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Hyun Lee,1 Chin Kook Rhee,2 Byung-Jae Lee,3 Dong-Chull Choi,3 Jee-Ae Kim,4 Sang Hyun Kim,5 Yoolwon Jeong,6 Tae-Hyung Kim,7 Gyu Rak Chon,8 Ki-Suck Jung,9 Sang Haak Lee,10 David Price,11 Kwang Ha Yoo,12,* Hye Yun Park1,* 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, 3Division of Allergy, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 4Pharmaceutical Policy Evaluation Research Team, Research Institution, Health Insurance Review and Assessment Service, 5Big Data Division, Health Insurance Review and Assessment Service, Seoul, 6Division of Chronic Disease Control, Korea Centers for Disease Control and Prevention, Osong, 7Division of Pulmonary and Critical Care Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Gyeonggi-do, 8Department of Pulmonary and Critical Care Medicine, Chungju Hospital, Konkuk University School of Medicine, Chungju City, 9Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang, 10Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, St Paul’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea; 11Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 12Division of Pulmonary, Allergy and Critical Care Medicine Department of Internal Medicine, Konkuk University School of Medicine, Seoul, South Korea *These authors contributed equally to this work Backround: Acute exacerbations are major drivers of COPD deterioration. However, limited data are available for the prevalence of severe exacerbations and impact of asthma on severe exacerbations, especially in patients with mild-to-moderate COPD.Methods: Patients with mild-to-moderate COPD (≥40 years) were extracted from Korean National Health and Nutrition Examination Survey data (2007–2012) and were linked to the national health insurance reimbursement database to obtain medical service utilization records.Results: Of the 2,397 patients with mild-to-moderate COPD, 111 (4.6%) had severe exacerbations over the 6 years (0.012/person-year). Severe exacerbations were more frequent in the COPD patients with concomitant self-reported physician-diagnosed asthma compared with only COPD patients (P

A chemical investigation of an ethyl acetate-soluble layer in the culture broth of Perenniporia medulla-panis resulted in the isolation of eight novel sesquiterpenes conjugated Gly ( 1 ), l-Val ( 2 ), l-Ala ( 3 ), l-Tyr ( 4 ), l-Thr ( 5 ), l-Ile ( 6 ), l-Leu ( 7 ), and l-Phe ( 8 ). Elucidation of their structures was performed through comprehensive spectroscopic analysis. The absolute configuration of the sesquiterpene skeleton was ascertained using modified Mosher's methods. The configurations of the amino acid units in compounds 2 - 8 were identified through acid hydrolysis followed by LC-MS analysis employing Marfey's method. Compounds 1 - 3 and 5 - 8 showed significant regulating effect on MAP kinase activity (p-ERK and p-JNK) in human diploid fibroblast (HDF) cells.

Three new nonenes, verrucanonenes A‒C (1‒3), were isolated from culture broth of marine-derived fungus Albifimbria verrucaria. These compounds were isolated using silica gel column chromatography, reversed-phase medium pressure liquid chromatography, Sephadex LH-20 column chromatography, and preparative HPLC. Their structures were determined using a spectroscopic method. Cytotoxicities of these isolated compounds to A549, DU145, HCT116, and HT1080 cancer cell lines were assessed. Compounds 1‒3 exhibited cytotoxicities to DU145 cancer cell line, with IC 50 values of 23.4, 28.6, and 20.1 µM, respectively. Compound 2 decreased H1N1-induced cytopathic effects on MDCK cells in a dose-dependent manner., (© 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

We investigated a flat-type p*-p LED composed of a p*-electrode with a local breakdown conductive channel (LBCC) formed in the p-type electrode region by applying reverse bias. By locally connecting the p*-electrode to the n-type layer via an LBCC, a flat-type LED structure is applied that can replace the n-type electrode without a mesa-etching process. Flat-type p*-p LEDs, devoid of the mesa process, demonstrate outstanding characteristics, boasting comparable light output power to conventional mesa-type n-p LEDs at the same injection current. However, they incur higher operating voltages, attributed to the smaller size of the p* region used as the n-type electrode compared to conventional n-p LEDs. Therefore, despite having comparable external quantum efficiency stemming from similar light output, flat-type p*-p LEDs exhibit diminished wall-plug efficiency (WPE) and voltage efficiency (VE) owing to elevated operating voltages. To address this, our study aimed to mitigate the series resistance of flat-type p*-p LEDs by augmenting the number of LBCCs to enhance the contact area, thereby reducing overall resistance. This structure holds promise for elevating WPE and VE by aligning the operating voltage more closely with that of mesa-type n-p LEDs. Consequently, rectifying the issue of high operating voltages in planar p*-p LEDs enables the creation of efficient LEDs devoid of crystal defects resulting from mesa-etching processes.

Three new phthalide derivatives (1‒3) together with two known compounds, erinaceolactone B (4) and hericerin III (5), were isolated from the culture broth of Dentipellis fragilis. The chemical structures of 1‒5 were determined by analyses of their 1D-, 2D-NMR, and MS. The absolute configuration of 1 was determined by CD analysis. The isolated compounds were assessed for their cytotoxic activities against A549, DU145, HCT116, and HT1080 cancer cell lines. Compounds 1‒5 showed strong cytotoxic activities against DU145, with IC 50 values ranging from 14.3 to 16.1 µM. Additionally, all compounds showed moderate or weak cytotoxic activities against all cell lines except for compounds 4 and 1 which showed no cytotoxic activities against A549 and HCT116 cancer cell lines, respectively. Against HT1080 cancer cell line, only compound 2 displayed moderate cytotoxic activity., (© 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

In somatic tissue differentiation, chromatin accessibility changes govern priming and precursor commitment towards cellular fates 1-3 . Therefore, somatic mutations are likely to alter chromatin accessibility patterns, as they disrupt differentiation topologies leading to abnormal clonal outgrowth. However, defining the impact of somatic mutations on the epigenome in human samples is challenging due to admixed mutated and wild-type cells. Here, to chart how somatic mutations disrupt epigenetic landscapes in human clonal outgrowths, we developed genotyping of targeted loci with single-cell chromatin accessibility (GoT-ChA). This high-throughput platform links genotypes to chromatin accessibility at single-cell resolution across thousands of cells within a single assay. We applied GoT-ChA to CD34 + cells from patients with myeloproliferative neoplasms with JAK2 V617F -mutated haematopoiesis. Differential accessibility analysis between wild-type and JAK2 V617F -mutant progenitors revealed both cell-intrinsic and cell-state-specific shifts within mutant haematopoietic precursors, including cell-intrinsic pro-inflammatory signatures in haematopoietic stem cells, and a distinct profibrotic inflammatory chromatin landscape in megakaryocytic progenitors. Integration of mitochondrial genome profiling and cell-surface protein expression measurement allowed expansion of genotyping onto DOGMA-seq through imputation, enabling single-cell capture of genotypes, chromatin accessibility, RNA expression and cell-surface protein expression. Collectively, we show that the JAK2 V617F mutation leads to epigenetic rewiring in a cell-intrinsic and cell type-specific manner, influencing inflammation states and differentiation trajectories. We envision that GoT-ChA will empower broad future investigations of the critical link between somatic mutations and epigenetic alterations across clonal populations in malignant and non-malignant contexts., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

