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Well-characterized in chronic rhinosinusitis, type 2 inflammation is frequently associated with nasal polyps, comorbid asthma, and nonsteroidal anti-inflammatory drug hypersensitivity. Despite medical and surgical treatment, it recurs in a significant proportion of patients. Thus, severe uncontrolled type 2 chronic rhinosinusitis with nasal polyps is the most difficult-to-treat phenotype of chronic rhinosinusitis. Recently, dupilumab, a monoclonal antibody against IL-4 receptor α, and omalizumab, a monoclonal antibody against immunoglobulin E, were approved for patients with chronic rhinosinusitis with nasal polyps in the United States, Europe, and Korea. Therefore, rhinologists should understand novel biologics and their use. Here, we provide a literature review of several biologics with their indications, effectiveness, and safety.

Background and Objectives Several studies have shown that three single nucleotide polymorphisms (SNPs) in the TAS2R38 gene demonstrate a strong association with the ability to sense the bitter taste of phenylthiocarbamide (PTC) in. We have previously reported about TAS2R38 genotypes in normal volunteers. The aim of this study was to investigate the role TAS2R38 gene plays in taste disorder by examining SNPs in the TAS2R38 gene in taste disorder patients.Subjects and Method Ninety-four patients with taste dysfunction from multiple etiologies were enrolled. The genotypes were defined by identifying SNPs on the TAS2R38 gene. The proportion of different TAS2R38 genotypes in the group was compared with that in the normal volunteers of our previous study. The whole mouth taste threshold tests were performed and the thresholds were compared among the three different genotypic groups.Results The proportion of each diplotype in taste disorder patients were as follows: PAV/ PAV 36.2% (34/94), PAV/AVI 34.0% (32/94), and AVI/AVI 29.8% (28/94). The proportion of AVI/AVI type was higher in the group than in the normal volunteers (p=0.031). The detection and recognition thresholds of all four basic tastes were increased in the order of PAV/PAV, PAV/AVI, and AVI/AVI genotypes.Conclusion The proportion of AVI/AVI homozygous was significantly higher in taste disorder patients than in the normal volunteers. Our findings suggest that the genotypes of TAS2R38 may represent one of the risk factors responsible for the development of taste disorders.

Two-dimensional materials have attracted great attention for their outstanding electronic properties. In particular, molybdenum disulfide (MoS2) shows great potential as a next-generation semiconductor due to its tunable direct bandgap with a high on-off ratio and extraordinary stability. However, the performance of MoS2 synthesized by physical vapor deposition has been limited by contact resistance between an electrode and MoS2, which determines overall device characteristics. Here, in order to reduce the contact resistance, we use in situ sulfurization of Mo by H2S gas treatment masked by a patterned graphene gas barrier, so that the Mo channel area can be selectively formed, resulting in a gradual edge contact between Mo and MoS2. Compared with field-effect transistors with a top contact between the Au/Ti electrode and the MoS2 channel, a gradual edge contact between the Mo electrode and the MoS2 channel provides a considerably enhanced electrical performance.

Background and Objectives Olfactory and gustatory dysfunctions have been known as characteristic symptoms of coronavirus disease 2019 (COVID-19). However, the study of the clinical features of olfactory and gustatory dysfunctions in COVID-19 is still insufficient.Subjects and Method Mild COVID-19 patients who complained of olfactory or gustatory dysfunctions in the telephone monitoring from March 8 to April 8, 2020 were included in this study. Patient information was collected using a Google questionnaire. COVID-19 symptoms, severity and improvement of olfactory and gustatory dysfunctions of patients were investigated.Results A total of 228 patients participated in this study. The number of male and female were 76 and 152, and the average age was 32.1±11.5 years. There were 210 patients (92.1%) of olfactory dysfunction, 179 patients (78.5%) of gustatory dysfunction, and 165 patients (71.4%) who complained of both symptoms. The 18.4% of patients complained only olfactory or gustatory dysfunction without other symptoms of COVID-19, and 51.1% of patients presented olfactory and gustatory dysfunctions as the first symptoms. Most of the patients (95.6%) improved olfactory and gustatory dysfunctions within several months, but only 79.8% of patients were normalized.Conclusion Since olfactory and gustatory dysfunctions are the first symptoms in the numerous COVID-19 patients, and continued research on these patients play an important role in the screening and prevention of COVID-19. Long-term observation and further studies of treatment are needed for 20.2% of patients who have not fully recovered.

