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Stress and its management among health professionals during the coronavirus disease 2019 (COVID-19) pandemic is a social issue. Stress in health professionals is caused not only by personal events but also by managing patients with COVID-19. The present study aimed to find effective interventions for managing stress related to COVID-19 among health professionals. As a result of a literature search, there were five studies related to interventions for managing stress related to COVID-19 among health professionals between 2020 and 2022. These interventions included mobile phone-based cognitive behavior therapy, music therapy, emotional freedom techniques, and safety group programs for stress management. These interventions were identified as being effective in managing stress related to COVID-19 among health professionals.

NMDA receptor (NMDAR) and GABA neuronal dysfunctions are observed in animal models of autism spectrum disorders, but how these dysfunctions impair social cognition and behavior remains unclear. We report here that NMDARs in cortical parvalbumin (Pv)-positive interneurons cooperate with gap junctions to promote high-frequency (>80 Hz) Pv neuronal burst firing and social cognition. Shank2–/– mice, displaying improved sociability upon NMDAR activation, show impaired cortical social representation and inhibitory neuronal burst firing. Cortical Shank2–/– Pv neurons show decreased NMDAR activity, which suppresses the cooperation between NMDARs and gap junctions (GJs) for normal burst firing. Shank2–/– Pv neurons show compensatory increases in GJ activity that are not sufficient for social rescue. However, optogenetic boosting of Pv neuronal bursts, requiring GJs, rescues cortical social cognition in Shank2–/– mice, similar to the NMDAR-dependent social rescue. Therefore, NMDARs and gap junctions cooperate to promote cortical Pv neuronal bursts and social cognition., How NMDAR and GABA neuronal dysfunctions result in impaired social behaviour is unclear. Here, the authors show that NMDARs and gap junctions in cortical PV interneurons modulate burst firing, affecting social behaviour.

Changes in thin-film transistor (TFT) characteristics can cause nonuniform brightness in organic light-emitting diode (OLED) displays, and external compensation circuits cannot address such changes if they occur rapidly. Our system acquires a short segment of the source voltage curve of the TFT driving each pixel, during the vertical blanking interval. It then estimates the threshold voltage ${V}_{\text {th}}$ and the mobility-related parameter ${k}$ of that TFT, using neural networks and recurrent conditional (RC) learning to perform expectation–maximization (EM). Finally, it corrects the pixel brightness accordingly. The average errors in the estimated ${V}_{\text {th}}$ and ${k}$ are, respectively, 7.3 mV and ${3.7} \times {10}^{-{11}}\,\,\text {F}/\text {V}\text {s}$ , and we demonstrate the visual effect of compensating with these estimates.

Rhizoremediation is a promising method based on the synergism between plant and rhizobacteria to remediate soil co-contaminated with heavy metals and total petroleum hydrocarbons (TPHs). A plant growth-promoting (PGP) rhizobacterium with diesel-degrading capacity and heavy metal tolerance was isolated from the rhizosphere of tall fescue (Festuca arundinacea L.), after which the effects of its inoculation on rhizoremediation performance were evaluated in heavy metal- and diesel-contaminated soil planted with tall fescue. The bacterial isolate (Novosphingobium sp. CuT1) was characterized by its indole-3-acetic acid (IAA) production, 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase activity, and siderophore productivity as PGP traits. CuT1 was able to grow on 1/10 LB-agar plates containing 5 mM of Cu or 5 mM of Pb. To evaluate the remediation effect of heavy metal- and diesel-contaminated soil by CuT1 inoculation, the experimental conditions were prepared as follows. The soil was artificially contaminated with heavy metals (Cu and Pb) at a final concentration of 500 ppm. The soil was then further contaminated with diesel at final concentrations of 0, 10,000, and 30,000 ppm. Finally, all plots were planted with tall fescue, a representative hyperaccumulating plant. Compared to the rhizoremediation performance of the co-contaminated soil (Cu + Pb + diesel) without inoculation, the bioavailable Cu concentrations in the soil and the tall fescue biomass were significantly increased in CuT1 inoculation. Additionally, the root growth of tall fescue was also promoted in CuT1 inoculation. Correlation analysis showed that Cu bioavailability and bioconcentration factor were positively correlated with CuT1 inoculation. The diesel removal efficiency showed a positive correlation with CuT1 inoculation, although the diesel removal was below 30%. CuT1 inoculation was positively correlated with IAA and dehydrogenase activity in the soil. Moreover, the dry biomass of the tall fescue's roots was highly associated with CuT1 inoculation. Collectively, our findings suggest that Novosphingobium sp. CuT1 can be utilized as an applicable bioresource to enhance rhizoremediation performance in heavy metal- and TPH-contaminated soils.

