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In this study, we analyzed the performance characteristics of an axial flow pump with different angles of internally installed inlet guide vanes (IGVs). We predicted the pump's performance based on changes in the IGV angle and analyzed the impact of these angle variations on pump operation in the low-flow region. Additionally, we used real operational data from two sewage treatment plants to propose efficient operational scenarios. For turbulence flow analysis, the Reynolds-averaged Navier-Stokes equations were discretized based on the finite volume method. The grid formation was evaluated using the grid convergence index to select the optimal grid. Then, the internal flow was analyzed in detail through transient-state analysis. Through fast Fourier transform analysis, we confirmed that adjusting the IGV angle during pump operation in the low-flow region in response to load changes results in more stable operation compared with the existing method (valve control). Overall, our findings verified that energy reduction and efficient operation can be achieved through IGV angle adjustment compared with valve control., (© 2024. The Author(s).)

Glioblastoma multiforme (GBM) is the most aggressive type of primary brain tumor, and the presence of glioma stem cells (GSCs) has been linked to its resistance to treatments and recurrence. Additionally, aberrant glycosylation has been implicated in the aggressiveness of cancers. However, the influence and underlying mechanism of N-glycosylation on the GSC phenotype and GBM malignancy remain elusive. Here, we performed an in-silico analysis approach on publicly available datasets to examine the function of N-glycosylation-related genes in GSCs and gliomas, accompanied by a qRT-PCR validation experiment. We found that high α-1,2-mannosidase MAN1C1 is associated with immunological functions and worse survival of glioma patients. Differential gene expression analysis and qRT-PCR validation revealed that MAN1C1 is highly expressed in GSCs. Furthermore, higher MAN1C1 expression predicts worse outcomes in glioma patients. Also, MAN1C1 expression is increased in the perinecrotic region of GBM and is associated with immunological and inflammatory functions, a hallmark of the GBM mesenchymal subtype. Further analysis confirmed that MAN1C1 expression is closely associated with infiltrating immune cells and disrupted immune response in the GBM microenvironment. These suggest that MAN1C1 is a potential biomarker for gliomas and may be important as an immunotherapeutic target for GBM., (© 2024. The Author(s).)

We propose a topological coherent perfect absorber that enables almost ideal performance with remarkably compact device footprint and tight incident beams. The proposed structure is based on a topological junction of two guided-mode-resonance gratings. The structure provides robust systematic ways of remarkably tight lateral confinement of the absorbing resonance mode and near-perfect mode-match to arbitrary incident beams, which are unavailable with the conventional approaches. We demonstrate an exemplary amorphous Si thin-film structure that enables near-perfect absorptance modulation between 1.7 and 99% with device footprint width of 30-μm and 10-μm-wide incident Gaussian beams. Therefore, our proposed approach greatly improves practicality of guided-mode-resonance coherent perfect absorbers., (© 2024. The Author(s).)

Investigation of the major factors determining tropical upper-level cloud radiative effect (TUCRE) is crucial for understanding cloud feedback mechanisms. We examined the TUCRE inferred from the outputs of historical runs and AMIP runs from CMIP6 models employing a radiative-convective equilibrium (RCE). In this study, we incorporated the RCE model configurations of atmospheric dynamics and thermodynamics from the climate models, while simplifying the intricate systems. Using the RCE model, we adjusted the global mean surface temperature to achieve energy balance, considering variations in tropical cloud fraction, regional reflectivity, and emission temperature corresponding to each climate model. Subsequently, TUCRE was calculated as a unit of K/%, representing the change in global mean surface temperature (K) in response to an increment in the tropical upper-level clouds (%). Our RCE model simulation indicates that the major factors determining the TUCRE are the emission temperatures of tropical moist-cloudy and moist-clear regions, as well as the fraction of tropical upper-level clouds. The higher determination coefficients between TUCRE and both the emission temperature of tropical moist regions and the upper-level cloud fraction are attributable to their contribution to the trapping effect on the outgoing longwave radiations, which predominantly determines TUCRE. Consequently, the results of this study underscore the importance of accurately representing the upper-level cloud fraction and emission temperature in tropical moist regions to enhance the representation of TUCRE in climate models., (© 2024. The Author(s).)

Limited information is available regarding the association between preoperative lung function and postoperative pulmonary complications (PPCs) in patients with esophageal cancer who undergo esophagectomy. This is a retrospective cohort study. Patients were classified into low and high lung function groups by the cutoff of the lowest fifth quintile of forced expiratory volume in 1 s (FEV 1 ) %predicted (%pred) and diffusing capacity of the carbon monoxide (DLco) %pred. The PPCs compromised of atelectasis requiring bronchoscopic intervention, pneumonia, and acute lung injury/acute respiratory distress syndrome. Modified multivariable-adjusted Poisson regression model using robust error variances and inverse probability treatment weighting (IPTW) were used to assess the relative risk (RR) for the PPCs. A joint effect model considered FEV 1 %pred and DLco %pred together for the estimation of RR for the PPCs. Of 810 patients with esophageal cancer who underwent esophagectomy, 159 (19.6%) developed PPCs. The adjusted RR for PPCs in the low FEV 1 group relative to high FEV 1 group was 1.48 (95% confidence interval [CI] = 1.09-2.00) and 1.98 (95% CI = 1.46-2.68) in the low DLco group relative to the high DLco group. A joint effect model showed adjusted RR of PPCs was highest in patients with low DLco and low FEV 1 followed by low DLco and high FEV 1 , high DLco and low FEV 1 , and high DLco and high FEV 1 (Reference). Results were consistent with the IPTW. Reduced preoperative lung function (FEV 1 and DLco) is associated with post-esophagectomy PPCs. The risk was further strengthened when both values decreased together., (© 2024. The Author(s).)