MRI-guided neuro interventions require rapid, accurate, and reproducible segmentation of anatomical brain structures for identification of targets during surgical procedures and post-surgical evaluation of intervention efficiency. Segmentation algorithms must be validated and cleared for clinical use. This work introduces a methodology for shape-constrained deformable brain segmentation, describes the quantitative validation used for its clinical clearance, and presents a comparison with manual expert segmentation and FreeSurfer, an open source software for neuroimaging data analysis. ClearPoint Maestro is software for fully-automatic brain segmentation from T1-weighted MRI that combines a shape-constrained deformable brain model with voxel-wise tissue segmentation within the cerebral hemispheres and the cerebellum. The performance of the segmentation was validated in terms of accuracy and reproducibility. Segmentation accuracy was evaluated with respect to training data and independently traced ground truth. Segmentation reproducibility was quantified and compared with manual expert segmentation and FreeSurfer. Quantitative reproducibility analysis indicates superior performance compared to both manual expert segmentation and FreeSurfer. The shape-constrained methodology results in accurate and highly reproducible segmentation. Inherent point based-correspondence provides consistent target identification ideal for MRI-guided neuro interventions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors are employed by the clinical science and research divisions of ClearPoint Neuro and Philips. They are strictly focused on scientific aspects and have no financial or competing interests that could influence the objectivity and validity of reported work. The goal of this manuscript is to present the methodology for shape-constrained deformable brain segmentation and to describe the quantitative performance analysis used to validate the accuracy and reproducibility of segmentation results., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: The methacholine challenge test (MCT) has high sensitivity but relatively low specificity for asthma diagnosis. This study aimed to develop and validate machine learning (ML) models to improve the diagnostic performance of MCT for asthma., Methods: Data from 1,501 patients with asthma symptoms who underwent MCT between 2015 and 2020 were analyzed. The patients were grouped as either the training (80%, n = 1,265) and test sets (20%, n = 236) depending on the time of referral. The conventional model (provocative concentration that causes a 20% decrease in forced expiratory volume in one second [FEV 1 ]; PC 20 ≤ 16 mg/mL) was compared with the prediction models derived from five ML methods: logistic regression, support vector machine, random forest, extreme gradient boosting, and artificial neural network. The area under the receiver operator characteristic curves (AUROC) and area under the precision-recall curves (AUPRC) of each model were compared. The prediction models were further analyzed using different input combinations of FEV 1 , forced vital capacity (FVC), and forced expiratory flow at 25%-75% of forced vital capacity (FEF 25%-75% ) values obtained during MCT., Results: In total, 545 patients (36.3%) were diagnosed with asthma. The AUROC of the conventional model was 0.856 (95% confidence interval [CI], 0.852-0.861), and the AUPRC was 0.759 (95% CI, 0.751-0.766). All the five ML prediction models had higher AUROC and AUPRC values than those of the conventional model, and random forest showed both highest AUROC (0.950; 95% CI, 0.948-0.952) and AUROC (0.909; 95% CI, 0.905-0.914) when FEV 1 , FVC, and FEF 25%-75% were included as inputs., Conclusions: Artificial intelligence-based models showed excellent performance in asthma prediction compared to using PC 20 ≤ 16 mg/mL. The novel technology could be used to enhance the clinical diagnosis of asthma., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2024 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

