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The path of tokamak fusion and International thermonuclear experimental reactor (ITER) is maintaining high-performance plasma to produce sufficient fusion power. This effort is hindered by the transient energy burst arising from the instabilities at the boundary of plasmas. Conventional 3D magnetic perturbations used to suppress these instabilities often degrade fusion performance and increase the risk of other instabilities. This study presents an innovative 3D field optimization approach that leverages machine learning and real-time adaptability to overcome these challenges. Implemented in the DIII-D and KSTAR tokamaks, this method has consistently achieved reactor-relevant core confinement and the highest fusion performance without triggering damaging bursts. This is enabled by advances in the physics understanding of self-organized transport in the plasma edge and machine learning techniques to optimize the 3D field spectrum. The success of automated, real-time adaptive control of such complex systems paves the way for maximizing fusion efficiency in ITER and beyond while minimizing damage to device components.

Sangmin Lee,1 Jae-Hun Kim,2 Wan Song,1 Hyun Hwan Sung,1 Hwang Gyun Jeon,1 Byong Chang Jeong,1 Seong Il Seo,1 Seong Soo Jeon,1 Se Hoon Park,3 Ji Hyun Lee,2 Jiwoong Yu,1,* Minyong Kang1,4,5,* 1Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 2Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 3Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 4Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea; 5Samsung Genome Institute, Samsung Medical Center, Seoul, Korea*These authors contributed equally to this workCorrespondence: Minyong Kang; Jiwoong Yu, Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea, Tel +82-2-3410-1138 ; +82-2-3410-3559, Fax +82-2-3410-6992 ; +82-2-3410-6990, Email dr.minyong.kang@gmail.com; darwin082smart@gmail.comPurpose: We investigated the relationship between body mass index (BMI), radiological body composition, and survival outcomes in patients with metastatic renal cell carcinoma (mRCC) underwent first-line immune checkpoint inhibitor (ICI)-based therapy.Methods: Analyzing data from 102 patients treated between November 2019 and March 2023, pre-treatment computed tomography (CT) scans assessed fat and muscle areas. BMI and body composition indices were examined, including skeletal muscle index, subcutaneous fat index (SFI), visceral fat index, and total fat index. Kaplan–Meier curves and Log rank tests compared progression-free survival (PFS) and overall survival (OS), while multivariable Cox proportional regression analysis was performed to identify the variables significantly associated with survival outcomes.Results: 54 patients (52.9%) experienced disease progression, and 26 (25.5%) died during a median follow-up of 17.4 months. High SFI was significantly associated with improved OS (p = 0.018) but not PFS (p = 0.090). Multivariable analysis confirmed the positive impact of high SFI on OS (adjusted HR: 0.37, p = 0.029) and suggested a trend towards improved PFS (adjusted HR: 0.61, p = 0.088). Notably, in the ipilimumab + nivolumab subgroup, high SFI significantly correlated with both PFS and OS (p = 0.047 and p = 0.012, respectively).Conclusion: High SFI predicts favorable OS in patients with mRCC receiving first-line ICI-based therapy, especially patients treated with ipilimumab + nivolumab displayed a significant association between high SFI and favorable PFS and OS.Keywords: immunotherapy, renal cell carcinoma, body composition, prognosis

Enkyu Noh,1,&ast; Hyungmin Jeong,1,&ast; In-So Cho,2 Min-Seok Chang,2 Iseul Yu,2 Sunmin Park,2 Ji-Ho Lee,2 Seok Jeong Lee,2 Won-Yeon Lee,2 Suk Joong Yong,2 Sang-Ha Kim2 1Yonsei University Wonju College of Medicine, Wonju, 26426, Korea; 2Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, 26426, Korea&ast;These authors contributed equally to this workCorrespondence: Sang-Ha Kim, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Korea, 20 Ilsanro, Wonju, 26426, Korea, Tel +82-33-741-0926, Fax +82-33-746-4667, Email sanghakim@yonsei.ac.krPurpose: Chronic obstructive pulmonary disease (COPD) and metabolic syndrome (MetS) are among the most prevalent conditions that might predispose individuals to life-threatening events. We aimed to examine their associations with cardiovascular (CV) events and mortality using a large-scale population dataset from the National Health Information Database in Korea.Patients and Methods: This population-based cohort study enrolled adults aged ≥ 40 years who had undergone more than two health examinations between 2009 and 2011. They were divided into four groups based on the presence of COPD and MetS. Analysis of the outcomes and CV events or deaths was performed from 2014 to 2019. We compared CV event incidence and mortality rates using a multivariate Cox proportional hazards model and Kaplan–Meier curves.Results: Totally, 5,101,810 individuals were included, among whom 3,738,458 (73.3%) had neither COPD nor MetS, 1,193,014 (23.4%) had only MetS, 125,976 (2.5%) had only COPD, and 44,362 (0.9%) had both. The risk of CV events was significantly higher in individuals with both COPD and MetS than in those with either COPD or MetS alone (HRs: 2.4 vs 1.6 and 1.8, respectively; all P < 0.001). Similarly, among those with both COPD and MetS, all-cause and CV mortality risks were also elevated (HRs, 2.9 and 3.0, respectively) compared to the risks in those with either COPD (HRs, 2.6 and 2.1, respectively) or MetS (HRs, 1.7 and 2.1, respectively; all P < 0.001).Conclusion: The comorbidity of MetS in patients with COPD increases the incidence of CV events and all-cause and cardiovascular mortality rates.Keywords: cardiovascular event, chronic obstructive pulmonary disease, metabolic syndrome

Mincheol Chae,1,&ast; Jae-Ho Lee,2,&ast; Jong Ho Park,2 Dong Yoon Keum,1 Hanna Jung,3 Youngok Lee,3 Deok Heon Lee3 1Department of Thoracic and Cardiovascular Surgery, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Korea; 2Department of Anatomy, Keimyung University School of Medicine, Daegu, Korea; 3Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Jung-gu, 41944, Korea&ast;These authors contributed equally to this workCorrespondence: Deok Heon Lee, Tel +82-53-200-5665, Fax +82-53-426-4765, Email ldhms@knu.ac.krBackground: TRF1, TRF2, and TERT (Telomerase reverse transcriptase) are telomere-associated factors that regulate telomere length. Genetic changes in these genes may be associated with cancer pathogenesis; however, this relationship has not yet been comprehensively elucidated in lung cancer.Aim: : Exploring the clinicopathologic and prognostic values of TRF1, TRF2, and TERT mRNA expression in non-small cell lung cancers (NSCLC).Methods: : The clinical significance of TRF1, TRF2, and TERT expression in 141 patients with NSCLC was investigated. Additionally, these findings were supported by the open big data from The Cancer Genome Atlas (TCGA).Results: : TRF1 and TRF2 expression levels tended to be associated with smoking, and TERT expression was positively correlated with age. The survival analysis showed that TRF1 expression predicted a better prognosis for squamous cell carcinoma (SCC), whereas TRF2 expression was associated with a shorter survival in adenocarcinoma. TCGA data also showed a better prognosis for SCC with TRF1 expression. However, the TRF2 results were not in agreement with our data.Conclusions: : We present the clinical and prognostic values of TRF1, TRF2, and TERT expression in NSCLC tissues and TCGA. Our findings suggest that TRF1 expression is a possible prognostic marker for NSCLC, particularly SCC.Keywords: TRF1, TRF2, TERT, telomere, lung cancer

En-Yi Lin,1,2 Shao-Xi Hsu,1 Bing-Hua Wu,1 Yu-Chen Deng,1,3 Wei Wuli,1 Yuan-Sheng Li,3 Jui-Hao Lee,3 Shinn-Zong Lin,2,4 Horng-Jyh Harn,2,5 Tzyy-Wen Chiou1 1Department of Life Science and Graduate Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan; 2Bioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan; 3Everfront Biotech Inc, Taipei, Taiwan; 4Department of Neurosurgery, Hualien Tzu Chi Hospital, Hualien, Taiwan; 5Department of Pathology, Hualien Tzu Chi Hospital, Hualien, TaiwanCorrespondence: Tzyy-Wen Chiou, Department of Life Science, National Dong Hwa University, No. 1, Sec. 2, Da Hsueh Road, Shou-Feng, Hualien, Taiwan, Tel +886-3-890-3638, Email twchiou@gms.ndhu.edu.tw Horng-Jyh Harn, Department of Pathology, Hualien Tzu Chi Hospital, Hualien, Taiwan, Tel +886-3-856-1825, Email arthewduke@gmail.comPurpose: Exosomes are membrane vesicles secreted by various cells and play a crucial role in intercellular communication. They can be excellent delivery vehicles for oligonucleotide drugs, such as microRNAs, due to their high biocompatibility. MicroRNAs have been shown to be more stable when incorporated into exosomes; however, the lack of targeting and immune evasion is still the obstacle to the use of these microRNA-containing nanocarriers in clinical settings. Our goal was to produce functional exosomes loaded with target ligands, immune evasion ligand, and oligonucleotide drug through genetic engineering in order to achieve more precise medical effects.Methods: To address the problem, we designed engineered exosomes with exogenous cholecystokinin (CCK) or somatostatin (SST) as the targeting ligand to direct the exosomes to the brain, as well as transduced CD47 proteins to reduce the elimination or phagocytosis of the targeted exosomes. MicroRNA-29b-2 was the tested oligonucleotide drug for delivery because our previous research showed that this type of microRNA was capable of reducing presenilin 1 (PSEN1) gene expression and decreasing the β-amyloid accumulation for Alzheimer’s disease (AD) in vitro and in vivo.Results: The engineered exosomes, containing miR29b-2 and expressing SST and CD47, were produced by gene-modified dendritic cells and used in the subsequent experiments. In comparison with CD47-CCK exosomes, CD47-SST exosomes showed a more significant increase in delivery efficiency. In addition, CD47-SST exosomes led to a higher delivery level of exosomes to the brains of nude mice when administered intravenously. Moreover, it was found that the miR29b-2-loaded CD47-SST exosomes could effectively reduce PSEN1 in translational levels, which resulted in an inhibition of beta-amyloid oligomers production both in the cell model and in the 3xTg-AD animal model.Conclusion: Our results demonstrated the feasibility of the designed engineered exosomes. The application of this exosomal nanocarrier platform can be extended to the delivery of other oligonucleotide drugs to specific tissues for the treatment of diseases while evading the immune system.Keywords: oligonucleotide drug, functional nanocarriers, hippocampus, SH-SY5Y, 3xTG-AD

Young Woo Um,1 Inwon Park,1 Jae Hyuk Lee,1 Hee Eun Kim,1 Dongkwan Han,1 Seung Hyun Kang,1 Seonghye Kim,1 You Hwan Jo1– 3 1Department of Emergency Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea; 2Department of Emergency Medicine, Seoul National University College of Medicine, Seoul, Korea; 3Disaster Medicine Research Center, Seoul National University Medical Research Center, Seoul, KoreaCorrespondence: Jae Hyuk Lee, Department of Emergency Medicine, Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Korea, Tel +82-31-787-7579, Fax +82-31-787-4055, Email hyukmd@gmail.comPurpose: Proper antibiotic administration is crucial for sepsis management. Given the escalating incidence of antimicrobial resistance, there is a pressing need for indicators of antimicrobial susceptibility with short turnaround times. This study aimed to investigate the potential of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as an early biomarker for in vivo antibiotic susceptibility in patients with sepsis.Patients and Methods: We conducted a retrospective analysis of plasma samples from patients enrolled in a pre-established study designed to investigate prognostic biomarkers in patients with sepsis or septic shock. Baseline and 6 h sTREM-1 levels were examined using enzyme-linked immunosorbent assays. The primary outcome of the study was the comparison of percentage changes in sTREM-1 levels at the 6 h relative to baseline with respect to antibiotic susceptibility.Results: Of the 596 patients enrolled in the pre-established study, 29 with a median age of 75.8 and a 28-day mortality rate of 17.2% were included in the present analysis. Among these patients, 24 were classified into the susceptible group, whereas the remaining five were classified into the resistant group. The trend in plasma sTREM-1 levels differed with respect to antibiotic susceptibility. Moreover, percentage change in sTREM-1 levels at the 6 h relative to baseline was significantly higher in the resistant group (P = 0.028).Conclusion: The trend in plasma sTREM-1 levels in patients with sepsis differed with respect to antibiotic susceptibility, with a higher percentage change in patients treated with inappropriate antibiotics. These findings indicate the potential utility of sTREM-1 as an early biomarker of antibiotic susceptibility.Keywords: anti-bacterial agents, biomarkers, drug resistance, sepsis, triggering receptor expressed on myeloid cells-1