In this study, numerical simulation was employed to predict the performance and internal flow characteristics of the inlet of an axial-flow pump by assigning an absolute flow angle to the inlet guide vane (IGV) trailing-edge flow. Further, the finite volume method based on the three-dimensional Reynolds-averaged Navier-Stokes equations was employed to discretize the governing equations. The shear stress transport model was used as the turbulence model, and an appropriate number of nodes were selected for the hexahedral grid system through a grid-dependency test. The performance curve and changes in the internal flow field were investigated based on the variation in the flow angle at the inlet of the axial-flow pump. These results can be used to establish an efficient operational plan by adjusting the IGV angle of IGV when installing a variable IGV for an axial-flow pump., (© 2023. The Author(s).)

The stall in an axial fan is directly related to detrimental phenomena such as performance degradation, vibration, noise, and flow instability at low flow rates. As a kind of passive control method to handle the stall, two-dimensional plates so-named anti-stall fin (ASF) were suggested by ourselves and were attached inside the casing. In this study, the ASF's effect on the internal flow pattern was visually investigated in the flow passage, and its tendency was discussed with the performance curve. Subsequently, the ASF's functional limitations for various design parameters, which the ASF can derive aerodynamically, were presented as the primary focus of this study. Each one-factor analysis was performed, and the internal flow pattern was observed in parallel at the point where the ASF lost its function. For the radial length, axial length, number of fins, and positive-tangential angle, the ASF almost retained its function up to the limitation to prevent instability but radically lost its function at a certain flow rate. For the axial gap and negative-tangential angle, the ASF gradually lost its function. Mostly, this study was based on numerical analysis, and the performance was validated through experimental tests., (© 2022. The Author(s).)

Prior experiences of successful and failed treatments are known to influence the efficacy of a newly applied treatment. However, whether that carry-over effect applies to non-pharmacological treatments is unknown. This study investigated how a failed treatment history with placebo analgesic cream affected the therapeutic outcomes of cold-pack treatment. The neural correlates underlying those effects were also explored using functional magnetic resonance imaging. The effect of the placebo analgesic cream was induced using placebo conditioning with small (44.5 °C to 43.7 °C, negative experience) and large (44.5 °C to 40.0 °C, positive experience) thermal stimuli changes. After the placebo conditioning, brain responses and self-reported evaluations of the effect of subsequent treatment with a cold-pack were contrasted between the two groups. The negative experience group reported less pain and lower anxiety scores in the cold-pack condition than the positive experience group and exhibited significantly greater activation in the right inferior parietal lobule (IPL), which is known to be involved in pain relief. These findings suggest that an unsatisfying experience with an initial pain-relief treatment could increase the expectations for the complementary treatment outcome and improve the analgesic effect of the subsequent treatment. The IPL could be associated with this expectation-induced pain relief process., (© 2022. The Author(s).)

The rates of early gastric cancer and type 2 diabetes mellitus(T2DM) are sharply increasing in Korea. Oncometabolic surgery in which metabolic surgery is conducted along with cancer surgery is a method used to treat gastric cancer and T2DM in one-stage operation. From 2011 to 2019, a total of 48 patients underwent long-limb Roux-en-Y gastrectomy (LRYG) in Inha University Hospital, and all data were reviewed retrospectively. A 75 g oral glucose tolerance test and serum insulin level test were performed before and 1 week and 1 year after surgery. One year after LRYG operation, 25 of 48 patients showed complete or partial remission and 23 patients showed non-remission of T2DM. The preoperative HbA1c level was significantly lower and the change in HbA1c was significantly greater in the T2DM remission group. Insulin secretion indices(insulinogenic index and disposition index) were increased significantly in the T2DM remission group. In contrast, the insulin resistance indices (homeostatic model assessment of insulin resistance (HOMA-IR) and Matsuda index) changed minimal. In the case of LRYG in T2DM patients, remnant β cell function is an important predictor of favorable glycemic control., (© 2022. The Author(s).)

Honey bees are important pollinators for the conservation of the ecosystem and agricultural products and provide a variety of products important for human use, such as honey, pollen, and royal jelly. Sacbrood disease (SD) is a devastating viral disease in Apis cerana; an effective preventive measure for SD is urgently needed. In this study, the relationship between the gut microbiome of honey bees and SD was investigated by pyrosequencing. Results revealed that sacbrood virus (SBV)-resistant A. cerana strains harbour a unique acetic acid bacterium, Bombella intestini, and the lactic acid bacteria (LAB) Lactobacillus (unclassified)_uc, Bifidobacterium longum, B. catenulatum, Lactococcus lactis, and Leuconostoc mesenteroides in larvae and Hafnia alvei, B. indicum, and the LAB L. mellifer and Lactobacillus HM215046_s in adult bees. Changes in the gut microbiome due to SBV infection resulted in loss of bacteria that could affect host nutrients and inhibit honey bee pathogens, such as Gilliamella JFON_s, Gilliamella_uc, Pseudomonas putida, and L. kunkeei in A. cerana larvae and Frischella_uc, Pantoea agglomerans, Snodgrassella_uc, and B. asteroides in adult bees. These findings provide important information for the selection of probiotics for A. cerana larvae and adults to prevent pathogenic infections and keep honey bees healthy., (© 2022. The Author(s).)