A new formanilide dimer, fraxinin (1), and three known formanilides (2‒4) were isolated from the culture broth of Perenniporia fraxinea using silica gel and Sephadex LH-20 column chromatographies, medium-pressure liquid chromatography (MPLC), and preparative HPLC. The structures of these compounds were determined by spectroscopic methods, such as NMR and mass analysis, and by comparison of the spectra with previously reported data. The free radical scavenging activities of the isolated compounds were assessed using 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. Compounds 1‒3 exhibited ABTS radical scavenging activity with IC 50 values in the range of 57.2-250.2 μM. Compounds 2 and 4 marginally reduced disease incidence of powdery mildew with a control value of 42% at 1.0 mg ml -1 in cucumber leaf disk assay., (© 2023. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Capacitive deionization (CDI) is an electrochemical-based water treatment technology that has attracted attention as an effective hardness-control process. However, few systematic studies have reported the criteria for the selection of suitable electrode materials for membrane capacitive deionization (MCDI) to control hardness. In this study, the effect of electrode material characteristics on the MCDI performance for hardness control was quantitatively analyzed. The results showed that the deionization capacity and the deionization rate were affected by the specific capacitance and BET-specific surface area of the activated carbon electrode. In addition, the deionization rate also showed significant relationship with the BET specific surface area. Furthermore, it was observed that the deionization capacity and the deionization rate have a highly significant relationship with the BET specific surface area divided by the wettability performance expressed as the minimum wetting rate (MWR). These findings highlighted that the electrode material should have a large surface area and good wettability to increase the deionization capacity and the deionization rate of MCDI for hardness control. The results of this study are expected to provide effective criteria for selecting MCDI electrode materials aiming hardness control., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Seven undescribed compounds, dentipellinones A‒D (1, 2, 5, and 6), dentipellinol (3), methoxyerinaceolactone B (4), and erinaceolactomer A (7), were isolated from the culture broth of Dentipellis fragilis. Chemical structures of these isolated compounds were determined by analyses of 1D and 2D-NMR and MS data in comparison with data reported in the literature. Absolute configurations of 1‒7 were also determined by Electronic Circular Dichroism calculations. The isolated compounds were evaluated for their anti-inflammatory effects on NO production and pro-inflammatory cytokines levels in LPS-stimulated RAW264.7 cells. Compounds 5 and 7 were evaluated for their anti-inflammatory effects on NO production and pro-inflammatory cytokine levels in LPS-stimulated RAW264.7 cells. They exhibited inhibitory effects on LPS-induced NO production in a dose-dependent manner, and significantly reduced the levels of inflammatory-related cytokines such as IL-1β and IL-6. TNF-α was not involved in the anti-inflammatory effects of these compounds. Finally, compounds 5 and 7 showed significant anti-inflammatory effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Ideally, the flow delivery of an infusion system is proportional only to the rate of mechanical actuation of the syringe pump plunger. However, in the real world, overall infusion system compliance may be affected by components such as an extension of tubing lines, or different sizes of syringes. With higher compliance, there may be greater chances of flow irregularity. In this experimental study, we investigated the effects of lengths of infusion lines and syringe sizes on the compliance of syringe pumps with low flow rate (2 ml h -1 ). In the first experiment, infusion system compliance was measured in various settings by occlusion release. As the infusion tubing length and size of the syringe increased, the time to reach each pressure was delayed and the infusion system compliance increased. The contributions to system compliance from syringes were significantly greater compared to those of extended infusion lines. In the occlusion alarm experiment, the occlusion alarm could be delayed by 69.76 ± 3.98 min for the 50-ml syringe with a 560 cm infusion line set-up. In conclusion, the compliance of a syringe pump system increases as the loaded syringe size, or the length of the infusion tubing increases. The occlusion alarm may be much delayed and not useful in highly compliant systems with respect to the potential occlusion of the infusion system, so more attention is required when using a highly compliant infusion system., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Revised cardiac risk index (RCRI) is widely used for surgical patients without containing age as a risk factor. We investigated age older than 65 years with respect to low-to-moderate risk of RCRI. From January 2011 to June 2019, a total of 203,787 consecutive adult patients underwent non-cardiac surgery at our institution. After excluding high-risk patients defined as RCRI score > 2, we stratified the patients into four groups according to RCRI and age (A: age < 65 with RCRI < 2, [n = 148,288], B: age ≥ 65 with RCRI < 2, [n = 42,841], C: age < 65 with RCRI = 2, [n = 5,271], and D: age ≥ 65 with RCRI = 2, [n = 5,698]). Incidence of major cardiac complication defined as a composite of cardiac death, cardiac arrest and myocardial infarction was compared. After excluding 1,689 patients with high risk (defined as RCRI score > 2), 202,098 patients were enrolled. The incidence with 95% confidence interval of major cardiac complication for A, B, C, and D groups was 0.3% (0.2-0.3), 1.1% (1.0-1.2), 1.8% (1.6-1.8), and 3.1% (2.6-3.6), respectively. In a direct comparison between B and C groups, old patients with RCRI < 2 showed a significantly lower risk compared to younger patients with RCRI = 2 (odd ratio, 0.62; 95% confidence interval, 0.50-0.78; p < 0.001). In non-cardiac surgery, the risk of age older than 65 years was shown to be comparable with low-to-moderate risk according to RCRI., (© 2023. Springer Nature Limited.)

Neurodegenerative diseases are characterized by a decline in neuronal function and structure, leading to neuronal death. Understanding the molecular mechanisms of neuronal death is crucial for developing therapeutics. MiRs are small noncoding RNAs that regulate gene expression by degrading target mRNAs or inhibiting translation. MiR dysregulation has been linked to many neurodegenerative diseases, but the underlying mechanisms are not well understood. As mitochondrial dysfunction is one of the common molecular mechanisms leading to neuronal death in many neurodegenerative diseases, here we studied miRs that modulate neuronal death caused by 1-methyl-4-phenylpyridinium (MPP + ), an inhibitor of complex I in mitochondria. We identified miR-593-5p, levels of which were increased in SH-SY5Y human neuronal cells, after exposure to MPP + . We found that intracellular Ca 2+ , but not of reactive oxygen species, mediated this miR-593-5p increase. Furthermore, we found the increase in miR-593-5p was due to enhanced stability, not increased transcription or miR processing. Importantly, we show the increase in miR-593-5p contributed to MPP + -induced cell death. Our data revealed that miR-593-5p inhibits a signaling pathway involving PTEN-induced putative kinase 1 (PINK1) and Parkin, two proteins responsible for the removal of damaged mitochondria from cells, by targeting the coding sequence of PINK1 mRNA. Our findings suggest that miR-593-5p contributes to neuronal death resulting from MPP + toxicity, in part, by impeding the PINK1/Parkin-mediated pathway that facilitates the clearance of damaged mitochondria. Taken together, our observations highlight the potential significance of inhibiting miR-593-5p as a therapeutic approach for neurodegenerative diseases., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Preoperative anxiety is an unpleasant experience that can adversely affect perioperative outcomes. Although clinical benefits of preoperative oral carbohydrate is well reported, the effect of adding chewing gum to carbohydrate loading has never been studied. We aimed to investigate the effect of adding gum-chewing to oral carbohydrates on preoperative anxiety and gastric volume in patients undergoing gynecologic surgery., Methods: One hundred and four patients were enrolled and randomized either into a carbohydrate drink group (CHD group) or CHD with gum group. The CHD group was instructed to drink 400 mL of oral carbohydrate the evening before and 200-400 mL 3 hours before surgery. The CHD with gum group was encouraged to chew gum freely during preanesthetic fasting in addition to consuming oral carbohydrates in the same manner. The primary endpoint was preoperative anxiety assessed using the Amsterdam preoperative anxiety and information scale (APAIS). The degree of patient-reported quality of recovery after surgery and gastric volume prior to general anesthesia were also compared as secondary outcomes., Results: Preoperative APAIS was lower in the CHD with gum group compared with the CHD group (16 [11.5, 20] vs. 20 [16.5, 23], p = 0.008). Patient-rated quality of recovery after surgery was also higher in the CHD with gum group and showed a significant negative correlation with preoperative APAIS score (correlation coefficient: -0.950, p = 0.001). Gastric volume were not different between the groups (0 [0-0.45] vs. 0 [0-0.22], p = 0.158)., Conclusion: The addition of gum chewing to oral carbohydrate loading during preoperative fasting was more effective in relieving preoperative anxiety than oral carbohydrate alone in women patients undergoing elective gynecologic surgery., Trial Registration: Clinical Research Information Services, CRIS identifier: KCT0005714, https://cris.nih.go.kr/cris/index.jsp., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Days alive and out of hospital (DAOH) is a simple estimator based on the number of days not in hospital within a defined period. In cases of mortality within the period, DAOH is regarded as zero. It has not been validated solely in off-pump coronary artery bypass grafting (OPCAB). This study aimed to demonstrate a correlation between DAOH and outcome of OPCAB. We identified 2211 OPCAB performed from January 2010 to August 2016. We calculated DAOH at 30 and 60 days. We generated a receiver-operating curve and compared outcomes. The median duration of hospital stay after OPCAB was 6 days. The median DAOH values at 30 and 60 days were 24 and 54 days. The estimated thresholds for 3-year mortality for DAOH at 30 and 60 days were 20 and 50 days. Three-year mortality was higher for short DAOH (1.2% vs. 5.7% and 1.1% vs. 5.6% DAOH at 30 and 60 days). After adjustment, the short DAOH 30 group showed significantly higher mortality during 3-year follow-up (hazard ratio 3.07; 95% confidence interval 1.45-6.52; p = 0.004). DAOH at 30 days after OPCAB showed a correlation with 3-year outcomes. DAOH 30 might be a reliable long-term outcome measure that can be obtained within 30 days after surgery., (© 2023. The Author(s).)

