with a higher parasympathetic nervous activity, a lower sympathetic nervous activity, and a lower heart rate than the urban environment. The subjective evaluation scores were generally in accordance with the physiological reactions and were significantly higher in the forest environment than in the urban environment. POMS measurements showed that the forest environment was psychologically relaxing and enhanced psychological vigor., Conclusions: This study provided clear scientific evidence of the physiological effects of forest therapy. The results will contribute to the development of forest therapy research and support the inclusion of forest therapy in preventive medicine.

PET/CT system reduces the scanning time and provides an anatomical image because it realizes a CT-based attenuation corrected image without using an isotope, such as 68 Ge or 137Cs, in the attenuation correcting method due to the recent technological development. On the other hand, artifacts are generated in a CT image by dental materials, which affect the attenuation corrected PET image. Against this backdrop, this study performed a clinical experiment and a phantom experiment. The clinical experiment targeted 40 patients without oral disease, including 20 patients who had metal prosthesis in their tooth and 20 patients who had a dental implant in tooth. In the phantom experiment, a dental cast was used for a PET/CT scan after the metal prosthesis and the dental implant was inserted in the original dental phantom to make a dental cast. According to the study results, when the patients had metal prosthesis, standard uptake value (SUV) decreased by approximately 19.6% in the dark streak artifact region and increased by approximately 90.1% in the bright streak artifact region, compared with the artifact free region. In the phantom with metal prosthesis, the SUV decreased by approximately 18.1% in the dark streak artifact region and increased by 18.0% in the bright streak artifact region, compared to the artifact free region. When the patients with dental implant, the SUV decreased by approximately 19.1% in the dark streak artifact region and increased by 96.6% in the bright streak artifact region, compared with the artifact free region. In the phantom with dental implant, the SUV decreased by approximately 14.4% in the dark streak artifact region and increased by 7.0% in the bright streak artifact region, compared to the artifact free region. Therefore, by considering these results, we can improve the diagnostic accuracy in oral and maxillofacial cancer.

Five million years has passed since a subset of primates recognizably became human. Because we have already spent more than 99.99% of our evolutionary history in natural environments, it is thought that we are essentially adaptive to nature. However, we live in a society characterized by urbanization and artificiality, despite our physiological functions still being adapted to nature. We conducted experiments involving 420 subjects at 35 different forests throughout Japan. As a result, these subjects sitting in natural surroundings showed decreases in the following physiological indices compared with the urban control group: 12.4% decrease in cortisol level, 7.0% decrease in sympathetic nervous activity, 1.4% decrease in systolic blood pressure, and 5.8% decrease in heart rate. This shows that stressful states can be relieved by forest therapy. It should also be noted that parasympathetic nerve activity increased by 55.0%, indicating a relaxed state. The results of walking experiments were also similar. Li et al. demonstrated that immune functions are enhanced by forest therapy. Middle-aged employees volunteered to participate in these experiments. NK (natural killer cells) activity, as an indicator of immune function, increased by 56% on the second day and returned to normal levels. A significant increase of 23% was maintained for 1 month even after these subjects returned to urban life, clearly illustrating the preventive medical effects of nature therapy. We expect nature therapy to play an increasingly important role in preventive medicine in the future.

Objectives: In the present study, we aimed to clarify the psychological effects of shinrin-yoku (taking in the atmosphere of the forest) by conducting field experiments., Methods: The experiments were conducted in 19 forested and urban areas in Japan during the 2007-2010 period. Twelve male students participated at each of the 19 areas (a total of 228 persons). Subjective ratings of "comfortable-uncomfortable", "soothing-stimulating", and "natural-artificial" feelings were conducted after each of the participants had viewed the scenery for 15 min in the forested and urban areas. A postviewing questionnaire on "stressed-refreshed" feelings was also administered and the Profile of Mood State (POMS) questionnaire was employed to assess six aspects of mood before and after viewing the sceneries., Results: The forest environments were perceived as significantly more "comfortable", "soothing", and "natural" than the urban environments after viewing the sceneries. The score for "refreshed feeling" was also significantly higher in the forested areas. The score for the "vigor" subscale of POMS was significantly higher after viewing the scenery in the forested areas, whereas the scores for negative feelings such as "tension-anxiety", "depression-dejection", "anger-hostility", "fatigue", and "confusion" significantly decreased., Conclusion: Collectively, these results suggest that the forest environments have significant beneficial and relaxing effects on human's moods compared with the urban environments.

Objective: To provide scientific evidence of the health benefits of forest therapy in terms of physiological indices., Design: Within-group comparison made by conducting field experiments., Participants: Forty-eight young male adults., Methods: Field experiments were conducted at four local sites in Japan. At each site, 12 adults participated in a three-day experiment. To compare physiological reactions between two environmental stimuli, experiments were conducted in forest and urban environments. The participants were randomly assigned to visit either the forest or an urban setting and were instructed to view the landscape in a seated position. The physiological reactions of each participant were recorded before, during, and after viewing the stimuli, and the differences in physiological indices were compared between the two groups., Results: Physiological data revealed that participants demonstrated significantly different reactions in the forest and urban environments. Analysis of heart rate revealed that participants showed a significantly higher ln(HF) and a lower ln(LF/HF) in the forest environment than in the urban environment. Systolic and diastolic blood pressures, pulse rate, and salivary cortisol concentration significantly decreased in the forest environment compared with the urban environment. Subjective evaluation data were generally in accordance with physiological reactions, showing significantly higher scores for "comfortable, natural, soothed, and refreshed feelings" in the forest environment than in the urban environment., Conclusions: This study provided very clear scientific evidence of the physiological effects of forest therapy. Our data indicate that forest therapy can decrease stress and facilitate physiological relaxation.