Extracellular PKM2 (exPKM2) levels have been reported to be increased in several cancers and inflammatory diseases, including rheumatoid arthritis (RA). This study aimed to investigate the association of circulating exPKM2 levels with radiographic progression in RA patients and the effect of exPKM2 on osteoclastogenesis. Plasma and synovial fluid exPKM2 levels were significantly elevated in RA patients. Plasma exPKM2 levels were correlated with RA disease activity and were an independent predictor for radiographic progression in RA patients with a disease duration of ≤ 12 months. CD14 + monocytes but not RA fibroblast-like synoviocytes secreted PKM2 upon stimulation with inflammatory mediators. Recombinant PKM2 (rPKM2) increased the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells and resorption pit in osteoclast precursors, dose-dependently, even in the absence of receptor activator of nuclear factor-kappa B ligand (RANKL). rPKM2 treatment upregulated the expression of dendrocyte-expressed seven transmembrane protein (DC-STAMP) and MMP-9 via the ERK pathway. Although rPKM2 did not directly bind to RAW264.7 cells, extracellular application of pyruvate, the end-product of PKM2, showed effects similar to those seen in rPKM2-induced osteoclastogenesis. These results suggest that exPKM2 is a potential regulator of RA-related joint damage and a novel biomarker for subsequent radiographic progression in patients with early-stage RA., (© 2022. The Author(s).)

Inferring molecular structures from experimentally measured nuclear magnetic resonance (NMR) spectra is an important task in many chemistry applications. Herein, we present a novel method implementing an automated molecular search by NMR spectrum. Given a query spectrum and a pool of candidate molecules, the matching score of each candidate molecule with respect to the query spectrum is evaluated by introducing a molecule-to-spectrum estimation procedure. The candidate molecule with the highest matching score is selected. This procedure does not require any prior knowledge of the corresponding molecular structure nor laborious manual efforts by chemists. We demonstrate the effectiveness of the proposed method on molecular search using 13 C NMR spectra., (© 2021. The Author(s).)

Evolutionary design has gained significant attention as a useful tool to accelerate the design process by automatically modifying molecular structures to obtain molecules with the target properties. However, its methodology presents a practical challenge-devising a way in which to rapidly evolve molecules while maintaining their chemical validity. In this study, we address this limitation by developing an evolutionary design method. The method employs deep learning models to extract the inherent knowledge from a database of materials and is used to effectively guide the evolutionary design. In the proposed method, the Morgan fingerprint vectors of seed molecules are evolved using the techniques of mutation and crossover within the genetic algorithm. Then, a recurrent neural network is used to reconstruct the final fingerprints into actual molecular structures while maintaining their chemical validity. The use of deep neural network models to predict the properties of these molecules enabled more versatile and efficient molecular evaluations to be conducted by using the proposed method repeatedly. Four design tasks were performed to modify the light-absorbing wavelengths of organic molecules from the PubChem library., (© 2021. The Author(s).)

Some craniofacial diseases or anatomical variations are found in radiographic images taken for other purposes. These incidental findings (IFs) can be detected in orthodontic patients, as various radiographs are required for orthodontic diagnosis. The radiographic data of 1020-orthodontic patients were interpreted to evaluate the rates of IFs in three-dimensional (3D) cone-beam-computed tomography (CBCT) with a large field of view (FOV) and investigate the effectiveness and accuracy of two-dimensional (2D) radiographs for detecting IFs compared to CBCT. Prevalence and accuracy in five areas was measured for sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). The accuracies of various 2D-radiograph were compared through a proportion test. A total of 709-cases (69.5%) of 1020-subjects showed one or more IFs in CBCT images. Nasal cavity was the most affected area. Based on the CBCT images as a gold standard, different accuracies of various 2D-radiographs were observed in each area of the findings. The highest accuracy was confirmed in soft tissue calcifications with comprehensive radiographs. For detecting nasal septum deviations, postero-anterior cephalograms were the most accurate 2D radiograph. In cases the IFs were not determined because of its ambiguity in 2D radiographs, considering them as an absence of findings increased the accuracy.

Chronic obstructive pulmonary disease (COPD), an established risk factor for lung cancer, remains largely undiagnosed and untreated before lung cancer surgery. We evaluated the effect of perioperative bronchodilator therapy on lung function changes in COPD patients who underwent surgery for non-small cell lung cancer (NSCLC). From a database including NSCLC patients undergoing lung resection, COPD patients were identified and divided into two groups based on the use of bronchodilator during the pre- and post-operative period. Changes in forced expiratory volume in 1 s (FEV 1 ) and postoperative complications were compared between patients treated with and without bronchodilators. Among 268 COPD patients, 112 (41.8%) received perioperative bronchodilator, and 75% (84/112) were newly diagnosed with COPD before surgery. Declines in FEV 1 after surgery were alleviated by perioperative bronchodilator even after adjustments for related confounding factors including surgical extent, surgical approach and preoperative FEV 1 (adjusted mean difference in FEV 1 decline [95% CI] between perioperative bronchodilator group and no perioperative bronchodilator group; - 161.1 mL [- 240.2, - 82.0], - 179.2 mL [- 252.1, - 106.3], - 128.8 mL [- 193.2, - 64.4] at 1, 4, and 12 months after surgery, respectively). Prevalence of postoperative complications was similar between two groups. Perioperative bronchodilator therapy was effective to preserve lung function, after surgery for NSCLC in COPD patients. An active diagnosis and treatment of COPD are required for surgical candidates of NSCLC.

