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Matthew E Sprong,1,2 Heaven Hollender,3 Bob Blankenberger,2 Stuart Rumrill,4 Yu-Sheng Lee,5 Travis Bland,2 Jeremiah Bailey,6 Kenneth Weber,1 James Gilbert,1 Ken Kriz,2 Frank D Buono7 1Edward Hines Jr. VA Medical Center, Hines, IL, USA; 2University of Illinois Springfield, School of Public Management and Policy, Springfield, IL, USA; 3Indiana University - Indianapolis, School of Health & Human Services, Indianapolis, IN, USA; 4Univerity of Illinois Urbana-Champaign, Department of Kinesiology and Community Health, Champaign, IL, USA; 5University of Illinois Springfield, School of Integrated Sciences, Sustainability, and Public Health, Springfield, IL, USA; 6Florida Agricultural and Mechanical University, Department of Sociology and Criminal Justice, Tallahassee, FL, USA; 7Yale School of Medicine, New Haven, CT, USACorrespondence: Matthew E Sprong, Email mspro2@uis.eduIntroduction: Veterans diagnosed with mental health and/or substance use disorders (SUD) often face significant barriers to employment and reintegration into civilian society. In the current study, we investigated whether how the VA healthcare system for mental health and/or SUD treatment predicted program enrollment into vocational rehabilitation, simultaneous mental health and/or SUD treatment while enrolled in vocational rehabilitation predicted employment at discharge, and mental health and/or SUD treatment continues and employment remain 60-days-post-vocational-rehabilitation discharge.Methods: An outcome-based, summative program evaluation design to measure quality assurance of vocational rehabilitation services provided to 402 veteran patients enrolled in a VA healthcare located within the Great Lakes Health Care System – Veterans Integrated Services Network.Results: Multivariable logistic regression analyses showed psychological empowerment (confidence in one’s ability to work or find work) is a significant factor determining whether a veteran is enrolled in the vocational rehabilitation program, prior mental health treatment (yes/no) and frequency of mental health treatment did not predict program enrollment, and frequency of SUD VA system treatment 60 days prior did not predict program enrollment. Other findings showed that simultaneous mental health and/or SUD treatment while enrolled in vocational rehabilitation did not predict employment at discharge, and employment at discharge did not predict continued mental health and/or SUD treatment post-discharge from vocational rehabilitation. However, veterans with both SUD and mental health and continued mental health treatment were less likely to be employed.Conclusion: Utilization of real-world program evaluation data from an actual VHA vocational rehabilitation program enhances the study’s ecological validity, offering practical implications for policymakers and practitioners in the field. The findings support the importance of veterans enrolling in mental health and/or SUD treatment simultaneously while enrolled in vocational rehabilitation services, as integrating vocational rehabilitation with mental health and SUD treatment services can lead to improved vocational and health outcomes for veterans (eg, development of targeted interventions to support veterans’ successful reintegration into the workforce and society).Keywords: substance use disorders, mental health, veterans affairs, health administration, veterans, vocational rehabilitation, treatment access

Jong Geol Jang,* Young Seok Lee,* Kyung Soo Hong, June Hong Ahn Division of Pulmonology and Allergy, Department of Internal Medicine, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, Republic of Korea*These authors contributed equally to this workCorrespondence: Jong Geol Jang; June Hong Ahn, Division of Pulmonology and Allergy, Department of Internal Medicine, College of Medicine, Yeungnam University and Regional Center for Respiratory Diseases, Yeungnam University Medical Center, 170 Hyeonchung-ro, Namgu, Daegu, 42415, Republic of Korea, Tel +82-53-620-4367 ; +82-53-640-6577, Email jang83@ynu.ac.kr; fireajh@gmail.comPurpose: The use of inhaled bronchodilators is the mainstay of treatment for patients with chronic obstructive pulmonary disease (COPD). Although the soft mist inhaler (SMI) was developed to overcome the disadvantages of pressurized metered dose and drug powder inhalers, misuse during handling has been frequently observed in many studies. However, few studies have focused on SMI misuse among patients with COPD. Thus, we aimed to assess and identify the risk factors associated with SMI misuse among patients with COPD.Patient and Methods: In this prospective, observational, cross-sectional study, we enrolled patients with COPD who were undergoing SMI treatment between January 2018 and March 2020. An advanced nurse practitioner assessed the participants’ handling of the device by using a check list.Results: Among 159 participants, 136 (85.5%) reported inhaler misuse. Duration of COPD and COPD assessment test (CAT) scores were positively associated with inhaler misuse; adherence and education level were negatively associated with inhaler misuse. In the multivariable analysis, a low educational level (less than high school), high CAT score (≥ 10), and short duration of COPD (≤ 2 years) were identified as risk factors for SMI misuse.Conclusion: SMI misuse remains common among patients with COPD. Therefore, clinicians should pay close attention to their patients using SMIs, especially in the early period after the diagnosis of COPD.Keywords: chronic obstructive pulmonary disease, bronchodilators, misuse, soft mist inhaler

Joan Kim,1 Seung Woo Choi,1 Young Shin Lee,1 Jung Myung Lee,1 Hyemoon Chung,1 Jong Shin Woo,1 Woo-Shik Kim,1 Yun Young Choi,2 Weon Kim1 1Department of Cardiology, Kyung Hee University Hospital, Seoul, Korea; 2Department of Medicine, Graduate School, Kyung Hee University, Seoul, KoreaCorrespondence: Weon Kim, Tel +82 2 958 8176, Email mylovekw@hanmail.netBackground: Lipoprotein(a) (Lp(a)) levels are associated with coronary artery disease (CAD) and aortic valve calcification. This study aimed to determine the correlation between Lp(a) levels and coronary artery calcium (CAC) scores in patients who underwent coronary computed tomography angiography (CCTA).Methods: This was a single-center observational study. The patients had not been previously diagnosed with CAD and underwent CCTA and Lp(a) measurement in a three-month timeframe. Coronary angiography and further management were performed according to the physician’s decision. Of the 252 patients, 81 and 171 patients underwent coronary revascularization and received medical treatment only, respectively. To examine the relationship between Lp(a) and CAC score and between Lp(a) and CAD, we divided the patients by Lp(a) level (50 mg/dL) and CAC score (400).Results: No relationship was observed between Lp(a) and CAD or other risk factors for CAD. There were no differences in the ratio of patients who underwent coronary revascularization or in the CAC score according to an Lp(a) level of 50 mg/dL. There was no difference in Lp(a) level at a CAC score of 400. The proportion of patients who underwent coronary revascularization was high in the high CAC score group (50.6% vs 23.7%, p = 0.000). No association was observed between Lp(a) level and CAC score in the Spearman correlation (0.000, p < 0.998).Conclusion: Correlations between Lp(a) level and CAC score and between Lp(a) and CAD were not observed in this Korean cohort study. However, a high CAC score was correlated with coronary revascularization.Keywords: lipoprotein(a), coronary calcium score, coronary artery disease

Jinhun Park,1 Yu-Cheol Lim,2 Deok-Sang Hwang,3 In-Hyuk Ha,2 Ye-Seul Lee2 1Department of Internal Medicine, Jaseng Hospital of Korean Medicine, Seoul, Republic of Korea; 2Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul, Republic of Korea; 3Department of OB & GY in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of KoreaCorrespondence: In-Hyuk Ha; Ye-Seul Lee, Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, 2F, 540 Gangnam-daero, Gangnam-gu, Seoul, 06110, Republic of Korea, Tel +82-2-2222-2740, Fax +82-2-2222-2737, Email hanihata@gmail.com; yeseul.j.lee@gmail.comPurpose: This study is a retrospective, cross-sectional study aiming to present basic data on the treatment modalities and cost of care for primary dysmenorrhea (PD) by analyzing healthcare utilization and patient distributions using the 2010 to 2018 Health Insurance Review and Assessment Service (HIRA) data.Patients and Methods: We used the HIRA-National Patient Sample (NPS) data to analyze medical service utilization for PD (ICD-10 code: N94.4, N94.6) in Western medicine (WM) or Korean medicine (KM) care between January 2010 and December 2018.Results: There were 41,139 patients diagnosed with PD who utilized Western medicine (WM) or Korean medicine (KM) care at least once during the study period. The number of claims and patients steadily rose over the years from 7430 claims for 3989 patients in 2010 to 11,523 claims for 6226 patients in 2018. The predominant age group was 15 to 24 years. Regarding the frequency of service categories for PD in the claims, consultation was the most common and costly service category in WM (72,120 cases, 47.89%; 631,912 USD, 69.74%), while injection and analogous treatments was the most common and costly service category in KM (97,157 cases, 72.41%; 314,696 USD, 55.86%). Regarding the drug prescriptions, nonsteroidal anti-inflammatory drugs (NSAIDs) (26,617 cases, 40.47%) were the most frequently prescribed drug for PD in pharmacies and hospitals.Conclusion: The result shows an annual increase in healthcare utilization for PD with the fastest rate in individuals aged 15 to 24 years. This study provides data on the current utilization of WM and KM care for PD for policymakers. Furthermore, we analyzed the frequency and cost of common treatment modalities in WM and KM, which would be useful data for clinicians and researchers.Keywords: primary dysmenorrhea, healthcare administrative claims, health care costs, medical use