Idiopathic pulmonary fibrosis (IPF) is a lung disease that results in scarring of the lungs for an unknown reason. Although many studies have been conducted on IPF, precise mechanisms and treatments have not yet been identified. In this study, we found that aucuparin, a natural product isolated from Sorbus aucuparia, inhibited pulmonary fibrosis in a bleomycin (BLM)-induced lung fibrosis mouse model. In the lung samples of mice treated with aucuparin, the gene expression of inflammation and macrophage activation markers was reduced compared to those treated with BLM alone. Moreover, aucuparin decreased the expression of profibrotic marker genes and increased the expression of antifibrotic marker genes. Finally, we observed that aucuparin significantly suppressed transforming growth factor-β-induced activation of inflammatory cytokine production and collagen synthesis from macrophages and fibroblasts, respectively. Taken together, these data demonstrate that aucuparin inhibits lung fibrosis via its anti-inflammatory action and support its potential to be a therapeutic drug for IPF treatment.

Background The accurate pathologic diagnosis and subtyping of high-grade endometrial carcinoma are often problematic, due to its atypical and overlapping histopathological features. Methods Three pathologists reviewed 21 surgically resected cases of advancedstage endometrial carcinoma. The primary diagnosis was based only on hematoxylin and eosin stained slides. When a discrepancy arose, a secondary diagnosis was made by additional review of immunohistochemical (IHC) stains. Finally, three pathologists discussed all cases and rendered a consensus diagnosis. Results The primary diagnoses were identical in 13/21 cases (62%). The secondary diagnosis based on the addition of IHC results was concordant in four of eight discrepant cases. Among four cases with discrepancies occurring in this step, two cases subsequently reached a consensus diagnosis after a thorough discussion between three reviewers. Next-generation sequencing (NGS) study was performed in two cases in which it was difficult to distinguish between serous carcinoma and endometrioid carcinoma. Based on the sequencing results, a final diagnosis of serous carcinoma was rendered. The overall kappa for concordance between the original and consensus diagnosis was 0.566 (moderate agreement). Conclusions We investigated stepwise changes in interobserver diagnostic reproducibility in advanced-stage endometrial carcinoma. We demonstrated the utility of IHC and NGS study results in the histopathological diagnosis of advanced-stage endometrial carcinoma.

In this article, we propose a novel real-time threshold voltage ( $V_{th}$ ) compensation method for AM-OLED display. The proposed method predicts $V_{th}$ shift of driving thin-film transistors (TFTs) based on the equation derived from the sensing line charging with TFT’s drain current. The prediction equation requires two consecutive source node voltages to consider the mobility variation, and only takes hundreds of microseconds to predict $V_{th}$ shift. It is short enough to monitor the real-time $V_{th}$ degradation, since the prediction can be carried out during the vertical blank time. Also, very high prediction accuracy was confirmed through Smart SPICE simulation. We simulated severe mobility variation and $V_{th}$ shift circumstances, and the simulation results showed that the prediction error was less than one just noticeable difference (JND) margin though out all gray levels. We expect that the proposed method can achieve more accurate and faster real-time $V_{th}$ degradation compensation for high resolution and large-sized OLED displays than conventional one.

Orthodontic treatment of posterior bite collapse due to early loss of molars and the consequent drift of adjacent teeth is complicated. When the posterior bite collapse occurs in patients with facial asymmetry, both transverse and vertical compensation are necessary for camouflage orthodontic treatment. In such cases, posterior maxillary segmental osteotomy (PMSO) can be an effective alternative procedure that simplifies the orthodontic treatment and shows long-term stability through dental compensation within the alveolar bone housing. This case report aimed to describe the orthodontic treatment of maxillary occlusal plane canting caused by severely extruded maxillary teeth in a patient with skeletal facial asymmetry that was corrected with PMSO along with protraction of the lower second molar to replace the space of the extracted first molar. The treatment duration was 18 months, and stable results were obtained after 2 years of retention.

