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Satoru Miura,1 Hyun Ae Jung,2 Shin Yup Lee,3 Seung Hyeun Lee,4 Min Ki Lee,5 Yong Chul Lee,6 Maximilian J Hochmair,7 Cheng-Ta Yang,8 Angela Märten,9 James Chih-Hsin Yang,10 Sanjay Popat11,12 1Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan; 2Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 3Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea; 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Seoul, South Korea; 5Department of Internal Medicine, Pusan National University School of Medicine, Busan, South Korea; 6Department of Internal Medicine, Research Center for Pulmonary Disorders, Jeonbuk National University Medical School, Jeonju, South Korea; 7Department of Respiratory & Critical Care Medicine, Karl Landsteiner Institute of Lung Research & Pulmonary Oncology, Vienna, Austria; 8Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 9Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany; 10Department of Medical Oncology, National Taiwan University Cancer Center and Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; 11Lung Unit, Royal Marsden National Health Service Foundation Trust, London, United Kingdom; 12The Institute of Cancer Research, London, United KingdomCorrespondence: Sanjay Popat, Lung Unit, Royal Marsden National Health Service Foundation Trust, 203 Fulham Road, Chelsea, London, SW3 6JJ, United Kingdom, Tel +44-20-7808-2132, Email sanjay.popat@rmh.nhs.ukObjective: Two recent non-interventional trials, GioTag and UpSwinG, demonstrated encouraging time-to-treatment failure (TTF) and overall survival (OS) in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) (Del19 or L858R) who received sequential afatinib/osimertinib, especially in Asians. Here, we have undertaken a combined analysis of Asian patients from both studies.Materials and Methods: Existing medical/electronic records were identified for consecutive EGFR-tyrosine kinase inhibitor (TKI)-naïve patients who received first-line afatinib/second-line osimertinib in “real-world” practice (all T790M-positive). Patients with active brain metastases were excluded. The primary objective was TTF. OS was a key secondary objective.Results: One hundred and sixty-eight patients were analyzed. Most patients were recruited from South Korea or Japan (52/21%). At the start of afatinib, median age (range) was 61.5 years (35– 88), 58% were female, Eastern Cooperative Oncology Group Performance Status (ECOG PS) (0/1/≥ 2) was 29/62/9%, 17% had brain metastases, and EGFR mutation status (Del19/L858R) was 65/35%. At the start of osimertinib, ECOG PS (0/1/≥ 2) was 22/61/17% and 14% had brain metastases. Median TTF and OS were 30.0 months (95% CI: 24.5– 32.5) and 45.2 months (95% CI: 41.7– 71.1), respectively. Median OS was 63.5 months in patients with a Del19 mutation. Median OS in patients with brain metastases or ECOG PS ≥ 2 was 26.4 and 33.1 months, respectively.Conclusion: Sequential afatinib/osimertinib showed encouraging activity in Asian patients with EGFR mutation-positive NSCLC and T790M-mediated acquired resistance, especially those with Del19-positive disease. Activity was observed across “real-world” patients including those with poor ECOG PS and/or brain metastases. ECOG PS and incidence of brain metastases remained stable prior to, and after, afatinib.Graphical Abstract: Keywords: EGFR, afatinib, osimertinib, sequential, T790M

Targeted protein degradation allows targeting undruggable proteins for therapeutic applications as well as eliminating proteins of interest for research purposes. While several types of degraders that harness the proteasome or the lysosome have been developed, a technology that simultaneously degrades targets and accelerates cellular autophagic flux remains unavailable. In this study, we developed a general chemical tool by which given intracellular proteins are targeted to macroautophagy for lysosomal degradation. This platform technology, termed AUTOTAC (AUTOphagy-TArgeting Chimera), employs bifunctional molecules composed of target-binding ligands (TBLs) linked to autophagy-targeting ligands (ATLs). Upon binding to targets via the TBL, the ATL binds the ZZ domain of the otherwise dormant autophagy receptor SQSTM1/p62 (sequestosome 1), which activates SQSTM1 associated with targets and sequesters them into oligomeric species for autophagic targeting and lysosomal degradation. AUTOTACs were used to degrade various oncoproteins or aggregation-prone proteins in neurodegeneration both in vitro and/or in vivo. We suggest that AUTOTAC provides a platform for selective proteolysis as a research tool and in drug development.

This paper proposes a novel method to impart intelligence to metal parts using additive manufacturing. A sensor-embedded metal bracket is prototyped via a metal powder bed fusion process to recognise partial screw loosening or total screw missing or identify the source of vibration with the assistance of artificial intelligence (AI). The digital metal bracket can recognise subtle changes in the screw fixation state with 90% accuracy and identify unknown sources of vibration with 84% accuracy. The von Mises stress distribution in the prototyped metal bracket is evaluated using a finite element analysis, which is learned by AI to match the real-time deformation analysis of the metal bracket in augmented reality. The proposed prototype can contribute to hyper-connectivity for developing next-generation metal-based mechanical components. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) [grant Nos. 2021M2D2A1A01050059 and 2021R1F1A1046079].