RNA polymerase III (Pol III) transcribes medium-sized non-coding RNAs (collectively termed Pol III genes). Emerging diverse roles of Pol III genes suggest that individual Pol III genes are exquisitely regulated by transcription and epigenetic factors. Here we report global Pol III expression/methylation profiles and molecular mechanisms of Pol III regulation that have not been as extensively studied, using nc886 as a representative Pol III gene. In a human mammary epithelial cell system that recapitulates early breast tumorigenesis, the fraction of actively transcribed Pol III genes increases reaching a plateau during immortalization. Hyper-methylation of Pol III genes inhibits Pol III binding to DNA via inducing repressed chromatin and is a determinant for the Pol III repertoire. When Pol III genes are hypo-methylated, MYC amplifies their transcription, regardless of its recognition DNA motif. Thus, Pol III expression during tumorigenesis is delineated by methylation and magnified by MYC.

Yu-Shan Lee,1 Lee-Ching Hwang,1,2 Hsin-Yin Hsu,1 Meng-Ting Tsou1,3 1Department of Family Medicine, Mackay Memorial Hospital, Taipei, Taiwan; 2Department of Medicine, MacKay Medical College, New Taipei City, Taiwan; 3Mackay Junior College of Medicine, Nursing, and Management, Taipei, TaiwanCorrespondence: Meng-Ting TsouDepartment of Family Medicine, Mackay Memorial Hospital, No. 92, Sec. 2, Zhongshan N. Road, Taipei City, 10449, Taiwan, R.O.C.Tel +886 2 2543 3535 (Ext. 2131 or 2132)Fax +886 2 2543 3642Email mttsou@gmail.comPurpose: To examine the association between different phenotypes of obesity or metabolic syndromes and liver fibrosis score in a Taiwanese elderly population with fatty liver.Patients and Methods: This cross-sectional study included 1817 participants aged ≥ 65 years with fatty liver diagnosed by sonography. We used ethnicity-specific criteria for body mass index and metabolic syndrome, and to define obesity phenotypes as metabolically healthy non-obese (MHNO), metabolically unhealthy non-obese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). Correlated fibrosis severity was calculated using the nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) and Fibrosis-4 (FIB-4). Fibrosis severity was divided into two categories according to NFS (no-to-mild fibrosis and advanced fibrosis, defined as NFS ≤ 0.676 and > 0.676, respectively) and FIB-4 score (no-to-mild fibrosis and advanced fibrosis, defined as FIB-4 score ≤ 2.67 and > 2.67, respectively).Results: Compared with that in the MHNO group, the associated risk (odds ratio [OR], 95% confidence interval [CI]) of advanced fibrosis by NFS was 2.43 (1.50– 3.93), 2.35 (1.25– 4.41), and 6.11 (3.90– 9.59), whereas that of advanced fibrosis by FIB-4 score was 1.34 (0.83– 2.18), 2.37 (1.36– 4.13), and 1.38 (0.82– 2.31) in the MUNO, MHO, and MUO groups, respectively.Conclusion: Both metabolic syndrome and obesity were positively associated with more advanced fibrosis according to NFS. The detrimental effect of obesity appears to be more than metabolic abnormalities per se in the elderly with more advanced fibrosis severity according to the FIB-4 score.Keywords: nonalcoholic fatty liver disease, obese phenotype, elderly population, NAFLD fibrosis score, Fibrosis-4

