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Blood pressure (BP) is a typical complex trait, and the genetic susceptibility of individuals to changes in BP induced by air pollution exposure is different. Although interactions of exposure to air pollutants with several candidate genes have been identified, genome-wide interaction studies (GWISs) are needed to understand the association between them with BP. Therefore, we aimed to discover the unique genetic loci for BP that interact with exposure to air pollutants in Korean adults. We ultimately included 1868 participants in the discovery step and classified them into groups of those with low-to-moderate exposure and high exposure to average annual concentration of particulate matter with an aerodynamic diameter ≤ 10 μm (PM 10 ). Because none of the single nucleotide polymorphisms (SNPs) achieved a genome-wide level of significance of p int  < 5 × 10 -8 for either systolic BP (SBP) or diastolic BP (DBP), we considered the top 10 ranking SNPs for each BP trait. To validate these suggestive SNPs, we finally selected six genetic variants for SBP and five variants for DBP, respectively. In a replication result for SBP, only one SNP (rs12914147) located in an intergenic region of the NR2F2 showed a significant interaction. We also identified several genetic susceptibility loci (e.g., CHST11, TEK, and ITGA1) implicated in candidate mechanisms such as inflammation and oxidative stress in the discovery step, although their interaction effects were not replicated. Our study reports the first GWIS finding to our knowledge, and the association between exposure to PM 10 and BP levels may be determined in part by several newly discovered genetic suggestive loci, including NR2F2., (© 2023. Springer Nature Limited.)

In studies evaluating the association between body mass index (BMI) and risk of tuberculosis (TB), the data for the underweight population has been limited and results were conflicting. Our study aimed to evaluate whether being underweight increases the risk of TB using a nationwide representative sample from the Republic of Korea. A large population-based cohort study of over ten million subjects who participated in the health screening in 2010 was performed using the Korean National Health Insurance database 2010-2017. We evaluated the incidence and risk of TB by BMI category (kg/m 2 ) for Asians using a multivariable Cox regression model, adjusting for age, sex, smoking, alcohol consumption, regular exercise, low-income state, and underlying hypertension, diabetes mellitus, and dyslipidemia. To evaluate the association between BMI and TB risk, the underweight population was further subdivided according to the degree of thinness. During 70,063,154.3 person-years of follow-up, 52,615 of 11,135,332 individuals developed active TB with an incidence of 0.75 per 1000 person-years. Overall, there was a log-linear inverse relationship between TB incidence and BMI, within the BMI range of 15-30 kg/m 2 (R 2  = 0.95). The estimated adjusted hazard ratio (HR) for incident TB in the underweight population (BMI < 18.5) was 2.08 (95% confidence intervals, CI 2.02-2.15), overweight (23 ≤ BMI < 25) was 0.56 (0.55-0.58) and obese (BMI ≥ 25) was 0.40 (0.39-0.41) relative to the normal weight population. Among the underweight population, TB risk increased as the degree of thinness increased (adjusted HR = 1.98, 1.91-2.05; 2.50, 2.33-2.68; and 2.83, 2.55-3.15, for mild, moderate and severe thinness, respectively) (p for trend < 0.001). We found a significant inverse relationship between BMI and TB incidence, which was especially profound in the underweight population. Public health strategies to screen TB more actively in the underweight population and improve their weight status may help reduce the burden of TB., (© 2022. The Author(s).)

Animals living in extreme environments, such as hydrothermal vents, would be expected to have evolved protective shells or exoskeletons to maintain homeostasis. The outer part of the exoskeleton of vent crabs (Austinograea sp.) in the Indian Ocean hydrothermal vent was one of the hardest (approximately 7 GPa) biological materials ever reported. To explore the exoskeletal characteristics of vent crabs which enable them to adapt to severe environments, a comparative analysis was conducted with the Asian paddle crab (Charybdis japonica) living in coastal areas. Nanoindentation, thermogravimetric analysis, scanning electron microscopy, energy dispersive x-ray analysis, and Raman spectroscopy were used to analyze the mechanical properties, thermal stability, structure, surface components, and the composition of compounds, respectively. Though both species have four-layered exoskeletons, the outermost layer of the vent crab, a nano-granular structure, was much thicker than that of the coastal crab. The proportions of aluminum and sulfur that constitute the epicuticle of the exoskeleton were higher in the vent crab than in the coastal crab. There was a lack of water or volatile substances, lots of CaCO 3 , and no carotenoid-based compounds in the exoskeleton of the vent crab. These might have improved the mechanical properties and thermal stability of the hydrothermal species., (© 2022. The Author(s).)