Background While ETV6- NTRK3 fusion is common in infantile fibrosarcoma, NTRK1/3 fusion in pediatric tumors is scarce and, consequently, not well known. Herein, we evaluated for the presence of NTRK1/3 fusion in pediatric mesenchymal tumors, clinicopathologically and immunophenotypically. Methods We reviewed nine NTRK fusion-positive pediatric sarcomas confirmed by fluorescence in situ hybridization and/or next-generation sequencing from Seoul National University Hospital between 2002 and 2020. Results One case of TPR-NTRK1 fusion-positive intracranial, extra-axial, high-grade undifferentiated sarcoma (12-year-old boy), one case of LMNA-NTRK1 fusion-positive low-grade infantile fibrosarcoma of the forehead (3-year-old boy), one case of ETV6-NTRK3 fusion-positive inflammatory myofibroblastic tumor (IMT) (3-months-old girl), and six cases of ETV6-NTRK3 fusion-positive infantile fibrosarcoma (median age: 2.6 months, range: 1.6–5.6 months, M: F = 5:1) were reviewed. The Trk immunopositivity patterns were distinct, depending on what fusion genes were present. We observed nuclear positivity in TPR-NTRK1 fusion-positive sarcoma, nuclear membrane positivity in LMNA-NTRK1 fusion-positive sarcoma, and both cytoplasmic and nuclear positivity in ETV6-NTRK3 fusion-positive IMT and infantile fibrosarcomas. Also, the TPR-NTRK1 fusion-positive sarcoma showed robust positivity for CD34/nestin, and also showed high mitotic rate. The LMNA-NTRK1 fusion-positive sarcoma revealed CD34/S100 protein/nestin/CD10 coexpression, and a low mitotic rate. The IMT with ETV6-NTRK3 fusion expressed SMA. Six infantile fibrosarcomas with ETV6-NTRK3 fusion showed variable coexpression of nestin (6/6)/CD10 (4/5)/ S100 protein (3/6). Conclusions All cases of NTRK1 and NTRK3 fusion-positive pediatric tumors robustly expressed the Trk protein. A Trk immunopositive pattern and CD34/S100/nestin/CD10/SMA immunohistochemical expression may suggest the presence of NTRK fusion partner genes. LMNA-NTRK1 fusion sarcoma might be a low-grade subtype of infantile fibrosarcoma. Interestingly, more than half of the infantile fibrosarcoma cases were positive for S100 protein and CD10. The follow-up period of TPR-NTRK1 and LMNA-NTRK1 fusion-positive tumors are not enough to predict prognosis. However, ETV6-NTRK3 fusion-positive infantile fibrosarcomas showed an excellent prognosis with no evidence of disease for an average of 11.7 years, after gross total resection of the tumor.

Although plasma complement factor B (CFB, NX_P00751), both alone and in combination with CA19-9 (i.e., the ComB-CAN), previously exhibited a reliable diagnostic ability for pancreatic cancer (PC), its detectability of the early stages and the cancer detection mechanism remained elusive. We first evaluated the diagnostic accuracy of ComB-CAN using plasma samples from healthy donors (HDs), patients with chronic pancreatitis (CP), and patients with different PC stages (I/II vs III/IV). An analysis of the area under the curve (AUC) by PanelComposer using logistic regression revealed that ComB-CAN has a superior diagnostic ability for early-stage PC (97.1.% [95% confidence interval (CI): (97.1-97.2)]) compared with CFB (94.3% [95% CI: 94.2-94.4]) or CA19-9 alone (34.3% [95% CI: 34.1-34.4]). In the comparisons of all stages of patients with PC vs CP and HDs, the AUC values of ComB-CAN, CFB, and CA19-9 were 0.983 (95% CI: 0.983-0.983), 0.950 (95% CI: 0.950-0.951), and 0.873 (95% CI: 0.873-0.874), respectively. We then investigated the molecular mechanism underlying the detection of early-stage PC by using stable cell lines of CFB knockdown and CFB overexpression. A global transcriptomic analysis coupled to cell invasion assays of both CFB-modulated cell lines suggested that CFB plays a tumor-promoting role in PC, which likely initiates the PI3K-AKT cancer signaling pathway. Thus our study establishes ComB-CAN as a reliable early diagnostic marker for PC that can be clinically applied for early PC screening in the general public.

Background Endoscopic sinus surgery (ESS) is the mainstay treatment for refractory chronic rhinosinusitis (CRS). Since various factors may contribute to the surgical outcome, it is challenging for physicians to predict surgical outcomes. The aim of study was to analyze the prognostic factors of postoperative outcomes and to establish the prediction model with the risk factors that impact the postoperative outcomes. Methods Medical records of CRS patients who underwent ESS at 9 institutions in 2005, 2010, and 2016 were retrospectively reviewed. We classified the patients into 2 groups based on postoperative objective endoscopic outcomes. Demographics, nose-specific symptoms, olfactory function, eosinophil counts in blood (EoB) and nasal tissue (EoT), and Lund-Mackay CT score (LMS) were collected. Univariate and multivariate analyses were performed and established a prediction equation for postoperative endoscopic objective outcomes. Results In total (n = 1,249), 27.0% were not satisfied under postoperative endoscopic examination. Of 10 variables, LMS (> 5), sinus dominancy (maxillary sinus and ethmoid sinus), EoB (> 210), and EoT (> 100) were statistically significant in univariate analysis (P < 0.05, all). In multivariate analysis, EoT (> 100) and LMS (> 5) were significantly associated with poor postoperative outcome. Furthermore, 5 significant variables were employed to establish the risk model of postoperative outcomes and P (the value of prediction probability) = 1 / (1 + exp [−0.392 + 1.088 × EoT (> 100) + 0.123 × mean LMS (> 5) − 0.366 × sinus dominancy (maxillary) + 0.064 × sinus dominancy (similar) + 0.200 × EoB (4%) + 0.344 × EoB (> 210)] was developed. Conclusion Tissue eosinophil count and radiographic severity predispose to a poorer outcome of ESS and the risk model established may be helpful to predict postoperative outcomes of ESS., Graphical Abstract

Fungus ball (FB) is the most common type of fungal rhinosinusitis and the prevalence of FB has increased over the past 10 years. The aim of this study was to compare the clinical characteristics of Korean adult patients with FB and chronic rhinosinusitis (CRS) without FB. We retrospectively analyzed data on 1362 patients (147 FB and 1215 CRS) who underwent endoscopic sinus surgery at nine Korean medical centers in 2005, 2010, and 2016. We evaluated the prevalence of FB and compared the clinical characteristics of FB and CRS. Medical records, computed tomography (CT) findings, atopic status, concomitant diseases, tissue, and blood eosinophil count were assessed. The prevalence of FB was significantly higher in 2016 (15.9%) than in the other years (7.8% in 2005 and 7.5% in 2010). The FB patients were more likely to be female, older, have unilateral disease and less likely to have allergy compared to the CRS patients. The most common main complaint related to CRS and FB was nasal obstruction. CT determined that unilateral disease and maxillary sinus dominancy were common in patients with FB. The incidence of concomitant diseases was much higher in FB, with lower tissue and blood eosinophilia. FB is commonly encountered in older women with the increased prevalence. FB had a different clinical presentation, radiological findings, and prognosis than CRS. Further studies are needed to understand the pathophysiologic mechanisms underlying the development of FB.