O1 The metabolomics approach to autism: identification of biomarkers for early detection of autism spectrum disorder A. K. Srivastava, Y. Wang, R. Huang, C. Skinner, T. Thompson, L. Pollard, T. Wood, F. Luo, R. Stevenson O2 Phenome-wide association study for smoking- and drinking-associated genes in 26,394 American women with African, Asian, European, and Hispanic descents R. Polimanti, J. Gelernter O3 Effects of prenatal environment, genotype and DNA methylation on birth weight and subsequent postnatal outcomes: findings from GUSTO, an Asian birth cohort X. Lin, I. Y. Lim, Y. Wu, A. L. Teh, L. Chen, I. M. Aris, S. E. Soh, M. T. Tint, J. L. MacIsaac, F. Yap, K. Kwek, S. M. Saw, M. S. Kobor, M. J. Meaney, K. M. Godfrey, Y. S. Chong, J. D. Holbrook, Y. S. Lee, P. D. Gluckman, N. Karnani, GUSTO study group O4 High-throughput identification of specific qt interval modulating enhancers at the SCN5A locus A. Kapoor, D. Lee, A. Chakravarti O5 Identification of extracellular matrix components inducing cancer cell migration in the supernatant of cultivated mesenchymal stem cells C. Maercker, F. Graf, M. Boutros O6 Single cell allele specific expression (ASE) IN T21 and common trisomies: a novel approach to understand DOWN syndrome and other aneuploidies G. Stamoulis, F. Santoni, P. Makrythanasis, A. Letourneau, M. Guipponi, N. Panousis, M. Garieri, P. Ribaux, E. Falconnet, C. Borel, S. E. Antonarakis O7 Role of microRNA in LCL to IPSC reprogramming S. Kumar, J. Curran, J. Blangero O8 Multiple enhancer variants disrupt gene regulatory network in Hirschsprung disease S. Chatterjee, A. Kapoor, J. Akiyama, D. Auer, C. Berrios, L. Pennacchio, A. Chakravarti O9 Metabolomic profiling for the diagnosis of neurometabolic disorders T. R. Donti, G. Cappuccio, M. Miller, P. Atwal, A. Kennedy, A. Cardon, C. Bacino, L. Emrick, J. Hertecant, F. Baumer, B. Porter, M. Bainbridge, P. Bonnen, B. Graham, R. Sutton, Q. Sun, S. Elsea O10 A novel causal methylation network approach to Alzheimer’s disease Z. Hu, P. Wang, Y. Zhu, J. Zhao, M. Xiong, David A Bennett O11 A microRNA signature identifies subtypes of triple-negative breast cancer and reveals MIR-342-3P as regulator of a lactate metabolic pathway A. Hidalgo-Miranda, S. Romero-Cordoba, S. Rodriguez-Cuevas, R. Rebollar-Vega, E. Tagliabue, M. Iorio, E. D’Ippolito, S. Baroni O12 Transcriptome analysis identifies genes, enhancer RNAs and repetitive elements that are recurrently deregulated across multiple cancer types B. Kaczkowski, Y. Tanaka, H. Kawaji, A. Sandelin, R. Andersson, M. Itoh, T. Lassmann, the FANTOM5 consortium, Y. Hayashizaki, P. Carninci, A. R. R. Forrest O13 Elevated mutation and widespread loss of constraint at regulatory and architectural binding sites across 11 tumour types C. A. Semple O14 Exome sequencing provides evidence of pathogenicity for genes implicated in colorectal cancer E. A. Rosenthal, B. Shirts, L. Amendola, C. Gallego, M. Horike-Pyne, A. Burt, P. Robertson, P. Beyers, C. Nefcy, D. Veenstra, F. Hisama, R. Bennett, M. Dorschner, D. Nickerson, J. Smith, K. Patterson, D. Crosslin, R. Nassir, N. Zubair, T. Harrison, U. Peters, G. Jarvik, NHLBI GO Exome Sequencing Project O15 The tandem duplicator phenotype as a distinct genomic configuration in cancer F. Menghi, K. Inaki, X. Woo, P. Kumar, K. Grzeda, A. Malhotra, H. Kim, D. Ucar, P. Shreckengast, K. Karuturi, J. Keck, J. Chuang, E. T. Liu O16 Modeling genetic interactions associated with molecular subtypes of breast cancer B. Ji, A. Tyler, G. Ananda, G. Carter O17 Recurrent somatic mutation in the MYC associated factor X in brain tumors H. Nikbakht, M. Montagne, M. Zeinieh, A. Harutyunyan, M. Mcconechy, N. Jabado, P. Lavigne, J. Majewski O18 Predictive biomarkers to metastatic pancreatic cancer treatment J. B. Goldstein, M. Overman, G. Varadhachary, R. Shroff, R. Wolff, M. Javle, A. Futreal, D. Fogelman O19 DDIT4 gene expression as a prognostic marker in several malignant tumors L. Bravo, W. Fajardo, H. Gomez, C. Castaneda, C. Rolfo, J. A. Pinto O20 Spatial organization of the genome and genomic alterations in human cancers K. C. Akdemir, L. Chin, A. Futreal, ICGC PCAWG Structural Alterations Group O21 Landscape of targeted therapies in solid tumors S. Patterson, C. Statz, S. Mockus O22 Genomic analysis reveals novel drivers and progression pathways in skin basal cell carcinoma S. N. Nikolaev, X. I. Bonilla, L. Parmentier, B. King, F. Bezrukov, G. Kaya, V. Zoete, V. Seplyarskiy, H. Sharpe, T. McKee, A. Letourneau, P. Ribaux, K. Popadin, N. Basset-Seguin, R. Ben Chaabene, F. Santoni, M. Andrianova, M. Guipponi, M. Garieri, C. Verdan, K. Grosdemange, O. Sumara, M. Eilers, I. Aifantis, O. Michielin, F. de Sauvage, S. Antonarakis O23 Identification of differential biomarkers of hepatocellular carcinoma and cholangiocarcinoma via transcriptome microarray meta-analysis S. Likhitrattanapisal O24 Clinical validity and actionability of multigene tests for hereditary cancers in a large multi-center study S. Lincoln, A. Kurian, A. Desmond, S. Yang, Y. Kobayashi, J. Ford, L. Ellisen O25 Correlation with tumor ploidy status is essential for correct determination of genome-wide copy number changes by SNP array T. L. Peters, K. R. Alvarez, E. F. Hollingsworth, D. H. Lopez-Terrada O26 Nanochannel based next-generation mapping for interrogation of clinically relevant structural variation A. Hastie, Z. Dzakula, A. W. Pang, E. T. Lam, T. Anantharaman, M. Saghbini, H. Cao, BioNano Genomics O27 Mutation spectrum in a pulmonary arterial hypertension (PAH) cohort and identification of associated truncating mutations in TBX4 C. Gonzaga-Jauregui, L. Ma, A. King, E. Berman Rosenzweig, U. Krishnan, J. G. Reid, J. D. Overton, F. Dewey, W. K. Chung O28 NORTH CAROLINA macular dystrophy (MCDR1): mutations found affecting PRDM13 K. Small, A. DeLuca, F. Cremers, R. A. Lewis, V. Puech, B. Bakall, R. Silva-Garcia, K. Rohrschneider, M. Leys, F. S. Shaya, E. Stone O29 PhenoDB and genematcher, solving unsolved whole exome sequencing data N. L. Sobreira, F. Schiettecatte, H. Ling, E. Pugh, D. Witmer, K. Hetrick, P. Zhang, K. Doheny, D. Valle, A. Hamosh O30 Baylor-Johns Hopkins Center for Mendelian genomics: a four year review S. N. Jhangiani, Z. Coban Akdemir, M. N. Bainbridge, W. Charng, W. Wiszniewski, T. Gambin, E. Karaca, Y. Bayram, M. K. Eldomery, J. Posey, H. Doddapaneni, J. Hu, V. R. Sutton, D. M. Muzny, E. A. Boerwinkle, D. Valle, J. R. Lupski, R. A. Gibbs O31 Using read overlap assembly to accurately identify structural genetic differences in an ashkenazi jewish trio S. Shekar, W. Salerno, A. English, A. Mangubat, J. Bruestle O32 Legal interoperability: a sine qua non for international data sharing A. Thorogood, B. M. Knoppers, Global Alliance for Genomics and Health - Regulatory and Ethics Working Group O33 High throughput screening platform of competent sineups: that can enhance translation activities of therapeutic target H. Takahashi, K. R. Nitta, A. Kozhuharova, A. M. Suzuki, H. Sharma, D. Cotella, C. Santoro, S. Zucchelli, S. Gustincich, P. Carninci O34 The undiagnosed diseases network international (UDNI): clinical and laboratory research to meet patient needs J. J. Mulvihill, G. Baynam, W. Gahl, S. C. Groft, K. Kosaki, P. Lasko, B. Melegh, D. Taruscio O36 Performance of computational algorithms in pathogenicity predictions for activating variants in oncogenes versus loss of function mutations in tumor suppressor genes R. Ghosh, S. Plon O37 Identification and electronic health record incorporation of clinically actionable pharmacogenomic variants using prospective targeted sequencing S. Scherer, X. Qin, R. Sanghvi, K. Walker, T. Chiang, D. Muzny, L. Wang, J. Black, E. Boerwinkle, R. Weinshilboum, R. Gibbs O38 Melanoma reprogramming state correlates with response to CTLA-4 blockade in metastatic melanoma T. Karpinets, T. Calderone, K. Wani, X. Yu, C. Creasy, C. Haymaker, M. Forget, V. Nanda, J. Roszik, J. Wargo, L. Haydu, X. Song, A. Lazar, J. Gershenwald, M. Davies, C. Bernatchez, J. Zhang, A. Futreal, S. Woodman O39 Data-driven refinement of complex disease classification from integration of heterogeneous functional genomics data in GeneWeaver E. J. Chesler, T. Reynolds, J. A. Bubier, C. Phillips, M. A. Langston, E. J. Baker O40 A general statistic framework for genome-based disease risk prediction M. Xiong, L. Ma, N. Lin, C. Amos O41 Integrative large-scale causal network analysis of imaging and genomic data and its application in schizophrenia studies N. Lin, P. Wang, Y. Zhu, J. Zhao, V. Calhoun, M. Xiong O42 Big data and NGS data analysis: the cloud to the rescue O. Dobretsberger, M. Egger, F. Leimgruber O43 Cpipe: a convergent clinical exome pipeline specialised for targeted sequencing S. Sadedin, A. Oshlack, Melbourne Genomics Health Alliance O44 A Bayesian classification of biomedical images using feature extraction from deep neural networks implemented on lung cancer data V. A. A. Antonio, N. Ono, Clark Kendrick C. Go O45 MAV-SEQ: an interactive platform for the Management, Analysis, and Visualization of sequence data Z. Ahmed, M. Bolisetty, S. Zeeshan, E. Anguiano, D. Ucar O47 Allele specific enhancer in EPAS1 intronic regions may contribute to high altitude adaptation of Tibetans C. Zeng, J. Shao O48 Nanochannel based next-generation mapping for structural variation detection and comparison in trios and populations H. Cao, A. Hastie, A. W. Pang, E. T. Lam, T. Liang, K. Pham, M. Saghbini, Z. Dzakula O49 Archaic introgression in indigenous populations of Malaysia revealed by whole genome sequencing Y. Chee-Wei, L. Dongsheng, W. Lai-Ping, D. Lian, R. O. Twee Hee, Y. Yunus, F. Aghakhanian, S. S. Mokhtar, C. V. Lok-Yung, J. Bhak, M. Phipps, X. Shuhua, T. Yik-Ying, V. Kumar, H. Boon-Peng O50 Breast and ovarian cancer prevention: is it time for population-based mutation screening of high risk genes? I. Campbell, M.-A. Young, P. James, Lifepool O53 Comprehensive coverage from low DNA input using novel NGS library preparation methods for WGS and WGBS C. Schumacher, S. Sandhu, T. Harkins, V. Makarov O54 Methods for large scale construction of robust PCR-free libraries for sequencing on Illumina HiSeqX platform H. DoddapaneniR. Glenn, Z. Momin, B. Dilrukshi, H. Chao, Q. Meng, B. Gudenkauf, R. Kshitij, J. Jayaseelan, C. Nessner, S. Lee, K. Blankenberg, L. Lewis, J. Hu, Y. Han, H. Dinh, S. Jireh, K. Walker, E. Boerwinkle, D. Muzny, R. Gibbs O55 Rapid capture methods for clinical sequencing J. Hu, K. Walker, C. Buhay, X. Liu, Q. Wang, R. Sanghvi, H. Doddapaneni, Y. Ding, N. Veeraraghavan, Y. Yang, E. Boerwinkle, A. L. Beaudet, C. M. Eng, D. M. Muzny, R. A. Gibbs O56 A diploid personal human genome model for better genomes from diverse sequence data K. C. C. Worley, Y. Liu, D. S. T. Hughes, S. C. Murali, R. A. Harris, A. C. English, X. Qin, O. A. Hampton, P. Larsen, C. Beck, Y. Han, M. Wang, H. Doddapaneni, C. L. Kovar, W. J. Salerno, A. Yoder, S. Richards, J. Rogers, J. R. Lupski, D. M. Muzny, R. A. Gibbs O57 Development of PacBio long range capture for detection of pathogenic structural variants Q. Meng, M. Bainbridge, M. Wang, H. Doddapaneni, Y. Han, D. Muzny, R. Gibbs O58 Rhesus macaques exhibit more non-synonymous variation but greater impact of purifying selection than humans R. A. Harris, M. Raveenedran, C. Xue, M. Dahdouli, L. Cox, G. Fan, B. Ferguson, J. Hovarth, Z. Johnson, S. Kanthaswamy, M. Kubisch, M. Platt, D. Smith, E. Vallender, R. Wiseman, X. Liu, J. Below, D. Muzny, R. Gibbs, F. Yu, J. Rogers O59 Assessing RNA structure disruption induced by single-nucleotide variation J. Lin, Y. Zhang, Z. Ouyang P1 A meta-analysis of genome-wide association studies of mitochondrial dna copy number A. Moore, Z. Wang, J. Hofmann, M. Purdue, R. Stolzenberg-Solomon, S. Weinstein, D. Albanes, C.-S. Liu, W.-L. Cheng, T.-T. Lin, Q. Lan, N. Rothman, S. Berndt P2 Missense polymorphic genetic combinations underlying down syndrome susceptibility E. S. Chen P4 The evaluation of alteration of ELAM-1 expression in the endometriosis patients H. Bahrami, A. Khoshzaban, S. Heidari Keshal P5 Obesity and the incidence of apolipoprotein E polymorphisms in an assorted population from Saudi Arabia population K. K. R. Alharbi P6 Genome-associated personalized antithrombotical therapy for patients with high risk of thrombosis and bleeding M. Zhalbinova, A. Akilzhanova, S. Rakhimova, M. Bekbosynova, S. Myrzakhmetova P7 Frequency of Xmn1 polymorphism among sickle cell carrier cases in UAE population M. Matar P8 Differentiating inflammatory bowel diseases by using genomic data: dimension of the problem and network organization N. Mili, R. Molinari, Y. Ma, S. Guerrier P9 Vulnerability of genetic variants to the risk of autism among Saudi children N. Elhawary, M. Tayeb, N. Bogari, N. Qotb P10 Chromatin profiles from ex vivo purified dopaminergic neurons establish a promising model to support studies of neurological function and dysfunction S. A. McClymont, P. W. Hook, L. A. Goff, A. McCallion P11 Utilization of a sensitized chemical mutagenesis screen to identify genetic modifiers of retinal dysplasia in homozygous Nr2e3rd7 mice Y. Kong, J. R. Charette, W. L. Hicks, J. K. Naggert, L. Zhao, P. M. Nishina P12 Ion torrent next generation sequencing of recessive polycystic kidney disease in Saudi patients B. M. Edrees, M. Athar, F. A. Al-Allaf, M. M. Taher, W. Khan, A. Bouazzaoui, N. A. Harbi, R. Safar, H. Al-Edressi, A. Anazi, N. Altayeb, M. A. Ahmed, K. Alansary, Z. Abduljaleel P13 Digital expression profiling of Purkinje neurons and dendrites in different subcellular compartments A. Kratz, P. Beguin, S. Poulain, M. Kaneko, C. Takahiko, A. Matsunaga, S. Kato, A. M. Suzuki, N. Bertin, T. Lassmann, R. Vigot, P. Carninci, C. Plessy, T. Launey P14 The evolution of imperfection and imperfection of evolution: the functional and functionless fractions of the human genome D. Graur P16 Species-independent identification of known and novel recurrent genomic entities in multiple cancer patients J. Friis-Nielsen, J. M. Izarzugaza, S. Brunak P18 Discovery of active gene modules which are densely conserved across multiple cancer types reveal their prognostic power and mutually exclusive mutation patterns B. S. Soibam P19 Whole exome sequencing of dysplastic leukoplakia tissue indicates sequential accumulation of somatic mutations from oral precancer to cancer D. Das, N. Biswas, S. Das, S. Sarkar, A. Maitra, C. Panda, P. Majumder P21 Epigenetic mechanisms of carcinogensis by hereditary breast cancer genes J. J. Gruber, N. Jaeger, M. Snyder P22 RNA direct: a novel RNA enrichment strategy applied to transcripts associated with solid tumors K. Patel, S. Bowman, T. Davis, D. Kraushaar, A. Emerman, S. Russello, N. Henig, C. Hendrickson P23 RNA sequencing identifies gene mutations for neuroblastoma K. Zhang P24 Participation of SFRP1 in the modulation of TMPRSS2-ERG fusion gene in prostate cancer cell lines M. Rodriguez-Dorantes, C. D. Cruz-Hernandez, C. D. P. Garcia-Tobilla, S. Solorzano-Rosales P25 Targeted Methylation Sequencing of Prostate Cancer N. Jäger, J. Chen, R. Haile, M. Hitchins, J. D. Brooks, M. Snyder P26 Mutant TPMT alleles in children with acute lymphoblastic leukemia from México City and Yucatán, Mexico S. Jiménez-Morales, M. Ramírez, J. Nuñez, V. Bekker, Y. Leal, E. Jiménez, A. Medina, A. Hidalgo, J. Mejía P28 Genetic modifiers of Alström syndrome J. Naggert, G. B. Collin, K. DeMauro, R. Hanusek, P. M. Nishina P31 Association of genomic variants with the occurrence of angiotensin-converting-enzyme inhibitor (ACEI)-induced coughing among Filipinos E. M. Cutiongco De La Paz, R. Sy, J. Nevado, P. Reganit, L. Santos, J. D. Magno, F. E. Punzalan , D. Ona , E. Llanes, R. L. Santos-Cortes , R. Tiongco, J. Aherrera, L. Abrahan, P. Pagauitan-Alan; Philippine Cardiogenomics Study Group P32 The use of “humanized” mouse models to validate disease association of a de novo GARS variant and to test a novel gene therapy strategy for Charcot-Marie-Tooth disease type 2D K. H. Morelli, J. S. Domire, N. Pyne, S. Harper, R. Burgess P34 Molecular regulation of chondrogenic human induced pluripotent stem cells M. A. Gari, A. Dallol, H. Alsehli, A. Gari, M. Gari, A. Abuzenadah P35 Molecular profiling of hematologic malignancies: implementation of a variant assessment algorithm for next generation sequencing data analysis and clinical reporting M. Thomas, M. Sukhai, S. Garg, M. Misyura, T. Zhang, A. Schuh, T. Stockley, S. Kamel-Reid P36 Accessing genomic evidence for clinical variants at NCBI S. Sherry, C. Xiao, D. Slotta, K. Rodarmer, M. Feolo, M. Kimelman, G. Godynskiy, C. O’Sullivan, E. Yaschenko P37 NGS-SWIFT: a cloud-based variant analysis framework using control-accessed sequencing data from DBGAP/SRA C. Xiao, E. Yaschenko, S. Sherry P38 Computational assessment of drug induced hepatotoxicity through gene expression profiling C. Rangel-Escareño, H. Rueda-Zarate P40 Flowr: robust and efficient pipelines using a simple language-agnostic approach;ultraseq; fast modular pipeline for somatic variation calling using flowr S. Seth, S. Amin, X. Song, X. Mao, H. Sun, R. G. Verhaak, A. Futreal, J. Zhang P41 Applying “Big data” technologies to the rapid analysis of heterogenous large cohort data S. J. Whiite, T. Chiang, A. English, J. Farek, Z. Kahn, W. Salerno, N. Veeraraghavan, E. Boerwinkle, R. Gibbs P42 FANTOM5 web resource for the large-scale genome-wide transcription start site activity profiles of wide-range of mammalian cells T. Kasukawa, M. Lizio, J. Harshbarger, S. Hisashi, J. Severin, A. Imad, S. Sahin, T. C. Freeman, K. Baillie, A. Sandelin, P. Carninci, A. R. R. Forrest, H. Kawaji, The FANTOM Consortium P43 Rapid and scalable typing of structural variants for disease cohorts W. Salerno, A. English, S. N. Shekar, A. Mangubat, J. Bruestle, E. Boerwinkle, R. A. Gibbs P44 Polymorphism of glutathione S-transferases and sulphotransferases genes in an Arab population A. H. Salem, M. Ali, A. Ibrahim, M. Ibrahim P46 Genetic divergence of CYP3A5*3 pharmacogenomic marker for native and admixed Mexican populations J. C. Fernandez-Lopez, V. Bonifaz-Peña, C. Rangel-Escareño, A. Hidalgo-Miranda, A. V. Contreras P47 Whole exome sequence meta-analysis of 13 white blood cell, red blood cell, and platelet traits L. Polfus, CHARGE and NHLBI Exome Sequence Project Working Groups P48 Association of adipoq gene with type 2 diabetes and related phenotypes in african american men and women: The jackson heart study S. Davis, R. Xu, S. Gebeab, P Riestra, A Gaye, R. Khan, J. Wilson, A. Bidulescu P49 Common variants in casr gene are associated with serum calcium levels in koreans S. H. Jung, N. Vinayagamoorthy, S. H. Yim, Y. J. Chung P50 Inference of multiple-wave population admixture by modeling decay of linkage disequilibrium with multiple exponential functions Y. Zhou, S. Xu P51 A Bayesian framework for generalized linear mixed models in genome-wide association studies X. Wang, V. Philip, G. Carter P52 Targeted sequencing approach for the identification of the genetic causes of hereditary hearing impairment A. A. Abuzenadah, M. Gari, R. Turki, A. Dallol P53 Identification of enhancer sequences by ATAC-seq open chromatin profiling A. Uyar, A. Kaygun, S. Zaman, E. Marquez, J. George, D. Ucar P54 Direct enrichment for the rapid preparation of targeted NGS libraries C. L. Hendrickson, A. Emerman, D. Kraushaar, S. Bowman, N. Henig, T. Davis, S. Russello, K. Patel P56 Performance of the Agilent D5000 and High Sensitivity D5000 ScreenTape assays for the Agilent 4200 Tapestation System R. Nitsche, L. Prieto-Lafuente P57 ClinVar: a multi-source archive for variant interpretation M. Landrum, J. Lee, W. Rubinstein, D. Maglott P59 Association of functional variants and protein physical interactions of human MUTY homolog linked with familial adenomatous polyposis and colorectal cancer syndrome Z. Abduljaleel, W. Khan, F. A. Al-Allaf, M. Athar , M. M. Taher, N. Shahzad P60 Modification of the microbiom constitution in the gut using chicken IgY antibodies resulted in a reduction of acute graft-versus-host disease after experimental bone marrow transplantation A. Bouazzaoui, E. Huber, A. Dan, F. A. Al-Allaf, W. Herr, G. Sprotte, J. Köstler, A. Hiergeist, A. Gessner, R. Andreesen, E. Holler P61 Compound heterozygous mutation in the LDLR gene in Saudi patients suffering severe hypercholesterolemia F. Al-Allaf, A. Alashwal, Z. Abduljaleel, M. Taher, A. Bouazzaoui, H. Abalkhail, A. Al-Allaf, R. Bamardadh, M. Athar