We aimed to examine whether metabolic syndrome (MetS) is associated with mobility in the older adults, using the timed up and go (TUG) test which is one of the most widely used tests for evaluating mobility. This is population-based study with the National Health Insurance Service-National Health Screening Cohort database of National Health Information Database. Participants included were those who completed the TUG as part of the National Screening Program for Transitional Ages. An abnormal TUG result was defined as a time ≥ 10 s. Multiple logistic regression models were used to assess the associations between MetS and TUG results. We constructed three models with different levels of adjustment. Furthermore, we conducted a stratified analysis according to the risk. Among the 40,767 participants included, 19,831 (48.6%) were women. Mean TUG value was 8.34 ± 3.07 s, and abnormal TUG test results were observed in 4,391 (10.8%) participants; 6,888 (16.9%) participants were categorised to have MetS. The worst TUG test results were obtained in participants with three or four MetS features, and a J-shaped relationship of each MetS feature, except triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-C), with TUG test was found. Participants with MetS had 18% higher likelihood of showing abnormal TUG test results in a fully adjusted model (adjusted odds ratio 1.183, 95% confidence interval 1.115-1.254). The stratified analysis revealed that participants with central obesity, high blood pressure, and normal HDL-C and TG were more likely to have abnormal TUG times. Participants with MetS had a higher risk of exhibiting abnormal TUG results, and except for HDL-C and TG, all other MetS features had a J-shaped relationship with TUG. Preventive lifestyle such as lower carbohydrate and higher protein intake, and endurance exercise is needed.

Leukapheresis is used for the mechanical removal of leukaemic cells in hyperleukocytosis. However, the effectiveness of leukapheresis remains unclear due to selection and confounding factors in the cohorts. We compared the effectiveness of leukapheresis among the subgroups according to either the 2016 World Health Organization classification or the number of cytogenetic abnormalities with a retrospective, single-centre study from January 2009 to December 2018. Acute myeloid leukaemia (AML, n = 212) and acute lymphoblastic leukaemia (ALL, n = 97) were included. The 30-day survival rates (95% confidence interval, 95% CI) for AML and ALL were 86.3% (81.6-90.9%) and 94.8% (90.3-99.2%), respectively. For AML, 'primary AML with myelodysplasia-related changes' and 'AML with biallelic mutation of CEBPA' showed better 30-day survival outcomes (P = 0.026) than the other subgroups. A higher platelet count after leukapheresis was associated with better 30-day survival in AML patients (P = 0.029). A decrease in blast percentage count after leukapheresis was associated with better 30-day survival in ALL patients (P = 0.034). Our study suggested that prophylactic platelet transfusion to raise the platelet count to 50 × 10 9 /L or greater might improve clinical outcome in AML patients undergoing leukapheresis.

Smoking is the number one risk factor for cancer mortality but only 15-20% of heavy smokers develop lung cancer. It would, therefore, be of great benefit to identify those at high risk early on so that preventative measures can be initiated. To investigate this, we evaluated the effects of smoking on inflammatory markers, innate and adaptive immune responses to bacterial and viral challenges and blood cell composition. We found that plasma samples from 30 heavy smokers (16 men and 14 women) had significantly higher CRP, fibrinogen, IL-6 and CEA levels than 36 non-smoking controls. Whole blood samples from smokers, incubated for 7 h at 37 °C in the absence of any exogenous stimuli, secreted significantly higher levels of IL-8 and a number of other cytokines/chemokines than non-smokers. When challenged for 7 h with E. coli, whole blood samples from smokers secreted significantly lower levels of many inflammatory cytokines/chemokines. However, when stimulated with HSV-1, significantly higher levels of both PGE 2 and many cytokines/chemokines were secreted from smokers' blood samples than from controls. In terms of blood cell composition, red blood cells, hematocrits, hemoglobin levels, MCV, MCH, MCHC, Pct and RDW levels were all elevated in smokers, in keeping with their compromised lung capacity. As well, total leukocytes were significantly higher, driven by increases in granulocytes and monocytes. In addition, smokers had lower NK cells and higher Tregs than controls, suggesting that smoking may reduce the ability to kill nascent tumor cells. Importantly, there was substantial person-to person variation amongst smokers with some showing markedly different values from controls and others showing normal levels of many parameters measured, indicating the former may be at significantly higher risk of developing lung cancer.