Seunghee Bae,1 Sowon Bae,1 Hee Su Kim,1 Ye Jin Lim,1 Gyeongmi Kim,2 In-Chul Park,2 Kyeong A So,3 Tae Jin Kim,3 Jae Ho Lee1 1Department of Cosmetics Engineering, Konkuk University, Seoul, 05029, Republic of Korea; 2Division of Fusion Radiology Research, Korea Institute of Radiological & Medical Sciences, Seoul, 01812, Republic of Korea; 3Department of Obstetrics and Gynecology, Konkuk University School of Medicine, Seoul, 05030, Republic of KoreaCorrespondence: Jae Ho Lee, Department of Cosmetics Engineering, Konkuk University, Seoul, 05029, Republic of Korea, Email jaeho390@konkuk.ac.krBackground: Ovarian cancer is one of women’s malignancies with the highest mortality among gynecological cancers. Paclitaxel is used in first-line ovarian cancer chemotherapy. Research on paclitaxel-resistant ovarian cancer holds significant clinical importance.Methods: Cell viability and flow cytometric assays were conducted at different time and concentration points of deguelin and paclitaxel treatment. Immunoblotting was performed to assess the activation status of key signaling molecules important for cell survival and proliferation following treatment with deguelin and paclitaxel. The fluo-3 acetoxymethyl assay for P-glycoprotein transport activity assay and cell viability assay in the presence of N-acetyl-L-cysteine were also conducted.Results: Cell viability and flow cytometric assays demonstrated that deguelin resensitized paclitaxel in a dose- and time-dependent manner. Cotreatment with deguelin and paclitaxel inhibited EGFR and its downstream signaling molecules, including AKT, ERK, STAT3, and p38 MAPK, in SKOV3-TR cells. Interestingly, cotreatment with deguelin and paclitaxel suppressed the expression level of EGFR via the lysosomal degradation pathway. Cotreatment did not affect the expression and function of P-glycoprotein. N-acetyl-L-cysteine failed to restore cell cytotoxicity when used in combination with deguelin and paclitaxel in SKOV3-TR cells. The expression of BCL-2, MCL-1, and the phosphorylation of the S155 residue of BAD were downregulated. Moreover, inhibition of paclitaxel resistance by deguelin was also observed in HeyA8-MDR cells.Conclusion: Our research showed that deguelin effectively suppresses paclitaxel resistance in SKOV3-TR ovarian cancer cells by downregulating the EGFR and its downstream signaling pathway and modulating the BCL-2 family proteins. Furthermore, deguelin exhibits inhibitory effects on paclitaxel resistance in HeyA8-MDR ovarian cancer cells, suggesting a potential mechanism for paclitaxel resensitization that may not be cell-specific. These findings suggest that deguelin holds promise as an anticancer therapeutic agent for overcoming chemoresistance in ovarian cancer. Keywords: ovarian cancer, paclitaxel-resistance, deguelin, EGFR, AKT

Dongjin Shin,1,&ast; Juhyun Kim,1,&ast; Jang Ho Lee,2,&ast; Jong-Il Kim,1,3– 5 Yeon-Mok Oh2 1Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea; 2Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 3Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Republic of Korea; 4Genomic Medicine Institute, Seoul National University, Seoul, Republic of Korea; 5Seoul National University Cancer Research Institute, Seoul, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Jong-Il Kim, Department of Biomedical Sciences, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea, Tel +82-2-740-8246, Email jongil@snu.ac.kr Yeon-Mok Oh, Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea, Tel +82-2-3010-3136, Fax +82-2-3010-6968, Email ymoh55@amc.seoul.krPurpose: The aim of the study was to use RNA sequencing (RNA-seq) data of lung from chronic obstructive pulmonary disease (COPD) patients to identify the bacteria that are most commonly detected. Additionally, the study sought to investigate the differences in these infections between normal lung tissues and those affected by COPD.Patients and Methods: We re-analyzed RNA-seq data of lung from 99 COPD patients and 93 non-COPD smokers to determine the extent to which the metagenomes differed between the two groups and to assess the reliability of the metagenomes. We used unmapped reads in the RNA-seq data that were not aligned to the human reference genome to identify more common infections in COPD patients.Results: We identified 18 bacteria that exhibited significant differences between the COPD and non-COPD smoker groups. Among these, Yersinia enterocolitica was found to be more than 30% more abundant in COPD. Additionally, we observed difference in detection rate based on smoking history. To ensure the accuracy of our findings and distinguish them from false positives, we double-check the metagenomic profile using Basic Local Alignment Search Tool (BLAST). We were able to identify and remove specific species that might have been misclassified as other species in Kraken2 but were actually Staphylococcus aureus, as identified by BLAST analysis.Conclusion: This study highlighted the method of using unmapped reads, which were not typically used in sequencing data, to identify microorganisms present in patients with lung diseases such as COPD. This method expanded our understanding of the microbial landscape in COPD and provided insights into the potential role of microorganisms in disease development and progression.Keywords: chronic obstructive pulmonary disease, next-generation sequencing, microbiome, metagenomics

Jang Ho Lee,1 Sehee Kim,2 Ye-Jee Kim,2 Sei Won Lee,1 Jae Seung Lee,1 Yeon-Mok Oh1 1Department of Pulmonary and Critical Care Medicine, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Republic of Korea; 2Department of Clinical Epidemiology and Biostatistics, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Republic of KoreaCorrespondence: Yeon-Mok Oh, Department of Pulmonary and Critical Care Medicine, University of Ulsan College of Medicine, Asan Medical Centre, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea, Tel +82-2-3010-3136, Fax +82-2-3010-6968, Email ymoh55@amc.seoul.krPurpose: To identify the risk factors for chronic obstructive pulmonary disease (COPD) in view of potential etiotypes in a general population and referred COPD patients.Patients and Methods: We performed a cross-sectional observational study utilizing two distinct datasets: a dataset of a general population including 2430 subjects with COPD from the Korea National Health and Nutrition Examination Survey (KNHANES) and another dataset of referral clinics including 579 patients with COPD from the Korean Obstructive Lung Disease (KOLD).Results: The mean age of both groups was 67 years, and 71.2% and 93.8% were male in the COPD subjects from the KNHANES and the KOLD, respectively. The mean forced expiratory volume in 1 second of predicted value was 79.1% (KNHANES) and 55.4% (KOLD). The frequency of risk factors of cigarette smoking (C), infection (I), pollution (P), and asthma (A) was 54.6%, 9.4%, 10.7%, and 7.9%, respectively, in the KNHANES COPD subjects, and 88.4%, 26.6%, 41.6%, and 35.2%, respectively, in the KOLD COPD subjects. Risk factors were unidentified in 32.6% (KNHANES) and 3.1% (KOLD) of COPD subjects. Additionally, 14.1% and 66.2% of subjects with COPD had two or more risk factors in the KNHANES and KOLD, respectively.Conclusion: The profiles of risk factors C, I, P, and A were identified and appeared to be different among the two COPD groups from a general population or referral clinics. In some of the COPD subjects, risk factors were not identified, so we should endeavour to find out unidentified COPD risk factors, especially in the general population.Keywords: chronic obstructive pulmonary disease, etiotype, smoking, tuberculosis, asthma, pollutants

Breda Cushen,1,&ast; Mariko Siyue Koh,2,&ast; Trung N Tran,3 Neil Martin,3,4 Ruth Murray,5 Thendral Uthaman,6 Celine Yun Yi Goh,5,6 Rebecca Vella,7 Neva Eleangovan,5,6 Lakmini Bulathsinhala,5,6 Jorge F Maspero,8,9 Matthew J Peters,10 Florence Schleich,11 Paulo Pitrez,12 George Christoff,13 Mohsen Sadatsafavi,14 Carlos A Torres-Duque,15,16 Celeste Porsbjerg,17 Alan Altraja,18 Lauri Lehtimäki,19 Arnaud Bourdin,20 Christian Taube,21 Nikolaos G Papadopoulos,22,23 Csoma Zsuzsanna,24 Unnur Björnsdóttir,25 Sundeep Salvi,26 Enrico Heffler,27 Takashi Iwanaga,28 Mona al-Ahmad,29 Désirée Larenas-Linnemann,30 Job FM van Boven,31 Bernt Bøgvald Aarli,32,33 Piotr Kuna,34 Cláudia Chaves Loureiro,35,36 Riyad Al-lehebi,37 Jae Ha Lee,38 Nuria Marina,39 Leif Bjermer,40 Chau-Chyun Sheu,41,42 Bassam Mahboub,43 John Busby,44 Andrew Menzies-Gow,45 Eileen Wang,46 David B Price5,6,47 On behalf of ISAR Inventory Study Group1Department of Respiratory Medicine, Beaumont Hospital, Dublin, Ireland; 2Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore; 3AstraZeneca, Gaithersburg, MD, USA; 4Department of Respiratory Medicine, University of Leicester, Leicester, UK; 5Optimum Patient Care Global, Cambridge, UK; 6Observational Pragmatic Research Institute, Singapore, Singapore; 7Optimum Patient Care, Brisbane, Queensland, Australia; 8Clinical Research for Allergy and Respiratory Medicine, CIDEA Foundation, Buenos Aires, Argentina; 9University Career of Specialists in Allergy and Clinical Immunology at the Buenos Aires University School of Medicine, Buenos Aires, Argentina; 10Department of Thoracic Medicine, Concord Hospital, Sydney, Australia; 11CHU Sart-Tilman, GIGA I3, University of Liege, Liège, Wallonia, Belgium; 12Pulmonology Division, Hospital Santa Casa de Porto Alegre, Porto Alegre, Brazil; 13Faculty of Public Health, Medical University, Sofia, Bulgaria; 14Respiratory Evaluation Sciences Program, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada; 15CINEUMO, Respiratory Research Center, Fundación Neumológica Colombiana, Bogotá, Colombia; 16Universidad de La Sabana, Chia, Colombia; 17Department of Respiratory Medicine and Infectious Diseases, Research Unit, Bispebjerg Hospital, Copenhagen, Denmark; 18Department of Pulmonology, University of Tartu and Lung Clinic, Tartu University Hospital, Tartu, Estonia; 19Allergy Centre, Tampere University Hospital, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; 20PhyMedExp, Univ Montpellier, CNRS, INSERM, CHU Montpellier, Montpellier, France; 21Department of Pulmonary Medicine, University Medical Center Essen-Ruhrlandklinik, Essen, Germany; 22Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK; 23Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece; 24Asthma Outpatient Clinic, National Koranyi Institute for Pulmonology, Budapest, Hungary; 25Department of Allergy and Respiratory Medicine, University Hospital, Reykjavik, Iceland; 26Pulmocare Research and Education Foundation, Pune, India; 27Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; 28Kindai University Hospital, Osakasayama, Japan; 29Microbiology Department, College of Medicine, Kuwait University, Kuwait, Al-Rashed Allergy Center, Ministry of Health, Kuwait City, Kuwait; 30Centro de Excelencia en Asma y Alergia, Hospital Médica Sur, Ciudad de México, Mexico; 31University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Department of Clinical Pharmacy & Pharmacology, Groningen, the Netherlands; 32Department of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway; 33Department of Clinical Science, University of Bergen, Bergen, Norway; 34Division of Internal Medicine Asthma and Allergy, Medical University of Lodz, Lodz, Poland; 35Pneumology Unit, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; 36Centre of Pneumology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; 37Department of Pulmonology, King Fahad Medical City, Riyadh, Saudi Arabia, Alfaisal University, Riyadh, Saudi Arabia; 38Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea; 39Pneumology Service, Biocruces, Cruces University Hospital, Barakaldo, Spain; 40Respiratory Medicine and Allergology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden; 41Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 42Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 43Rashid Hospital, Dubai Health Authority (DHA), Dubai, United Arab Emirates; 44Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, Northern Ireland, UK; 45Lung Division, Royal Brompton & Harefield Hospital, London, UK; 46Division of Allergy and Clinical Immunology, Department of Medicine, National Jewish Health and University of Colorado School of Medicine, Denver and Aurora, CO, USA; 47Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, Scotland, UK&ast;These authors contributed equally to this workCorrespondence: David B Price, Observational and Pragmatic Research Institute (OPRI) Pte Ltd, 22 Sin Ming Lane, &num;06-76, Midview City, 573969, Singapore, Tel +65 3105 1489, Email dprice@opri.sgAim: The International Severe Asthma Registry (ISAR; http://isaregistries.org/) uses standardised variables to enable multi-country and adequately powered research in severe asthma. This study aims to look at the data countries within ISAR and non-ISAR countries reported collecting that enable global research that support individual country interests.Methods: Registries were identified by online searches and approaching severe asthma experts. Participating registries provided data collection specifications or confirmed variables collected. Core variables (results from ISAR’s Delphi study), steroid-related comorbidity variables, biologic safety variables (serious infection, anaphylaxis, and cancer), COVID-19 variables and additional variables (not belonging to the aforementioned categories) that registries reported collecting were summarised.Results: Of the 37 registries identified, 26 were ISAR affiliates and 11 non-ISAR affiliates. Twenty-five ISAR-registries and 4 non-ISAR registries reported collecting > 90% of the 65 core variables. Twenty-three registries reported collecting all optional steroid-related comorbidity variables. Twenty-nine registries reported collecting all optional safety variables. Ten registries reported collecting COVID-19 variables. Twenty-four registries reported collecting additional variables including data from asthma questionnaires (10 Asthma Control Questionnaire, 20 Asthma Control Test, 11 Asthma Quality of Life Questionnaire, and 4 EuroQol 5-dimension 5-level Questionnaire). Eight registries are linked to databases such as electronic medical records and national claims or disease databases.Conclusion: Standardised data collection has enabled individual severe asthma registries to collect unified data and increase statistical power for severe asthma research irrespective of ISAR affiliations.Keywords: Asia-Pacific, biologics, COVID-19, Europe, ISAR, International Severe Asthma Registry, oral corticosteroids, Registry, Middle East, Severe Asthma, Latin America, USA