We have developed a high-power ultraviolet (UV) nanosecond-pulsed laser based on a rod-type photonic crystal fiber. The UV pulse energy and the pulse repetition rate are 0.75 mJ and 100 kHz, respectively, yielding 75-W UV average power. The temporal pulse shape and the linewidth of a 1030-nm seed laser are optimized for efficient third-harmonic generation, and the high conversion efficiency of 50% is achieved with a good beam quality ( M 2 ∼ 1.2 ). To our knowledge, this is the highest UV pulse energy from fiber lasers.

Post-traumatic stress disorder (PTSD) is a debilitating neuropsychiatric disease with a projected lifetime risk of 8.7%. PTSD is highly comorbid with depressive disorders including major depressive disorder (MDD) and bipolar disorder (BD). It is hypothesized that the overlap in symptoms stems from partially shared underlying neurobiological mechanisms. To better understand shared and unique transcriptional patterns of PTSD and MDD we performed RNA-sequencing in the postmortem brain of two prefrontal cortex (PFC) regions and two amygdala (AMY) regions, from neurotypical donors (N=109) as well as donors with diagnoses of PTSD (N=107) or MDD (N=109) across 1285 RNA-seq samples. We identified a small number of differentially expressed genes (DEGs) specific to PTSD, mostly in the cortex compared to amygdala. PTSD-specific DEGs were preferentially enriched in cortistatin-expressing cells, a subpopulation of somatostatin interneurons. These PTSD DEGs also showed strong enrichment for gene sets associated with immune-related pathways and microglia, largely driven by decreased expression of these genes in PTSD donors. While we identified a greater number of DEGs for MDD, there were only a few that were specific to MDD as they showed high overlap with PTSD DEGs. Finally, we used weighted gene co-expression network analysis (WGCNA) as an orthogonal approach to confirm the observed cellular and molecular associations. These findings highlight the sub-population of cortistatin-expressing interneurons as having potential functional significance in PTSD and provide supporting evidence for dysregulated neuroinflammation and immune signaling in MDD and PTSD pathophysiology.

PURPOSE: We developed predictive models using different programming languages and different computing platforms for machine learning (ML) and deep learning (DL) that classify clinical diagnoses in patients with epiphora. We evaluated the diagnostic performance of these models. METHODS: Between January 2016 and September 2017, 250 patients with epiphora who underwent dacryocystography (DCG) and lacrimal scintigraphy (LS) were included in the study. We developed five different predictive models using ML tools, Python-based TensorFlow, R, and Microsoft Azure Machine Learning Studio (MAMLS). A total of 27 clinical characteristics and parameters including variables related to epiphora (VE) and variables related to dacryocystography (VDCG) were used as input data. Apart from this, we developed two predictive convolutional neural network (CNN) models for diagnosing LS images. We conducted this study using supervised learning. RESULTS: Among 500 eyes of 250 patients, 59 eyes had anatomical obstruction, 338 eyes had functional obstruction, and the remaining 103 eyes were normal. For the data set that excluded VE and VDCG, the test accuracies in Python-based TensorFlow, R, multiclass logistic regression in MAMLS, multiclass neural network in MAMLS, and nuclear medicine physician were 81.70%, 80.60%, 81.70%, 73.10%, and 80.60%, respectively. The test accuracies of CNN models in three-class classification diagnosis and binary classification diagnosis were 72.00% and 77.42%, respectively. CONCLUSIONS: ML-based predictive models using different programming languages and different computing platforms were useful for classifying clinical diagnoses in patients with epiphora and were similar to a clinician’s diagnostic ability. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13139-019-00574-1) contains supplementary material, which is available to authorized users.

Background While ETV6-NTRK3 fusion is common in infantile fibrosarcoma, NTRK1 fusion in pediatric sarcoma is extremely rare and consequently not well known. Herein, we evaluated NTRK1 fusion pediatric sarcomas to determine their clinicopathological nature and differential diagnosis from classic ETV6-NTRK3 fusion infantile fibrosarcoma. Methods We retrieved and reviewed eight NTRK-fusion pediatric sarcomas confirmed by fluorescence in situ hybridization and/or next-generation sequencing from Seoul National University Hospital between 2002 and 2019. Results The NTRK1 fusion-positive tumors included one case of TPR-NTRK1 fusion in a 12-year-old boy with an intracranial extra-axial high-grade undifferentiated sarcoma and an LMNA-NTRK1 fusion in a 3-year-old boy with a low-grade infantile fibrosarcoma of the forehead. Six cases of infantile fibrosarcoma with ETV6-NTRK3 fusion were identified (median age: 2.6 months, range: 1.6–5.6 months, M: F = 5:1). The TPR-NTRK1 fusion sarcoma showed nuclear Trk expression, robust CD34/nestin expression (S100 protein-negative), and high mitoses. The LMNA-NTRK1 fusion sarcoma showed nuclear membrane Trk expression, CD34/S100 protein/nestin/CD10 coexpression, and a low mitotic rate. The six cases of infantile fibrosarcoma with ETV6-NTRK3 fusion showed S100 protein (3/6)/nestin(6/6)/CD10 (4/5) coexpression and both cytoplasmic and nuclear Trk expression but were CD34-negative. Conclusions All cases of NTRK1 and NTRK3 fusion-positive pediatric sarcomas robustly expressed the Trk protein. A Trk immunopositive pattern and CD34/S100/nestin/CD10 immunohistochemical profile may suggest NTRK fusion partner genes. TPR-NTRK1 and LMNA-NTRK1 fusions might be surrogate markers for pediatric mesenchymal tumors, while LMNA-NTRK1 fusion sarcoma might be a low-grade infantile fibrosarcoma subtype. More than half of the infantile fibrosarcoma cases were S100 protein and CD10-positive. The cases of infantile fibrosarcoma showed good prognoses regardless of tumor cellularity, Ki-67 index, and mitoses.