A novel wide-field electron arc technique with a scatterer is implemented for widespread Kaposi's sarcoma (KS) in the distal extremities. Monte Carlo beam modeling for electron arc beams was established to achieve <2% deviation from the measurements, and used for dose calculation. MC-based electron arc plan was performed using CT images of a foot and leg mimicking phantom and compared with in-vivo measurement data. We enrolled one patient with recurrent KS on the lower extremities who had been treated with photon radiation therapy. The 4- and 6-MeV electron arc plans were created, and then compared to two photon plans: two opposite photon beam and volumetric modulated arc with bolus. Compared to the two photon techniques, the electron arc plans resulted in superior dose saving to normal organs beneath the skin region, although it shows inferior coverage and homogeneity for PTV. The electron arc treatment technique with scatterer was successfully implemented for the treatment of widespread KS in the distal extremities with lower radiation exposure to the normal organs beyond the skin lesions, which could be a treatment option for recurrent skin cancer in the extremities.

Segmentation of normal organs is a critical and time-consuming process in radiotherapy. Auto-segmentation of abdominal organs has been made possible by the advent of the convolutional neural network. We utilized the U-Net, a 3D-patch-based convolutional neural network, and added graph-cut algorithm-based post-processing. The inputs were 3D-patch-based CT images consisting of 64 × 64 × 64 voxels designed to produce 3D multi-label semantic images representing the liver, stomach, duodenum, and right/left kidneys. The datasets for training, validating, and testing consisted of 80, 20, and 20 CT simulation scans, respectively. For accuracy assessment, the predicted structures were compared with those produced from the atlas-based method and inter-observer segmentation using the Dice similarity coefficient, Hausdorff distance, and mean surface distance. The efficiency was quantified by measuring the time elapsed for segmentation with or without automation using the U-Net. The U-Net-based auto-segmentation outperformed the atlas-based auto-segmentation in all abdominal structures, and showed comparable results to the inter-observer segmentations especially for liver and kidney. The average segmentation time without automation was 22.6 minutes, which was reduced to 7.1 minutes with automation using the U-Net. Our proposed auto-segmentation framework using the 3D-patch-based U-Net for abdominal multi-organs demonstrated potential clinical usefulness in terms of accuracy and time-efficiency.

This study aimed to investigate the association between adolescent overweight and obesity and PTC risk in adulthood. We conducted a case-control study in the Republic of Korea with 1,549 PTC patients and 15,490 controls individually matched for age and sex. We estimated body mass index (BMI) at age 18 years from self-reported weight at this age. Compared with BMI < 23.0 at age 18 years, BMI ≥ 25.0 at age 18 years was associated with higher PTC risk (odds ratio [OR] = 4.31, 95% confidence interval [CI]: 3.57, 5.22). The association between BMI ≥ 25.0 at age 18 years and PTC risk was stronger among men (OR = 6.65, 95% CI: 4.78, 9.27) than among women (OR = 3.49, 95% CI: 2.74, 4.43), and stronger among individuals with current BMI ≥ 25.0 (OR = 8.21, 95% CI: 6.34, 10.62) than among those with current BMI < 25.0 (OR = 2.21, 95% CI: 1.49, 3.27). Among PTC patients, BMI ≥ 25.0 at age 18 years was associated with extra-thyroidal extension and T stage ≥2, but not with N stage ≥1 or BRAF V600E mutation. Adolescent overweight and obesity was associated with higher risk of PTC in adulthood. Our results emphasise the importance of weight management in adolescence to decrease the PTC risk.

Acoustics is the primary means of sensing and communication in the ocean for humans and many marine animals. Natural fluctuations in the ocean, however, degrade these abilities in ways that have been previously difficult to forecast. Here, we address this issue by predicting sensing and communication degradation in terms of acoustic attenuation, dispersion and temporal decorrelation at typical operational ranges and frequencies in continental-shelf environments. This is done with analytic expressions derived from first physical principles. The analytic expressions provide the statistics of the acoustic field after forward propagating through an ocean waveguide containing 3-D random inhomogeneities from the independent or combined effects of rough sea-surfaces, near-sea-surface air bubbles and internal waves. The formulation also includes Doppler effects caused by the inhomogeneities' random horizontal motion, enabling modeling and prediction over a wide range of environments and frequencies. Theoretical predictions are confirmed with available acoustic measurements in several continental-shelf environments using standard oceanographic measurements for environmental support. We quantify how the acoustic signals decorrelate over timescales determined by the underlying temporal coherence of ocean dynamic processes. Surface gravity waves and near-sea-surface air bubbles decorrelate acoustic signals over seconds or less, whereas internal waves affect acoustic coherence at timescales of several to tens of minutes. Doppler spread caused by the inhomogeneities' motion further reduces acoustic temporal coherence, and becomes important at the high frequencies necessary for communication and fine-scale sensing. We also show that surface gravity waves and bubbles in high sea states can cause increasingly significant attenuation as frequency increases. The typical durations of marine mammal vocalizations that carry over great distances are found to be consistent with the coherence timescales quantified here and so avoid random distortion of signal information even by incoherent reception.