Tou-Yuan Tsai,1– 3,&ast; Jen-Feng Lin,4,&ast; Yu-Kang Tu,3 Jian-Heng Lee,4 Yu-Ting Hsiao,4 Sheng-Feng Sung,5 Ming-Jen Tsai4 1Department of Emergency Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan; 2School of Medicine, Tzu Chi University, Hualien, Taiwan; 3Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; 4Department of Emergency Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City, Taiwan; 5Division of Neurology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City, Taiwan&ast;These authors contributed equally to this workCorrespondence: Sheng-Feng Sung, Division of Neurology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City, Taiwan, Tel +886 5 276 5041 Ext 7283, Fax +886 5 278 4257, Email sfusng@cych.org.tw; richard.sfsung@gmail.com Ming-Jen Tsai, Department of Emergency Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City, Taiwan, Tel +886 5 276 5041 Ext 1909, Fax +886 5 277 4511, Email tshi33@gmail.comPurpose: Distinguishing ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) is crucial in acute myocardial infarction (AMI) research due to their distinct characteristics. However, the accuracy of International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes for STEMI and NSTEMI in Taiwan’s National Health Insurance (NHI) database remains unvalidated. Therefore, we developed and validated case definition algorithms for STEMI and NSTEMI using ICD-10-CM and NHI billing codes.Patients and Methods: We obtained claims data and medical records of inpatient visits from 2016 to 2021 from the hospital’s research-based database. Potential STEMI and NSTEMI cases were identified using diagnostic codes, keywords, and procedure codes associated with AMI. Chart reviews were then conducted to confirm the cases. The performance of the developed algorithms for STEMI and NSTEMI was assessed and subsequently externally validated.Results: The algorithm that defined STEMI as any STEMI ICD code in the first three diagnosis fields had the highest performance, with a sensitivity of 93.6% (95% confidence interval [CI], 91.7– 95.2%), a positive predictive value (PPV) of 89.4% (95% CI, 87.1– 91.4%), and a kappa of 0.914 (95% CI, 0.900– 0.928). The algorithm that used the NSTEMI ICD code listed in any diagnosis field performed best in identifying NSTEMI, with a sensitivity of 82.6% (95% CI, 80.7– 84.4%), a PPV of 96.5% (95% CI, 95.4– 97.4), and a kappa of 0.889 (95% CI, 0.878– 0.901). The algorithm that included either STEMI or NSTEMI ICD codes listed in any diagnosis field showed excellent performance in defining AMI, with a sensitivity of 89.4% (95% CI, 88.2– 90.6%), a PPV of 95.6% (95% CI, 94.7– 96.4%), and a kappa of 0.923 (95% CI, 0.915– 0.931). External validation confirmed these algorithms’ efficacy.Conclusion: Our results provide valuable reference algorithms for identifying STEMI and NSTEMI cases in Taiwan’s NHI database.Keywords: administrative claims data, acute myocardial infarction, diagnosis, ICD-10-CM, non-ST-elevation myocardial infarction, ST-elevation myocardial infarction

Yune-Young Shin,1,&ast; Sojung Park,1,&ast; Kyung Joo Kim,2 Chin Kook Rhee,2 Kwang Ha Yoo,3 Ki-Suck Jung,4 Jin Hwa Lee1 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea; 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea; 3Division of Pulmonary and Allergy Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea; 4Division of Pulmonary Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University Medical School, Anyang, Gyeonggi-do, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Jin Hwa Lee, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Ewha Womans University, 25 Magokdong-ro 2-gil Gangseo-gu, Seoul, 07804, Republic of Korea, Tel +82 2 6986 1631, Fax +82 2-2655-2076, Email jinhwalee@ewha.ac.krPurpose: To investigate the clinical characteristics and medical utilization of smokers with preserved ratio impaired spirometry (PRISm).Patients and Methods: We used data from the Korean National Health and Nutrition Examination Survey between 2007 and 2012, linked to the Health Insurance Review and Assessment Service. Clinical characteristics and medical utilization, including inpatient admission, emergency department visit, prescribed medication, and medical cost, were retrospectively compared among three groups: normal spirometry, PRISm, and chronic obstructive pulmonary disease (COPD).Results: A total of 7115 smokers were included (4743 normal spirometry, 689 PRISm, and 1683 COPD subjects). The mean age was the highest in the COPD group, followed by the PRISm and normal groups, and the proportion of women was the highest in the PRISm group. The tobacco exposure, socioeconomic status (SES), and schooling level of the PRISm group were at levels between those of the normal and COPD groups. However, the PRISm group had the highest proportion of current smokers, highest body mass index (BMI), and lowest mean FEV1 and FVC % predicted. During the study period, the medical utilization of 92 smokers (13.4%) in the PRISm group and 436 smokers (25.9%) in the COPD group was related to respiratory diseases. Emergency department visit or hospitalization and overall medical cost of the PRISm group were comparable to those of the COPD group, except for outpatient clinic visit. Old age, women, low BMI, low SES, low schooling level, high amount of tobacco exposure, wheezing, and decreased FEV1 and FVC % predicted were factors associated with medical utilization in PRISm.Conclusion: Medical utilization was comparable between the PRISm and COPD groups. Smokers with PRISm who were older, women, or heavy smokers with low BMI, low SES and schooling level, wheezing, or low FEV1 and FVC might need close observation and early treatment.Keywords: emergency department, hospitalization, lung function, restrictive lung disease, wheezing

Min-Cheol Park,1,2,&ast; Ju-Hyun Lee,3,&ast; Eun-Jin Seong,4 Dong-Sung Lee,5 Eun-Heui Jo2,6 1Department of Korean Medicine Ophthalmology and Otolaryngology and Dermatology, Wonkwang University Korean Medicine Hospital, Iksan, Jeollabuk-do, 54538, Republic of Korea; 2Research Center of Traditional Korean Medicine, Wonkwang University, Iksan, Jeollabuk-do, 54538, Republic of Korea; 3Department of Medical Support, Imsil-Gun Medical Center, Imsil, Jeollabuk-do, 55927, Republic of Korea; 4Seoul Clinic, Hanam, Gyeonggi-do, 12945, Republic of Korea; 5College of Pharmacy, Chosun University, Gwangju, Jeollanam-do, 61452, Republic of Korea; 6Department of Acupuncture and Moxibustion, Wonkwang University Korean Medicine Hospital, Jeonju, Jeollabuk-do, 54887, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Dong-Sung Lee, College of Pharmacy, Chosun University, 309, Pilmundae-ro, Dong-gu, Gwangju, Jeollanam-do, 61452, Republic of Korea, Tel +82-62-230-6386, Fax +82-62-232-8834, Email dslee2771@chosun.ac.kr Eun-Heui Jo, Department of Acupuncture and Moxibustion, Wonkwang University Korean Medicine Hospital, 99, Garyeonsan-ro, Deokjin-gu, Jeonju, Jeollabuk-do, 54887, Republic of Korea, Tel +82-63-270-1022, Fax +82-63-270-1199, Email freezo@wonkwang.ac.krPurpose: This study is to report a case of chronic atopic dermatitis (AD) with eosinophilia, which did not respond to conventional therapy and was improved by Daesiho-tang (DSHT).Patients and Methods: The patient visited our clinic with symptoms of atopic dermatitis including skin lesions and pruritus. Based on her symptoms, DSHT was prescribed. At each visit, the Scoring Atopic Dermatitis (SCORAD), Dermatology Life Quality Index (DLQI), and accompanying systemic symptoms (ASS) were measured. Multiple Allergen Simultaneous Test (MAST) was initially performed for 108 allergens and analyzed by Western blotting using an Alternate Scoring Method (ASM) according to the specific IgE concentration. Also, peripheral blood laboratory (Lab) tests were performed three times during the patient’s visit.Results: After taking DSHT, the total SCORAD score improved from 62.9 to 23.5, while the patient’s ASS also improved. The DLQI score improved from 19 to 5. The total number of eosinophils in the peripheral blood, which showed a mild increase, recovered from 17.2% (0.98 x103/μL) to 4.5% (0.24 x103/μL). The total IgE slightly decreased, while AST and ALT were also restored to normal ranges.Conclusion: Based on this case, DSHT is considered a potential alternative treatment for AD.Graphical Abstract: Keywords: case report, atopic dermatitis, eosinophilia, Daesiho-tang