Transition metal dichalcogenides (TMDs) possess great potential for use in gas sensing applications because, in contrast to conventional metal oxides, they have unique semiconducting properties with band gaps that can be tuned by adjusting thickness and composition. However, one issue is that their recovery time at room temperature is too long for them to be used practically in sustainable sensing applications. We found that incorporating Se atoms weaken interactions with gas molecules compared to when S atoms are used alone, therefore, the responsivity, as well as the recovery properties, of MoSxSe2-x sensors were significantly enhanced by increasing the ratio of Se to S. Herein, we demonstrate high-performance gas sensors that are based on reduced graphene oxide (rGO) fibers coated with MoSxSe2-x, the fabricated sensor could efficiently refresh its surface to allow fast, complete recovery at room temperature. Furthermore, it was shown that the porosity of rGO fibers with their large surface-to-volume ratio leads to enhanced sensing at room temperature.

Background Upper airway barrier dysfunction has been associated with chronic rhinosinusitis and allergic rhinitis. Alternaria is commonly found in nasal secretion and plays a role in the pathogenesis of airway diseases. The aim of this study was to investigate the effects of Alternaria on the junctional complex of nasal epithelial cells. Methods Air-liquid interface nasal epithelial cultures from the inferior turbinate of septal surgery patients were stimulated with Alternaria alternate. Production of intracellular reactive oxygen species (ROS) and transepithelial resistance (TER) was measured. The expression of tight junction (TJ) and adherens junction (AJ) molecules was determined using real-time reverse transcriptase-polymerase chain reaction, Western blot analysis, and confocal microscopy. Protease activity in Alternaria was determined using protease inhibitors and heat inactivation. Results Alternaria enhanced the production of ROS and reduced the TER. Alternaria decreased the messenger RNA and protein expression of TJs (zonula occludens-1, occludin, and claudin-1), but did not influence the AJ molecule. When Alternaria was pretreated with serine protease inhibitor and heat inactivation, ROS, TER, and TJ molecule expression returned to their nonstimulated levels. Conclusion Serine protease in Alternaria altered nasal epithelial barrier function. Intracellular ROS induced by Alternaria may influence the barrier function of nasal epithelial cells and enhance the inflammatory process of nasal mucosa.

Echinococcus granulosus sensu lato (s.l.) is a causative agent of cystic echinococcosis or cystic hydatid disease in humans and domestic and wild animals. The disease is a serious health problem in countries associated with poverty and poor hygiene practices, particularly in livestock raising. We introduced a practical algorism for genotyping the parasite, which may be useful to many developing countries. To evaluate the efficiency of the algorism, we genotyped 3 unknown strains isolated from human patients. We found that unknowns 1 and 3 were included in G1, G2, and G3 genotypes group and unknown 2 was included in G4 genotype (Echinococcus equinus) according to the algorisms. We confirmed these results by sequencing the 3 unknown isolates cox1 and nad1 PCR products. In conclusion, these new algorisms are very fast genotype identification tools that are suitable for evaluating E. granulosus s.l. isolated from livestock or livestock holders, particularly in developing countries.

RNA sequencing (RNA-seq) is a powerful approach for measuring gene expression levels in cells and tissues, but it relies on high-quality RNA. We demonstrate here that statistical adjustment using existing quality measures largely fails to remove the effects of RNA degradation when RNA quality associates with the outcome of interest. Using RNA-seq data from molecular degradation experiments of human primary tissues, we introduce a method—quality surrogate variable analysis (qSVA)—as a framework for estimating and removing the confounding effect of RNA quality in differential expression analysis. We show that this approach results in greatly improved replication rates (>3×) across two large independent postmortem human brain studies of schizophrenia and also removes potential RNA quality biases in earlier published work that compared expression levels of different brain regions and other diagnostic groups. Our approach can therefore improve the interpretation of differential expression analysis of transcriptomic data from human tissue.

In this letter, we have investigated the properties of In0.53Ga0.47As quantum-well (QW) metal–oxide–semiconductor field-effect-transistors (MOSFETs) on a 300-mm(100) Si wafer. We have explored the impact of scaling down In0.53Ga0.47As channel thickness ( $\text{t}_{\mathrm {ch}})$ from 15 to 5 nm. The fabricated devices show excellent electrostatic integrity, such as subthreshold-swing (SS) $\mu _{\textit {n$\_{}$eff}})$ of the fabricated devices to investigate the carrier transport properties of the InGaAs MOSFETs with different values of $\text{t}_{\mathrm {ch}}$ . The device with $\text{t}_{\mathrm {ch}} = 15$ nm displayed a value of $\mu _{\textit {n$\_{}$eff}} = 2,190$ cm2/V-s at room temperature. This valuewas found to decrease as $\text{t}_{\mathrm {ch}}$ was scaled down.