The pelvic floor muscle (PFM) plays a role not only in lumbopelvic stabilization, but also in incontinence and sexual function.This study aimed to determine the effectiveness of PFM training by electrical stimulation (ES) on urinary incontinence, PFM performance (i.e. strength and power), lumbopelvic control, and abdominal muscle thickness in women with stress urinary incontinence (SUI).Participants were randomized into ES and control groups. The ES group underwent PFM ES for 8 weeks, whereas the control group underwent only a walking program. The impact of urinary incontinence on quality of life was assessed by the Incontinence Impact Questionnaire (IIQ)-7. PFM strength and power were measured using a perineometer. Lumbopelvic control was measured by one and double-leg-lowering tests. Abdominal muscle thickness was measured by sonography.The ES group showed significantly improved IIQ-7 scores and PFM performance, and had significantly higher values in both one and double-leg lowering tests (PFM ES could improve lumbopelvic control and PFM performance, and reduce subjective symptoms of urinary incontinence in women with SUI.

This study compared perspectives of highly trauma-exposed Oklahoma City bombing survivors (N=141) with and without PTSD. Survivors' responses to questions about the effects of the bombing on their perspectives were hand-recorded and transcribed, six themes identified, and interrater reliability established. Both diagnostic groups (with and without PTSD) expressed greater appreciation for life, greater concern with human vulnerability and mortality, and positive changes in religion/spirituality as consequences of the bombing. Survivors with PTSD also expressed negative religious/spiritual changes and substantive gains in self-confidence. Results indicate that disaster survivors may experience profound changes in their perspectives with ramifications for their mental health.

Hyehyun Jeong,1,* Hyeon-Su Im,1,2,* Wanlim Kim,3 Jong-Seok Lee,3 Si Yeol Song,4 Joon Seon Song,5 Kyung-Ja Cho,5 Hye Won Chung,6 Min Hee Lee,6 Jeong Eun Kim,1,* Jin-Hee Ahn1,* 1Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 2Division of Hematology and Oncology, Ulsan University Hospital, Ulsan, Republic of Korea; 3Department of Orthopedic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 4Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 5Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 6Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea*These authors contributed equally to this workCorrespondence: Jeong Eun Kim; Jin-Hee AhnDepartment of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of KoreaTel +82-2-3010-3945; +82-2-3010-3222Fax +82-2-3010-6961Email jeongeunkim@amc.seoul.kr; drjiny@amc.seoul.krPurpose: Because of the heterogeneity of sarcomas, establishing a well-collected, sarcoma-specific database is important for sarcoma research. We analyzed the first histology-based, sarcoma-specific institutional registry in Korea, which collected 28 years of patient data according to a predefined data format.Patients and Methods: Adult bone and soft tissue sarcoma patients who were treated from June 1989 to January 2017 were identified and analyzed, based on the ICD-O-3 codes.Results: Among the 3420 patients included, soft tissue and bone sarcomas comprised 77.8% (n = 2661) and 22.2% (n = 759), respectively. Median age at diagnosis was 50 (range, 16– 98) in soft tissue sarcomas and 37 (range, 16– 85) in bone sarcomas. Males and females comprised 45.5% and 54.5% of soft tissue sarcomas and 52.7% and 47.3% of bone sarcomas, respectively. Among the 3407 patients with treatment data available, 90.5% of the patients with soft tissue sarcomas and 80.8% of the patients with bone sarcomas received surgery first, of which 57.8% and 71.7% did not receive any subsequent treatment, respectively. Overall, the proportion of patients who received surgery alone decreased from 85.7% to 60.5% from the pre-2000 period to the 2010– 2017 period. However, the use of adjuvant chemotherapy increased in patients with soft tissue sarcomas (from 8.0% to 17.2% in the same period), and the use of perioperative radiotherapy also increased in both groups (from 1.4% to 22.7% in soft tissue sarcomas, and 0% to 14.5% in bone sarcomas in the same period). In both soft tissue and bone sarcomas, old age (≥ 65 years) and diagnosis in the early study period were associated with poorer survival.Conclusion: We presented a comprehensive summary of our sarcoma registry, including the demographics, changes in treatment patterns, and survival outcomes. This study will provide a framework for future studies.Keywords: bone sarcoma, soft tissue sarcoma, sarcoma-specific registry, real-world evidence

This study aims to determine whether companies with surpluses are more capable of maintaining their dividend rate if they issue cash dividends from capital reserves. Further, it considers whether s...