Jieun Shin,1 Ji-Hoon Lee,1 Nam-Yi Kim2 1Department of Biomedical Informatics, College of Medicine, Konyang University, Daejeon, Republic of Korea; 2Department of Nursing, Konyang University, Daejeon, Republic of KoreaCorrespondence: Nam-Yi Kim, Department of Nursing, Konyang University, Daejeon, 35365, Republic of Korea, Tel +82-42-600-8586, Fax +82-42-600-8555, Email namyi00@konyang.ac.kr; namyi8213@gmail.comPurpose: To address the increasing number of patient safety incidents, their scope and extent should be assessed and the situations in which they occur determined. This study employed a decision tree analysis based on patient safety incident cases to identify groups at high risk for adverse patient safety incidents and provide data to develop prevention strategies for minimizing their occurrence or recurrence.Methods: In total, 8934 patient safety incidents were analyzed using the “ 2021 Patient Safety Report Data”, which were systematically collected by the Korea Institute for Healthcare Accreditation. A decision tree analysis (Chi-square Automatic Interaction Detection) was employed to identify the characteristics associated with the degree of risk for patient safety incidents.Results: The groups most vulnerable to adverse events were those who experienced healthcare-associated infections (HAI) in long-term care facilities, followed by those experiencing HAI in tertiary hospitals, general hospitals, or clinics, and those experiencing fall-related events in neuropsychiatry departments of tertiary hospitals, general hospitals, or clinics.Conclusion: The most important factor in the degree of harm in patient safety accidents was the type of accident, followed by the type of medical institution, and then the treatment department. Particularly, HAI and falls are the most important factors determining the degree of harm in patient safety accidents.Keywords: decision tree, infection, incident, patient safety, prevention

Jung Hwan Lee,1 Jun Ho Lee,2 Min Cheol Chang3 1Namdarun Rehabilitation Clinic, Yongin-City, Gyeonggi-Do, South Korea; 2Department of Neurosurgery, Kyung Hee University Medical Center, Seoul, 02447, South Korea; 3Department of Physical Medicine and Rehabilitation, College of Medicine, Yeungnam University, Daegu, 705-717, Republic of KoreaCorrespondence: Min Cheol Chang, Department of Physical Medicine and Rehabilitation, College of Medicine, Yeungnam University, 317-1, Daemyungdong, Namku, Daegu, 705-717, Republic of Korea, Tel +82-53-620-4862, Email wheel633@gmail.comPurpose: This study aimed to evaluate the effect of transforaminal epidural steroid injection (TFESI) in patients with lumbosacral disc herniation by comparing its effect between those diagnosed by clinical evaluation and plain radiography only (X-ray group) and those by additional magnetic resonance imaging (MRI) (MRI group). Additionally, we investigated the accuracy of the preliminary clinical assumption in the X-ray group using confirmative post-injection MRI.Patients and Methods: We retrospectively recruited 367 patients with back and radicular pain due to lumbosacral disc herniation from a single pain clinic. Among them, 201 and 166 patients were categorized into the X-ray and MRI groups, respectively. In the X-ray group, the pathological level assumed initially by clinical evaluation and plain radiography concurred with that confirmed later on post-injection MRI in 139 patients (corresponding group); the remaining 62 patients lacked this concurrence (non-corresponding group). The NRS scores and Macnab criteria results were compared between the X-ray and MRI groups as well as the corresponding and non-corresponding groups.Results: Both the X-ray and MRI groups showed significant reductions in the NRS scores at 2 and 10 weeks post-injection when compared with the pretreatment scores. However, no significant difference was noted between the groups in terms of the magnitude of clinical improvement assessed by successful reduction in the NRS or Macnab scores. Furthermore, similar results were obtained in the comparison between the corresponding and non-corresponding groups of the X-ray group.Conclusion: TFESI guarantees favorable clinical outcomes even in the absence of confirmative MRI in patients with back and radicular pain. The preemptive application of this procedure could be prioritized and justified in patients suspected of lumbosacral disc herniation based on clinical evaluation and plain radiography only without the preceding MRI verification.Keywords: lumbosacral disc herniation, epidural injection, transforaminal, numeric rating scale, plain radiography

Hyocheong Chae,1,2,&ast; Hongmin Chu,1,3,&ast; Junghun Lee,1 Hagdong Kim,1 Dongha Kim,1 Sebong Park,1 Kwanghwan Lim,1 Minsu Jeong,1 Kyungho Kang,1 Gyeongchan Kim,1 Joo Hyun Lee,1 Sehun Jung,1 Jaehyo Kim,4 Yongjoo Kim,5 Myungseok Ryu1,6 On behalf of Korean Medical Society of Acupotomology KM Doctors Group1Departmental Research Committee, Korean Medical Society of Acupotomology, Seoul, Republic of Korea; 2Sunyujae Korean Medicine Clinic, Yongin, Republic of Korea; 3Department of Korean Internal Medicine, College of Korean Medicine, Wonkwang University, Iksan, Republic of Korea; 4Department of Meridian & Acupoint, College of Korean Medicine, Wonkwang University, Iksan, Republic of Korea; 5College of Korean Medicine, Sangji University, Wonju, Republic of Korea; 6Clinic Department, Daemyeong Korean Medicine Clinic, Seoul, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Myungseok Ryu, Clinic Department of Daemyung Korean Medicine Clinic, Wonwoo b/d 3rd fl, Yangpyeong-ro, Yeongdeungpo-gu, Seoul, 07208, Republic of Korea, Tel +82-2-2671-7191, Fax +82-2-2676-1297, Email yeonbu16@gmail.comObjective: Shoulder pain is a common complaint in outpatient clinics and can result in an inability to work or perform household activities, leading to significant socioeconomic burden. Acupotomy, as one kind acupuncture that has flat knife-shaped tip, has been widely used for treating shoulder pain. However, despite the widespread use of acupotomy in primary medical institutions, large sample size clinical trials have not sufficiently been performed. In this respect, this multi-center retrospective study aimed to investigate the effectiveness and safety of acupotomy in reducing shoulder pain and disability using data from multi-center primary care clinics.Methods: This study was conducted in 25 Korean medicine clinics affiliated with the Korean Medical Society of Acupotomology, Republic of Korea, from August 2021 to December 2021. The medical records of patients who visited the clinics complaining of shoulder pain were gathered, and among them were those of patients who underwent acupotomy treatment and those who received acupuncture combined therapy. The Numeric Rating Scale (NRS), SPADI (Shoulder Pain and Disability Index), Range of Motion (ROM) and adverse event were evaluated at each visit. A linear mixed-effects models and paired t-test were used to identify the effectiveness of the treatment.Results: Overall analysis showed that the NRS score of patients decreased from 4.95 ± 1.97 before treatment to 3.78 ± 2.03 after treatment (n = 332, difference in NRS score, 1.17; 95% CI: 0.96– 1.38, t = 10.89 p < 0.001). SPADI score decreased from 19.05 ± 20.44 at baseline before treatment to 12.12 ± 17.26 after the last visit, which was statistically significant (n = 332, mean difference in SPADI score, 6.93; 95% CI: 4.71– 9.15, t = 6.150, p < 0.001). No serious adverse event was reported in both groups.Conclusion: This study showed the effectiveness of acupotomy therapy for shoulder pain, and as the treatment sessions increased, the effect of pain reduction and shoulder function improvement were also increased.Keywords: acupotomy, shoulder pain, retrospective study, multicenter study

Electromagnetic ion cyclotron (EMIC) waves play important roles in particle loss processes in the magnetosphere. Determining the evolution of EMIC waves as they propagate and how this evolution affects wave-particle interactions requires accurate knowledge of the wave vector, k. We present a technique using the curl of the wave magnetic field to determine k observationally, enabled by the unique configuration and instrumentation of the Magnetospheric MultiScale (MMS) spacecraft. The wave curl analysis is demonstrated for synthetic arbitrary electromagnetic waves with varying properties typical of observed EMIC waves. The method is also applied to an EMIC wave interval observed by MMS on October 28, 2015. The derived wave properties and k from the wave curl analysis for the observed EMIC wave are compared with the Waves in Homogenous, Anisotropic, Multi-component Plasma (WHAMP) wave dispersion solution and with results from other single- and multi-spacecraft techniques. We find good agreement between k from the wave curl analysis, k determined from other observational techniques, and k determined from WHAMP. Additionally, the variation of k due to the time and frequency intervals used in the wave curl analysis is explored. This exploration demonstrates that the method is robust when applied to a wave containing at least 3-4 wave periods and over a rather wide frequency range encompassing the peak wave emission. These results provide confidence that we are able to directly determine the wave vector properties using this multi-spacecraft method implementation, enabling systematic studies of EMIC wave k properties with MMS.

We report measurements of the parity-conserving beam-normal single-spinelastic scattering asymmetries $B_n$ on $^{12}$C and $^{27}$Al, obtained withan electron beam polarized transverse to its momentum direction. Thesemeasurements add an additional kinematic point to a series of previousmeasurements of $B_n$ on $^{12}$C and provide a first measurement on $^{27}$Al.The experiment utilized the Qweak apparatus at Jefferson Lab with a beam energyof 1.158 GeV. The average lab scattering angle for both targets was 7.7degrees, and the average $Q^2$ for both targets was 0.02437 GeV$^2$ (Q=0.1561GeV). The asymmetries are $B_n$ = -10.68 $\pm$ 0.90 stat) $\pm$ 0.57 (syst) ppmfor $^{12}$C and $B_n$ = -12.16 $\pm$ 0.58 (stat) $\pm$ 0.62 (syst) ppm for$^{27}$Al. The results are consistent with theoretical predictions, and arecompared to existing data. When scaled by Z/A, the Q-dependence of all thefar-forward angle (theta < 10 degrees) data from $^{1}$H to $^{27}$Al can bedescribed by the same slope out to $Q \approx 0.35$ GeV. Larger-angle data fromother experiments in the same Q range are consistent with a slope about twiceas steep.

We report measurements of the parity-conserving beam-normal single-spinelastic scattering asymmetries $B_n$ on $^{12}$C and $^{27}$Al, obtained withan electron beam polarized transverse to its momentum direction. Thesemeasurements add an additional kinematic point to a series of previousmeasurements of $B_n$ on $^{12}$C and provide a first measurement on $^{27}$Al.The experiment utilized the Qweak apparatus at Jefferson Lab with a beam energyof 1.158 GeV. The average lab scattering angle for both targets was 7.7degrees, and the average $Q^2$ for both targets was 0.02437 GeV$^2$ (Q=0.1561GeV). The asymmetries are $B_n$ = -10.68 $\pm$ 0.90 stat) $\pm$ 0.57 (syst) ppmfor $^{12}$C and $B_n$ = -12.16 $\pm$ 0.58 (stat) $\pm$ 0.62 (syst) ppm for$^{27}$Al. The results are consistent with theoretical predictions, and arecompared to existing data. When scaled by Z/A, the Q-dependence of all thefar-forward angle (theta < 10 degrees) data from $^{1}$H to $^{27}$Al can bedescribed by the same slope out to $Q \approx 0.35$ GeV. Larger-angle data fromother experiments in the same Q range are consistent with a slope about twiceas steep.