A deep-neural-network (DNN) was successfully used to predict clinically-acceptable dose distributions from organ contours for intensity-modulated radiotherapy (IMRT). To provide the next step in the DNN-based plan automation, we propose a DNN that directly generates beam fluence maps from the organ contours and volumetric dose distributions, without inverse planning. We collected 240 prostate IMRT plans and used to train a DNN using organ contours and dose distributions. After training was done, we made 45 synthetic plans (SPs) using the generated fluence-maps and compared them with clinical plans (CP) using various plan quality metrics including homogeneity and conformity indices for the target and dose constraints for organs at risk, including rectum, bladder, and bowel. The network was able to generate fluence maps with small errors. The qualities of the SPs were comparable to the corresponding CPs. The homogeneity index of the target was slightly worse in the SPs, but there was no difference in conformity index of the target, V 60Gy of rectum, the V 60Gy of bladder and the V 45Gy of bowel. The time taken for generating fluence maps and qualities of SPs demonstrated the proposed method will improve efficiency of the treatment planning and help maintain the quality of plans.

It has been reported that hypomagnetic fields (HMFs) have a negative influence on mammalian physiological functions. We previously reported that HMFs were detrimental to cell fate changes during reprogramming into pluripotency. These studies led us to investigate whether HMFs affect cell fate determination during direct differentiation. Here, we found that an HMF environment attenuates differentiation capacity and is detrimental to cell fate changes during the in vitro differentiation of embryonic stem cells (ESCs). Moreover, HMF conditions cause abnormal DNA methylation through the dysregulation of DNA methyltransferase3b (Dnmt3b) expression, eventually resulting in incomplete DNA methylation during differentiation. Taken together, these results suggest that an appropriate electromagnetic field (EMF) environment may be essential for favorable epigenetic remodeling during cell fate determination via differentiation.

This study aimed to evaluate hepatic toxicity after repeated stereotactic body radiation therapy (SBRT) for recurrent hepatocellular carcinoma (HCC) using deformable image registration (DIR). Between January 2007 and December 2015, 85 patients who underwent two sessions of SBRT for HCC treatment were retrospectively analyzed. A DIR technique was used to calculate the cumulative dose of the first and second SBRT to the normal liver by matching two computed tomography simulation images. The Dice similarity coefficient (DSC) index was calculated to evaluate DIR accuracy. Before the first and second SBRT, 6 (7.1%) and 12 (14.1%) patients were Child-Pugh class B, respectively. Median tumor size was 1.7 cm before both SBRT treatments. Mean DSC index value was 0.93, being >0.9 in 79 (92.9%) registrations. Median cumulative mean liver dose (MLD) was 9.3 Gy (interquartile range, 7.6-11.7). Radiation-induced liver disease developed in three patients, and two of them, with Child-Pugh class B, experienced irreversible liver function deterioration following the second SBRT. The DIR method provided reliable information regarding cumulative doses to the liver. In patients with Child-Pugh class A liver function, repeated SBRT for small recurrent HCC could be safely performed with acceptable hepatic toxicity.

The spin-torque driven dynamics of antiferromagnets with Dzyaloshinskii-Moriya interaction (DMI) were investigated based on the Landau-Lifshitz-Gilbert-Slonczewski equation with antiferromagnetic and ferromagnetic order parameters (l and m, respectively). We demonstrate that antiferromagnets including DMI can be described by a 2-dimensional pendulum model of l. Because m is coupled with l, together with DMI and exchange energy, close examination of m provides fundamental understanding of its dynamics in linear and nonlinear regimes. Furthermore, we discuss magnetization reversal as a function of DMI and anisotropy energy induced by a spin current pulse.

Organic semiconductors including rubrene, Alq3, copper phthalocyanine and pentacene are crystallized by the eutectic melt crystallization. Those organic semiconductors form good eutectic systems with the various volatile crystallizable additives such as benzoic acid, salicylic acid, naphthalene and 1,3,5-trichlorobenzene. Due to the formation of the eutectic system, organic semiconductors having originally high melting point (Tm > 300 °C) are melted and crystallized at low temperature (Te = 40.8-133 °C). The volatile crystallizable additives are easily removed by sublimation. For a model system using rubrene, single crystalline rubrene nanowires are prepared by the eutectic melt crystallization and the eutectic-melt-assisted nanoimpinting (EMAN) technique. It is demonstrated that crystal structure and the growth direction of rubrene can be controlled by using different volatile crystallizable additives. The field effect mobility of rubrene nanowires prepared using several different crystallizable additives are measured and compared.