Min-Hee Lee,1 Seung Ku Lee,1 Robert J Thomas,2 Jee-Eun Yoon,3 Chang-Ho Yun,4,* Chol Shin1,5,* 1Institute of Human Genomic Study, College of Medicine, Korea University Ansan Hospital, Ansan, Republic of Korea; 2Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; 3Department of Neurology, Uijeongbu Eulji Medical Center, Uijeongbu, Republic of Korea; 4Department of Neurology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; 5Department of Pulmonary Sleep and Critical Care Medicine Disorder Center, College of Medicine, Korea University, Ansan, Republic of Korea*These authors contributed equally to this workCorrespondence: Chang-Ho YunDepartment of Neurology, Bundang Clinical Neuroscience Institute, Seoul National University Bundang Hospital, 82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam, 13620, Republic of KoreaTel +82 31 787 7469Fax +82 31 787 4059Email ych333@gmail.comChol ShinDivision of Pulmonary, Sleep, and Critical Care Medicine, Department of Internal Medicine, Korea University Ansan Hospital and Institute of Human Genomic Study, Korea University Ansan Hospital, 516, Gojan-1-dong, Danwon-gu, Ansan, Gyeonggi-do, 15355, Republic of KoreaTel +82 31 412 5541Fax +82 31 412 5604Email chol-shin@korea.ac.krPurpose: Obstructive sleep apnea (OSA) is associated with altered pairwise connections between brain regions, which might explain cognitive impairment and daytime sleepiness. By adopting a deep learning method, we investigated brain connectivity related to the severity of OSA and daytime sleepiness.Patients and Methods: A cross-sectional design applied a deep learning model on structural brain networks obtained from 553 subjects (age, 59.2 ± 7.4 years; men, 35.6%). The model performance was evaluated with the Pearson’s correlation coefficient (R) and probability of absolute error less than standard deviation (PAE

The aim of this study was to determine pharmacokinetics of α-amanitin, a toxic bicyclic octapeptide isolated from the poisonous mushrooms, following intravenous (iv) or oral (po) administration in mice using a newly developed and validated liquid chromatography-high resolution mass spectrometry. The iv injected α-amanitin disappeared rapidly from the plasma with high a clearance rate (26.9-30.4 ml/min/kg) at 0.1, 0.2, or 0.4 mg/kg doses, which was consistent with a rapid and a major excretion of α-amanitin via the renal route (32.6%). After the po administration of α-amanitin at doses of 2, 5, or 10 mg/kg to mice, the absolute bioavailability of α-amanitin was 3.5-4.8%. Due to this low bioavailability, 72.5% of the po administered α-amanitin was recovered from the feces. When α-amanitin is administered po, the tissue to plasma area under the curve ratio was higher in stomach > large intestine > small intestine > lung ~ kidneys > liver but not detected in brain, heart, and spleen. The high distribution of α-amanitin to intestine, kidneys, and liver is in agreement with the previously reported major intoxicated organs following acute α-amanitin exposure. In addition, α-amanitin weakly or negligibly inhibited cytochrome P450 and 5'-diphospho-glucuronosyltransferase enzymes activity in human liver microsomes as well as major drug transport functions in mammalian cells overexpressing transporters. Data suggested remote drug interaction potential may be associated with α-amanitin exposure.

The South Korean government enforces strict censorship against pornography. In spite of such regulations, there is a vibrant webcam modelling industry in Korea that operates under the radar. I exam...

Host cell membrane-trafficking pathways are often manipulated by bacterial pathogens to gain cell entry, avoid immune responses, or to obtain nutrients. The 1,369-residue OtDUB protein from the obligate intracellular human pathogen Orientia tsutsugamushi bears a deubiquitylase (DUB) and additional domains. Here we show that OtDUB ectopic expression disrupts membrane trafficking through multiple mechanisms. OtDUB binds directly to the clathrin adaptor-protein (AP) complexes AP-1 and AP-2, and the OtDUB(275–675) fragment is sufficient for binding to either complex. To assess the impact of OtDUB interactions with AP-1 and AP-2, we examined trans-Golgi trafficking and endocytosis, respectively. Endocytosis is reduced by two separate OtDUB fragments: one contains the AP-binding domain (OtDUB(1–675)), and the other does not (OtDUB(675–1369)). OtDUB(1–675) disruption of endocytosis requires its ubiquitin-binding capabilities. OtDUB(675–1369) also fragments trans- and cis-Golgi structures. Using a growth-based selection in yeast, we identified viable OtDUB(675–1369) point mutants that also no longer caused Golgi defects in human cells. In parallel, we found OtDUB(675–1369) binds directly to phosphatidylserine, and this lipid binding is lost in the same mutants. Together these results show that OtDUB contains multiple activities capable of modulating membrane trafficking. We discuss how these activities may contribute to Orientia infections.