Minha Hong,1 JJ Sandra Kooij,2,3 Bongseog Kim,4 Yoo-Sook Joung,5 Hanik K Yoo,6 Eui-Jung Kim,7 Soyoung Irene Lee,8 Soo-Young Bhang,9 Seung Yup Lee,10 Doug Hyun Han,11 Young Sik Lee,11 Geon Ho Bahn10 1Department of Psychiatry, Myongji Hospital, Hanyang University College of Medicine, Goyang, Korea; 2PsyQ, Psycho-Medical Programs, Expertise Center Adult ADHD, The Hague, The Netherlands; 3Department of Psychiatry, Amsterdam University Medical Center, Amsterdam, The Netherlands; 4Department of Psychiatry, Inje University College of Medicine, Seoul, Korea; 5Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 6Department of Clinical Psychiatry, Seoul Brain Research Institute, Seoul, Korea; 7Department of Psychiatry, College of Medicine, Ewha Womans University, Seoul, Korea; 8Department of Psychiatry, Soonchunhyang University College of Medicine, Bucheon, Korea; 9Department of Psychiatry, Nowon Eulji University Hospital, Eulji University School of Medicine, Seoul, Korea; 10Department of Psychiatry, Kyung Hee University School of Medicine, Seoul, Korea; 11Department of Psychiatry, Chung-Ang University College of Medicine, Seoul, KoreaCorrespondence: Geon Ho Bahn Department of PsychiatryKyung Hee University School of Medicine, 23 Kyungheedae-Ro, Dongdaemungu, Seoul 02447, KoreaTel +82-2-958-8556Fax +82-2-957-1997Email mompeian@khu.ac.krBackground: This study was to assess the validity of the Korean version of the semi-structured Diagnostic Interview for Adult ADHD, third edition (DIVA-5). The secondary aim was to compare sociodemographic and psychiatric comorbidities in adult patients with and without a diagnosis of ADHD.Methods: A total of 279 participants were recruited from nine psychiatric outpatient clinics in Korea. All participants were administered the Mini-International Neuropsychiatric Interview (MINI) Plus v.5.0.0, the Adult ADHD Self-Report Scale v1.1 (ASRS-v1.1) Symptom Checklist, and DIVA-5. Diagnosis concordance between two board-certified psychiatrists and DIVA-5 were analysed.Results: The DIVA-5 showed a diagnostic accuracy of 92%, a sensitivity of 91.30%, and a specificity of 93.62%. Significant clinical and demographic differences between ADHD and control groups were found.Conclusion: The Korean version of DIVA-5 is a reliable tool for assessing and diagnosing ADHD in adult Korean populations.Keywords: adult ADHD, validity, DIVA-5, Korean