Background: Cardiac troponin I (cTnI) is a gold-standard biomarker for detecting myocardial infarction. Recently, the prognostic role of cTnI was reported for stable coronary artery disease and other chronic diseases. This study aimed to evaluate the usefulness of cTnI testing at scheduled admission of patients with comorbidities., Methods: We retrospectively enrolled patients with comorbidities who were admitted through the outpatient clinic from April 2010 to December 2018. The enrolled patients were divided into two groups depending on whether cTnI was measured at admission. The primary endpoint was the mortality rate at one year after admission. Secondary endpoints included 30-day and in-hospital mortality rates., Results: A population of 50,119 patients was divided into two groups, with 43,974 (87.8%) patients included in the no cTnI group and 6,145 (12.2%) patients included in the cTnI group. The multivariable analysis showed a reduction of mortality at one year in the cTnI group [5.9% vs. 3.8%, hazard ratio (HR) =0.78; 95% confidence interval (CI): 0.68-0.89; P<0.001]. Among 5,882 propensity score-matched pairs, this trend persisted, and the mortality rate was significantly lower in the cTnI group (5.3% vs. 3.9%, HR =0.77; 95% CI: 0.65-0.91; P=0.002). Patients with cTnI measurements taken at admission underwent cardiac evaluation and therapy more frequently., Conclusions: The measurement of cTnI at scheduled admission may affect the mortality during one year of follow-up. Further studies are needed to validate our results., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-3681/coif). The authors declare no conflicts of interest., (2023 Annals of Translational Medicine. All rights reserved.)

A new p-terphenyl derivative, hydroxystrepantibin D (1), was isolated along with two known p-terphenyls (2 and 3) from the culture broth of Phlebiopsis castanea. These compounds were isolated using silica gel column chromatography, reversed-phase medium-pressure liquid chromatography, Sephadex LH-20 column chromatography, and preparative HPLC. Their structures were determined based on spectroscopic methods. These compounds exhibited free radical scavenging activities with IC 50 values in the range from 22.2 to 158.4 μM against 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical and in the range from 161.1 to 356.1 μM against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical., (© 2022. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Background: The sequential organ failure assessment (SOFA) score has been validated in various clinical situations. However, it has not been investigated during a short stay in the intensive care unit (ICU). This study aimed to evaluate the association between the SOFA score and outcomes in patients who were monitored for less than one day after non-cardiac surgery. Methods: From a total of 203,787 consecutive adult patients who underwent non-cardiac surgery between January 2011 and June 2019, we selected 17,714 who were transferred to the ICU immediately after surgery and stayed for less than 24 h. Patients were divided according to quartile value and change between the initial and follow-up levels of SOFA score. Results: Three-year mortality tended to increase with a higher initial SOFA score (11.7%, 11.8%, 15.1%, and 17.8%, respectively). The patients were divided according to changes in the SOFA score at the midnight postoperative follow-up check: 16,176 (91.3%) in the stable group and 1538 (8.7%) in the worsened group. The worsened group showed significantly higher three-year mortality and complications (13.2% vs. 18.6%; HR [hazard ratio]: 1.236; 95% CI [confidence interval]: 1.108−1.402; p ≤ 0.0021 for three-year mortality and 3.8% vs. 9.1%; HR: 2.13; 95% CI: 1.73−2.60; p < 0.001 for acute kidney injury). Conclusions: The SOFA score during a short stay in the ICU after non-cardiac surgery showed an association with mortality. The change in SOFA score may need to be considered at discharge from the ICU.

Background: Ear, nose, and throat involvement are common in eosinophilic granulomatosis with polyangiitis (EGPA). Among otologic manifestation, middle ear effusion (MEE) is less recognized but a problematic condition as it may progress to hearing impairment when left untreated. This study aimed to evaluate the characteristics, risk factors and clinical outcomes of MEE in EGPA patients., Methods: This is a case-control study of patients who were diagnosed and treated for EGPA from January 1995 to November 2018. Patients with ear symptoms (ear fullness, ear discharge, tinnitus or hearing loss) were assessed by otologists and were included in the case group (n = 23) if clinically relevant. The other patients without MEE were included in the control group (n = 52). Risk of MEE was calculated using the Cox proportional-hazard model., Results: During median follow-up of 9.9 years, 23 (30.7%) out of 75 patients had MEE. In MEE group, 12 (52.2%) patients had hearing loss; conductive type in 10 (10/12, 83.3%) and mixed type in two (2/12, 16.7%). In multivariable regression analysis, major organ involvement at diagnosis (adjusted hazard ratio [aHR] 65.4; 95% confidence interval [CI], 1.50-2838.39; P = 0.030] , early onset of ear symptom after systemic therapy (< 6 months) (aHR 40.0; 95% CI, 1.35-1183.43; P = 0.033) and continuing the maintenance steroid without cessation (aHR 8.59; 95% CI, 1.13-65.42; P = 0.038) were independently associated with a risk of MEE. To control MEE, 16 (69.6%) patients had to increase maintenance steroid dose and 9 (39.1%) patients experienced recurrent MEE whenever maintenance dose was tapered., Conclusions: MEE is a common but frequently neglected condition in EGPA which is often intractable. The maintenance steroid dose should be adequately adjusted to control MEE and to prevent from progressive hearing loss. Novel biologic agents possibly have a role in controlling MEE in EGPA., (© 2022. The Author(s).)