Beyond being one the most widely used psychoactive drugs in the world, cannabis has been identified as an environmental risk factor for psychosis. Though the relationship between cannabis use and psychiatric disorders remains controversial, consistent association between early adolescent cannabis use and the subsequent risk of psychosis suggested adolescence may be a particularly vulnerable period. Previous findings on gene by environment interactions indicated that cannabis use may only increase the risk for psychosis in the subjects who have a specific genetic vulnerability. The type 1 cannabinoid receptor (CB1), encoded by the CNR1 gene, is a key component of the endocannabinoid system. As the primary endocannabinoid receptor in the brain, CB1 is the main molecular target of the endocannabinoid ligand, as well as tetrahydrocannabinol (THC), the principal psychoactive ingredient of cannabis. In this study, we have examined mRNA expression and DNA methylation of CNR1 in human prefrontal cortex (PFC), hippocampus, and caudate samples. The expression of CNR1 is higher in fetal PFC and hippocampus, then drops down dramatically after birth. The lifespan trajectory of CNR1 expression in the DLPFC differentially correlated with age by allelic variation at rs4680, a functional polymorphism in the COMT gene. Compared with COMT methionine158 carriers, Caucasian carriers of the COMT valine158 allele have a stronger negative correlation between the expression of CNR1 in DLPFC and age. In contrast, the methylation level of cg02498983, which is negatively correlated with the expression of CNR1 in PFC, showed the strongest positive correlation with age in PFC of Caucasian carriers of COMT valine158. Additionally, we have observed decreased mRNA expression of CNR1 in the DLPFC of patients with schizophrenia. Further analysis revealed a positive eQTL SNP, rs806368, which predicted the expression of a novel transcript of CNR1 in human DLPFC, hippocampus and caudate. This SNP has been associated with addiction and other psychiatric disorders. THC or ethanol are each significantly associated with dysregulated expression of CNR1 in the PFC of patients with affective disorder, and the expression of CNR1 is significantly upregulated in the PFC of schizophrenia patients who completed suicide. Our results support previous studies that have implicated the endocannabinoid system in the pathology of schizophrenia and provided additional insight into the mechanism of increasing risk for schizophrenia in the adolescent cannabis users.

Radiogenomics or imaging genomics is a novel omics strategy of associating imaging data with genetic information, which has the potential to advance personalized medicine. Imaging features extracted from PET or PET/CT enable assessment of in vivo functional and physiological activity and provide comprehensive tumor information non-invasively. However, PET features are considered secondary to features on conventional imaging, and there has not yet been a review of the radiogenomic approach using PET features. This review article summarizes the current state of PET-based radiogenomic research for cancer, which discusses some of its limitations and directions for future study.

BackgroundAcacia honey is known to have antioxidant, immune-modulatory, and antiproliferative properties. Nasal fibroblasts participate in local immune responses that control the recruitment of inflammatory cells and the production of extracellular matrix.ObjectivesThe aim of this study was to determine the effect of acacia honey on myofibroblast differentiation and matrix metalloproteinase-9 (MMP-9) production in nasal polyp fibroblasts.MethodsPrimary nasal fibroblasts were isolated from nasal polyps and treated with transforming growth factor-beta 1 (TGF-β1). Reverse transcription-polymerase chain reaction and Western blot analysis were then performed to determine α-smooth muscle actin (α-SMA), tissue inhibitors of matrix metalloproteinase-1, and MMP-9 mRNA expression and protein production in nasal polyp fibroblasts. Phosphorylated Smad ( pSmad) 2/3 and phosphorylated adenosine monophosphate-activated protein kinase ( pAMPK) were then determined by Western blotting.ResultsTGF-β1 stimulation increased α-SMA and MMP-9 mRNA expression and protein production in nasal polyp fibroblasts. Acacia honey effectively suppressed α-SMA and MMP-9 mRNA expression and protein production. It also prevented phosphorylation of Smad 2/3 and AMPK.ConclusionAcacia honey can inhibit TGF-β1-induced myofibroblast differentiation and MMP-9 production in nasal fibroblasts. These results suggest that acacia honey might be useful for inhibiting nasal polyp formation.

In this paper, we have fabricated and characterized In 0.7 Ga 0.3 As quantum-well (QW) metal-oxide-semiconductor field-effect-transistors (MOSFETs). We have employed the gate dielectric of the Al 2 O 3 /HfO 2 (0.6/2 nm) bi-layer stack by ALD. The fabricated device with L g = 4 μm exhibits a record maximum transconductance ( g m_max ) in excess of 520 μS/μm at >1 μm region, and reasonably good electrostatic integrity, such as SS = 110 mV/decade and DIBL = 43 mV/V. Also, we have investigated the gate length scaling behavior in terms of output, transconductance, and transfer characteristics. In particular, our devices feature very uniform values of the electrostatic integrity, such as SS = 100–110 mV/decade, V T = −0.25 V to −0.2 V and DIBL = 40–50 mV/V, as L g decreases from 10 μm to 4 μm. Furthermore, we have explored the impact of source resistance ( R S ) onto the device characteristics of the InGaAs QW MOSFETs. In doing so, we have modeled both measured extrinsic transconductance ( g m_ext ) and intrinsic transconductance ( g m_int ) as a function of L g .

We have fabricated highly efficient green phosphorescent organic light-emitting diodes by solution process. Very interestingly, we found that the device efficiency is affected by interface between hole transport layer (HTL) and emission layer (EML). It was proved through spin cleaning process of cross-linkable HTL after curing which may affect the interface mixing. In addition, we tried to add complement layer to manipulate such effects. As a result, we significantly improved device efficiency (up to 72.7 cd/A) after spin cleaning process of the cross-linkable HTL material.