This paper introduces novel driving methods of the pull-down unit in a gate driver circuit for enhancement- and depletion-mode a-IGZO thin-film transistors (TFTs). The proposed gate driver circuit can achieve uniform output characteristics and effectively reduce the $\text{V}_{\mathrm{ OUT}}$ ripple voltage because the threshold voltage ( $\text{V}_{\mathrm{ TH}}$ ) of the pull-down units is compensated regardless of the a-IGZO TFT operation characteristics (enhancement mode: positive value of $\text{V}_{\mathrm{ TH}}$ , depletion mode: negative value of $\text{V}_{\mathrm{ TH}}$ ). Many groups proposed the $\text{V}_{\mathrm{ TH}}$ compensation method for pull-down TFTs in the gate driver circuit using a diode connection structure. However, the diode connection structure to extract the $\text{V}_{\mathrm{ TH}}$ value cannot be applied in the depletion-mode oxide TFTs because TFT enters the turn-on state even when the $\text{V}_{\mathrm{ GS}}$ value is 0 V. To solve this problem, we adopted the $\text{V}_{\mathrm{ TH}}$ extraction period only once in one frame time. As a result, our circuit can compensate for $\text{V}_{\mathrm{ TH}}$ of the pull-down unit in the enhancement mode and can be normally operated in the depletion mode. Adjunctively, two low signals (VGL1 and VGL2) and QC node were designed to prevent the leakage current path for Q and $\text{V}_{\mathrm{ OUT}}$ nodes. To verify the threshold voltage tolerance for various stress conditions, we demonstrated the reliability of the circuit according to the threshold voltage change of the TFTs. The simulation result shows that all the $\text{V}_{\mathrm{ OUT}}$ waveforms are maintained at +28 V (VGH) under the $\text{V}_{\mathrm{ TH}}$ shift conditions from −7 V to +11 V; further, the rising time and falling time are less than $0.62~{\mu }\text{s}$ and $0.96~{\mu }\text{s}$ , respectively. Based on a 120-Hz ultra-high definition (UHD) graphics ( $3840{\times }2160$ ) display panel, the proposed circuit has uniform $\text{V}_{\mathrm{ OUT}}$ characteristics compared to previous $\text{V}_{\mathrm{ TH}}$ compensation circuit when $\Delta \text{V}_{\mathrm{ TH}}$ changes from −3 V to +11 V. When $\Delta \text{V}_{\mathrm{ TH}}$ changes from −4 V to −7 V, there is also no circuit malfunction, even with slight increase in the falling time and power consumption.

The objective of this study was to explore the seasonal characteristics of rhizoremediation and the bacterial community structure over the course of a year in soil contaminated with diesel oil. The soil was contaminated with diesel oil at a total petroleum hydrocarbon (TPH) concentration of 30,000 mg-TPH·kg-soil

Elevated cardiac troponin (cTn) showed associations with mortality even in stable patients, but management has not been established. We aimed to investigate whether consultation to cardiologists could reduce mortality of stable patients with cTn elevation at admission. We identified 1329 patients with elevated cTn level at hospitalization from outpatient clinic to any department other than cardiology or cardiac surgery between April 2010 and December 2018. The patients were divided into two groups according to cardiologist consultation at admission. For primary outcome, mortality during one year was compared in the crude and propensity-score-matched populations. In 1329 patients, 397 (29.9%) were consulted to cardiologists and 932 (70.1%) were not. Mortality during the first year was significantly lower in patients consulted to cardiologists compared with those who were not (9.8% vs. 14.2%; hazard ratio (HR), 0.50; 95% confidence interval (CI), 0.35–0.72; p < 0.001). After propensity-score matching, 324 patients were in the cardiologist consultation group and 560 patients were in the no cardiologist consultation group. One-year mortality was consistently lower in the cardiologist consultation group (10.5% vs. 14.6%; HR, 0.58; 95% CI, 0.39–0.86; p = 0.01). Cardiologist consultation may be associated with lower mortality in stable patients with cTn elevation at admission. Further studies are needed to identify effective management strategies for stable patients with elevated cTn.