Eun Kyung Jun,1,&ast; Sunghwan Lim,2,&ast; Joonho Seo,3 Kae Hong Lee,1 Jae Hee Lee,1 Deukhee Lee,2 Jae Chul Koh1 1Department of Anesthesiology and Pain Medicine, Korea University Anam Hospital, Seoul, Korea; 2Center for Healthcare Robotics, Artificial Intelligence and Robotics Institute, Korea Institute of Science and Technology, Seoul, Korea; 3Department of Medical Assistant Robot, Korea Institute of Machinery and Materials, Daegu, Korea&ast;These authors contributed equally to this workCorrespondence: Deukhee Lee, Center for Bionics, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul, 136-791, Republic of Korea, Tel +82-2-958-5633, Fax +82-2-920-2275, Email dkylee@kist.re.kr Jae Chul Koh, Department of Anesthesiology and Pain Medicine, Korea University Anam Hospital, 73, Goryeodae-ro, Seongbukgu, Seoul, 02841, Korea, Tel +82-2-920-5632, Fax +82-2-920-2275, Email jaykoh@korea.ac.krPurpose: Multiple studies have attempted to demonstrate the benefits of augmented reality (AR)-assisted navigation systems in surgery. Lumbosacral transforaminal epidural injection is an effective treatment commonly used in patients with radiculopathy due to spinal degenerative pathologies. However, few studies have applied AR-assisted navigation systems to this procedure. The study aimed to investigate the safety and effectiveness of an AR-assisted navigation system for transforaminal epidural injection.Patients and Methods: Through a real-time tracking system and a wireless network to the head-mounted display, computed tomography images of the spine and the path of a spinal needle to the target were visualized on a torso phantom with respiration movements installed. From L1/L2 to L5/S1, needle insertions were performed using an AR-assisted system on the left side of the phantom, and the conventional method was performed on the right side.Results: The procedure duration was approximately three times shorter, and the number of radiographs required was reduced in the experimental group compared to the control group. The distance from the needle tips to the target areas in the plan showed no significant difference between the two groups. (AR group 1.7 ± 2.3mm, control group 3.2 ± 2.8mm, P value 0.067).Conclusion: An AR-assisted navigation system may be used to reduce the time required for spinal interventions and ensure the safety of patients and physicians in view of radiation exposure. Further studies are essential to apply AR-assisted navigation systems to spine interventions.Keywords: interventional procedure, epidural injection, augmented reality, navigation system, radiation exposure

Jung Hee Lee,1,&ast; Hyun-Jong Lee,1,&ast; Sang Ha Woo,1 Yu-Kyeong Park,1 Ji Hoon Han,1 Ga-Young Choi,1 Eun Sil Heo,1 Jae Soo Kim,1 Chung A Park,2 Woo Dong Lee,3 Chang Sop Yang,4 Ae-Ran Kim,5 Chang-Hyun Han4,6 1Department of Acupuncture & Moxibustion, College of Korean Medicine, Daegu Haany University, Daegu, Republic of Korea; 2Department of Diagnostics, College of Korean Medicine, Daegu Haany University, Daegu, Republic of Korea; 3Pre-Major of Cosmetics and Pharmaceutics, College of Herbal Bio-Industry, Daegu Haany University, Daegu, Republic of Korea; 4KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 5Clinical Research Coordinating Team, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 6Korean Convergence Medicine, University of Science & Technology (UST), Campus of Korea Institute of Oriental Medicine, Daejeon, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Chang-Hyun Han, KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, 34054, Republic of Korea, Tel +82 42 868 9498, Fax +82 42 869 2775, Email chhan@kiom.re.krPurpose: In Korea, complex treatments such as acupotomy, acupuncture, and physical therapy are performed for lumbar spinal stenosis (LSS). Although there are reports of acupotomy as monotherapy or acupuncture treatment for LSS, pragmatic studies are lacking. Therefore, this study aimed to determine the effectiveness and safety of acupotomy for LSS to provide baseline evidence for a large-scale study.Materials and Methods: This pragmatic randomized controlled pilot study enrolled 34 participants and randomly assigned them to two groups (n=17/group). The intervention was conducted for 8 weeks. Acupotomy plus and usual care groups received acupuncture (17 acupoints) and interferential current therapy (ICT) twice weekly; however, the acupotomy plus group received an additional acupotomy (7 acupoints) for treatment of the usual care group. The primary outcome was measured using visual analog scales (VAS), and secondary outcomes were assessed using the self-rated walking distance, short-form McGill Pain Questionnaire (SF-MPQ), and the Oswestry Disability Index (ODI). Outcome measurements were conducted at baseline and 4, 8, and 12 weeks after the commencement of the intervention. Adverse events were assessed at each visit. Hematological and biochemical examinations were performed at screening and week 8.Results: Overall, 33 of the 34 participants completed the study, and one participant in the usual care group dropped out. In both groups, VAS scores at weeks 4, 8, and 12 significantly improved compared to baseline. Also, self-rated walking distance, SF-MPQ, and ODI scores were significantly improved at weeks 4, 8, and 12 than at baseline. However, there were no significant differences in the time-dependent and group-to-time interactions between the two groups. In addition, no severe adverse reactions were reported, and there were no significant differences in hematological and biochemical results.Conclusion: This study provides baseline data for large-scale studies on the effectiveness and safety of acupotomy in LSS.Clinical Trial Number: KCT0006234.Keywords: complementary therapy, pragmatic clinical trial, low back pain, acupuncture therapy

Jang Ho Lee,1,&ast; Sehee Kim,2,&ast; Yeon-Mok Oh1 1Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Republic of Korea; 2Department of Clinical Epidemiology and Biostatistics, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Yeon-Mok Oh, Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Centre, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea, Tel +82-2-3010-3136, Fax +82-2-3010-6968, Email ymoh55@amc.seoul.krPurpose: The aims of this study were to develop a scoring model that predicts the effects of withdrawing inhaled corticosteroids (ICSs) from triple therapy and to examine its adaptability when applied to assess the effect of adding ICSs to dual bronchodilators patients with chronic obstructive pulmonary disease (COPD).Patients and Methods: A scoring model was developed using the IMPACT study dataset, consisting of 2389 COPD patients treated with triple therapy before enrollment (ICS withdrawal dataset). The developed model consisted of COPD duration, Acute exacerbation history, Sex, Pulmonary function tests, blood Eosinophil count, and Race (CASPER) and was used to predict composite events of moderate-to-severe exacerbation, all-cause mortality, and pneumonia. Treatment heterogeneity was assessed using Cox interaction analyses. The CASPER model was applied to 540 COPD patients treated with dual bronchodilator before enrollment (ICS addition dataset). Validity was assessed using Harrell’s C-index, time-dependent receiver operating characteristic curves, and calibration plots.Results: The cumulative incidence of the composite event was 60.1% over 12 months in the ICS withdrawal dataset. Cox interaction analyses revealed that ICS was different according to race and blood eosinophil counts. The hazard ratios (HRs) for dual bronchodilator compared with triple therapy were 1.318 (95% confidence interval (CI)=1.170– 1.485; P-value < 0.001) in whites and 0.922 (95% CI = 0.712– 1.195; P-value=0.541) in other races. The treatment effect was different in the eosinophil count ≥ 0.3 group (HR = 1.586; 95% CI = 1.274– 1.975) and in the eosinophil count = 0.1– 0.3 group (HR = 1.211; 95% CI = 1.041– 1.408), but it was same in the eosinophil count < 0.1 (HR = 1.009; P-value=0.940). The CASPER model performed well with good discrimination and calibration, which were superior to the prediction based on exacerbation history and blood eosinophil count.Conclusion: The presented CASPER model might be able to predict and compare the risk of composite events when dual bronchodilator or triple therapy is administered to COPD patients.Keywords: chronic obstructive pulmonary disease, inhaled corticosteroid, exacerbation, mortality, pneumonia

Capturing and utilizing CO2 as carbon feedstock for chemicals, fuels, or polymers is frequently discussed to replace fossil carbon and thereby help mitigate climate change. Emission reductions by Carbon Capture and Utilization (CCU) depend strongly on the choice of the CO2 source because CO2 sources differ in CO2 concentration and the resulting energy demand for capture. From a climate-change perspective, CO2 should be captured at the CO2 source with the lowest CO2 emissions from capture. However, reported carbon footprints differ widely for CO2 captured, from strongly negative to strongly positive for the same source. The differences are due to methodological ambiguity in the treatment of multifunctionality in current assessment practice. This paper reviews methodological approaches for determining the carbon footprint of captured CO2 as carbon feedstock, and shows why some approaches lead to suboptimal choices of CO2 sources and that increased consistency in life cycle assessment (LCA) studies on CCU is needed. Based on strict application of Life Cycle Assessment (LCA) standards and guidelines, it is shown that substitution should be applied to avoid suboptimal choices of CO2 sources. The resulting methodological recommendations are applied to estimate the carbon footprint of feedstock CO2 for current CO2 sources in Europe and for future CO2 sources in a scenario for a low carbon economy. For all CO2 sources, the cradle-to-gate footprint of captured CO2 is negative ranging from -0.95 to -0.59 kg CO2 eq. per kg of feedstock CO2 today and from -0.99 to -0.98 kg CO2 eq. in a low carbon economy. The carbon footprints of different CO2 sources differ mainly due to their energy demands. The presented assessment method and the carbon footprints of the CO2 feedstocks CO2 provide the basis for future assessments of carbon capture and utilization processes. This journal is

Understanding the physical properties and controlling the generation of intrinsic and extrinsic defects is central to the technological adoption of 2D materials in devices. Here we identify a charged carbon-hydrogen complex at a chalcogen site (CHX) as a common, charged impurity in synthetically grown transition metal dichalcogenides (TMDs). This conclusion is drawn by comparing high resolution scanning probe microscopy measurements of nominally undoped and intentionally carbon doped TMD samples. While CH impurity densities in undoped CVD-grown WS2 and MOCVD-grown WSe2 can range anywhere from parts per million to parts per thousand, CH densities in the percentage levels were selectively generated by a post-synthetic methane plasma treatment. Our study indicates that methane plasma treatment is a selective and clean method for the controlled introduction of a charged carbon-hydrogen complex at a surface chalcogen site, a defect that is commonly present in synthetic TMDs.

The present study examined the interaction effects between teachers’ choice of language in lexical explanation and second language (L2) learners’ proficiency level on the learning of phrasal verbs and listening comprehension in a meaning-focused listening activity. Undergraduate L2 learners with two different levels of proficiency (intermediate and advanced) were assigned to three different conditions. These conditions included (1) code-switching, in which teachers briefly switched to learners’ first language for vocabulary teaching purposes, (2) L2-only, in which teachers maintained L2 for overall instruction and vocabulary teaching, and (3) control condition, in which learners were not given instruction about target vocabulary. The results revealed that teachers’ instruction about target vocabulary brought about more gains in learning of phrasal verbs than lack thereof. In addition, teachers’ use of code-switching benefited intermediate-level learners most, who were able to gain similar levels of vocabulary learning and listening comprehension to advanced learners.

A detailed understanding of charged defects in two-dimensional semiconductors is needed for the development of ultrathin electronic devices. Here, we study negatively charged acceptor impurities in monolayer WS2 using a combination of scanning tunneling spectroscopy and large-scale atomistic electronic structure calculations. We observe several localized defect states of hydrogenic wave function character in the vicinity of the valence band edge. Some of these defect states are bound, while others are resonant. The resonant states result from the multivalley valence band structure of WS2, whereby localized states originating from the secondary valence band maximum at Γ hybridize with continuum states from the primary valence band maximum at K/K′. Resonant states have important consequences for electron transport as they can trap mobile carriers for several tens of picoseconds.