Image compression is used in several clinical organizations to help address the overhead associated with medical imaging. These methods reduce file size by using a compact representation of the original image. This study aimed to analyze the impact of image compression on the performance of deep learning-based models in classifying mammograms as "malignant"-cases that lead to a cancer diagnosis and treatment-or "normal" and "benign," non-malignant cases that do not require immediate medical intervention. In this retrospective study, 9111 unique mammograms-5672 normal, 1686 benign, and 1754 malignant cases were collected from the National Cancer Center in the Republic of Korea. Image compression was applied to mammograms with compression ratios (CRs) ranging from 15 to 11 K. Convolutional neural networks (CNNs) with three convolutional layers and three fully-connected layers were trained using these images to classify a mammogram as malignant or not malignant across a range of CRs using five-fold cross-validation. Models trained on images with maximum CRs of 5 K had an average area under the receiver operating characteristic curve (AUROC) of 0.87 and area under the precision-recall curve (AUPRC) of 0.75 across the five folds and compression ratios. For images compressed with CRs of 10 K and 11 K, model performance decreased (average 0.79 in AUROC and 0.49 in AUPRC). Upon generating saliency maps that visualize the areas each model views as significant for prediction, models trained on less compressed (CR <  = 5 K) images had maps encapsulating a radiologist's label, while models trained on images with higher amounts of compression had maps that missed the ground truth completely. In addition, base ResNet18 models pre-trained on ImageNet and trained using compressed mammograms did not show performance improvements over our CNN model, with AUROC and AUPRC values ranging from 0.77 to 0.87 and 0.52 to 0.71 respectively when trained and tested on images with maximum CRs of 5 K. This paper finds that while training models on images with increased the robustness of the models when tested on compressed data, moderate image compression did not substantially impact the classification performance of DL-based models.

To evaluate risk factors leading to non-alcoholic fatty liver disease (NAFLD) occurrence in polycystic ovarian syndrome (PCOS) women. A retrospective cohort study of a total of 586 women diagnosed with PCOS aged 13-35 years at the gynecology department at a university hospital was done to evaluate PCOS phenotype, metabolic syndrome (MetS) diagnosis, body composition, insulin sensitivity, sex hormones, lipid profile, liver function, and transient elastography (TE). In PCOS women with NAFLD compared to those without, MetS diagnosis (Hazard ratio [HR] 5.6, 95% Confidence interval [CI] 2.2-14.4, p < 0.01) and hyperandrogenism (HA) (HR 4.4, 95% CI 1.4-13.4, p = 0.01) were risk factors significantly associated with subsequent NAFLD occurrence, whereas 2-h insulin level in 75 g glucose tolerance test (GTT) (HR 1.2, 95% CI 0.5-2.5, p = 0.70) and body mass index (BMI) > 25 kg/m 2 (HR 2.2, 95% CI 0.6-8.0, p = 0.24) was not. Among NAFLD patients who underwent TE, a higher number of MetS components indicated a worse degree of fibrosis and steatosis. MetS diagnosis and HA at PCOS diagnosis were risk factors associated with NAFLD, while 2-h insulin level in 75 g GTT and obesity were not. Although elevated aspartate aminotransferase levels were significant for NAFLD risk, liver enzyme elevations may not be present until late liver damage. Further prospective studies of PCOS women with MetS or HA are warranted to determine whether patients without liver enzyme elevations should undergo preemptive liver examinations.

With recent advances in biotechnology and sequencing technology, the microbial community has been intensively studied and discovered to be associated with many chronic as well as acute diseases. Even though a tremendous number of studies describing the association between microbes and diseases have been published, text mining methods that focus on such associations have been rarely studied. We propose a framework that combines machine learning and natural language processing methods to analyze the association between microbes and diseases. A hierarchical long short-term memory network was used to detect sentences that describe the association. For the sentences determined, two different parse tree-based search methods were combined to find the relation-describing word. The ensemble model of constituency parsing for structural pattern matching and dependency-based relation extraction improved the prediction accuracy. By combining deep learning and parse tree-based extractions, our proposed framework could extract the microbe-disease association with higher accuracy. The evaluation results showed that our system achieved an F-score of 0.8764 and 0.8524 in binary decisions and extracting relation words, respectively. As a case study, we performed a large-scale analysis of the association between microbes and diseases. Additionally, a set of common microbes shared by multiple diseases were also identified in this study. This study could provide valuable information for the major microbes that were studied for a specific disease. The code and data are available at https://github.com/DMnBI/mdi&#95;predictor .