Moumita Rakshit,1 Archana Gautam,1 Li Zhen Toh,2 Ying Shi Lee,2 Hui Ying Lai,1 Tina T Wong,1,2 Kee Woei Ng1,3– 5 1School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798, Singapore; 2Ocular Therapeutics and Drug Delivery, Singapore Eye Research Institute, Singapore 169856, Singapore; 3Environmental Chemistry and Materials Centre, Nanyang Environment & Water Research Institute, Singapore 637141, Singapore; 4Skin Research Institute of Singapore, Singapore 138648, Singapore; 5Center for Nanotechnology and Nanotoxicology, Harvard T.H. Chan School of Public Health, Cambridge, MA 02115, USACorrespondence: Tina T Wong; Kee Woei Ng Tel +65 6322 8313; +65 6513 8294Email tina.wong.t.l@singhealth.com.sg; kwng@ntu.edu.sgBackground: Hydroxyapatite (HA) [Ca5(PO4)3(OH)] is a naturally occurring calcium phosphate which makes up 60– 70% of the dry weight of human bones. Nano-scale HA particles are increasingly being used as carriers for controlled and targeted delivery of bioactive agents like drugs, proteins, and nucleic acids due to their high porosity, negative charge, and biodegradability.Purpose: Although much effort has been devoted to understanding the delivery kinetics and effects of the payloads in such carriers, a thorough understanding of the influence of the carriers themselves is lacking.Methods: HA particles (300 μg/mL) were administered to primary human dermal fibroblasts (HDFs). The uptake and intracellular localization of the particles were determined by flow cytometry, confocal imaging, and transmission electron microscopy (TEM). Immunological assays and PCR were performed to determine the levels of pro-inflammatory cytokines and collagens in cell lysates and media supernatant.Results: The current study explores the effects of poly-dispersed HA particles on primary HDFs as a model system. The majority of the particles were determined to range between 150 and 200 nm in diameter. Upon exposure to HA suspensions, primary HDFs internalized the particles by endocytosis within 6 hours of exposure, showing maximum uptake at 72 hours following which the particles were exocytosed by 168 hours. This correlated to reduced secretion of various pro-inflammatory and pro-collagenic cytokines. Biochemical analysis further revealed a reduction in Type I collagen expression and secretion.Conclusion: HA particles have an immune-modulatory effect on dermal fibroblasts and reduce collagen production, which may impact the integrity of the extracellular matrix (ECM). This study demonstrates the need to consider the secondary effects of particulate carriers like HA, beyond basic cytotoxicity, in the specific tissue environment where the intended function is to be realized.Keywords: carrier particles, collagen expression, extracellular matrix, time-weighted average exposure