Purpose: Because of disease heterogeneity, limited studies on effective chemotherapies and therapeutic agents for advanced gastric cancer are available. Erythrocyte membrane protein band 4.1-like 5 (EPB41L5) has critical roles in renal and breast cancer metastasis. However, its role in metastatic gastric cancer remains unknown. Experimental Design: The specimens of 78 gastric cancer patients were analyzed by oligonucleotide microarray and survival analysis. In vitro experiments and metastatic mice models were used to assess the effects of EPB41L5 on gastric cancer metastasis. Results: Gastric cancer patients with high EPB41L5 levels had poor prognosis and low survival rate. Further, TGFβ1-induced EPB41L5 expression promoted gastric cancer cell migration and invasion by Smad-dependent TGFβ signaling. Phospho-Smad3 recruitment to the EPB41L5 promoter was significantly inhibited by a TGFβ inhibitor. EPB41L5 overexpression increased lung metastasis of gastric cancer cells in nude mice, which was completely reversed by anti-EPB41L5 monoclonal antibody treatment. Importantly, p120-catenin knockdown abolished EPB41L5-enhanced gastric cancer cell metastasis. Anti-EPB41L5 monoclonal antibody treatment blocked the association of EPB41L5 with p120-catenin. Conclusions: TGFβ/EPB41L5/p120-catenin axis regulates gastric cancer cell metastasis, and EPB41L5 is a promising therapeutic target for advanced gastric cancer.

Idiopathic pulmonary fibrosis (IPF) causes progressive fibrosis and worsening pulmonary function. Prognosis is poor and no effective therapies exist. We show that programmed cell death 5 (PDCD5) expression is increased in the lungs of patients with IPF and in mouse models of lung fibrosis. Lung fibrosis is significantly diminished by club cell-specific deletion of Pdcd5 gene. PDCD5 mediates β-catenin/Smad3 complex formation, promoting TGF-β-induced transcriptional activation of matricellular genes. Club cell Pdcd5 knockdown reduces matricellular protein secretion, inhibiting fibroblast proliferation and collagen synthesis. Here, we demonstrate the club cell-specific role of PDCD5 as a mediator of lung fibrosis and potential therapeutic target for IPF., Idiopathic pulmonary fibrosis (IPF) is a fatal adult lung disease. Here the authors investigate the functional significance of PDCD5 in club cells as a mediator of lung fibrosis and potential therapeutic target for IPF.

Background Endosomal trafficking and amyloidogenic cleavage of amyloid precursor protein (APP) is believed to play a role in the neurodegeneration observed in Alzheimer’s disease (AD). Recent evidence has suggested that packaging and secretion of APP and its amyloidogenic cleaved products into small extracellular vesicles (EVs) may facilitate uptake of these neurotoxic factors during disease progression. However, the molecular mechanisms underlying trafficking of APP into EVs are poorly understood. Results In this study, the mechanism and impact of APP trafficking into extracellular vesicles (EVs) were assessed by a series of inducible gene knockdowns. We demonstrate that vesicle-associated proteins Alix and Syntenin-1 are essential for proper subcellular localization and efficient EV secretion of APP via an endosomal sorting complexes required for transport (ESCRT)-independent pathway. The neurotoxic C-terminal fragment (CTFβ) of APP is similarly secreted in association with small vesicles. These mechanisms are conserved in terminally differentiated neuron-like cells. Furthermore, knockdown of Alix and Syntenin-1 alters the subcellular localization of APP, sequestering the precursor protein to endoplasmic reticulum and endolysosomal compartments, respectively. Finally, transfer of small EVs containing mutant APP confers an increase in reactive oxygen species production and neurotoxicity to human induced pluripotent stem cell-derived cortical neurons and naïve primary neurons, an effect that is ameliorated by Alix and Syntenin-1 depletion. Conclusions Altogether these findings elucidate a novel mechanism for understanding the intracellular trafficking of APP and CTFβ into secreted extracellular vesicles, and the resultant potential impact on neurotoxicity in the context of Alzheimer’s disease amyloidopathy.