We have achieved 140-nm channel length graphene thin-film transistors (TFTs) on flexible glass with a 95-GHz intrinsic cutoff frequency and greater than 30-GHz intrinsic power frequency after standard de-embedding. The flexible glass substrate offers subnanometer surface smoothness as well as high thermal conductivity, 1 W/ $\textrm {m}\,\cdot \, \textrm {K}$ , which can prevent thermomechanical failure, which is a limitation of plastic and rubber substrates. In addition, we developed a flexible 60-nm polyimide thin film as gate dielectric with low surface roughness less than 0.35 nm for optimal carrier transport and facilitate edge-injection contacts for low contact resistance. The maximum electron (hole) mobility is 4540 (1100) cm2/ $\textrm {V}\cdot \textrm {s}$ , and the extracted contact resistance in the electron (hole) branch is 1140 (720) $\Omega \cdot \mu \text{m}$ . The intrinsic cutoff frequency is 196% higher than our previous results on polymeric substrates. Importantly, the experimental saturation velocity of the graphene TFT is the highest for any flexible transistor on any material system reported so far.

Long-channel In0.7Ga0.3As/In0.52Al0.48As quantum-well (QW) metal-oxide-semiconductor field-effect-transistors (MOSFETs) on InP substrate have been fabricated and characterised. The fabricated device with Lg = 4 μm exhibits excellent maximum transconductance (gm_max ) in excess of 0.48 mS/μm at V DS = 0.95 V, together with reasonably good electrostatic integrity of drain-induced-barrier-lowering < 40 mV/V and subthreshold-swing

The present study aims to investigate the immunomodulatory effects of essential oil from Chamaecyparis obtusa (EOCO) in an ovalbumin (OVA)-induced allergic rhinitis (AR) mouse model. BALB/c mice were intraperitoneally sensitized and stimulated with OVA. From day 22 to 35, 0.01% and 0.1% ECOC was intranasally administered 1 h before OVA stimulation. Nasal symptoms, as well as serum total and OVA-specific immunoglobulin (Ig) E levels, were measured. Interleukin (IL)-4, IL-10, interferon (IFN)-&gamma, and tumor necrosis factor (TNF)-&alpha, levels in nasal lavage fluid (NLF) and their production by activated splenocytes were measured. Histological changes in the sinonasal mucosa were evaluated through hematoxylin and eosin and periodic acid-Schiff staining procedure. Th cytokines and their transcription factor mRNA expressions were determined using reverse-transcription polymerase chain reaction. Intranasal EOCO administration significantly suppressed allergic symptoms, OVA-specific IgE level, sinonasal mucosal inflammatory cell infiltration, and mucus-producing periodic acid-Schiff (PAS) positive cell count. EOCO also significantly inhibited IL-4, IL-10, and TNF-&alpha, levels in NLF and activated splenocytes. Th2 and Treg related cytokines and their transcription factors in sinonasal mucosa were significantly suppressed through intransal EOCO instillation. In conclusion, repetitive EOCO intranasal instillation showed anti-inflammatory and anti-allergic effects by suppressing nasal symptoms and inhibiting the production and expression of inflammatory mediators in the OVA-induced AR mouse model.

Airborne fungi are associated with upper and lower airway inflammatory diseases. Alternaria is commonly found in nasal secretions and induces the production of chemical mediators from sinonasal mucosa. This study aimed to establish an Alternaria-induced chronic rhinosinusitis (CRS) mouse model and determine the influence of host allergic background on the immunopathological characteristics of CRS. BALB/c mice were used for establishing the CRS model. Alternaria was intranasally instilled for 8 or 16 weeks with or without ovalbumin (OVA) presensitization. Total serum IgE and Alternaria-specific IgE levels were measured by enzyme-linked immunosorbent assay (ELISA). Interleukin (IL)-4, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α levels in nasal lavage fluid (NLF) and splenocytes were measured by ELISA and their mRNAs and levels of associated transcription factors in sinonasal mucosa were determined with quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). Hematoxylin-eosin staining and periodic acid-Schiff staining were performed to evaluate histological changes. Total serum IgE was increased in both allergic and non-allergic CRS. IL-4 was strongly expressed in NLF in both allergic and non-allergic CRS at 16 weeks and not only eosinophils but also neutrophils were increased in NLF of non-allergic CRS mice. The levels of Th1, Th2, and Treg cytokines and transcription factor mRNAs were significantly increased in sinonasal mucosa of non-allergic CRS mice. Both inflammatory cell infiltration and goblet cell hyperplasia were increased in CRS mice. Repeated intranasal instillation of Alternaria results in sinonasal inflammation with inflammatory cell infiltration. The sinonasal mucosal immune responses against Alternaria were shown to differ depending on the host allergic background.

Cigarette smoking during pregnancy is a major public health concern. While there are well-described consequences in early child development, there is very little known about the effects of maternal smoking on human cortical biology during prenatal life. We therefore performed a genome-wide differential gene expression analysis using RNA sequencing (RNA-seq) on prenatal (N = 33; 16 smoking-exposed) as well as adult (N = 207; 57 active smokers) human postmortem prefrontal cortices. Smoking exposure during the prenatal period was directly associated with differential expression of 14 genes; in contrast, during adulthood, despite a much larger sample size, only two genes showed significant differential expression (FDR

Recent development in mobile electronic devices and electric vehicles requires electrical wires with reduced weight as well as enhanced stability. In addition, since electric energy is mostly generated from power plants located far from its consuming places, mechanically stronger and higher electric power transmission cables are strongly demanded. However, there has been no alternative materials that can practically replace copper materials. Here, we report a method to prepare ultrastrong graphene fibers (GFs)-Cu core-shell wires with significantly enhanced electrical and mechanical properties. The core GFs are synthesized by chemical vapor deposition, followed by electroplating of Cu shells, where the large surface area of GFs in contact with Cu maximizes the mechanical toughness of the core-shell wires. At the same time, the unique electrical and thermal characteristics of graphene allow a ∼10 times higher current density limit, providing more efficient and reliable delivery of electrical energies through the GFs-Cu wires. We believe that our results would be useful to overcome the current limit in electrical wires and cables for lightweight, energy-saving, and high-power applications.