With the progression of acute cholecystitis, antimicrobial therapy becomes important for infection control. Current antibiotic recommendations were mostly based on reports of patients with acute cholangitis whose bile specimens were sampled from the biliary tract. However, as most infections of acute cholecystitis are limited to the gallbladder, direct sampling from the site increases the probability of identifying the causative pathogen. We investigated 321 positive bile cultures from 931 patients with acute cholecystitis who underwent laparoscopic cholecystectomy between January 2003 and December 2017. The frequency of enterococci declined (P = 0.041), whereas that of Enterobacteriales (P = 0.005), particularly Escherichia (P = 0.008), increased over time. The incidence of ciprofloxacin-resistant Enterobacteriales showed a significant increasing trend (P = 0.031). Vancomycin-resistant E.faecium, carbapenem-resistant Enterobacteriales, and extended-spectrum beta-lactamase-producing Enterobacteriales were recently observed. In grade I and II acute cholecystitis, there were no significant differences in perioperative outcomes in patients with and without early appropriate antimicrobial therapy. In conclusion, the changing incidence of frequently isolated microorganisms and their antibiotic resistance over time would be considered before selecting antibiotics for the treatment of acute cholecystitis. Surgery might be a crucial component of infection control in grade I and II acute cholecystitis.

Identification of obstructive level is crucial for successful surgical outcomes in patients with obstructive sleep apnea (OSA). Unfortunately, most of the dynamic airway evaluations are performed for a short duration under drug-induced sleep; therefore, it is uncertain whether they represent airway events that occur during a whole night of sleep. This study was aimed to evaluate the correlation between obstructive levels that were identified by a short-time and a whole-night test in patients with OSA. Total 101 patients with OSA underwent drug-induced sleep fluoroscopy (DISF) and pressure manometry (PM). For DISF, the obstructive pattern was classified into one of three groups: soft palate, tongue-based, and a combined obstruction. PM was used to measure the proportion of retroglossal events out of total whole-night obstructive events in each patient. The mean age of the patients was 43.8 years. The obstructive pattern was identified as soft palate in 56 patients, combined in 38 patients, and tongue-based in 7 patients following DISF. Results from PM showed that the mean percentage of retroglossal obstructive events was 31.2 ± 30.7%. The average proportion of retroglossal obstructive events that were identified by PM in patients with soft palate, combined, and tongue-based obstruction was 27.2%, 32.1%, and 59.0%, respectively (p = 0.033). There are limitations of evaluating obstructive events that occur during a whole night with short-time tests. Surgeons should be aware the possibility of disagreement in the obstructive level between short-time and whole-night tests.

To investigative whether radiomics features in bilateral hippocampi from MRI can identify temporal lobe epilepsy (TLE). A total of 131 subjects with MRI (66 TLE patients [35 right and 31 left TLE] and 65 healthy controls [HC]) were allocated to training (n = 90) and test (n = 41) sets. Radiomics features (n = 186) from the bilateral hippocampi were extracted from T1-weighted images. After feature selection, machine learning models were trained. The performance of the classifier was validated in the test set to differentiate TLE from HC and ipsilateral TLE from HC. Identical processes were performed to differentiate right TLE from HC (training set, n = 69; test set; n = 31) and left TLE from HC (training set, n = 66; test set, n = 30). The best-performing model for identifying TLE showed an AUC, accuracy, sensitivity, and specificity of 0.848, 84.8%, 76.2%, and 75.0% in the test set, respectively. The best-performing radiomics models for identifying right TLE and left TLE subgroups showed AUCs of 0.845 and 0.840 in the test set, respectively. In addition, multiple radiomics features significantly correlated with neuropsychological test scores (false discovery rate-corrected p-values < 0.05). The radiomics model from hippocampus can be a potential biomarker for identifying TLE.

This study was performed to evaluate the long-term cardiovascular safety of gemigliptin in patients with type 2 diabetes mellitus (T2DM). After screening, eligible patients with T2DM were enrolled, received gemigliptin, and were followed up for a median of 2.50 years. The primary outcome was a composite of confirmed cardiovascular death, nonfatal myocardial infarction, or nonfatal ischemic stroke (3-point major adverse cardiovascular event [MACE]). The key secondary outcomes were incidence of all-cause mortality and any other cardiovascular events. A total of 5179 patients were included in the study and 5113 were treated with gemigliptin. Overall, the primary outcome occurred in 26 patients within 12 months (estimated incidence by Cox proportional hazard model 0.49%, 95% CI 0.29-0.69%) and in 54 patients within 54 months (estimated incidence from Cox proportional hazard model 1.35%, 95% CI 0.92-1.77%). During the study period, the incidence rates of each component of the primary composite outcome were 0.04% (0.2 events per 1000 person-years) for cardiovascular death, 0.51% (2.2 events per 1000 person-years) for nonfatal myocardial infarction, and 0.61% (2.5 events per 1000 person-years) for nonfatal ischemic stroke. The incidence of all-cause mortality was 0.82% (3.2 events per 1000 person-years) and the incidences of other cardiovascular events were all less than 0.3%. In conclusion, T2DM patients who received gemigliptin exhibited a low incidence of the primary composite MACE and all-cause mortality. Therefore, the use of gemigliptin is expected to be safe without an increase in cardiovascular risk.Trial registration: The study was registered at ClinicalTrials.gov (identifier: NCT02290301).