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial lung disease with a poor prognosis similar to that of malignancy. The causes of IPF are not clearly known, and there is no effective therapy to date. In this study, the natural compound plumbagin, which was isolated from Plumbago rosea root extract, was screened for p300 inhibitory activity. Plumbagin specifically inhibited the activity of p300 toward histone acetyltransferases. Plumbagin treatment significantly suppressed transforming growth factor-β-induced profibrotic target-gene expression and proliferation of fibroblast cell lines. Moreover, plumbagin significantly inhibited bleomycin-induced pulmonary fibrosis in mice. Taken together, these data demonstrate the inhibitory effects of plumbagin on lung fibrosis and its promise as a therapeutic agent for IPF.

Introduction Because nonalcoholic fatty liver disease (NAFLD) is becoming a leading cause of chronic liver disease, noninvasive evaluations of its severity are immediately needed. This prospective cross-sectional study evaluated the effectiveness of noninvasive assessments of hepatic steatosis, fibrosis, and steatohepatitis. Methods Patients underwent laboratory tests, liver biopsy, transient elastography, and MRI. Multiparametric MR was used to measure MRI proton density fat fraction, MR spectroscopy, T1 mapping, and MR elastography (MRE). Results We enrolled 130 patients between October 2016 and July 2019. For the diagnosis of moderate-to-severe steatosis (grade ≥ 2), the area under the receiver operating characteristic curve (AUROC) was lower in controlled attenuation parameter (0.69; 95% confidence interval [CI], 0.60-0.76) than MRI proton density fat fraction (0.82; 95% CI, 0.75-0.89; P = 0.008) and MR spectroscopy (0.83; 95% CI, 0.75-0.89; P = 0.006). For the diagnosis of advanced fibrosis (stage ≥ 3), the AUROC of MRE (0.89; 95% CI, 0.83-0.94) was superior compared with those of the Fibrosis-4 index (0.77; 95% CI, 0.69-0.84; P = 0.010), NAFLD fibrosis score (0.81; 95% CI, 0.73-0.87; P = 0.043), and transient elastography (0.82; 95% CI, 0.74-0.88; P = 0.062). For detecting advanced fibrosis or nonalcoholic steatohepatitis, the AUROC of MRE (0.86; 95% CI, 0.79-0.91) was higher than that of TE (0.76; 95% CI, 0.68-0.83) with statistical significance (P = 0.018). Discussion Multiparametric MR accurately identified a severe form of NAFLD. Multiparametric MR can be a valuable noninvasive method for evaluating the severity of NAFLD.

Non-alcoholic steatohepatitis (NASH) is a complex disease consisting of various components including steatosis, lobular inflammation, and ballooning degeneration, with or without fibrosis. Therefore, it is difficult to diagnose NASH with only one imaging modality. This study was aimed to evaluate the feasibility of magnetic resonance imaging (MRI) for predicting NASH and to develop a non-invasive multiparametric MR index for the detection of NASH in non-alcoholic fatty liver disease (NAFLD) patients. This prospective study included 47 NAFLD patients who were scheduled to undergo or underwent ultrasound-guided liver biopsy within 2 months. Biopsy specimens were graded as NASH or non-NASH. All patients underwent non-enhanced MRI including MR spectroscopy (MRS), MR elastography (MRE), and T1 mapping. Diagnostic performances of MRS, MRE, and T1 mapping for grading steatosis, activity, and fibrosis were evaluated. A multiparametric MR index combining fat fraction (FF), liver stiffness (LS) value, and T1 relaxation time was developed using linear regression analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of the newly devised MR index. Twenty NASH patients and 27 non-NASH patients were included. Using MRS, MRE, and T1 mapping, the mean areas under the curve (AUCs) for grading steatosis, fibrosis, and activity were 0.870, 0.951, and 0.664, respectively. The multiparametric MR index was determined as 0.037 × FF (%) + 1.4 × LS value (kPa) + 0.004 × T1 relaxation time (msec) −3.819. ROC curve analysis of the MR index revealed an AUC of 0.883. The cut-off value of 6 had a sensitivity of 80.0% and specificity of 85.2%. The multiparametric MR index combining FF, LS value, and T1 relaxation time showed high diagnostic performance for detecting NASH in NAFLD patients.