The current cut-off value for diagnosing exercise-induced bronchoconstriction (EIB) in adults-percent fall in FEV1 (ΔFEV1) ≥ 10% after exercise challenge test (ECT)-has low specificity and weak evidences. Therefore, this study aimed to identify the cut-off value for EIB that provides the highest diagnostic sensitivity and specificity. Participants who underwent the ECT between 2007 and 2018 were categorized according to ΔFEV1: definite EIB (ΔFEV1 ≥ 15%), borderline (10% ≤ ΔFEV1 < 15%), and normal (ΔFEV1 < 10%). Distinct characteristics of the definite EIB group were identified and explored in the borderline EIB group. A receiver operating characteristic curve was plotted to determine the optimal cut-off value. Of 128 patients, 60 were grouped as the definite EIB group, 23 as the borderline group, and 45 as the normal group. All participants were men, with a median age of 20 years (interquartile range [IQR:] 19-23 years). The definite EIB group exhibited wheezing on auscultation (P < 0.001), ΔFEV1/FVC ≥ 10% (P < 0.001), and ΔFEF25-75% ≥ 25% (P < 0.001) compared to other groups. Eight (8/23, 34.8%) patients in the borderline group had at least one of these features, but the trend was more similar to that of the normal group than the definite EIB group. A cut-off value of ΔFEV1 ≥ 13.5% had a sensitivity of 98.5% and specificity of 93.5% for EIB. Wheezing on auscultation, ΔFEV1/FVC ≥ 10%, and ΔFEF25-75% ≥ 25% after ECT may be useful for the diagnosis of EIB, particularly in individuals with a ΔFEV1 of 10-15%. For EIB, a higher cut-off value, possibly ΔFEV1 ≥ 13.5%, should be considered as the diagnostic criterion., Competing Interests: The authors have declared that no competing interests exist.

During the search for natural antioxidants from fungal metabolites, three new sesquiterpene derivatives (1-3) have been isolated from the culture broth of Coprinopsis echinospora. Their structures were determined by spectroscopic methods, mainly NMR and mass spectrometric analyses. These compounds exhibited antioxidant activity with IC 50 values in the range of 34.4-144.5 μM in the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical-scavenging assay., (© 2021. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

In our ongoing search for new secondary metabolites from fungal strains, one novel compound ( 1 ) and nine known compounds ( 2-10 ) were isolated from the EtOAc-soluble layer of the culture broth of Panus rudis . The culture broth of P. rudis was extracted in acetone and fractionated by solvent partition; column chromatography using silica gel, Sephadex LH-20, and Sephadex G-10; MPLC; and HPLC. The structures of isolated compounds were elucidated by one- and two-dimensional NMR and LC-ESI-mass measurements. One new compound, panepoxydiol ( 1 ), and nine known compounds, ( E )-3-(3-hydroxy-3-methylbut-1-en-1-yl)-7-oxabicyclo[4.1.0]hept-3-ene-2,5-diol ( 2 ), isopanepoxydone ( 3 ), neopanepoxydone ( 4 ), panepoxydone ( 5 ), panepophenanthrin ( 6 ), 4-hydroxy-2,2-dimethyl-6-methoxychromane ( 7 ), 6-hydroxy-2,2-dimethyl-3-chromen ( 8 ), 2,2-dimethyl-6-methoxychroman-4-one ( 9 ), 3,4-dihydroxy-2,2-dimethyl-6-methoxychromane ( 10 ), were isolated from the culture broth of P. rudis . This is the first report of isolation of a new compound panepoxydiol ( 1 ) and nine other chemical constituents ( 2 - 5 , 7 - 10 ) from the culture broth of P. rudis ., Competing Interests: No potential conflict of interest was reported by the authors., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of the Korean Society of Mycology.)

In our effort to find antimicrobial agents from higher fungi, we isolated a new compound, dentipellin (1), along with three known glycosylated diterpenes, erinacines A-C (2-4) from culture broth of Dentipellis fragilis. Their chemical structures were determined by spectroscopic methods including NMR and mass measurements. These compounds exhibited weak antibacterial and antifungal activities., (© 2021. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Thirteen ( Z )-2-(substituted benzylidene)benzimidazothiazolone analogs were synthesized and evaluated for their inhibitory activity against mushroom tyrosinase. Among the compounds synthesized, compounds 1 - 3 showed greater inhibitory activity than kojic acid (IC 50 = 18.27 ± 0.89 μM); IC 50 = 3.70 ± 0.51 μM for 1 ; IC 50 = 3.05 ± 0.95 μM for 2 ; and IC 50 = 5.00 ± 0.38 μM for 3 , and found to be competitive tyrosinase inhibitors. In silico molecular docking simulations demonstrated that compounds 1 - 3 could bind to the catalytic sites of tyrosinase. Compounds 1 - 3 inhibited melanin production and cellular tyrosinase activity in a concentration-dependent manner. Notably, compound 2 dose-dependently scavenged ROS in B16F10 cells. Furthermore, compound 2 downregulated the protein kinase A (PKA)/cAMP response element-binding protein (CREB) and mitogen-activated protein kinase (MAPK) signaling pathways, which led to a reduction in microphthalmia-associated transcription factor (MITF) expression, and decreased tyrosinase, tyrosinase related protein 1 (TRP1), and TRP2 expression, resulting in anti-melanogenesis activity. Hence, compound 2 may serve as an anti-melanogenic agent against hyperpigmentation diseases.