The present study describes evaluation of epigenetic regulation by a small molecule as the therapeutic potential for treatment of Huntington’s disease (HD). We identified 5-allyloxy-2-(pyrrolidin-1-yl)quinoline (APQ) as a novel SETDB1/ESET inhibitor using a combined in silico and in vitro cell based screening system. APQ reduced SETDB1 activity and H3K9me3 levels in a HD cell line model. In particular, not only APQ reduced H3K9me3 levels in the striatum but it also improved motor function and neuropathological symptoms such as neuronal size and activity in HD transgenic (YAC128) mice with minimal toxicity. Using H3K9me3-ChIP and genome-wide sequencing, we also confirmed that APQ modulates H3K9me3-landscaped epigenomes in YAC128 mice. These data provide that APQ, a novel small molecule SETDB1 inhibitor, coordinates H3K9me-dependent heterochromatin remodelling and can be an epigenetic drug for treating HD, leading with hope in clinical trials of HD., Graphical Abstract

The gut microbiome influences the development of allergic diseases during early childhood. However, there is a lack of comprehensive understanding of microbiome-host crosstalk. Here, we analyzed the influence of gut microbiome dynamics in early childhood on atopic dermatitis (AD) and the potential interactions between host and microbiome that control this homeostasis. We analyzed the gut microbiome in 346 fecal samples (6-36 months; 112 non-AD, 110 mild AD, and 124 moderate to severe AD) from the Longitudinal Cohort for Childhood Origin of Asthma and Allergic Disease birth cohort. The microbiome-host interactions were analyzed in animal and

Introduction Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely prescribed for type 2 diabetes (T2D) and their glycemic control effects are well studied. However, information regarding the effects of switching DPP-4 inhibitors is limited, especially in older patients. Research Design and Methods We investigated whether switching from linagliptin to teneligliptin decreases blood glucose in older (≥65 years) T2D patients. In total, 164 patients with T2D who switched from linagliptin to teneligliptin for >12 weeks were included and the primary outcome was glycemic changes. Results Switching from linagliptin to teneligliptin ameliorated fasting blood glucose (148.1 ± 47.1 to 139.6 ± 43.4 mg/dL), glycated hemoglobin (HbA1c; 7.9 ± 1.3 to 7.5 ± 1.2%), and postprandial blood glucose (224.8 ± 77.4 to 205.8 ± 70.8 mg/dL) levels (all P 8.0%) and chronic kidney disease (estimated glomerular filtration rate

Hot press formed parts in a fully martensitic structure limit its application in the centre pillar, which requires high collision resistance. In this study, the combined effect of the patchwork and...

Microbial-induced calcite precipitation has recently emerged as an attractive sustainable ground improvement technique. In present study, the stress-deformation responses of a bio-mediated residual...

Many car components have been fabricated with different materials to improve collision toughness and safety during a car crash. However, as yet, no evaluation standard has been established that eva...

Nuclear protein HMGB1 is secreted in response to various stimuli and functions as a danger-associated molecular pattern. Extracellular HMGB1 induces inflammation, cytokine production, and immune cell recruitment via activation of various receptors. As HMGB1 does not contain an endoplasmic reticulum-targeting signal peptide, HMGB1 is secreted via the endoplasmic reticulum-Golgi independently via an unconventional secretion pathway. However, the mechanism underlying HMGB1 secretion remains largely unknown. Here, we investigated the role of secretory autophagy machinery and vesicular trafficking in HMGB1 secretion. We observed that HSP90AA1 (heat shock protein 90 alpha family class A member 1), a stress-inducible protein, regulates the translocation of HMGB1 from the nucleus to the cytoplasm and its secretion through direct interaction. Additionally, geldanamycin, an HSP90AA1 inhibitor, reduced HMGB1 secretion. GORASP2/GRASP55 (golgi reassembly stacking protein 2), ARF1Q71L (ADP ribosylation factor 1), and SAR1AT39N (secretion associated Ras related GTPase 1A), which promoted unconventional protein secretion, increased HMGB1 secretion. HMGB1 secretion was inhibited by an early autophagy inhibitor and diminished in ATG5-deficient cells even when GORASP2 was overexpressed. In contrast, a late autophagy inhibitor increased HMGB1 secretion under the same conditions. The multivesicular body formation inhibitor GW4869 dramatically decreased HMGB1 secretion under HMGB1 secretion-inducing conditions. Thus, we demonstrated that secretory autophagy and multivesicular body formation mediate HMGB1 secretion.