Wntless/GPR177 functions as WNT ligand carrier protein and activator of WNT/β-catenin signaling, however, its molecular role in gastric cancer (GC) has remained elusive. We investigated the role of GPR177 in gastric tumorigenesis and provided the therapeutic potential of a clinical development of anti-GPR177 monoclonal antibodies. GPR177 mRNA expression was assessed in GC transcriptome data sets (GSE15459, n = 184; GSE66229, n = 300); protein expression was assessed in independent patient tumor tissues (Yonsei TMA, n = 909). GPR177 expression were associated with unfavorable prognosis [log-rank test, GSE15459 (P = 0.00736), GSE66229 (P = 0.0142), and Yonsei TMA (P = 0.0334)] and identified as an independent risk predictor of clinical outcomes: GSE15459 [hazard ratio (HR) 1.731 (95% confidence interval; CI; 1.103- 2.715), P = 0.017], GSE66229 [HR 1.54 (95% CI, 1.10-2.151), P = 0.011], and Yonsei TMA [HR 1.254 (95% CI, 1.049- 1.500), P = 0.013]. Either antibody treatment or GPR177 knockdown suppressed proliferation of GC cells and sensitized cells to apoptosis. And also inhibition of GPR177 suppresses in vitro and in vivo tumorogenesis in GC cells and inhibits WNT/β-catenin signaling. Finally, targeting and inhibition of GPR177 with antibody suppressed tumorigenesis in PDX model. Together, these results suggest GPR177 as a novel candidate for prognostic marker as well as a promising target for treatment of GC patients. [BMB Reports 2018; 51(5): 255-260].

Preservation of muscle stem cell function is critical for muscle homeostasis and the regenerative capacity of stem cells declines with age, leading to muscle loss. Previously, daidzein, a natural isoflavone from Leguminosae, has been shown to prevent TNF-α-induced muscle atrophy. However, the molecular mechanisms of daidzein in these processes are currently unknown. In this study, we demonstrate a positive effect of black soybean extract (BS Ext) and daidzein on myoblast differentiation and myotube growth. Daidzein prevents dexamethasone-induced myotube atrophy through Akt activation. The promyogenic effect of BS Ext and daidzein is mediated through two promyogenic kinases, Akt and p38MAPK that in turn activates a key myogenic transcription factor MyoD. Additionally, BS Ext and daidzein promote myotube growth through Akt/mTOR/S6K pathway. Finally, daidzein augments MyoD-dependent myogenic conversion of mouse embryonic fibroblasts. Taken together, our data suggest that daidzein promotes myogenic differentiation and myotube hypertrophy through p38 and Akt/mTOR/S6K pathway.

During spinal cord development, endogenous progenitors expressing nestin can migrate into the target and differentiate into neurons and other glial cells. Microglial cells can also be derived from nestin+ progenitor cells, even in the adult brain. Knockdown of Jak kinase 3 (Jak3) signaling can increase neurogenesis with longer neurite outgrowth in cortical progenitor cells. This study investigated the effect of Jak3 signaling on differentiation from nestin+ progenitor cells using E13.5 spinal progenitor cell cultures. In growth factors-enriched culture, developing neurons could not survive after several days and also a significant proportion of nestin-expressing cells transformed into ameboid Iba1+ microglial cells, which increased exponentially after 5 days. This microgliogenesis was predominantly regulated by Jak3 signaling, which was confirmed by transcription factors responsible for microgliogenesis, and microglial migration and phagocytosis, such as Pu.1, Irf8, and Runx1. Jak3 inhibition also significantly increased the Tuj1+ growing neurites with little microglial activation. These results indicated that neuronal and microglial cell differentiation was regulated primarily by Jak3 signaling and the developing neurons and neurite outgrowth might also be regulated by Jak3-dependent microglial activity.

Epithelioid angiomyolipoma (EAML) of liver is a rare neoplasm. Hepatic EAML is often misdiagnosed as other neoplasms such as hepatocellular carcinoma due to non-specific clinical and radiologic features. The morphologic features under microscope and immunohistochemistry staining profile are important in the diagnosis EAML. Here, we report a case of 52-year-old man who found 1.2 cm mass in liver by routine checkup. On the impression of hepatocellular carcinoma, lateral sectionectomy of the liver was done. Microscopically, the tumor is composed of predominant epithelioid cells with vascular component and foamy cells. These cells were positive for HMB45, MelanA, and smooth muscle actin and negative for epithelial membrane antigen. The final diagnosis was hepatic EAML.