Sung-Soo Kim,1,&ast; Sojung Won,2,&ast; Ha Eun Lee,2 Seung Hyun Ryu,2 Dong Joon Choi,2 Sung Ig Cho,2 Byoung Joo Gwag,2 Hwa-Young Youn,3 Jin Hwan Lee2 1VIP Animal Medical Center KR, Seoul, 02830, Republic of Korea; 2GNT Pharma, Yongin, Gyeonggi, 17096, Republic of Korea; 3Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Jin Hwan Lee, GNT Animal Health Business Unit, Yongin, Gyeonggi, 17096, Republic of Korea, Tel +82 10 8878 0456, Fax +82 31 8005 9931, Email jhlee@gntpharma.comPurpose: Nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX)-2 selective inhibitors are the most widely used drugs to treat pain. Conventional NSAIDs and COX-2 selective inhibitors, however, cause several side effects such as gastric damage, kidney damage, and cardiovascular problems. Our previous study showed that 2-acetoxy-5-(2-4-(trifluoromethyl)-phenethylamino)-benzoic acid ie, flusalazine (also known as ND-07), which exerts dual actions by serving both as an anti-inflammatory agent and a free radical scavenger, is an effective and safe treatment for severe inflammatory diseases in mice. The goal of the present study was to examine the potential analgesic action and safety of flusalazine in mice models of pain.Methods and Results: Flusalazine showed a significant analgesic effect in an acetic acid-induced abdominal constriction model. Likewise, total paw licking was reduced significantly in neurogenic (early stage) and inflammatory (late stage) pain induced by formalin in flusalazine-treated mice. In the tail immersion test, flusalazine significantly increased tail withdrawal time at 2 h after its administration. Also, the formation of paw edema in the flusalazine-treated group was significantly inhibited in a carrageenan-induced inflammatory pain model. Gastric damage was not induced by flusalazine even up to 1000 mg/kg, while aspirin and indomethacin caused critical gastric bleeding.Conclusion: These findings suggest that flusalazine’s safety profile and analgesic effects have high translational potential for the clinical treatment of patients experiencing pain.Keywords: analgesic effect, aspirin, flusalazine, indomethacin, NSAIDs

Hyung Joon Yim,1,&ast; Ji Hoon Kim,2,&ast; Yong Kyun Cho,3 Young Oh Kweon,4 Hyun Chin Cho,5 Jae Seok Hwang,6 Changhyeong Lee,7 Moon Soo Koh,8 Yang-Hyun Baek,9 Young-Min Park,10 Jeong-Hoon Lee,11 Seung Up Kim,12 Min-Kyu Kang,13 Neung Hwa Park,14 June Sung Lee,15 Young Eun Chon,16 Gab Jin Cheon,17 Hee Bok Chae,18 Joo Hyun Sohn,19 Young-Suk Lim20 1Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Seoul, Korea; 2Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea; 3Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea; 4Department of Internal Medicine, Kyungpook National University, School of Medicine, Daegu, Korea; 5Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea; 6Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea; 7Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea; 8Department of Internal Medicine, Dongguk University Ilsan Hospital, College of Medicine, Dongguk University, Goyang, Korea; 9Department of Gastroenterology, DongA University College of Medicine, Busan, Korea; 10Department of Internal Medicine, Bundang Jesaeng General Hospital, Seongnam, Korea and Hepatology Center, Bundang Jesaeng General Hospital, Seongnam, Korea; 11Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea; 12Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea, and Yonsei Liver Center, Severance Hospital, Seoul, Korea; 13Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea; 14Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea; 15Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea; 16Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea; 17Department of Medicine, GangNeung Asan Hospital, Ulsan University College of Medicine, Gangwon-do, Korea; 18Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Korea; 19Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea, and Hanyang University Guri Hospital, Guri, Korea; 20Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea&ast;These authors contributed equally to this workCorrespondence: Young-Suk Lim, Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, 43-Gil 88, Olympic-Ro, Songpa-Gu, Seoul, Korea, Tel +82-2-3010-3190, Fax +82-2-485-5782, Email limys@amc.seoul.krPurpose: Tenofovir disoproxil (TD), modified from tenofovir disoproxil fumarate (TDF), was developed as a salt-free formulation, removing fumarate to improve the ease of oral intake by reducing the tablet’s size. We evaluated the maintenance of antiviral effects and overall safety profile of TD 245 mg after switching from TDF 300 mg in patients with chronic hepatitis B (CHB).Patients and Methods: CHB patients with HBV-DNA < 69 IU/mL after ≥ 24 weeks of TDF therapy were enrolled. The primary efficacy endpoint was the HBV-DNA suppression rate (HBV-DNA < 69 IU/mL) at week 48; We evaluated the non-inferiority (10% margin) of TD to TDF in terms of efficacy. Safety was assessed based on adverse events (AEs), laboratory tests, bone mineral density, and renal function abnormalities.Results: Overall, 189 subjects were randomized in a 2:1 ratio, and 117 and 66 subjects in the TD and TDF groups, respectively, completed the study. In the per-protocol set, the HBV-DNA suppression rate at week 48 was 99.1% and 100% in the TD and TDF groups, respectively. The lower limit of the 97.5% one-sided confidence interval for the intergroup difference in HBV-DNA suppression rate was − 2.8%, which was greater than the prespecified margin of non-inferiority. The changes in creatinine clearance from baseline to week 48 was significantly less in the TD group and in the TDF group; − 0.8 ± 9.8 versus − 2.4 ± 12.8 mL/min, respectively (P=0.017).Conclusion: TD was non-inferior to TDF for maintaining viral suppression in CHB patients, showing the less decline of renal function.Keywords: viral DNA, bone density, antiviral agents, viral suppression

Hye Jung Park,1 Soyoung Jeon,2 Hye Sun Lee,2 Bo Yeon Kim,3 Yu Jin Chae,3 Gui Ok Kim,3 Jung-Won Park,4,5 Jae-Hyun Lee4,5 1Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; 2Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Republic of Korea; 3Healthcare Insurance Review & Assessment Service, Wonju, Republic of Korea; 4Division of Allergy and Immunology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; 5Institute of Allergy, Yonsei University College of Medicine, Seoul, Republic of KoreaCorrespondence: Jae-Hyun Lee, Division of Allergy and Immunology, Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea, Tel +82-2-2228-1977, Fax +82-2-393-6884, Email jhleemd@yuhs.acBackground: Although a wide variety of asthma medications have been developed and are used in clinical practice, there is limited evidence of their comparative effects on asthma exacerbations.Methods: We used claims data provided by the Health Insurance Review and Assessment Service. We selected subjects commencing asthma treatment between July 1, 2017 and June 30, 2018, with no change in drug regimen. The primary outcome was asthma exacerbation requiring systemic corticosteroids. Cox regression analysis was used to assess outcomes considering the exacerbation-free period.Results: Of the 254,951 asthma subjects, 107,694 subjects (42.2%) experienced asthma exacerbation. Inhaled corticosteroids (ICSs) (hazard ratio [HR], 0.378– 0.508), ICS-long-acting β2-agonist (LABAs) (HR, 0.284– 0.479), long-acting muscarine antagonists (LAMAs) (HR, 0.432– 0.572), leukotriene receptor antagonists (LTRAs) (HR, 0.371– 0.419), and xanthines (HR, 0.326– 0.482) significantly reduced the rate of first and second exacerbation of asthma (all P-values, < 0.001). The clinical effectiveness of asthma medications varied according to the active ingredient (HR 0.164– 0.670) and was significant for all active ingredients (all P-values, < 0.001). The effectiveness of combination treatment using ICS-LABA and LTRA varied (HR, 0.159– 0.670); however, all combination treatment options evaluated were effective in preventing asthma exacerbations (all P-values, < 0.001). Long-term use of ICS-LABA (HR, 0.278– 0.653), LTRA (HR, 0.259– 0.628), and xanthines (HR, 0.351– 0.783) showed consistent effectiveness (all P-values, < 0.001).Conclusion: This real-world study showed that the effectiveness of asthma medications varied according to drug type, active ingredient, combination, and period of use, although effectiveness was significant in all cases studied.Keywords: asthma, medication, exacerbation, real-world data, drug, combination

Jisoo Park,1 Eun-Kyung Kim,1 Se Hee Lee,1 Mi-Ae Kim,1 Jung-Hyun Kim,1 Sang Min Lee,2,3 Jae Seung Lee,4,5 Yeon-Mok Oh,4,5 Sang-Do Lee,4,5 Ji-Hyun Lee1 On behalf of the KOLD Study Group1Department of Pulmonology, Allergy and Critical Care Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea; 2Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 3Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 4Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 5Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of KoreaCorrespondence: Ji-Hyun Lee, Department of Pulmonology, Allergy and Critical Care Medicine, CHA Bundang Medical Center, CHA University, 59, Yatap-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13496, Republic of Korea, Tel +82-31-780-5205, Fax +82-31-780-2992, Email plmjhlee@cha.ac.krPurpose: We explored the differences in clinical manifestations of COPD patients regarding emphysema distribution along with evidence of airway involvement in chest computed tomography (CT) scans.Patients and Methods: The patients were divided into three groups according to the emphysema distribution: the upper dominant (UD), lower dominant (LD), and homogeneous (HD) groups. Airway wall thickness was quantitatively measured and the presence of bronchiectasis and/or bronchial wall thickening (BE/BWT) was visually assessed. Baseline characteristics including the evidence of airway involvement and long-term outcomes were compared among the three groups. Non-severe patients of each group were first treated with 3 months of ICS/LABA combination after 2 weeks of wash-out period and lung functions before and after the treatment were compared.Results: Of the 425 patients, 141 were in the UD, 107 in LD, and 177 in HD. The LD had more severe airway obstruction with lower emphysema index (EI) than the UD (LD vs UD; FEV1, 49.5– 14.9 vs 54.6– 16.5; EI, 21.0 [IQR: 14.0– 33.1] vs 26.3 [IQR: 15.8– 39.0]). The LD showed thicker airways (higher WA% and Pi10) and more severe air trapping (higher RV and RV/TLC) than UD. A larger proportion of patients in LD had BE/BWT (35.5% in LD vs 11.3% in UD). In LD, more patients experienced acute exacerbations and the time to first exacerbation was shorter than UD. Non-severe patients in LD treated with 3 months of ICS/LABA combined inhalers showed a notable reduction of RV than UD (LD vs UD; − 531.1– 936.5 vs − 86.5– 623.5).Conclusion: The LD showed a more prominent airway involvement than UD, which may cause more frequent exacerbations and a marked reduction of RV after the ICS/LABA combination treatment in LD. Phenotyping of the COPD patients using quantitatively measured emphysema distribution would be useful for predicting treatment response and exacerbation.Keywords: pulmonary disease, chronic obstructive, computed tomography, emphysema

The DESI Legacy Imaging Surveys (http://legacysurvey.org/) are a combination of three public projects (the Dark Energy Camera Legacy Survey, the Beijing-Arizona Sky Survey, and the Mayall z-band Legacy Survey) that will jointly image ≈14,000 deg2 of the extragalactic sky visible from the northern hemisphere in three optical bands (g, r, and z) using telescopes at the Kitt Peak National Observatory and the Cerro Tololo Inter-American Observatory. The combined survey footprint is split into two contiguous areas by the Galactic plane. The optical imaging is conducted using a unique strategy of dynamically adjusting the exposure times and pointing selection during observing that results in a survey of nearly uniform depth. In addition to calibrated images, the project is delivering a catalog, constructed by using a probabilistic inference-based approach to estimate source shapes and brightnesses. The catalog includes photometry from the grz optical bands and from four mid-infrared bands (at 3.4, 4.6, 12, and 22 μm) observed by the Wide-field Infrared Survey Explorer satellite during its full operational lifetime. The project plans two public data releases each year. All the software used to generate the catalogs is also released with the data. This paper provides an overview of the Legacy Surveys project.