In this study, we investigated Ti-doped ITO films formed through ionized physical vapor deposition (IPVD) using inductively coupled plasma (ICP). Ti-doped ITO thin films showed an enhanced mobility with ICP power; owing to the improved crystallinity, and the sheet resistance of the Ti-doped ITO (30 nm) largely decreased from 295.1 to 134.5 ohm/sq, even during at room temperature. Therefore, IPVD technology offers a useful tool for transparent electrodes with a large area window-unified touch-screen panel.

High-frequency characteristics of L g = 60 nm In 0.7 Ga 0.3 As MOS-high-electron-mobility transistor (HEMTs) with a 3 nm aluminium oxide grown by atomic-layer-deposition is reported. Fabricated In 0.7 Ga 0.3 As MOS-HEMTs with L g = 60 nm exhibit subthreshold-swing (SS) = 89 mV/dec., drain-induced-barrier-lowering = 98 mV/V, g m_max = 1.1 mS/μm, f T = 187 GHz and f max = 202 GHz at V DS = 0.5 V. The high-frequency characteristics showed is the best balanced demonstration of f T and f max in the buried-channel indium gallium arsenide MOS-HEMTs, revealing a strong potential of the buried-channel design scheme for future high frequency, low-noise and high-performance logic applications.

Ready mixed acrylic paste (RMAP) is a material used in exterior insulation systems of buildings; it consists of liquids and aggregates. However, it is considerably difficult to use an admixture to control the physical properties of the RMAP owing to problems associated with strength and workability. Thus, to improve the properties of RMAP, this study evaluates the properties of a mortar produced with RMAP as well as pozzolanic materials and atomizing slag, which is a by-product from the steelmaking industry. It was observed that if the density difference is large, a liquid RMAP may experience segregation. Through our experiments, we confirm that segregation resistance could be achieved even at 20% atomizing slag, which has a high density, by increasing the viscosity by approximately 1000 cP through the use of 10% fly ash and 3% metakaolin in the RMAP. Despite the increase in viscosity with the addition of the atomizing slag, the flow of the RMAP increased from 160 to 175 mm due to the spherical particle shape of the slag; in addition, the strength and water absorption coefficient also improved. In particular, the adhesion tension increased from 1.8 N/mm2 to 2.4 N/mm2 or higher.

Cigarette smoking during pregnancy is a major public health concern. While there are well-described consequences in early child development, there is very little known about the effects of maternal smoking on human cortical biology during prenatal life. We therefore performed a genome-wide differential gene expression analysis using RNA sequencing (RNA-seq) on prenatal (N=33; 16 smoking-exposed) as well as adult (N=207; 57 active smokers) human post-mortem prefrontal cortices. Smoking exposure during the prenatal period was directly associated with differential expression of 14 genes; in contrast, during adulthood, despite a much larger sample size, only 2 genes showed significant differential expression (FDRin utero exposure to smoking and the heightened risks for the subsequent development of neuropsychiatric disorders.One Sentence SummaryMaternal smoking during pregnancy alters the expression of genes within the developing human cortex and these changes are enriched for genes implicated in neuropsychiatric disorders.

OBJECTIVE Patients with sleep-related breathing disorders are known to have more severe psychiatric symptoms than good sleepers. The aim of this study was to compare the psychiatric symptoms of participants with obstructive sleep apnea (OSA), those with simple snoring (SS), and normal controls (NC). METHODS A total of 386 participants (260 with OSA, 75 with SS, and 51 NC) completed self-report questionnaires including the Symptoms Checklist 90-Revised and underwent nocturnal polysomnography. The scores of nine primary symptom dimensions and three global distress indices of the Symptoms Checklist 90-Revised were compared among the three groups, adjusting for age, sex, and body mass index. RESULTS Participants with suspected OSA (OSA + SS) reported more severe psychiatric symptoms than the NC group. Compared with the participants with OSA, those with SS manifested more severe obsessive-compulsive (1.4 (1.0) versus 1.1 (0.7), p = .008) and depressive (1.2 (1.2) versus 0.8 (0.8), p = .031) symptoms and higher Global Severity Index (1.0 (0.9) versus 0.7 (0.6), p = .039) and Positive Symptom Distress Index (2.0 (0.8) versus 1.7 (0.6), p = .009). Only higher Pittsburgh Sleep Quality Index values predicted higher Global Severity Index (B = 0.11, p = .041) and Positive Symptom Distress Index (B = 0.46, p = .007) in suspected OSA participants. CONCLUSIONS This study found that individuals with suspected OSA experienced more severe psychiatric symptoms than NCs and that psychiatric symptoms were more severe in the SS group than in the OSA group. The psychiatric symptoms of suspected OSA patients were associated with subjective sleep quality rather than with the apnea-hypopnea index.

Bee venom (BV) has long been used as anti-inflammatory agent in traditional oriental medicine; however, the effect of BV on chronic rhinosinusitis (CRS) is not commonly studied. The aim of the present study was to determine the anti-inflammatory effect of BV on an allergic CRS mouse model. An allergic CRS mouse model was established following the administration of ovalbumin with Staphylococcus aureus enterotoxin B (SEB) into the nose. A total of 0.5 or 5 ng/ml of BV were intranasally applied 3 times a week for 8 weeks. Histopathological alterations were observed using hematoxylin and eosin, and Periodic acid Schiff staining. The levels of inflammatory cell infiltration, interleukin (IL)‑4, IL‑10 and interferon (INF)‑γ in nasal lavage fluid (NLF) were measured. Nuclear factor (NF)‑κB and activator protein (AP)‑1 expressions were also determined by immunohistochemical staining. The group treated with BV had significantly decreased inflammatory cell infiltration and PAS‑positive cells. The levels of INF‑γ, and neutrophil and eosinophil counts in NLF were significantly decreased, and the SEB‑induced NF‑κB and AP‑1 expressions in mouse nasal mucosa were significantly suppressed by 0.5 and 5 ng/ml BV. Thus, BV exerted significant anti‑inflammatory effects in an allergic CRS mouse model and may have potential value for the treatment of CRS.