We developed two-photon (TP) probes for DNA (ABI-Nu), cytoplasm (Pyr-CT), and mitochondria (BF-MT). We found that ABI-Nu binds to AT in the minor groove, while ABI-Nu and BF-MT are effective for tracking in the cytoplasm and mitochondria, respectively. These probes showed very large effective two-photon action cross section values of 2230, 1555, and 790 Göppert-Mayer units (1 GM  =  10(-50) cm(4) s photon(-1) molecule(-1)) at 740 nm with emission maxima at 473, 561, and 560 nm, respectively, in each organelle. Using these probes, we quantitatively estimated the mean nuclear area and the ratios of nuclei to cytoplasm and mitochondria to nuclei in human colon tissues by dual-colour two-photon microscopy imaging within 2  h after biopsy. The mean nuclear area and the nuclei to cytoplasm and mitochondria to cytoplasm ratios increased in the following order: normal colon mucosa

Mitochondria are important in many essential cellular functions, including energy production, calcium homeostasis, and apoptosis. The organelles are scattered throughout the cytoplasm, but their distribution can be altered in response to local energy demands, such as cell division and neuronal maturation. Mitochondrial distribution is closely associated with mitochondrial fission, and blocking the fission-promoting protein dynamin-related protein 1 (Drp1) activity often results in mitochondrial elongation and clustering. In this study, we observed that mitochondria were preferentially localized at the leading process of migratory adult neural stem cells (aNSCs), whereas neuronal differentiating cells transiently exhibited perinuclear condensation of mitochondria. Inhibiting Drp1 activity altered the typical migratory cell morphology into round shapes while the polarized mitochondrial distribution was maintained. With these changes, aNSCs failed to migrate, and neuronal differentiation was prevented. Because Drp1 blocking also impaired the mitochondrial membrane potential, we tested whether supplementing with L-carnitine, a compound that restores mitochondrial membrane potential and ATP synthesis, could revert the defects induced by Drp1 inhibition. Interestingly, L-carnitine fully restored the aNSC defects, including cell shrinkage, migration, and impaired neuronal differentiation. These results suggest that Drp1 is required for functionally active mitochondria, and supplementing with ATP can restore the defects induced by Drp1 suppression.

Two-dimensional (2D) molybdenum disulphide (MoS2) atomic layers have a strong potential to be used as 2D electronic sensor components. However, intrinsic synthesis challenges have made this task difficult. In addition, the detection mechanisms for gas molecules are not fully understood. Here, we report a high-performance gas sensor constructed using atomic-layered MoS2 synthesised by chemical vapour deposition (CVD). A highly sensitive and selective gas sensor based on the CVD-synthesised MoS2 was developed. In situ photoluminescence characterisation revealed the charge transfer mechanism between the gas molecules and MoS2, which was validated by theoretical calculations. First-principles density functional theory calculations indicated that NO2 and NH3 molecules have negative adsorption energies (i.e., the adsorption processes are exothermic). Thus, NO2 and NH3 molecules are likely to adsorb onto the surface of the MoS2. The in situ PL characterisation of the changes in the peaks corresponding to charged trions and neutral excitons via gas adsorption processes was used to elucidate the mechanisms of charge transfer between the MoS2 and the gas molecules.

Transparent electrodes have been widely used in electronic devices such as solar cells, displays, and touch screens. Highly flexible transparent electrodes are especially desired for the development of next generation flexible electronic devices. Although indium tin oxide (ITO) is the most commonly used material for the fabrication of transparent electrodes, its brittleness and growing cost limit its utility for flexible electronic devices. Therefore, the need for new transparent conductive materials with superior mechanical properties is clear and urgent. Ag nanowire (AgNW) has been attracting increasing attention because of its effective combination of electrical and optical properties. However, it still suffers from several drawbacks, including large surface roughness, instability against oxidation and moisture, and poor adhesion to substrates. These issues need to be addressed before wide spread use of metallic NW as transparent electrodes can be realized. In this study, we demonstrated the fabrication of a flexible transparent electrode with superior mechanical, electrical and optical properties by embedding a AgNW film into a transparent polymer matrix. This technique can produce electrodes with an ultrasmooth and extremely deformable transparent electrode that have sheet resistance and transmittance comparable to those of an ITO electrode.