Obesity and inflammation are both risk factors for a variety of cancers, including breast cancer in postmenopausal women. Intake of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) decreases the risk of breast cancer, and also reduces obesity-associated inflammation and insulin resistance, but whether the two effects are related is currently unknown. We tested this hypothesis in a postmenopausal breast cancer model using ovariectomized, immune-competent female mice orthotopically injected with Py230 mammary tumor cells. Obesity, whether triggered genetically or by high-fat diet (HFD) feeding, increased inflammation in the mammary fat pad and promoted mammary tumorigenesis. The presence of tumor cells in the mammary fat pad further enhanced the local inflammatory milieu. Tumor necrosis factor-alpha (TNF-α) was the most highly upregulated cytokine in the obese mammary fat pad, and we observed that TNF-α dose-dependently stimulated Py230 cell growth in vitro. An ω-3 PUFA-enriched HFD (referred to as fish oil diet, FOD) reduced inflammation in the obese mammary fat pad in the absence of tumor cells and inhibited Py230 tumor growth in vivo. Although some anti-inflammatory effects of ω-3 PUFAs were previously shown to be mediated by the G-protein-coupled receptor 120 (GPR120), the FOD reduced Py230 tumor burden in GPR120-deficient mice to a similar degree as observed in wild-type mice, indicating that the effect of FOD to reduce tumor growth does not require GPR120 in the host mouse. Instead, in vitro studies demonstrated that ω-3 PUFAs act directly on tumor cells to activate c-Jun N-terminal kinase, inhibit proliferation and induce apoptosis. Our results show that obesity promotes mammary tumor progression in this model of postmenopausal breast cancer and that ω-3 PUFAs, independent of GPR120, inhibit mammary tumor progression in obese mice.

© 2015 The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.Enzyme-mediated modifications at the wobble position of tRNAs are essential for the translation of the genetic code. We report the genetic, biochemical and

We investigate near-field infrared spectroscopy and superfluid polariton imaging experiments on conventional and unconventional superconductors. Our modeling shows that near-field spectroscopy can measure the magnitude of the superconducting energy gap in Bardeen-Cooper-Schrieffer-like superconductors with nanoscale spatial resolution. We demonstrate how the same technique can measure the c-axis plasma frequency, and thus the c-axis superfluid density, of layered unconventional superconductors with a similar spatial resolution. Our modeling also shows that near-field techniques can image superfluid surface mode interference patterns near physical and electronic boundaries. We describe how these images can be used to extract the collective mode dispersion of anisotropic superconductors with subdiffractional spatial resolution. © 2014 American Physical Society.

Jaewon Lee,1,* Sam-Wook Choi,2,* Kyoung Min Kim,3 Young Sik Lee,4 Jun Won Kim51Department of Psychiatry, Easybrain Center, Seoul, Republic of Korea; 2Department of Psychiatry, True Mind Mental Health Clinic, Seoul, Republic of Korea; 3Department of Psychiatry, Dankook University Hospital, Cheonan, Republic of Korea; 4Department of Psychiatry, Chung-Ang University, College of Medicine, Seoul, Republic of Korea; 5Department of Psychiatry, Catholic University of Daegu School of Medicine, Daegu, Republic of Korea*These authors contributed equally to this work Purpose: Gambling disorder is a psychiatric condition characterized by persistent and recurrent maladaptive gambling. In the present study, we evaluated the characteristics of resting-state electroencephalogram (EEG) recordings in patients with gambling disorder. In addition, we explored the association between the EEG characteristics of the patients and the stages of change in a transtheoretical model.Methods: All participants were men who visited a gambling disorder clinic in Seoul, Korea. At the assessment, questionnaires, including the Readiness to Change Questionnaire (RCQ), were administered and resting-state EEGs were carried out. Participants were grouped based on Ward’s method for cluster analysis. Independent sample t-tests were used to evaluate group differences. To assess the relationship between the clinical data and the EEG recordings, we used Pearson’s partial correlation analysis.Results: Overall, 63 male participants were enrolled. Cluster analysis of the alpha activity revealed two clusters. No significant differences were observed in the demographic or clinical data between the two groups except for the Beck Depression Inventory (BDI). We found that the precontemplation score of the RCQ was positively correlated with the z-score of the relative alpha power in almost all cortical regions.Conclusion: This study suggests that EEG parameters, particularly alpha activity, could inform us about the subtypes or stages of change in gambling disorder. Alpha power is the predominant EEG rhythm in a relaxed, alert person; thus, alpha power serves as an index of relaxation. We expect that the level of alpha activity could be utilized as an additional parameter to help clinicians assess and treat patients with gambling disorder.Keywords: quantitative electroencephalography, gambling disorder, stages-of-change model, alpha activity

Juwhan Choi, Jee Youn Oh, Young Seok Lee, Gyu Young Hur, Sung Yong Lee, Jae Jeong Shim, Kyung Ho Kang, Kyung Hoon MinDivision of Respiratory, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of KoreaIntroduction: The use of antibiotics is based on the clinician’s experience and judgment, and antibiotics may often be overused in the treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Eosinophils have been studied as biomarkers of bacterial infection and prognostic factors in chronic obstructive pulmonary disease and AECOPD. Thus, the purpose of this study was to determine whether eosinophils could be used to determine bacterial infection in AECOPD events.Methods: We retrospectively analyzed the medical records of patients admitted to Korea University Guro Hospital for AECOPD between January 2011 and May 2017. Data pertaining to baseline characteristics, results of previous pulmonary function tests, treatment information during the admission period, and history of pulmonary treatment were collected before admission.Results: A total of 736 AECOPD events were eligible for inclusion and were divided into two groups based on the eosinophil count: those involving eosinophil counts of less than 2% (546 events) and those involving counts of 2% or more (190 events). In univariate analysis, the only bacterial pathogen identification events and bacterial-viral pathogen co-identification events were significantly more frequent in the group with eosinophil counts of less than 2% (P=0.010 and P=0.001, respectively). In logistic regression analysis, the rates of only bacterial pathogen identification [odds ratios =1.744; 95% confidence interval, 1.107–2.749; P=0.017] and bacterial-viral pathogen co-identification [odds ratios=2.075; 95% confidence interval, 1.081–3.984; P=0.028] were higher in the group with eosinophil count less than 2%.Conclusion: In conclusion, eosinophil counts of less than 2% are potential indicators of a bacterial infection in AECOPD events. Eosinophils could thus serve as a reference for the use of antibiotics in AECOPD treatment.Keywords: chronic obstructive pulmonary disease, acute exacerbation, bacterial infection, eosinophil

Heavily electron-doped surfaces of Bi$_2$Se$_3$ have been studied by spin andangle resolved photoemission spectroscopy. Upon doping, electrons occupy aseries of {\bf k}-split pairs of states above the topological surface state.The {\bf k}-splitting originates from the large spin-orbit coupling and resultsin a Rashba-type behavior, unequivocally demonstrated here via the spinanalysis. The spin helicities of the lowest laying Rashba doublet and theadjacent topological surface state alternate in a left-right-left sequence.This spin configuration sets constraints to inter-band scattering channelsopened by electron doping. A detailed analysis of the scattering rates suggeststhat intra-band scattering dominates with the largest effect coming fromwarping of the Fermi surface.