The global incidence of Mycobacterium abscessus (Mabc), a rapidly growing nontuberculous mycobacterial strain that causes treatment-refractory pulmonary diseases, is increasing. Despite this, the host factors that allow for protection against infection are largely unknown. In this study, we found that sirtuin 3 (SIRT3), a mitochondrial protein deacetylase, plays a critical role in host defense against Mabc infection. Mabc decreased SIRT3 and upregulated mitochondrial oxidative stress in macrophages. SIRT3 deficiency led to increased bacterial loads, histopathological, and mitochondrial damage, and pathological inflammation during Mabc infection. Administration of scavengers of mitochondrial reactive oxygen species significantly decreased the in vivo Mabc burden and excessive inflammation, and induced SIRT3 expression in infected lungs. Notably, SIRT3 agonist (resveratrol) significantly decreased Mabc growth and attenuated inflammation in mice and zebrafishes, indicating the key role for SIRT3 in metazoan host defense. Collectively, these data strongly suggest that SIRT3 is a host-directed therapeutic target against Mabc infection by controlling mitochondrial homeostasis.

McCarthy (1998) defined Artificial Intelligence (AI) as both “the science and engineering of in- telligent machines, especially computer programs” and the “computational part of the ability to achi...

Background: The phase 3 studies, VOYAGE 1 and 2, were conducted to assess guselkumab in the treatment of patients with moderate-to-severe psoriasis.Objectives: To investigate the efficacy and safety of guselkumab in Korean patients.Methods: The Korean sub-population of VOYAGE 1 and 2 study patients were included in this analysis. Efficacy and safety were evaluated through Weeks 24 and 28, respectively.Results: Of 126 randomized Korean patients, 30, 63, and 33 received placebo, guselkumab, and adalimumab, respectively. At Week 16, guselkumab was superior to placebo in achieving an Investigator's Global Assessment (IGA) score of 0 or 1 (cleared or minimal; 90.5 vs. 20.0%, p

Objectives Metabolites are the intermediate and final products of biological processes and ultimately reflect the responses of these processes to genetic regulation and environmental perturbations, including those involved in attention deficit/hyperactivity disorder (ADHD). Methods We identified a quantitative profile of plasma metabolites in 58 ADHD patients (mean age 9.0 years, 77.6% males) and 38 healthy control subjects (mean age 10.2 years, 55.3% males) using the high-performance chemical isotope labelling (CIL)-based liquid chromatography-mass spectrometry (LC-MS). Using a volcano plot and orthogonal projections to latent structure-discriminant analysis (OPLS-DA), we determined nine metabolites with differentially expressed levels in ADHD plasma samples. Results Compared to the control group, the plasma levels of guanosine, O-phosphoethanolamine, phenyl-leucine, hypoxanthine, 4-aminohippuric acid, 5-hydroxylysine, and L-cystine appeared increased in the ADHD patients, whilegentisic acid and tryptophyl-phenylalanine were down-regulated in the patients with ADHD. We found that the plasma levels of all nine metabolites were able to discriminate the ADHD group from the control group. Levels of O-phosphoethanolamine, 4-aminohippuric acid, 5-hydroxylysine, L-cystine, tryptophyl-phenylalanine, and gentisic acid were significantly correlated with clinical ADHD symptoms. Conclusions This study is the first to use the CIL-based LC-MS to profile ADHD plasma metabolites, and we identified nine novel metabolite biomarkers of ADHD.

Purpose Literature suggests that attention deficit hyperactivity disorder (ADHD) is associated with a high risk of unintentional injury. However, few studies have focused on whether risk of burn injury is relatively high among patients with ADHD. The aim of this study was to investigate whether ADHD affects the risk of burn injury. Materials and Methods Individuals aged

Background Disease-specific knowledge is associated with outcomes of patients, but the knowledge level of chronic obstructive pulmonary disease (COPD) patients is known to be low. Objective We measured the level of disease-specific knowledge and defined factors associated with poor disease knowledge in COPD patients. Materials and Methods A cross-sectional survey was performed in five hospitals in South Korea. At enrolment, all patients completed the Bristol COPD Knowledge Questionnaire (BCKQ), Satisfaction with Life Scale (SWLS), Personal Resource Questionnaire (PRQ), St. George's Respiratory Questionnaire (SGRQ), 36-item Short-Form Health Survey (SF-36), and the Hospital Anxiety and Depression Scale (HADS). The data were analyzed via linear regression to identify factors associated with low-level knowledge of COPD. Results A total of 245 COPD patients were enrolled in this study. The mean total BCKQ score was 28.1 (SD, 7.4). The lowest scores were seen for items exploring knowledge of "Oral steroids" and "Inhaled steroids". In univariate analysis, higher level of education (r = 0.17), low income (r = 0.13), the post-bronchodilator FEV1, % predicted (r = -0.24), the post-bronchodilator FEV1/FVC ratio (r = -0.13), SWLS (r = 0.15), PRQ (r = 0.16), SF-36 MCS (r = 0.13), HADS-A (r = -0.17), and HADS-D (r = -0.28) scores correlated with the BCKQ score (all p < 0.05). FEV1 (r = -0.25, p < 0.001) and HADS-D score (r = -0.29, p < 0.001) were significantly associated with the total BCKQ score in multivariate analysis. Conclusion Our Korean patients with COPD lacked knowledge on oral and inhaled steroid treatments. In particular, patients with higher-level lung function and/or depressive symptoms exhibited poorer disease-specific knowledge; such patients may require additional education.