Brain-derived neurotrophic factor (BDNF) is known to promote fear learning as well as avoidant behavioral responses to chronic social defeat stress, but, conversely, this peptide can also have antidepressant effects and can reduce depressant-like symptoms such as social avoidance. The purpose of this study was to use a variety of approaches to determine whether BDNF acting on tropomyosin receptor kinase B (TrkB) promotes or prevents avoidant phenotypes in hamsters and mice that have experienced acute social defeat stress. We utilized systemic and brain region-dependent manipulation of BDNF signaling before or immediately following social defeat stress in Syrian hamsters, TrkB F616A knock-in mice, and C57Bl/6J mice and measured the subsequent behavioral response to a novel opponent. Systemic TrkB receptor agonists reduced, and TrkB receptor antagonists enhanced, behavioral responses to social defeat in hamsters and mice. In the neural circuit that we have shown mediates defeat-induced behavioral responses, BDNF in the basolateral amygdala, but not the nucleus accumbens, also reduced social avoidant phenotypes. Conversely, knockdown in the basolateral amygdala of TrkB signaling in TrkB F616A mice enhanced defeat-induced social avoidance. These data demonstrate that systemic administration of BDNF-TrkB drugs at the time of social defeat alters the behavioral response to the defeat stressor. These drugs appear to act, at least in part, in the basolateral amygdala and not the nucleus accumbens. These findings were generalizable to two rodent species with very different social structures and, within mice, to a variety of strains providing converging evidence that BDNF-TrkB signaling reduces anxiety- and depression-like symptoms following short-term social stress., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the comparative effects and safety of topical diclofenac sodium, fluorometholone, and dexamethasone for controlling inflammation after routine strabismus surgery., Methods: This was a randomized clinical trial. Ninety-nine patients admitted for surgery to treat intermittent exotropia were randomly assigned to receive 1 of 3 postoperative eye drops between January 2015 and February 2016. The primary efficacy outcomes were pain and conjunctival injection. Pain score from 0 to 10 was evaluated in each patient at postoperative days 1, 2, 3, and 5, in addition to weeks 1, 2, and 4. Conjunctival injection was graded from 1 to 4 at postoperative weeks 1, 2, and 4. We also evaluated intraocular pressure (IOP), discomfort attributed to the drops, and development of any other side effects., Results: Conjunctival injection grade was the lowest in the diclofenac sodium group at postoperative weeks 1 and 2 (P < 0.001 and P = 0.03). There was no significant difference in pain score among the 3 groups. Mean IOP was the highest in the dexamethasone group at postoperative weeks 1, 2, and 4 (P < 0.001, P < 0.001, and P = 0.02). Significant IOP elevation (≥10 mmHg relative to preoperative IOP) was observed in 6 patients in the dexamethasone group. There was no difference in discomfort upon administration of the drops among the 3 groups, and no other adverse events developed., Conclusion: Diclofenac sodium was more effective against conjunctival injection than the 2 topical corticosteroids tested, but had a similar effect on postoperative pain as them. IOP elevation developed only in the dexamethasone group.

Alpha-Synuclein (α-Syn) is an important protein in the pathogenesis of Parkinson disease (PD) as it accumulates as fibrillar inclusions in affected brain regions including dopaminergic neurons in the substantia nigra. Elevated levels of α-Syn seem to be crucial in mediating its toxicity. Thus, detailed information regarding the regulatory mechanism of α-Syn expression in several layers such as transcription, post-transcription and post-translation is needed in order to devise therapeutic interventions for PD. Previously, we reported that expression of α-Syn is repressed by microRNA-7 (miR-7) through its effect on the 3'-untranslated region (UTR) of α-Syn mRNA. Here, we show that miR-7 also accelerates the clearance of α-Syn and its aggregates by promoting autophagy in differentiated ReNcell VM cells. Further, miR-7 facilitates the degradation of pre-formed fibrils of α-Syn transported from outside the cells. This additional mechanism for reducing α-Syn levels show miR-7 to be an important molecular target for PD and other alpha-synucleinopathies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Data on the clinical characteristics of asthma patients including utilization of medical facilities, disease management, and healthcare costs by types of health care are insufficient., Methods: We evaluated data on 729,343 asthma patients from the Health Insurance Review and Assessment Service (HIRA) database of Korea between July 2013 and June 2014., Results: Most asthma patients were treated via primary care (81.7%), followed by tertiary (17.8%) and secondary (0.5%) care. Patients requiring secondary or tertiary care exhibited more comorbidities and exacerbations than those treated via primary care, and utilized more medical facilities (associated with higher medical costs). The prescription rate of leukotriene receptor antagonists (LTRAs) was relatively high for those receiving all types of health care, ranging from 62% to 78%. However, the prescription rate of inhalants containing corticosteroids was significantly lower in patients treated via primary care than those receiving secondary or tertiary care (P<0.001). In addition, pulmonary function testing (PFT) was performed less often in patients treated via primary care than in those receiving secondary or tertiary care (P<0.001)., Conclusions: Most patients with asthma were treated via primary care; however, those receiving secondary or tertiary care exhibited substantial utilization of medical facilities with high costs. Diagnostic measures and the prescription of inhalants containing corticosteroids in primary care require urgent attention., Competing Interests: Conflicts of Interest: Chin Kook Rhee has received consulting/lecture fees from MSD, AstraZeneca, Novartis, GSK, Takeda, Mundipharma, Sandoz, Boehringer-Ingelheim, and Teva-Handok. Hye Yun Park has received lecture fees from AstraZeneca, Novartis, and Boehringer-Ingelheim. The other authors have no conflicts of interest to declare.