Jee Youn Oh,1 Young Seok Lee,1 Kyung Hoon Min,1 Gyu Young Hur,1 Sung Yong Lee,1 Kyung Ho Kang,1 Chin Kook Rhee,2 Seoung Ju Park,3 Jae Jeong Shim1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea; 2Division of Pulmonary Medicine, Department of Internal Medicine, Catholic University Seoul Hospital, Seoul, Republic of Korea; 3Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Republic of Korea Purpose: Improvement in the diagnosis of asthma and chronic obstructive pulmonary disease (COPD) overlap (ACO), and identification of biomarkers for phenotype recognition will encourage good patient care by providing optimal therapy. We investigated club cell secretory protein (CC-16), a protective and anti-inflammatory mediator, as a new candidate biomarker for diagnosing ACO.Patients and methods: We performed a multicenter cohort study. A total of 107 patients were divided into three groups – asthma, COPD, and ACO – according to the Spanish guidelines algorithm, and enrolled into the study. Serum CC-16 levels were measured using commercial ELISA kits.Results: Serum CC-16 levels were the lowest in patients with ACO. Low serum CC-16 levels were a significant marker for the ACO even after adjustment for age, sex, and smoking intensity. Serum CC-16 levels were positively correlated with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), forced expiratory flow at 25%–75% of FVC, FEV1/FVC, vital capacity, and diffusing capacity of the lung for carbon monoxide, and were negatively correlated with smoking amount (pack-years), bronchodilator response, fractional residual capacity, residual volume, and number of exacerbations per year. FEV1 and serum CC-16 levels were significantly lower in patients with frequent exacerbations.Conclusion: Serum CC-16 has the potential to be a biomarker for ACO diagnosis and also treat frequent exacerbations in patients with chronic inflammatory airway diseases. Keywords: asthma, COPD, ACO, exacerbation, club cell secretory protein-16, smoking

Jee Youn Oh,1 Young Seok Lee,1 Kyung Hoon Min,1 Gyu Young Hur,1 Sung Yong Lee,1 Kyung Ho Kang,1 Chin Kook Rhee,2 Seoung Ju Park,3 Jae Jeong Shim1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea; 2Division of Pulmonary Medicine, Department of Internal Medicine, Catholic University Seoul Hospital, Seoul, Republic of Korea; 3Division of Pulmonary Medicine, Department of Internal Medicine, Chonbuk National University Hospital, Jeonju, Republic of Korea Purpose: Tuberculosis-associated COPD (T-COPD) has clinical characteristics similar to those of smoking-associated COPD (S-COPD), such as dyspnea, sputum production, and acute exacerbation (AE). However, the degree of systemic inflammation and prognosis might be different because of difference in the pathophysiology. The aim of this study was to compare the lung function, systemic inflammatory markers, and their impacts on AE in patients with S-COPD and T-COPD.Patients and methods: We performed a multicenter cross-sectional cohort study. We evaluated clinical characteristics, pulmonary function tests, levels of inflammatory markers, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and IL-6, and the association of these markers with AE in patients with S-COPD and T-COPD.Results: Patients with T-COPD included more women and had lesser smoking history and higher St George Respiratory Questionnaire score than did patients with S-COPD. Although the FEV1 of both groups was similar, FVC, vital capacity, total lung capacity, and functional residual capacity were lower in patients with T-COPD than in those with S-COPD. CRP, ESR, and IL-6 levels were significantly higher in patients with T-COPD compared to patients with S-COPD. According to a multivariate logistic regression analysis, FEV1 was a significant factor predicting AE in S-COPD, and IL-6 was a significant factor predicting AE in T-COPD. IL-6 level greater than 2.04 pg/mL was a cutoff for predicting exacerbation of T-COPD (sensitivity 84.8%, specificity 59.3%, P

Juwhan Choi, Jee Youn Oh, Young Seok Lee, Gyu Young Hur, Sung Yong Lee, Jae Jeong Shim, Kyung Ho Kang, Kyung Hoon Min Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea Introduction: Acute exacerbation of COPD (AECOPD) leads to rapid deterioration of pulmonary function and quality of life. It is unclear whether the prognosis for AECOPD differs depending on the bacterium or virus identified. The purpose of this study is to determine whether readmission of patients with severe AECOPD varies according to the bacterium or virus identified.Methods: We performed a retrospective review of medical records of 704 severe AECOPD events at Korea University Guro Hospital from January 2011 to May 2017. We divided events into two groups, one in which patients were readmitted within 30 days after discharge and the other in which there was no readmission.Results: Of the 704 events, 65 were followed by readmission within 30 days. Before propensity score matching, the readmission group showed a higher rate of bacterial identification with no viral identification and a higher rate of identification with the Pseudomonas aeruginosa (P=0.003 and P=0.007, respectively). Using propensity score matching, the readmission group still showed a higher P. aeruginosa identification rate (P=0.030), but there was no significant difference in the rate of bacterial identification, with no viral identification (P=0.210). In multivariate analysis, the readmission group showed a higher P. aeruginosa identification rate than the no-readmission group (odds ratio, 4.749; 95% confidence interval, 1.296–17.041; P=0.019).Conclusion: P. aeruginosa identification is associated with a higher readmission rate in AECOPD patients. Keywords: acute exacerbation of COPD, Pseudomonas aeruginosa, readmission, bacterium, virus

The existing glenohumeral joint kinematic protocols are highly effective for studying in vivo shoulder kinematics but are not anatomically specific enough to address the asymmetric changes in glenohumeral joint kinematics and do not provide clear anatomic definitions for landmarks and directions. Therefore, the objective of this study was to develop an anatomically relevant and specimen-specific three-dimensional glenohumeral joint kinematic method as a new standard definition protocol for the glenohumeral coordinate systems (CSs). The in situ kinematic data of the intra-capsular glenoid-based CS of the glenohumeral joint were mathematically determined from the kinematic data of the extra-capsular CSs measured with an intact capsule. To minimize irreproducibility arising from discrepancy in initial specimen condition and error in determining CSs, several techniques were employed to determine anatomical landmarks and directions. To examine and demonstrate the details of this method, six fresh frozen cadaveric shoulders were used with a custom shoulder testing system. The accuracy and repeatability in the humeral head center (HHC) measurement were 0.44 and 0.41 mm, respectively. The inter-observer reliability for the location of the glenoid CS origin and HHC were 0.37 and 0.30 mm, respectively. The smaller anteroposterior (AP) depth of the glenoid with respect to the superoinferior (SI) depth (27.3 ± 16.5%) was significantly correlated to the larger AP/SI translation ratio of the humeral head apex (191.4 ± 43.8%, R = 0.90, p = 0.02). This study provides a glenohumeral kinematic protocol that enables the assessment of asymmetric glenohumeral kinematics determined by a precise and reproducible method using anatomic landmarks. © 2010 The Author(s).

Il-Young Jang,1,2 Hee-Won Jung,3 Hyelim Park,1,2 Chang Ki Lee,4 Sang Soo Yu,2 Young Soo Lee,1 Eunju Lee,1 Robert J Glynn,5,6 Dae Hyun Kim6,7 1Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 2PyeongChang Health Center & County Hospital, Pyeongchang, Gangwon-Do, Republic of Korea; 3Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea; 4Goldman Urology Clinic, Seoul, Republic of Korea; 5Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA; 6Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA; 7Division of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA Purpose: The primary aim of this study was to evaluate the effectiveness of a 6-month multicomponent intervention on physical function in socioeconomically vulnerable older adults in rural communities. As secondary aims, we evaluated the effectiveness of the intervention on frailty and other geriatric syndromes, sustained benefit at 12 months, and baseline characteristics associated with poor response. Patients and methods: This designed-delay study was conducted in 187 adults (mean age: 77 years; 75% women) who were living alone or on a low income in three rural regions of Korea. A 24-week multicomponent program that consisted of group exercise, nutritional supplementation, depression management, deprescribing medications, and home hazard reduction was implemented with a planned 6-month interval from August 2015 through January 2017. The primary outcome was physical function, measured using the Short Physical Performance Battery (SPPB) score (range: 0–12; minimum clinically important difference ≥1) at 6 months. Secondary outcomes included frailty phenotype, sarcopenia, Mini Nutritional Assessment-Short Form score (range: 0–14), Center for Epidemiologic Studies-Depression Scale score (range: 0–60), and falls. Results: At 6 months, the SPPB score increased by 3.18 points (95% CI: 2.89, 3.48) from baseline. The program improved frailty (odds ratio: 0.06; 95% CI: 0.02, 0.16), sarcopenia (odds ratio: 0.32; 95% CI: 0.15, 0.68), Mini Nutritional Assessment-Short Form score by 1.67 points (95% CI: 1.28, 2.06), and Center for Epidemiologic Studies-Depression Scale score by -3.83 points (95% CI: -5.26, -2.39), except for fall (rate ratio: 0.99; 95% CI: 0.69, 1.43). These beneficial effects were sustained at 12 months. Body mass index ≥27 kg/m2 and instrumental activities of daily living disability at baseline were associated with poor improvement in the SPPB score. Conclusion: This 24-week multicomponent program had sustained beneficial effects up to 1 year on physical function, frailty, sarcopenia, depressive symptoms, and nutritional status in socioeconomically vulnerable older adults in rural communities. (ClinicalTrials.gov, NCT 02554994) Keywords: clinical trial, exercise, frailty, geriatric assessment, malnutrition, public health practice