Hye Soon Kim,1 Jae Myung Yu,2 Hak Chul Jang,3 Eui Kwang Choi,4 Jeong Hyun Park,5 Ho Sang Shon,6 Choon Hee Chung,7 Keun-Gyu Park,8 Jae Hyoung Cho,9 Won Kim,10 Kyoung Hwa Lee,10 Jee Hyun Lee,10 Soon Jib Yoo11 1Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea; 2Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University Medical Center, Hallym University College of Medicine, Seoul, Republic of Korea; 3Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; 4Department of Internal Medicine, Naedang Dr. Choi’s Clinic, Seoul, Republic of Korea; 5Department of Internal Medicine, College of Medicine, Inje University, Busan, Republic of Korea; 6Department of Internal Medicine, Catholic University of Daegu, School of Medicine, Daegu, Republic of Korea; 7Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea; 8Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea; 9Department of Endocrinology and Metabolism, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 10Medical Department Sanofi-Aventis Korea, Seoul, Republic of Korea; 11Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Republic of KoreaCorrespondence: Soon Jib Yoo, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon, 14647, Republic of Korea, Tel +82-32-340-7011, Fax +82-32-340-2039, Email sjyoomt@gmail.comPurpose: Although rapid-acting insulins (RAIs) are used frequently in Korean clinical settings, evidence on their use is limited. This study explores the pattern and clinical effectiveness of the use of RAIs in Korean patients with type 2 diabetes mellitus (T2DM).Patients and Methods: This non-interventional, observational study enrolled patients (aged > 18 years) with T2DM who were prescribed RAIs. The pattern of use and effectiveness of RAI analogs were evaluated over 6 months.Results: A total of 299/451 patients were analyzed. Approximately 90% (n/N=270/299) of the patients received insulin glulisine, which significantly reduced their levels of glycated hemoglobin (HbA1c: n=270, mean± standard deviation [SD]; − 1.16± 6.02%, p=0.0017), fasting plasma glucose (n=40; mean±SD: − 54.9± 90.89 mg/dl, p=0.0005), and post prandial blood glucose (n=35, mean±SD: − 89.46± 105.68 mg/dl, p< 0.0001) at 6 months, with a corresponding increase in body weight (BW) (n=197, mean±SD:1.45± 3.64 kg, p< 0.0001). At 6 months, more patients receiving an intensive regimen (basal insulin+≥ 2 RAI injections/day) had HbA1c < 7% than those receiving a non-intensive regimen (basal insulin+1 RAI injection/day) (20.69% vs 7.46%; p=0.0333); the corresponding reduction in HbA1c was also higher in patients receiving the intensive regimen (p< 0.0001). About one-fourth patients (n/N=22/95) were switched to the intensive regimen (from 1 to ≥ 2 RAI injections/day), and only 4.41% (n/N=9/204) of the patients were switched to 1 RAI injection/day. The patients receiving the intensive regimen showed higher levels of HbA1c reductions (mean±SD: − 1.27± 1.96%) compared with the maintenance group-1 RAI injection/day (mean±SD: − 0.72± 1.66%) (p=0.0459), without a significant increase in BW and body mass index.Conclusion: The insulin glulisine intensification regimen showed glycemic target achievement and can be considered a therapeutic tool in the management of T2DM patients.Keywords: glycated hemoglobin, insulin glulisine, intensification, RAI analogs

Hyewon Seo,1 Yun Su Sim,2 Kyung Hoon Min,3 Jae Ha Lee,4 Byung-Keun Kim,5 Yeon Mok Oh,6 Seung Won Ra,7 Tae-Hyung Kim,8 Yong Il Hwang,9 Jeong-Woong Park10 1Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 2Division of Pulmonary, Allergy and Critical Care Medicine, Kangnam Sacred Heart Hospital, Seoul, Republic of Korea; 3Division of Pulmonology, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea; 4Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea; 5Division of Pulmonology, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea; 6Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 7Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea; 8Division of Pulmonary and Critical Care Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Republic of Korea; 9Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea; 10Department of Allergy, Pulmonary and Critical Care Medicine, Gachon University Gil Medical Center, Incheon, Republic of KoreaCorrespondence: Jeong-Woong Park, Department of Allergy, Pulmonary and Critical Care Medicine, Gachon University Gil Medical Center, Namdong-daero 774 beon-gil, Namdong, Incheon, 21565, Republic of Korea, Tel +82-10-5574-0164, Fax +82-32-469-4320, Email jwpark@gilhospital.comPurpose: Data regarding the relationship between microbiologic features and comorbidities in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are limited. The aim of this study was to correlate microbiologic findings with comorbidities in patients with moderate to severe AECOPD.Patients and Methods: This multicenter observational study included patients with AECOPD seen at 28 hospitals in South Korea between January 2015 and December 2018, and the data were retrospectively collected. Pathogens were examined in patients with either pulmonary or extrapulmonary comorbidities, and compared to those of patients without comorbidities. The relationship between pathogen type and the number of comorbidities was also evaluated.Results: Bacterial infections (178 [37.2%] vs 203 [28.7%], p = 0.002) and co-infections with bacteria and viruses (65 [13.6%] vs 57 [8.1%], p = 0.002) were more prevalent in patients with pulmonary comorbidities. Bacterial pathogens (280 [34.7%] vs 101 [26.7%], p=0.006) were detected at a higher rate in patients with extrapulmonary comorbidities. Previous pulmonary tuberculosis (PTB), bronchiectasis, and diabetes mellitus were risk factors for bacterial infection, and congestive heart failure was a risk factor for bacterial and viral co-infection. As the number of comorbidities increased, the risk of bacterial infection increased considerably. Pseudomonas aeruginosa was more frequently identified in patients with previous PTB (57 [15.3%] vs 59 [7.4%], p < 0.001) and bronchiectasis (33 [19.6%] vs 83 [8.3%], p < 0.001).Conclusion: AECOPD patients with comorbidities were more likely to experience infection-related exacerbations compared to those without comorbidities. As the overall number of comorbidities increased, the risk of bacterial infection increased significantly.Keywords: chronic obstructive pulmonary disease, acute exacerbation, comorbidity, bacteria, virus

The ultrafast motion of oxygen vacancies in solids is crucial for various future applications, such as oxide electrolytes. Visualization and quantification can offer unforeseen opportunities to probe the collective dynamics of defects in crystalline solids, but little research has been conducted on oxygen vacancy electromigration using these approaches. Here, we visualize electric-field-induced creation and propagation of oxygen-vacancy-rich and -poor competing phases and their interface with optical contrast in Ca-substituted BiFeO3 that contains a high density of mobile oxygen vacancies. We quantitatively determined the drift velocity of collective migration to be on the order of 100 μm s−1 with an activation barrier of 0.79 eV, indicating a significantly large ionic mobility of 2 × 10−6 cm2 s−1 V−1 at a remarkably low temperature of 390 °C. In addition, visualization enables direct observation of fluidic behavior, such as the enhancement of conduction at channel edges, which results in U-shaped viscous propagation of the phase boundary and turbulence under a reverse electric field. All of these results provide new insights into the collective motion of defects.

Over the past decade, various online communication platforms have empowered citizens to express themselves politically. Although the political impact of online citizen expression has drawn considerable attention, research has largely focused on whether and how citizen-generated messages influence the public as an information alternative to traditional news outlets. The present study aims to provide a new perspective on understanding citizen expression by examining its political implications for the expressers themselves rather than those exposed to the expressed ideas. Data from a national survey and an online discussion forum study suggest that expressing oneself about politics provides self-reinforcing feedback. Political expressions on social media and the online forum were found to (a) reinforce the expressers’ partisan thought process and (b) harden their pre-existing political preferences. Implications for the role the Internet plays in democracy will be discussed.

Minseok Albert Kim,1 Heejoon Jang,1 Na Ryung Choi,1 Joon Yeul Nam,1 Yun Bin Lee,1 Eun Ju Cho,1 Jeong-Hoon Lee,1 Su Jong Yu,1 Hyo-Cheol Kim,2 Jin Wook Chung,2 Jung-Hwan Yoon,1 Yoon Jun Kim1 1Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea; 2Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South KoreaCorrespondence: Yoon Jun KimDepartment of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South KoreaTel +82-2-2072-3081Fax +82-2-743-6701Email yoonjun@snu.ac.krBackground: Both trans-arterial radioembolization (TARE) and conventional trans-arterial chemoembolization (TACE) can effectively control hepatocellular carcinoma (HCC) in patients who are not suitable for curative resection. This study compared the effectiveness of TARE and conventional TACE as the initial trans-arterial treatment for hepatocellular carcinoma (HCC) assessed by tumor response and clinical outcomes.Material and Methods: Data were retrospectively analyzed the propensity score-matched cohort for overall survival (OS), progression-free survival (PFS), and intrahepatic PFS in patients who have received TARE or TACE as the first HCC treatment from March 2012 to December 2017.Results: A total of 138 patients initially treated with TARE (n = 54) or TACE (n = 84) was included in this study. Of 138 patients, median age was 59 years and the mean follow-up period was 27.6 months. TARE showed better OS (hazard ratio [HR] = 0.54, 95% confidence interval [CI] = 0.31– 0.92, log-rank P = 0.02), better PFS (HR = 0.51, 95% CI = 0.36– 0.97, log-rank P = 0.04), and better intrahepatic PFS (HR = 0.51, 95% CI = 0.30– 0.88, log-rank P = 0.01) compared with TACE. TARE was an independent prognostic factor for OS (adjusted HR [aHR] = 0.52, 95% CI = 0.30– 0.90, P = 0.02), PFS (aHR = 0.57, 95% CI = 0.35– 0.94, P = 0.03), and intrahepatic PFS (aHR = 0.49, 95% CI = 0.28– 0.84, P = 0.01).Conclusion: TARE as initial trans-arterial treatment is associated with better clinical outcomes such as longer OS compared with TACE in patients with HCC.Keywords: liver neoplasms, brachytherapy, yttrium radioisotopes, embolization

Eun Kyung Kim,1 Mi-Ae Kim,1 Jae Seung Lee,2 Sang Min Lee,3 Soyeoun Lim,4 Jisoo Park,1 Jung-Hyun Kim,1 Yeon-Mok Oh,2 Sang-Do Lee,2 Se Hee Lee,1 Ji-Hyun Lee1 On behalf of the KOLD Study Group1Department of Pulmonology, Allergy and Critical Care Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea; 2Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 3Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 4Department of Radiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of KoreaCorrespondence: Ji-Hyun LeeDepartment of Pulmonology, Allergy and Critical Care Medicine, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam, 13496, Republic of KoreaTel +82-31-780-5205Fax +82-31-780-2992Email plmjhlee@cha.ac.krPurpose: Bronchiectasis (BE) is a poor prognostic factor in COPD. However, it is not clear whether the poor prognosis is a result of BE alone or accompanying chronic bronchitis symptoms. Therefore, we investigated the effect of chronic bronchitis symptoms on clinical outcomes in COPD patients with BE.Patients and Methods: We analyzed data of COPD patients from the Korean Obstructive Lung Disease (KOLD) cohort. The presence of BE was verified by chest computed tomography. Chronic bronchitis symptoms were determined using items in the symptomatic domain of the SGRQ, which is also used as an alternative definition of chronic bronchitis (CB). Patients were divided into four groups according to the presence of BE and CB symptoms: BE/CB, BE-only, CB-only, and no BE/CB. Demographic features and clinical outcomes were compared among these groups.Results: In total, 389 COPD patients were included in the analysis. BE was present in 148 (38%) patients and CB symptoms were found in 123 patients (33.2%). The patients were divided according to BE and CB symptoms, and the numbers and percentages of each group were as follows: BE/CB, 52 (13.4%); BE-only, 96 (24.7%); CB-only, 77 (19.8%); no BE/CB, 164 (42.2%). No significant differences were observed in baseline characteristics of lung function, radiological findings, and inflammatory markers among the four groups. The proportion of annual exacerbators was higher in the BE/CB and CB-only groups than the other two groups. After adjusting other parameters, the BE/CB group was significantly associated with acute exacerbation of COPD (AE-COPD) (OR = 2.110, p = 0.045).Conclusion: BE accompanying CB symptoms is associated with AE-COPD, while BE alone was not significantly associated. This finding suggests that it is more important to examine chronic bronchitis symptoms of BE to predict acute exacerbation than simply to identify BE in COPD patients.Keywords: COPD, bronchiectasis, chronic bronchitis, exacerbation

Jae-Hwa Choi,1,&ast; Keun-Bae Jeong,1,&ast; You Hyun Park,2 Iseul Yu,1 Seok Jeong Lee,1 Myoung Kyu Lee,1 Sang-Ha Kim,1 Won-Yeon Lee,1 Suk Joong Yong,1 Ji-Ho Lee1 1Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea; 2Department of Biostatistics, Yonsei University, Seoul, Korea&ast;These authors contributed equally to this workCorrespondence: Ji-Ho LeeDepartment of Internal Medicine, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju, 26426, KoreaTel +82-33-741-0926Fax +82-33-741-0928Email airwayleejh@yonsei.ac.krIntroduction: Inhaled corticosteroids (ICSs) play an important role in lowering the risk of acute exacerbation of chronic obstructive pulmonary disease (COPD). However, ICSs are known to increase the risk of pneumonia. Moreover, previous studies have shown that the incidence rate of pneumonia varies depending on the type of ICS. In this study, the risk of pneumonia according to the type of ICS was investigated in a population-based cohort.Methods: A retrospective cohort study was conducted using claims data of the entire population from the Korean National Health Insurance Service. Patients who were newly diagnosed with COPD and prescribed fluticasone propionate or budesonide were enrolled as study subjects. Cumulative doses of ICSs were classified into categorical variables to analyze the risk of pneumonia within identical ICS doses.Results: A total of 47,473 subjects were identified and allocated as 14,518 fluticasone propionate and 14,518 budesonide users through 1:1 propensity score matching. Fluticasone propionate users were more likely to develop pneumonia than budesonide users (14.22% vs 10.66%, p< 0.0001). The incidence rate per 100,000 person-years was 2,914.77 for fluticasone propionate users and 2,102.90 for budesonide users. The hazard ratio (HR) of pneumonia in fluticasone propionate compared to budesonide was 1.34 (95% CI 1.26– 1.43, p< 0.0001). The risk of pneumonia for fluticasone propionate compared to budesonide increased with higher ICS cumulative doses: 1.06 (0.93– 1.21), 1.41 (1.19– 1.66), 1.41 (1.23– 1.63), and 1.49 (1.33– 1.66) from the lowest to highest quartiles, respectively.Conclusion: ICS types and doses need to be carefully considered during treatment with ICSs in patients with COPD.Keywords: inhaled corticosteroid, chronic obstructive pulmonary disease, pneumonia, fluticasone propionate, budesonide