Purpose This study explored and compared the effects of depression and antidepressants on sexual dysfunction in men with diabetes mellitus (DM). Patients and methods Patients older than 18 years who had been newly diagnosed with DM (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 250) between 1999 and 2010 were identified from Taiwan's National Health Insurance Research Database and were followed up until 2013. Patients with preexisting depression or sexual dysfunction were excluded. A total of 636,210 patients with DM were enrolled. These patients were divided into two groups: DM with comorbid depression and a matched cohort without depression. The groups were followed up until the end of 2010 for the first diagnosis of sexual dysfunction (ICD-9-CM codes 302.70, 302.71, 302.72, 302.74, 302.75, 302.76, 302.79, 607.84, and V417). A Cox proportional hazard model and a Cox regression model with time-dependent covariates were applied. Results Patients with DM and depression had a higher risk of sexual dysfunction than those with DM without depression (hazard ratio [HR] = 1.44; 95% confidence interval [CI], 1.33-1.55). The risk of sexual dysfunction was lower in the subgroup who used antidepressants (per 28 cumulative defined daily doses [cDDDs]), HR = 0.96; 95% CI, 0.94-0.97). A significantly lower incidence of sexual dysfunction was also associated with the use of selective serotonin reuptake inhibitors (SSRIs, per 28 cDDD). The adjusted HR was 0.95 (95% CI, 0.93-0.97). Subgroup analysis indicated that SSRI use was significantly associated with an amelioration of erectile dysfunction (per 28 cDDD), with an HR of 0.95 (95% CI, 0.92-0.97). Conclusion Male patients with DM and depression are at increased risk of sexual dysfunction. Antidepressant use had a small inverse association with the risk of sexual dysfunction in men with DM and depression. Antidepressants, in particular SSRIs, did not increase the risk of sexual dysfunction in this population.

Background Blood-based biomarkers (liquid biopsy) are increasingly used in precision oncology. Yet, little is known about cancer patients' perspectives in clinical practice. We explored patients' depth of preferences for liquid vs tissue biopsies and knowledge regarding the role of blood biomarkers on their cancer. Methods Three interviewer-administered trade-off scenarios and a 54-item self-administered questionnaire were completed by cancer outpatients across all disease sites at the Princess Margaret Cancer Centre. Results Of 413 patients, 54% were female; median age was 61 (range 18-101) years. In trade-off scenario preference testing, 90% (n=372) preferred liquid over tissue biopsy at baseline; when wait times for their preferred test were increased from 2 weeks, patients tolerated an additional mean of 1.8 weeks (SD 2.1) for liquid biopsy before switching to tissue biopsy (with wait time 2 weeks). Patients also tolerated a 6.2% decrease (SD 8.8) in the chance that their preferred test would conclusively determine optimal treatment before switching from the baseline of 80%. 216 patients (58%) preferred liquid biopsy even with no chance of adverse events from tissue biopsy. Patients' knowledge of blood-based biomarkers related to their cancer was low (mean 23%); however, the majority viewed development of blood biomarkers as important. Conclusion Patients had limited understanding of cancer-specific blood-based biomarkers, but 90% preferred liquid over tissue biopsies to assess biomarkers. There was little tolerance to wait longer for results, or for decreased test-conclusiveness. Developing accurate, low-risk tests for cancer diagnosis and management for blood biomarkers is therefore desirable to patients.

Beginning in the twenty-first century, Korean television dramas became a transnational media phenomenon called Hallyu (also known as the Korean Wave, Han’ryu, Hanliu). Some Hallyu fans not only wat...

In this study, we reviewed 76 journal articles on employing drawing assessment as a research tool in science education. Findings from the systematic review suggest four justifications for using dra...

Purpose This study aimed to evaluate the incidence and severity of biliary complications after treating periductal hepatocellular carcinomas (HCCs) using either cryoablation (CA) or radiofrequency ablation (RFA) and assess independent risk factors for biliary complications after treatment. Materials and methods Between July 2008 and August 2018, 949 patients with treatment-naïve HCCs underwent either RFA or CA in our institution. Of these, patients with multiple HCCs, tumors equal to or larger than 3 cm or smaller than 1 cm, and tumors with non-periductal locations were excluded. Finally, 31 patients and 25 patients were included in the RFA group and the CA group, respectively. The incidence and severity of biliary complications were compared between the RFA and CA groups. The risk factors for biliary complications were assessed using univariable and multivariable logistic regression analyses using the following variables: age, sex, tumor size, Child–Pugh score, tumor location (peripheral duct versus central duct), ablation method (RFA versus CA), the number of applicators, ablation time, and ablation volume. Results The incidence and severity of biliary complications were significantly higher in the RFA group than in the CA group (p = 0.007 and p = 0.002, respectively). In univariable and multivariable analyses, the ablation method was an independent risk factor for biliary complications (p = 0.004 and 0.013, respectively). Conclusions The incidence and severity of biliary complications after treating HCCs abutting the bile duct are lower in CA than RFA, demonstrating that CA is safer than RFA for ablating small periductal HCCs.