We report a universal terahertz (THz) emission behavior from simple Ni, Fe, and Co metallic ferromagnetic films, triggered by the femtosecond laser pulse and subsequent photoinduced demagnetization on an ultrafast time scale. THz emission behavior in ferromagnetic films is found to be consistent with initial magnetization states controlled by external fields, where the hysteresis of the maximal THz emission signal is observed to be well-matched with the magnetic hysteresis curve. It is experimentally demonstrated that the ultrafast THz emission by the photoinduced demagnetization is controllable in a simple way by external fields as well as pump fluences.

Antenatal magnesium sulfate (MgSO 4 ) treatment is widely used for fetal neuroprotection in women at risk of preterm delivery. However, some studies have recently suggested that in utero MgSO 4 exposure is associated with an increased risk of necrotizing enterocolitis (NEC). This study aimed to investigate the association between antenatal MgSO 4 treatment and risk of NEC. This retrospective cohort study included 756 infants born at 24‒31 weeks' gestation. Subjects were classified into three groups: period 1, when MgSO 4 treatment protocol for fetal neuroprotection was not adopted (n = 267); period 2, when the protocol was adopted (n = 261); and period 3, when the protocol was withdrawn because of concern of risk of NEC (n = 228). Rates of NEC (≥ stage 2b) were analyzed according to time period and exposure to antenatal MgSO 4 . Significant difference in the rate of NEC was not found across the three time periods (2.6% vs. 6.5% vs. 4.8% in periods 1, 2 and 3, respectively, p = 0.103). The rate of NEC was comparable between the infants exposed and unexposed to antenatal MgSO 4 (5.1% vs. 3.6%, p = 0.369). These results showed that antenatal MgSO 4 treatment was not associated with risk of NEC in our study population.

Understanding of ultrafast spin dynamics is crucial for future spintronic applications. In particular, the role of non-thermal electrons needs further investigation in order to gain a fundamental understanding of photoinduced demagnetization and remagnetization on a femtosecond time scale. We experimentally demonstrate that non-thermal electrons existing in the very early phase of the photoinduced demagnetization process play a key role in governing the overall ultrafast spin dynamics behavior. We simultaneously measured the time-resolved reflectivity (TR-R) and the magneto-optical Kerr effect (TR-MOKE) for a Co/Pt multilayer film. By using an extended three-temperature model (E3TM), the quantitative analysis, including non-thermal electron energy transfer into the subsystem (thermal electron, lattice, and spin), reveals that energy flow from non-thermal electrons plays a decisive role in determining the type I and II photoinduced spin dynamics behavior. Our finding proposes a new mechanism for understanding ultrafast remagnetization dynamics.

The use of programmed intermittent epidural bolus for postoperative analgesia may have greater analgesic efficacy than continuous epidural infusion. However, the rapid delivery speed used with an epidural bolus is more likely to increase intracranial pressure. We compared the effects of lumbar epidural bolus versus continuous infusion epidural analgesia on intracranial pressure in children using optic nerve sheath diameter as a marker. We randomly assigned 40 paediatric patients to bolus or infusion groups. Epidural analgesia (0.15% ropivacaine 0.3 ml·kg -1 ) was administered via bolus or infusion. Ultrasonography was used to measure the optic nerve sheath diameter before (T0), at 3 min (T1), 10 min (T2), and 70 min (T3) after starting the pump. There were statistically significant between-group differences in optic nerve sheath diameter over time (P Group x Time  = 0.045). From T0-T3, the area under the curve values were similar between the two groups. Although there were differences in the patterns of optic nerve sheath diameter change according to the delivery mode, the use of lumbar epidural bolus did not increase the risk of intracranial pressure increase over that of continuous infusion. Further research is needed to investigate intracranial pressure changes after continuous application of each delivery mode.

With the trend of amplified warming in the Arctic, we examine the observed and modeled top-of-atmosphere (TOA) radiative responses to surface air-temperature changes over the Arctic by using TOA energy fluxes from NASA's CERES observations and those from twelve climate models in CMIP5. Considerable inter-model spreads in the radiative responses suggest that future Arctic warming may be determined by the compensation between the radiative imbalance and poleward energy transport (mainly via transient eddy activities). The poleward energy transport tends to prevent excessive Arctic warming: the transient eddy activities are weakened because of the reduced meridional temperature gradient under polar amplification. However, the models that predict rapid Arctic warming do not realistically simulate the compensation effect. This role of energy compensation in future Arctic warming is found only when the inter-model differences in cloud radiative effects are considered. Thus, the dynamical response can act as a buffer to prevent excessive Arctic warming against the radiative response of 0.11 W m -2 K -1 as measured from satellites, which helps the Arctic climate system retain an Arctic climate sensitivity of 4.61 K. Therefore, if quantitative analyses of the observations identify contribution of atmospheric dynamics and cloud effects to radiative imbalance, the satellite-measured radiative response will be a crucial indicator of future Arctic warming.

