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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.)