Red tide is one of the most devastating phenomena that have impacted coastal environments and fishery on a local scale in the worldwide seas. Satellite imagery can provide a synoptic view of the re...

Aims: We aimed to assess treatment persistence of tumor necrosis factor (TNF) inhibitors and non-TNF inhibitors in two groups of rheumatoid arthritis (RA) patients: biologic disease-modifying antir...

Composite beams comprising concrete slabs supported by steel beams typically constitute more than 70% of the total volume of the structure of an office building. Little, if any, research has been c...

Min K Park,1,* Song H Kang,2,* Jo Y Son,2 Min K Lee,3 Jin S Ju,2 Yong C Bae,4 Dong K Ahn2 1Department of Dental Hygiene, Kyungwon University, Gumi, Korea; 2Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu, Korea; 3Department of Dental Hygiene, Dong-Eui University, Busan, Korea; 4Department of Oral Anatomy, School of Dentistry, Kyungpook National University, Daegu, Korea*These authors contributed equally to this workCorrespondence: Dong K AhnDepartment of Oral Physiology, School of Dentistry, Kyungpook National University, 2177 Dalgubeol-daero, Chung-gu, Daegu 41940, KoreaTel +82-53-660-6840Email dkahn@knu.ac.krBackground: The traditional analgesics used to treat neuropathic pain such as anticonvulsants, opioids, and nonsteroidal anti-inflammatory drugs (NSAIDs) lack efficacy and/or carry unpleasant side effects. The present study aimed to investigate the synergistic antinociceptive effects of co-administered low doses of ibuprofen and dexamethasone in rats with trigeminal neuropathic pain.Materials and methods: A Sprague-Dawley rat model for trigeminal neuropathic pain was produced using mal-positioned dental implants. The left mandibular second molar was extracted under anesthesia and replaced with a miniature dental implant to induce injury to the inferior alveolar nerve.Results: Monotherapy with intraperitoneal injection of high-dose ibuprofen (30 mg/kg) or dexamethasone (10 mg/kg) but not low-dose ibuprofen (1, 5, 10 mg/kg) or dexamethasone (0.01, 1 mg/kg) attenuated the neuropathic mechanical allodynia in the rats with inferior alveolar nerve injury. We examined the synergistic antinociceptive effects of co-administered ibuprofen (5 mg/kg) and dexamethasone (0.01, 0.1, 1 mg/kg). The early co-administration of ibuprofen (5 mg/kg) with dexamethasone (0.1, 1 mg/kg) on postoperative days (POD) 1–3 significantly inhibited mechanical allodynia before the pain had been established. We also observed the synergistic antinociceptive effects of the same doses the combined treatment on mechanical allodynia on POD 7–9, when the pain had already been established. The attenuation of c-fos immuno-positive cells in the ipsilateral trigeminal subnucleus caudalis after the intraperitoneal co-administration of ibuprofen (5 mg/kg) with dexamethasone (1 mg/kg) confirmed these synergistic antinociceptive effects. Moreover, the magnitude of the effects of this co-administration was comparable with that of gabapentin both before and after the pain had been established.Conclusion: These results suggest that a combination of ibuprofen and dexamethasone at low doses is an alternative therapeutic strategy for neuropathic pain and provide a rationale for the use of such drug combinations in patients who are unable to tolerate high-dose monotherapy.Keywords: neuropathic pain, synergistic antinociceptive effects, ibuprofen, dexamethasone, trigeminal

A growing body of evidence is being published regarding the safety and efficacy of minimally invasive image-guided ablation techniques. While clinical applications of these techniques are increasing, international societies have started to publish treatment guidelines and to make efforts to standardize both terminology and reporting criteria for image-guided thyroid ablations. Laser ablation and radiofrequency ablation (RFA) are among the most common ablation techniques either for benign and malignant thyroid nodules. Unlike laser ablation and RFA in the treatment of benign thyroid nodules, where safety and efficacy have been widely demonstrated, evidence regarding local tumor control of thyroid malignancies is still limited. However, preliminary results are encouraging and image-guided thermal ablation techniques can be considered a valid alternative to surgery for the treatment of benign thyroid nodules and recurrent thyroid cancers. This review evaluates the basic concept of RFA and laser ablations, their techniques, clinical outcomes, and complications based on the suggestions of several society guidelines. Multidisciplinary collaboration remains critical to identify patients which may benefit from minimally invasive image-guided thermal ablations, especially if surgery or radioiodine therapy are not feasible options.