Background: Molecular mechanisms underlying psychological sequelae of exposure to stressful experiences, such as posttraumatic stress disorder (PTSD) and depression, are not well understood., Methods: Using convergent evidence from animal and human transcriptomic and genomic studies, we aimed to identify genetic mechanisms underlying depression and anxiety after traumatic experiences., Results: From a transcriptome-wide analysis in mice, we found the Ppm1f gene to be differentially expressed in the amygdala and medial prefrontal cortex (mPFC) a week after immobilization stress. Next, we found that PPM1F messenger RNA levels in human blood were downregulated in cases with symptoms of comorbid PTSD and depression and consistently in cases with anxiety symptoms in a separate human dataset. Furthermore, we showed that a genetic variant of PPM1F, rs17759843, was associated with comorbid PTSD and depression and with PPM1F expression in both human brain and blood. Given prior reported mechanistic links between PPM1F and CAMK2 (CAMKII), we examined blood messenger RNA level of CAMK2G in humans and found it to be lower in cases with comorbid PTSD and depression. We also found that PPM1F protein levels and colocalization with CAMK2G were altered in amygdala and mPFC of male mice. Additionally, we found that a systemic dose of corticosterone blocked the depressive-like phenotype elicited by stress in female mice. Lastly, corticosterone rescued the anxiety-like phenotype and messenger RNA levels of Ppm1f in amygdala and mPFC in male mice and in mPFC of female mice., Conclusions: Taken together, our data suggest a mechanistic pathway involving PPM1F and CAMK2G in stress- and trauma-related manifestation of anxiety and depression across species., (Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Although Syrian hamsters are thought to be naturally solitary, recent evidence from our laboratory demonstrates that hamsters may actually prefer social contact. Hamsters increase their preference for a location associated with an agonistic encounter regardless of whether they have "won" or "lost". It has also been reported that social housing as well as exposure to intermittent social defeat or to a brief footshock stressor increase food intake and body mass in hamsters. By contrast, it has also been suggested that housing hamsters in social isolation causes anxiety-induced anorexia and reductions in body mass selectively in females. The purpose of this study was to determine the physiological consequences of housing hamsters in social isolation versus in social groups. Male and female hamsters were housed singly or in stable groups of 5 for 4weeks after which they were weighed and trunk blood was collected. In addition, fat pads and thymus and adrenal glands were extracted and weighed. Serum and fecal cortisol were measured using an enzyme-linked immunoassay. Housing condition had no effect on serum or fecal cortisol, but socially housed hamsters displayed modest thymus gland involution. Socially housed females weighed more than did any other group, and socially housed females and males had more fat than did socially isolated hamsters. No wounding or tissue damage occurred in grouped hamsters. Overall, these data suggest that Syrian hamsters tolerate both stable social housing and social isolation in the laboratory although social housing is associated with some alteration in stress-related and bioenergetic measures., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We estimated the exposure to ambient air pollutants and analyzed the associations with allergic diseases. We enrolled 177 children with atopic dermatitis (AD) and 70 asthmatic adults living in Seoul Metropolitan Area, Korea, and followed for 17months between August 2013 and December 2014. Parents or patients recorded symptom scores on a daily basis. Exposure to particulate matter with a diameter <10μm (PM 10 ) and nitrogen dioxide (NO 2 ) was estimated in four different ways in each individual, using the AQ1 (measurements from the nearest air quality monitoring station to residential houses), AQ2 (measurements modified from AQ1 with the indoor level of air pollutants and time activity of each individual), AQ1-DI, and AQ2-DI (measurements modified from AQ1 and AQ2, respectively, with daily inhalation intakes of air pollutants). A generalized linear mixed model (GLMM) was used to analyze the associations between exposure metrics and clinical symptoms after adjusting for ambient temperature and humidity, age, season, gender, and time trend. The exposure metrics for PM 10 and NO 2 showed different distributions. Symptoms of AD and asthma were positively associated with exposure to PM 10 , but not NO 2 , in all exposure metrics. The effect size of PM 10 exposure on asthma symptoms was slightly greater in metrics with inhalation capacity (AQ-DIs) than in those without (AQs). This pattern was not observed in AD. Exposure to PM 10 is associated with symptom aggravation in childhood AD and adult asthma. Different exposure estimates may be used to evaluate the impact of air pollution on different allergic diseases., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background and Purpose: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic small-vessel vasculitis accompanied by asthma, eosinophilia, and eosinophilic inflammation of various tissues including the peripheral nerves. This study investigated the clinical course and long-term outcomes of peripheral neuropathy in patients with EGPA., Methods: Seventy-one patients with physician-diagnosed EGPA were identified at Samsung Medical Center between January 1995 and April 2014. Sixty-one of these patients were followed-up for more than 1 year and received corticosteroid therapy with or without intravenous cyclophosphamide pulse therapy for 6 to 18 months. Medical records of the 61 patients including demographic data, clinical features, laboratory and pathological findings, treatments, and outcomes were reviewed., Results: Peripheral neuropathy as a manifestation of EGPA was present in 46 (75%) of the 61 patients. The mean follow-up duration of the patients with neuropathy was 6.4 years (range 1.2-18.8 years). The scores on the neurological functional disability scale before and after the combination treatment with corticosteroid and cyclophosphamide were 2.43±0.86 and 0.54±0.95 (mean±SD; p<0.001), respectively. The peripheral neuropathy relapsed in one patient., Conclusions: The long-term clinical outcome of peripheral neuropathy in patients with EGPA receiving initial corticosteroid and cyclophosphamide combination therapy was favorable with a very low relapse rate., Competing Interests: The authors have no financial conflicts of interest.

Histone acetylation has emerged as a critical factor regulating learning and memory both during and after exposure to stressful stimuli. There are drugs that we now know affect histone acetylation that are already in use in clinical populations. The current study uses these drugs to examine the consequences of acutely increasing or decreasing histone acetylation during exposure to social stress. Using an acute model of social defeat in Syrian hamsters, we systemically and site-specifically administered drugs that alter histone acetylation and measured subsequent behavior and immediate-early gene activity. We found that systemic administration of a histone deacetylase inhibitor enhances social stress-induced behavioral responses in males and females. We also found that systemic administration completely blocks defeat-induced neuronal activation, as measured by Fos-immunoreactivity, in the infralimbic cortex, but not in the amygdala, after a mild social defeat stressor. Lastly, we demonstrated that site-specific administration of histone deacetylase inhibitors in the infralimbic region of the prefrontal cortex, but not in the basolateral amygdala, mimics the systemic effect. Conversely, decreasing acetylation by inhibiting histone acetyltransferases in the infralimbic cortex reduces behavioral responses to defeat. This is the first demonstration that acute pharmacological manipulation of histone acetylation during social defeat alters subsequent behavioral responses in both males and females. These results reveal that even systemic administration of drugs that alter histone acetylation can significantly alter behavioral responses to social stress and highlight the importance of the infralimbic cortex in mediating this effect., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Selective and precise control of the layer number of graphene remains a critical issue for the practical applications of graphene. First, it is highly challenging to grow a continuous and uniform few-layer graphene since once the monolayer graphene fully covers a copper (Cu) surface, the growth of the second layer stops, resulting in mostly nonhomogeneous films. Second, from the selective adlayer growth point of view, there is no clear pathway for achieving this. We have developed the selective growth of a graphene adlayer in layer-by-layer via chemical vapor deposition (CVD) which makes it possible to stack graphene on a specific position. The key idea is to deposit a thin Cu layer (∼40 nm thick) on pre-grown monolayer graphene and to apply additional growth. The thin Cu atop the graphene/Cu substrate acts as a catalyst to decompose methane (CH4) gas during the additional growth. The adlayer is grown selectively on the pre-grown graphene, and the thin Cu is removed through evaporation during CVD, eventually forming large-area and uniform double layer graphene. With this technology, highly uniform graphene films with precise thicknesses of 1 to 5 layers and graphene check patterns with 1 to 3 layers were successfully demonstrated. This method provides precise LBL growth for a uniform graphene film and a technique for the design of new graphene devices.

We report a simple and mass-scalable approach for thin MoS2 films via RF sputtering combined with the post-deposition annealing process. We have prepared as-sputtered film using a MoS2 target in the sputtering system. The as-sputtered film was subjected to post-deposition annealing to improve crystalline quality at 700 °C in a sulfur and argon environment. The analysis confirmed the growth of continuous bilayer to few-layer MoS2 film. The mobility value of ~29 cm(2)/Vs and current on/off ratio on the order of ~10(4) were obtained for bilayer MoS2. The mobility increased up to ~173-181 cm(2)/Vs, respectively, for few-layer MoS2. The mobility of our bilayer MoS2 FETs is larger than any previously reported values of single to bilayer MoS2 grown on SiO2/Si substrate with a SiO2 gate oxide. Moreover, our few-layer MoS2 FETs exhibited the highest mobility value ever reported for any MoS2 FETs with a SiO2 gate oxide. It is presumed that the high mobility behavior of our film could be attributed to low charged impurities of our film and dielectric screening effect by an interfacial MoOxSiy layer. The combined preparation route of RF sputtering and post-deposition annealing process opens up the novel possibility of mass and batch production of MoS2 film.