Introduction Although consultations are essential for delivering safe, high-quality care to patients in emergency departments, they contribute to emergency department patient flow problems and overcrowding which is associated with several adverse outcomes, such as increases in patient mortality and poor quality care. This study aimed to investigate how time flow metrics including emergency department length of stay is influenced by changes to the internal medicine consultation policy. Method This study is a pre- and post-controlled interventional study. We attempted to improve the internal medicine consultation process to be more concise. After the intervention, only attending emergency physicians consult internal medicine chief residents, clinical fellows, or junior staff of each internal medicine subspecialty who were on duty when patients required special care or an admission to internal medicine. Results Emergency department length of stay of patients admitted to the department of internal medicine prior to and after the intervention decreased from 996.94 min to 706.62 min. The times from consultation order to admission order and admission order to emergency department departure prior to and after the intervention were decreased from 359.59 min to 180.38 min and from 481.89 min to 362.37 min, respectively. The inpatient mortality rates and Inpatient bed occupancy rates prior to and after the intervention were similar. Conclusion The improvements in the internal medicine consultation process affected the flow time metrics. Therefore, more comprehensive and cooperative strategies need to be developed to reduce the time cycle metrics and overcrowding of all patients in the emergency department.

Background Chronic rhinosinusitis with nasal polyps (NP) (CRSwNP) is classified into eosinophilic and noneosinophilic types based on the level of tissue eosinophilia. The immunopathologic features of Western and Asian CRSwNP differ. Objectives The aim of this study was to investigate the immunopathologic characteristics of Korean patients with eosinophilic NP versus noneosinophilic NP and those with atopic NP versus nonatopic NP. Methods Tissue samples were collected from 81 patients with NP and 24 controls. The clinical characteristics of all the patients were analyzed. Tissues were investigated for expression of chemical mediators, including interleukin (IL) 5, IL-10, IL-17, interferon-γ, and tumor growth factor-β1; transcription factors, including GATA binding protein 3 (GATA-3), forkhead box P3 (Foxp3), retinoic acid–related orphan receptor C (RORC), and T-box transcription factor (T-bet), and extracellular matrix, including collagen type I, fibronectin, tissue inhibitor of metalloproteinase 1, and matrix metalloproteinase (MMP) 9. Results Although the clinical characteristics differed between eosinophilic and noneosinophilic NPs, atopic status did not affect the clinical findings of CRSwNP. Both T-helper 1 and 2 cytokines increased significantly in patients with eosinophilic NP, but atopic status did not affect the expression of any of the chemical mediators. GATA-3 messenger RNA (mRNA) expression increased significantly in patients with eosinophilic NP, and RORC mRNA expression increased significantly in patients with noneosinophilic NP. T-bet, RORC, and Foxp3 mRNA expression increased significantly in patients with nonatopic NP. Fibronectin and MMP-9 mRNA expression increased significantly in patients with noneosinophilic NP, whereas only MMP-9 mRNA increased significantly in patients with eosinophilic and those with noneosinophilic NP. Conclusion The immunopathologic characteristics differed between eosinophilic NP and noneosinophilic NP and between atopic NP and nonatopic NP. The different underlying pathogenic processes may influence the development of Korean NP.

We report on the impact of H2 high-pressure annealing (HPA) onto In0.7Ga0.3As MOSCAPs and quantum-well (QW) MOSFETs with Al2O3/HfO2 gate-stack. After HPA with process condition of 300 °C, H2 ambient and pressure of 20 atm, we observed notable improvements of the capacitance–voltage (CV) characteristics in InGaAs MOSCAPs with Al2O3/HfO2 gate-stack, such as reduction of equivalent-oxide-thickness and less frequency dispersion in the accumulation region. There was 20% improvement of the interfacial trap density ( $D_{{\rm {it}}})$ . Then, we incorporated the HPA process into the fabrication of sub-100-nm In0.7Ga0.3As QW MOSFETs, to investigate the impact of HPA process. After HPA process, the device with $L_{g} = 50$ nm exhibits improved subthreshold-swing (SS) = 105 mV/decade, in comparison with SS = 130 mV/decade for the reference device without HPA process. Finally, we carried out reliability assessment under a constant-voltage-stress (CVS), and it turns out that the HPA process was effective in mitigating a shift of threshold voltage ( $\Delta \text{V}_{T})$ during the CVS. These are attributed to the effective passivation of oxide traps in the high- $k$ dielectric layer and interfacial traps, after HPA process in the H2 ambient.

Metal-semiconductor–metal (MSM) varactor diodes based on InAlN/GaN high electron mobility transistor structures were fabricated and characterized. Among the MSM varactors with gate lengths ranging from 90 to 270 nm and gate distances of 2 and $4~\mu \text{m}$ , the highest performance was obtained from the MSM varactor with gate length of 90 nm and gate spacing of 2 $\mu \text{m}$ . The capacitance switching ratio ( $C_{\max }/C_{\min })$ of 2.31 together with a high cutoff frequency ( $f_{o})$ of 308 GHz was demonstrated. The calculated figures of merit (FOMs), which were defined to be $f_{o}\cdot C_{\max }/C_{\min }$ for the comparison of devices performance, were 523 and 769 GHz for devices with gate spacing of 4 and 2 $\mu \text{m}$ , respectively. The FOMs were not dependent on gate length of the devices, but highly dependent on gate spacing.