Background: Kaempferol (K) is a recognized anticancer drug that can conjugate with small-size gold nanoclusters (AuNCs). Materials and methods: K-AuNCs were synthesized and their use as an anticancer drug was explored using A549 lung cancer cells. Colony formation and cell migration assays were carried out. The morphology of the K-AuNCs treated A549 cells was explored using bio-atomic force microscopy. Results: The K-AuNCs were 1-3 nm in diameter and emitted strong fluorescent at 650 nm following excitation at 550 nm. The stretching and bending nature of the K-AuNCs were analyzed by the Fourier transform infrared spectroscopy. The presence of kaempferol in the AuNCs were confirmed by the PL spectroscopy. Conclusion: The synthesized K-AuNCs mainly targeted and damaged the nuclei of the cancer cells. This composite nanocluster was less toxicity to the normal human cell and higher toxicity to the A549 lunch cancer cell and these material is potential for anticancer drug delivery and bio imaging applications.

Background: Acute unilateral vestibulopathy (AUV) is common but, the course of disease recovery is variable. Moreover, the final recovery status might vary between subjects. The remaining symptoms ...

Background: Adverse drug reactions (ADRs) increase health-care resource utilization, including that for emergency department (ED) visits. However, cost analyses of ADRs resulting in ED visits are scarce. Therefore, we aimed to estimate the direct medical costs before and after ADR occurrence and analyzed the cost-driving factors.Methods: The ADR cases were identified by a retrospective review of medical records of patients who visited the ED of three tertiary hospitals in South Korea from July to December 2014. The direct medical cost was estimated by the difference in costs six months before and after the ED visit. A generalized linear model was used to identify the ADR-associated cost-driving factors.Results: The mean cost per ADR increased by 26.1% (±SD = 4.3) during the six-month follow-up compared with that during the six months before the ED visit (p < 0.05). Preventable ADRs accounted for approximately 19.9% of the cost increase among all ADR cases. The regression analysis revealed that 'ADR-related hospitalization' was a significant (p < 0.05) factor leading to an increase in the direct medical costs.Conclusion: Drug-related ED visits increase the burden on health insurance systems and patients' out-of-pocket costs, mostly due to the hospitalization costs.

This study intends to examine two major challenges in high-frequency (intraday) volatility analysis: first, the selection of a suitable realized volatility and second, the appropriate statistical m...

Benzoic, sorbic and propionic acid are used as preservatives in foods and can also be naturally present in processed foods. The levels of preservatives in 939 vegetables were determined. Benzoic and sorbic acid were analysed by high-performance liquid chromatography with a diode-array detector and further confirmed by liquid chromatography-tandem mass spectrometry, whereas propionic acid was analysed using a gas chromatography-flame ionization detector and further confirmed by gas chromatography-mass spectrometry. Benzoic and propionic acid were found in 10.9% and 36.2%, respectively, of the samples. In contrast, sorbic acid was not found in any of the samples. The highest amounts of benzoic and propionic acid were found in perilla leaves (0.33-298 mg kg-1) and ginseng (

Context: Surfer’s myelopathy (SM) is an acute syndrome identified by nontraumatic paraparesis or paraplegia. Though traditionally tied to first-time surfers, the condition encompasses any activity involving hyperextension of the back such as gymnastics, yoga, and Pilates. Methods: MEDLINE(®) and Google Scholar literature searches were gathered to identify relevant case reports for determining the etiology, pathogenesis, evaluation, and management of SM. Results: While the rare nature of SM limits its full understanding, studies have pinpointed that hyperextension in the back leads to vasculature insufficiency secondary to dynamic compression of the artery of Adamkiewicz. In surfing, this hyperextension combined with the execution of the Valsalva maneuver while trying to stand up on the surfboard likely increases intraspinal pressure. Due to its nontraumatic origin, the presence of SM is not immediately clear. Moreover, its similarity in clinical and radiological presentations with other entities can further complicate diagnosis. Seemingly, idiopathic urological symptoms can be explained by the physician if they conduct a thorough history. Conclusion: In an effort to raise awareness for the practicing physician, we presently review the etiology, diagnosis, treatment, and prolonged effects of SM. With the surging popularity of surfing as well as the advent of children participating in precarious sports and activities at an earlier age, we can expect a rising incidence of traumatic and nontraumatic spinal cord injuries. Neurologists, urologists, emergency medicine and sports medicine physicians alike can utilize this review to build a high index of suspicion for SM. The risk factors for SM should be conveyed to those participating in novices in surfing, yoga, gymnastics, ballet, and any activity enabling sustained or repeated spinal extension. Increased general awareness will facilitate increased symptom recognition in order to arrest aggravation of injury.