Cardiac involvement is the most important prognostic factor in eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome). The aims of this study were to describe findings of cardiac magnetic resonance (CMR) in patients with active EGPA and to find factors associated with cardiac involvement detected by CMR that could help identify patients who would benefit from the examination. Medical records and CMR images in 16 consecutive EGPA patients (8 women and 8 men, median age of 47 years ranging from 34 to 68 years) were reviewed. Clinical features and results of laboratory tests were compared according to the presence of myocardial late gadolinium enhancement (LGE) on CMR images. The patients were followed for the development of cardiac symptoms and signs (mean follow up duration, 40.5 ± 12.8 months). Among the total of 16 patients, 8 (50 %) had myocardial LGE according to CMR, located in the subendocardial layer in 7 of them (87.5 %). The extent of LGE had a significant negative correlation with left ventricular ejection fraction (LVEF, ρ = -0.723, p = 0.043). The presence of LGE was associated with larger end-systolic left ventricle internal dimension (34 vs. 28 mm, p = 0.027) and presence of diastolic dysfunction (75 vs. 0 %, p = 0.008) on echocardiography, elevated NT-proBNP (75 vs. 12.5 %, p = 0.012), and elevated CK-MB (62.5 vs. 0 %, p = 0.010) compared to the group without LGE. Only one patient (6.3 %) had cardiac symptoms before CMR and another patient (6.3 %) developed heart failure 4 years later during remission. The other 14 patients remained free from cardiac signs and symptoms during the follow-up period. In patients with active EGPA, CMR enables detection of cardiac involvement when cardiac symptoms are not present. Echocardiographic diastolic dysfunction and elevated NT-proBNP or CK-MB may help identify active EGPA patients who can benefit from CMR to detect cardiac involvement without cardiac symptoms.

Mitochondrial dysfunction is one of the major contributors to neurodegenerative disorders including Parkinson disease. The mitochondrial permeability transition pore is a protein complex located on the mitochondrial membrane. Under cellular stress, the pore opens, increasing the release of pro-apoptotic proteins, and ultimately resulting in cell death. MicroRNA-7 (miR-7) is a small non-coding RNA that has been found to exhibit a protective role in the cellular models of Parkinson disease. In the present study, miR-7 was predicted to regulate the function of mitochondria, according to gene ontology analysis of proteins that are down-regulated by miR-7. Indeed, miR-7 overexpression inhibited mitochondrial fragmentation, mitochondrial depolarization, cytochrome c release, reactive oxygen species generation, and release of mitochondrial calcium in response to 1-methyl-4-phenylpyridinium (MPP(+)) in human neuroblastoma SH-SY5Y cells. In addition, several of these findings were confirmed in mouse primary neurons. Among the mitochondrial proteins identified by gene ontology analysis, the expression of voltage-dependent anion channel 1 (VDAC1), a constituent of the mitochondrial permeability transition pore, was down-regulated by miR-7 through targeting 3'-untranslated region of VDAC1 mRNA. Similar to miR-7 overexpression, knockdown of VDAC1 also led to a decrease in intracellular reactive oxygen species generation and subsequent cellular protection against MPP(+). Notably, overexpression of VDAC1 without the 3'-UTR significantly abolished the protective effects of miR-7 against MPP(+)-induced cytotoxicity and mitochondrial dysfunction, suggesting that the protective effect of miR-7 is partly exerted through promoting mitochondrial function by targeting VDAC1 expression. These findings point to a novel mechanism by which miR-7 accomplishes neuroprotection by improving mitochondrial health., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Drug-induced anaphylaxis is a big pitfall in patients receiving antineoplastic chemotherapy. We report a case of lung cancer patient who experienced two near-fatal anaphylactic reactions that resulted from paclitaxel and multivitamin, seperately. Recurrent severe reactions to different agents led to further investigation to which material the patient was hypersensitive. The skin prick test revealed sensitization to cremophor, which is a commonly used emulsifying agent. This case emphasizes the importance of correctly identifying the culprit drug of anaphylaxis to avoid potentially fatal reaction.

In this article, we report layer-controlled, continuous and large-area molydenum sulfide (MoS2) growth onto a SiO2/Si substrate by RF sputtering combined with sulfurization. A two-step process was employed to synthesize MoS2 films. In the first step, an atomically thin MoO3 film was deposited by RF magnetron sputtering at 300 °C. Subsequently, the as-sputtered MoO3 film was further subjected to post-annealing and sulfurization processes at 650 °C for 1 hour. It was observed that the number of layers of MoS2 can be controlled by adjusting the sputtering time. The fabricated MoS2 transistors exhibited high mobility values of ∼21 cm(2) V(-1) s(-1) (bilayer) and ∼25 cm(2) V(-1) s(-1) (trilayer), on/off ratios in the range of ∼10(7) (bilayer) and 10(4)-10(5) (trilayer), respectively. We believe that our proposed paradigm can start a new method for the growth of MoS2 in future electronics and optoelectronics applications.

In this paper a novel filtering scheme combined with a lighting method is proposed for defect detection in steel surfaces. A steel surface has non-uniform brightness and various shaped defects, which cause difficulties in defect detection. To solve this problem we propose a sub-optimal filtering that is combined with a switching-lighting method. First, dual-light switching lighting (DLSL) is explained, which decreases the effect of non-uniformity of surface brightness and improves the detection accuracy. By using the DLSL method, defects are represented as alternated black and white patterns regardless of the size, shape, or orientation of defects. Therefore, defects can be detected by finding alternated black and white patterns. Second, we propose a scheme for detecting defects in steel-surface images acquired using the DLSL method. The presence of scales strongly affects the optical properties of the surface. Moreover, the textures of steel-plate images vary greatly because of the temperature and grade of steel. Therefore, conventional filter-design methods are not effective for different image textures. A sub-optimal scheme based on an optimized general-finite impulse-response filter is also proposed. Finally, experimental results conducted on steel-surface images from an actual steel-production line show the effectiveness of the proposed algorithm.