Ji Eun Park,1,&ast; Mi Jeong Hong,2,3,&ast; Shin Yup Lee,1,4 Jang Hyuck Lee,2,4 Jin Eun Choi,2,3 Hyo-Gyoung Kang,2,3 Sook Kyung Do,2,3 Ji Yun Jeong,5 Kyung Min Shin,6 Won Kee Lee,7 Sun Ha Choi,1 Yong Hoon Lee,1 Hye won Seo,1 Seung Soo Yoo,1 Jaehee Lee,1 Seung Ick Cha,1 Chang Ho Kim,1 Jae Yong Park1,2 1Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 2Department of Biochemistry, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 3Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 4BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea; 5Department of Pathology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 6Department of Radiology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 7Department of Medical Informatics, School of Medicine, Kyungpook National University, Daegu, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Shin Yup Lee; Jae Yong ParkDepartment of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of KoreaTel +82-53-200-2632Fax +82-53-200-2027Email shinyup@knu.ac.kr; jaeyong@knu.ac.krIntroduction: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have represented the prototype of targeted therapy in NSCLC. Patients with EGFR-mutant lung adenocarcinoma extract an extraordinary clinical benefit from EGFR-TKIs. However, the extent and duration of these responses are heterogeneous, suggesting the existence of genetic modifiers affecting an individual’s response to TKIs. We investigated whether genetic variants in miRNA binding sites are associated with the clinical outcome of EGFR-TKIs in lung adenocarcinoma patients.Methods: One hundred SNPs at miRNA binding sites in cancer-related genes were selected for the analysis using the crosslinking, ligation and sequencing of hybrids (CLASH) and CancerGenes database. qRT-PCR and luciferase assays were conducted to evaluate the functional relevance of the SNPs.Results: NUP62 rs9523A>G were significantly associated with worse response to EGFR-TKIs, overall survival (OS), and progression-free survival (PFS). The other three SNPs (DVL2 rs2074216G>A, ARF1 rs11541557G>T, and UHRF1 rs2261988C>A) were significantly associated with worse OS and PFS. The rs9523A>G was significantly associated with decreased NUP62 expression in tumor tissues. In addition, a significantly decreased luciferase activity was noted in NUP62 rs9523 G allele compared to A allele.Conclusion: Genetic variants in miRNA binding sites, especially NUP62 rs9523A>G, may be useful in predicting the clinical outcomes of EGFR-mutant lung adenocarcinoma patients treated with EGFR-TKIs.Keywords: lung adenocarcinoma, EGFR-TKI, clinical outcome, miRNA binding site, polymorphism

Mihir Gandhi,1– 4 Wen-Huan Ling,5 Chien-Hung Chen,6 Joon Hyeok Lee,7 Masatoshi Kudo,8 Rawisak Chanwat,9 Simone I Strasser,10 Zhu Xu,11 Soh-Han Lai,5 Pierce Kah-Hoe Chow12,13 1Biostatistics, Singapore Clinical Research Institute, Singapore; 2Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore; 3Lien Centre for Palliative Care, Duke-NUS Medical School, Singapore; 4Tampere Center for Child, Adolescent, and Maternal Health Research, Tampere University, Tampere, Finland; 5Programme in Translational and Clinical Liver Research, National Cancer Centre Singapore, Singapore; 6Department of Internal Medicine, National Taiwan University Hospital, Douliu City, Yunlin, Taiwan; 7Division of Gastroenterology, Sungkyunkwan University School of Medicine, Samsung Medical Centre, Seoul, Korea; 8Department of Gastroenterology and Hepatology, Kindai University Hospital, Osaka, Japan; 9Department of Surgery, National Cancer Institute, Bangkok, Thailand; 10AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia; 11Department of Interventional Therapy, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, People’s Republic of China; 12Department of Hepatopancreatobiliary and Transplant Surgery, National Cancer Centre Singapore and Singapore General Hospital, Singapore; 13Surgery Academic Clinical Programme, Duke-NUS Medical School, SingaporeCorrespondence: Pierce Kah-Hoe ChowDivision of Surgery and Surgical Oncology, National Cancer Centre Singapore, 11 Hospital Crescent, 169610, SingaporeTel +65 6576 2151Email pierce.chow.k.h@singhealth.com.sgPurpose: The COVID-19 pandemic has altered healthcare priorities which may adversely impact cancer management. We aimed to evaluate the impact of the pandemic on the diagnosis, treatment, and consultation methods for patients with hepatocellular carcinoma (HCC).Patients and Methods: We conducted a survey among 27 hospitals from 14 Asia-Pacific countries, collecting hospital-level information on the number of newly diagnosed HCC cases during a pre-pandemic period (February to May 2019) and for the same period during the pandemic (February to May 2020). Information was also collected on delays in diagnosis and treatment, changes in treatment modalities and complication rates, changes in patient enrollment in clinical trials, and modes of patient consultation. The information was stratified by the Barcelona Clinic Liver Cancer (BCLC) stage.Results: The survey included cohorts of 2789 and 2045 patients newly diagnosed with HCC during the pre- and pandemic period, respectively. A decline of 26.7% in new HCC cases was reported during the pandemic compared to the pre-pandemic. A sizable proportion of institutions reported delays in diagnosis (48.2% in BCLC 0/A/B and 51.9% in BCLC C), delays in treatment (66.7% in BCLC 0/A/B and 63.0% in BCLC C), changes in treatment modality (33.3% in BCLC 0/A/B and 18.5% in BCLC C), an increase in treatment complications (about 15% across all BCLC stages), and no growth in clinical trial enrollments during the pandemic. Furthermore, there was a decline of 27.3% in face-to-face patient consultations and an increase of 18.3% in video/telephonic consultations during the pandemic. A considerable variation in changes in HCC management was observed among countries.Conclusion: The COVID-19 pandemic has significantly impacted the management of HCC among Asia-Pacific countries. The impact varies according to the disease stage and country. Well thought-through long-term strategies are required to ameliorate the negative impact of the pandemic on HCC patients.Keywords: hepatocellular carcinoma, liver cancer, COVID-19, Asia-Pacific

Jung Hyun Kim,1 Jae-Hoon Lee,2 Hye Sun Lee,3 Su-Jin Shin,4 Eun Jung Park,1 Eun-Suk Cho,5 Seung Hyuk Baik,1 Kang Young Lee,6 Jeonghyun Kang1 1Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; 2Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; 3Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Republic of Korea; 4Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; 5Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; 6Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of KoreaCorrespondence: Jeonghyun KangDepartment of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul, 06273, Republic of KoreaTel +82-2-2019-3372Fax +82-2-3462-5994Email ravic@naver.comBackground: Recent data suggest that alterations in the neutrophil-to-lymphocyte ratio (NLR) in the perioperative periods can serve as prognostic factors. However, research on the clinical impact has been limited and even discordant in patients with colorectal cancer (CRC).Patients and Methods: The optimal cut-off value of preoperative NLR (NLR-pre), postoperative NLR (NLR-post), and its change (NLR-delta) were determined to maximize differences in overall survival (OS) between groups. Patients were categorized into four groups (NLR-trend) as follows: G1, low NLR-pre and NLR-post; G2, low NLR-pre and high NLR-post; G3, high NLR-pre and low NLR-post; and G4, high NLR-pre and NLR-post. Discriminatory performance was compared using integrated AUC (iAUC) between all indicators.Results: A total of 576 patients diagnosed with stage I–IV CRC were included. The cut-off points were determined as 2.33 for NLR-pre, 2.06 for NLR-post, and − 1.08 for NLR-delta. Subgroup dichotomization using NLR-pre, NLR-post, NLR-delta and NLR-trend were all identified as significant prognostic factors by univariate analysis. However, NLR-trend was only remained as an independent prognostic factor in the multivariate analysis. The iAUC of the NLR-trend was superior to that of NLR-pre (bootstrap iAUC mean difference=0.036; 95% CI 0.013– 0.073), NLR-post (bootstrap iAUC mean difference=0.045; 95% CI 0.019– 0.081) and NLR-delta (bootstrap iAUC mean difference=0.061; 95% CI 0.025– 0.104).Conclusion: Risk stratification and combining of preoperative and postoperative NLR (NLR-trend) can improve prognostic discrimination compared with single measurements or simple changes in NLR in patients with CRC.Keywords: NLR, colorectal cancer, survival, iAUC

Su-Jeong Kim,1,&ast; Jae-Ho Lee,2,&ast; Woo-Jae Park,1 Shin Kim3– 5 1Department of Biochemistry, College of Medicine, Gachon University, Yeonsu-gu, Incheon, 21999, Republic of Korea; 2Department of Anatomy, School of Medicine, Keimyung University, Dalseo-gu, Daegu, 42601, Republic of Korea; 3Department of Immunology, School of Medicine, Keimyung University, Dalseo-gu, Daegu, 42601, Republic of Korea; 4Institute of Medical Science, Keimyung University, Dalseo-gu, Daegu, 42601, Republic of Korea; 5Institute for Cancer Research, Keimyung University Dongsan Medical Center, Dalseo-gu, Daegu, 42601, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Shin Kim Email god98005@dsmc.or.krIntroduction: Sphingolipid metabolism is a highly controlled process that is involved in regulating bioactive lipid signaling pathways and serves important roles in several cellular processes in breast cancer. Invasive ductal carcinoma (IDC), which is characterized by the malignant proliferation of the ductal epithelium and stromal invasion, is the most common type of breast cancer. Recent advances in genetic research have accelerated the discovery of novel prognostic factors and therapeutic targets for the disease. The aim of the present study was to investigate the expression and prognostic significance of sphingolipid metabolism-related genes in female IDC.Methods: The present study used gene expression RNAseq data obtained from The Cancer Genome Atlas breast invasive carcinoma (TCGA BRCA) datasets.Results: Sphingolipid metabolism-related genes exhibited dysregulated mRNA expression levels in IDC. The Student’s t-test revealed that SMPDL3B, B4GALNT1, LPAR2, and LASS2 were significantly upregulated, while LASS3, LPAR1, B4GALT6, GAL3ST1, HPGD, ST8SIA1, UGT8, and S1PR1 were significantly downregulated in female IDC tissues compared with normal solid tissues. Kaplan–Meier survival analyses revealed that high SMPDL3B mRNA expression levels were associated with good prognosis in female IDC, suggesting that SMPDL3B plays a tumor suppressor role. To the best of our knowledge, the present study was the first to report that dysregulated expressions of SMPDL3B are significantly associated with age, estrogen receptor status, progesterone receptor status, and histological subtype.Conclusion: Taken together, our study indicated that SMPDL3B may have a pathophysiological role and serve as a novel prognostic biomarker in IDC.Keywords: SMPDL3B, sphingolipid metabolism, invasive ductal carcinoma, TCGA