Corticosteroids have been empirically administered to reduce the rate of acute respiratory distress syndrome (ARDS) after esophagectomy. However, their efficacy remains controversial, and corticosteroids may increase the risk of graft dehiscence and infection, which are major concerns after esophagectomy. Therefore, we compared the incidence of composite complications (ARDS, graft dehiscence and infection) after esophagectomy between patients who received a preventive administration of corticosteroids and those who did not. All patients who underwent esophagectomy from 2010 to 2015 at a tertiary care university hospital were reviewed retrospectively (n = 980). Patients were divided into Steroid (n = 120) and Control (n = 860) groups based on the preventive administration of 100 mg hydrocortisone during surgery. The primary endpoint was the incidence of composite complications. The incidence of composite complications was not different between the Control and Steroid groups (17.4% vs. 21.7% respectively; P = 0.26). The incidence rates of complications in each category were not different between the Control and Steroid groups: ARDS (3.8% vs. 5.0%; P = 0.46), graft dehiscence (4.8% vs. 6.7%; P = 0.37), and infection (12.8% vs. 15.8%; P = 0.36). Propensity score matching revealed that composite complications (20.0% vs. 21.7%; P = 0.75), ARDS (4.3% vs. 5.2%; P = 0.76) and infection (16.5% vs. 15.7%; P = 0.86) were not different between the Control and Steroid group, but the incidence of graft dehiscence was higher in the Steroid group than in the Control group (0.9% vs. 7.0%; P = 0.0175). In conclusions, the preventive use of corticosteroids did not reduce the incidence of ARDS, but may be related to an increased incidence of graft dehiscence. Therefore, routine administration of corticosteroids to prevent ARDS is not recommended in esophagectomy.

Mitochondria are essential organelles involved in the maintenance of cell growth and function, and have been investigated as therapeutic targets in various diseases. Recent studies have demonstrated that direct mitochondrial transfer can restore cellular functions of cells with inherited or acquired mitochondrial dysfunction. However, previous mitochondrial transfer methods are inefficient and time-consuming. Here, we developed a simple and easy mitochondrial transfer protocol using centrifugation, which can be applied to any cell type. By our simple centrifugation method, we found that the isolated mitochondria could be successfully transferred into target cells, including mitochondrial DNA-deleted Rho 0 cells and dexamethasone-treated atrophic muscle cells. We found that mitochondrial transfer normalised ATP production, mitochondrial membrane potential, mitochondrial reactive oxygen species level, and the oxygen consumption rate of the target cells. Furthermore, delivery of intact mitochondria blocked the AMPK/FoxO3/Atrogene pathway underlying muscle atrophy in atrophic muscle cells. Taken together, this simple and rapid mitochondrial transfer method can be used to treat mitochondrial dysfunction-related diseases.

This research aimed to evaluate the potential therapeutic effects of Rg3 on endometriosis and identify target miRNAs. We designed an in vitro study using human endometrial stromal cells (HESCs) obtained from patients with endometriosis and an in vivo study using mouse models. HESCs were treated with Rg3-enhanced red ginseng extract (Rg3E); real-time PCR and microarray profiling, transfection, and western blot were performed. Mouse endometriosis models were developed and supplemented with Rg3E for 8 weeks. Gross lesion size and fibrotic character were analyzed in the mouse models. RNA levels of Ki-67, col-1, CTGF, fibronectin, TGF-β1, MMP2 and MMP9 significantly decreased in HESCs after Rg3E treatment. Microarray analysis revealed downregulation of miR-27b-3p, which is related to fibrosis modulation. Expression of miR-27b-3p was significantly higher in HESCs from patients with endometriosis than that of controls, and Rg3E treatment significantly decreased its expression; the contraction and migration assay revealed significant reductions in both fibrosis and migration potential in Rg3E-treated HESCs from endometriosis patients. A decrease in size and fibrotic character of endometrial lesions from the Rg3E groups was observed in vivo. In conclusion, Rg3 effectively altered fibrotic properties of HESCs from patients with endometriosis, which is likely associated with miR-27b-3p modulation.

Tyrosinase efficiently catalyzes the ortho-hydroxylation of monophenols and the oxidation of diphenols without any additional cofactors. Although it is of significant interest for the biosynthesis of catechol derivatives, the rapid catechol oxidase activity and inactivation of tyrosinase have hampered its practical utilization as a monophenol monooxygenase. Here, we prepared a functional tyrosinase that exhibited a distinguished monophenolase/diphenolase activity ratio (V max mono/ V max di = 3.83) and enhanced catalytic efficiency against L -tyrosine (k cat  = 3.33 ± 0.18 s -1 , K m  = 2.12 ± 0.14 mM at 20 °C and pH 6.0). This enzyme was still highly active in ice water (>80%), and its activity was well conserved below 30 °C. In vitro DOPA modification, with a remarkably high yield as a monophenol monooxygenase, was achieved by the enzyme taking advantage of these biocatalytic properties. These results demonstrate the strong potential for this enzyme's use as a monophenol monooxygenase in biomedical and industrial applications.

As opposed to the common understanding that diffusion into a cubic-structured single crystal is independent of its crystalline orientation, the diffusion of Li to crystalline Si (c-Si) is anisotropic, which acts as the major cause for the fracture of Si anodes in Li-ion batteries. Here, by conducting comprehensive/multi-scale simulation studies based on molecular dynamics and density functional theory, we elucidate how and why Li diffusion in c-Si is anisotropic. We found that Li ions diffuse to c-Si by following a particular atomic-scale space corresponding to the lowest value of the valence orbital in c-Si, causing Li ions to take a tortuous diffusion pathway. The degree of the tortuosity of the pathway differs depending on the crystallographic orientation of Si, and it acts as the major cause for anisotropic lithiation. We also develop a structural parameter that can quantitatively evaluate the orientation dependency of the lithiation of c-Si.

Lung neuroendocrine (NE) tumors are a heterogeneous group of tumors arising from neuroendocrine cells that includes typical carcinoid, atypical carcinoid, small cell lung cancer (SCLC), and large cell NE cancer. The subtyping of NE tumors is based on the number of mitoses per high powered field and the presences of necrosis. However, the best diagnostic criteria to differentiate various subtypes of lung NE tumors remains controversial and few diagnostic markers distinguish typical and atypical carcinoid. In this study, we show that FAIM2, an inhibitory molecule in the Fas-apoptosis pathway, is significantly overexpressed in SCLC compared to non-small cell lung cancer. In addition, FAIM2 expression is significantly higher in atypical carcinoid than typical carcinoid. As atypical carcinoid has been shown to have worse clinical outcomes than typical carcinoid, our data suggests that FAIM2 may be a useful diagnostic marker for atypical carcinoid. Knockdown of FAIM2 expression increases Fas-induced apoptotic cell death in SCLC cells. Etoposide treatment combined with FAIM2 inhibition also shows modest but significant reduction of viable SCLC cells. Taken together, our results suggest that FAIM2 is a potential NE tumor marker with higher expression in atypical carcinoid and SCLC, and could be a new therapeutic target for SCLC.

Oral lichen planus (OLP) is a chronic T cell-mediated mucocutaneous disease of unknown etiopathogenesis. Although various antigens have been considered, what actually triggers the inflammatory response of T cells is unknown. In the present study, we propose that intracellular bacteria present within tissues trigger T cell infiltration and provide target antigens. Sections of OLP (n = 36) and normal (n = 10) oral mucosal tissues were subjected to in situ hybridization using a universal probe targeting the bacterial 16S rRNA gene and immunohistochemistry with anti-CD3, anti-CD4, anti-CD8, and anti-macrophage-specific antibodies. Bacteria were abundant throughout the epithelium and the lamina propria of OLP tissues, which exhibited positive correlations with the levels of infiltrated CD3(+), CD4(+), and CD8(+) cells. Furthermore, bacteria were detected within the infiltrated T cells. Pyrosequencing analysis of the mucosal microbiota from OLP patients (n = 13) and control subjects (n = 11) revealed a decrease in Streptococcus and increases in gingivitis/periodontitis-associated bacteria in OLP lesions. Using the selected bacterial species, we demonstrated that certain oral bacteria damage the epithelial physical barrier, are internalized into epithelial cells or T cells, and induce production of T cell chemokines CXCL10 and CCL5. Our findings provide insights into the pathogenesis of OLP.

Belgian Malinois (BM), one of the excellent military dog breeds in South Korea, is usually castrated before sexual maturation. Therefore, the transfer of their genetic features to the next generation is difficult. To overcome this, testicular cells from 4-month-old BMs were frozen. Testicular cells were thawed after 3 months and cultured in StemPro-34 medium. Spermatogonial stem cell (SSC) characteristics were determined by the transplantation of the cultured germ cell-derived colonies (GDCs) into empty testes, containing only several endogenous SSCs and Sertoli cells, of immunodeficient mice, 4 weeks after busulfan treatment. Following the implantation, the transplanted cells localized in the basement membrane of the seminiferous tubules, and ultimately colonized the recipient testes. Xenotransplantation of GDCs together with testicular somatic cells conjugated with extracellular matrix (ECM), led to the formation of de novo seminiferous tubules. These seminiferous tubules were mostly composed of Sertoli cells. Some germ cells were localized in the basement membrane of seminiferous tubules. This study revealed that BM-derived SSCs, obtained from the castrated testes, might be a valuable tool for the transfer of BM genetic features to the next generation.

Vortex structures in soft magnetic nanodisks are highly attractive due to their scientific beauty and potential technological applications. Here, we experimentally demonstrated the resonant amplification of vortex oscillations by application of simple coherent field pulses tuned to optimal width and time intervals. In order to investigate vortex excitations on the sub-ns time scale, we employed state-of-the-art time-resolved full-field soft X-ray microscopy of 70 ps temporal and 25 nm lateral resolution. We found that, due to the resonant enhancement of the vortex gyration motion, the signal input power can be significantly reduced to ~ 1 Oe in field strength, while increasing signal gains, by increasing the number of the optimal field pulses. We identified the origin of this behavior as the forced resonant amplification of vortex gyration. This work represents an important milestone towards the potential implementation of vortex oscillations in future magnetic vortex devices.

A wide variety of coupled harmonic oscillators exist in nature. Coupling between different oscillators allows for the possibility of mutual energy transfer between them and the information-signal propagation. Low-energy input signals and their transport with negligible energy loss are the key technological factors in the design of information-signal processing devices. Here, utilizing the concept of coupled oscillators, we experimentally demonstrated a robust new mechanism for energy transfer between spatially separated dipolar-coupled magnetic disks - stimulated vortex gyration. Direct experimental evidence was obtained by a state-of-the-art experimental time-resolved soft X-ray microscopy probe. The rate of energy transfer from one disk to the other was deduced from the two normal modes' frequency splitting caused by dipolar interaction. This mechanism provides the advantages of tunable energy transfer rates, low-power input signals and negligible energy loss in the case of negligible intrinsic damping. Coupled vortex-state disks might be implemented in applications for information-signal processing.