Hee-Won Jung,1,2,* Il-Young Jang,3,4,* Chang Ki Lee,5 Sang Soo Yu,4 Jae Kyoon Hwang,4 Chawoong Jeon,4 Young Soo Lee,3 Eunju Lee3 1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea; 2Geriatric Center, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea; 3Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 4PyeongChang Health Center & County Hospital, PyeongChang-gun, Gangwon-Do, Republic of Korea; 5Goldman Urology Clinic, Seoul, Republic of Korea *These authors contributed equally to this work Purpose: We aimed to describe the age- and sex-specific distributions of gait speed and to evaluate associations with longitudinal outcomes in Korean rural community-dwelling older adults.Patients and methods: A total of 1,348 people (mean age: 76 years, 55% women) in the population-based, prospective cohort of Aging Study of Pyeongchang Rural Area (ASPRA) between October 2014 and June 2017. All participants underwent a comprehensive geriatric assessment, including 4-m usual gait speed, and were followed annually.Results: Among the 1,348 participants, women had a slower gait speed than men (mean 0.709 m/s vs 0.850 m/s, P < 0.001). Gait speed was inversely associated with age, frailty index; slow gait speed as classified by sex-specific quartile was associated with the prevalence of common geriatric syndromes. During the mean follow-up period of 21.5 months (SD 7.88), future survival without mortality or institutionalization was affected by sex-specific gait-speed quartile (log rank test P < 0.001): the 1st quartile of sex-specific gait speed was associated with increased risk of death or institutionalization.Conclusion: Gait speed was related to age, sex, frailty status, and geriatric health outcomes in Korean rural community-dwelling older adults. Since this gait-speed distribution in an older Korean population differs from previous data on other populations, we should consider a gait-speed cutoff value based on sex-specific quartiles to prevent misclassification in sarcopenia and frailty diagnosis. Keywords: cohort studies, frailty, gait speed, geriatric assessment, physical function

Jee Youn Oh,1 Young Seok Lee,1 Kyung Hoon Min,1 Gyu Young Hur,1 Sung Yong Lee,1 Kyung Ho Kang,1 Chin Kook Rhee,2 Seoung Ju Park,3 Adnan Khan,4 Jinhyuk Na,4 Youngja H Park,4 Jae Jeong Shim1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea; 2Division of Pulmonary Medicine, Department of Internal Medicine, Catholic University Seoul Hospital, Seoul, Republic of Korea; 3Division of Pulmonary Medicine, Department of Internal Medicine, Chonbuk National University Hospital, Jeonju, Republic of Korea; 4Metabolomics Laboratory, College of Pharmacy, Korea University, Sejong, Republic of Korea Purpose: Asthma–COPD overlap (ACO) is heterogeneous in nature and requires a unified diagnostic approach. We investigated the urinary levels of L-histidine, a precursor of histamine related to inflammatory responses, as a new candidate biomarker for diagnosing this condition.Patients and methods: We performed a prospective multicenter cohort study with retrospective analysis of 107 patients, who were divided into three groups: asthma, COPD, and ACO, according to the Spanish guidelines algorithm. Urinary L-histidine levels were measured using liquid chromatography-mass spectrometry. High-resolution metabolomic analysis, coupled with liquid chromatography-mass spectrometry and followed by multivariate statistical analysis, was performed on urine samples to discriminate between the metabolic profiles of the groups.Results: Urinary L-histidine levels were significantly higher in patients with ACO than in those with asthma or COPD, but the subgroups of ACO, classified according to disease origin, did not differ significantly. High urinary L-histidine level was a significant factor for the diagnosis of ACO even after adjusting for age, sex, and smoking amount. Among patients with airflow obstruction, the urinary L-histidine levels were elevated in patients with a documented history of asthma before the age of 40 years or bronchodilator responsiveness ≥400 mL; bronchodilator responsiveness ≥200 mL of forced expiratory volume in 1 second and exceeding baseline values by 12% on two or more visits; blood eosinophil count ≥300 cells·mm−3; and frequent exacerbations (P < 0.05).Conclusion: Urinary l-histidine could be a potential biomarker for ACO, regardless of the diversity of diagnostic definitions used. Keywords: asthma, COPD, ACO, urinary L-histidine, metabolomics, inhaled corticosteroid

Juwhan Choi, Jee Youn Oh, Young Seok Lee, Kyung Hoon Min, Gyu Young Hur, Sung Yong Lee, Kyung Ho Kang, Jae Jeong Shim Division of Respiratory, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea Introduction: Particulate matter and air pollution in Korea are becoming worse. There is a lack of research regarding the impact of particulate matter on patients with COPD. Therefore, the purpose of this study was to investigate the effects of various air pollution factors, including particulate matter, on the incidence rate of severe acute exacerbations of COPD (AECOPD) events. Methods: We analyzed the relationship between air pollutants and AECOPD events that required hospitalization at Guro Hospital in Korea from January 1, 2015 to May 31, 2017. We used general linear models with Poisson distribution and log-transformation to obtain adjusted relative risk (RR). We conducted further analysis through the Comprehensive Air-quality Index (CAI) that is used in Korea. Results: Among various other air pollutants, particulate matter was identified as a major source of air pollution in Korea. When the CAI score was over 50, the incidence rate of severe AECOPD events was statistically significantly higher [RR 1.612, 95% CI, 1.065–2.440, P=0.024]. Additionally, the particulate matter levels 3 days before hospitalization were statistically significant [RR 1.003, 95% CI, 1.001–1.005, P=0.006]. Conclusion: Particulate matter and air pollution increase the incidence rate of severe AECOPD events. COPD patients should be cautioned against outdoor activities when particulate matter levels are high. Keywords: air pollution, particulate matter, air quality index, acute exacerbation, COPD

Il-Young Jang,1,2 Chang Ki Lee,3 Hee-Won Jung,4,5 Sang Soo Yu,2 Young Soo Lee,1 Eunju Lee,1 Dae Hyun Kim6,7 1Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 2PyeongChang Health Center & County Hospital, PyeongChang, Gangwon-Do, Republic of Korea; 3Goldman Urology Clinic, Seoul, Republic of Korea; 4Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea; 5Geriatric Center, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-Do, Republic of Korea; 6Division of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; 7Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA Purpose: Frailty is an important consideration in the management of lower urinary tract symptoms and erectile dysfunction in older men; frailty increases vulnerability to treatment-related adverse outcomes, but its burden is not known. The authors aimed to examine the burden of frailty and associated geriatric conditions in community-dwelling older men.Patients and methods: A cross-sectional study was conducted with 492 community-dwelling older men (mean age, 74.2 years; standard deviation, 5.6 years). All the participants were administered the International Prostate Symptom Score (IPSS) (range: 0–35) and a five-item version of the International Index of Erectile Function (IIEF-5) (range: 5–25). Frailty phenotype was assessed based on exhaustion, inactivity, slowness, weakness, and weight loss. Prevalence of frailty phenotype and geriatric conditions were assessed by the IPSS severity category (mild, 0–7; moderate, 8–19; severe, 20–35 points) and the first IIEF-5 question, which assesses the confidence in erectile function (low, 1–2; moderate, 3; high, 4–5 points).Results: Older men with severe urologic symptoms had a high prevalence of frailty. According to the IPSS questionnaire, the prevalence of frailty was 7.3% (21/288) in the mild category, 16.3% (26/160) in the moderate category, and 43.2% (19/44) in the severe category. Participants in the severe IPSS category showed high prevalence of dismobility (45.5%), multimorbidity (43.2%), malnutrition risk (40.9%), sarcopenia (40.9%), and polypharmacy (31.8%). According to erectile confidence based on the first IIEF-5 question, the prevalence of frailty was 18.7% (56/300) for low confidence, 5.3% (6/114) for moderate confidence, and 5.1% (4/78) for high confidence. Participants with low confidence in erectile function showed high prevalence of sarcopenia (39.0%), multimorbidity (37.7%), dismobility (35.7%), malnutrition risk (33.3%), and polypharmacy (23.0%).Conclusion: The prevalence of frailty and geriatric conditions was higher in older men with severe urologic symptoms. A frailty screening should be routinely administered in urology practices to identify older men who are vulnerable to treatment-related adverse events. Keywords: erectile dysfunction, frailty, geriatric assessment, lower urinary tract symptoms, risk management

Il-Young Jang,1,2,* Hee-Won Jung,3,4,* Chang Ki Lee,5 Sang Soo Yu,2 Young Soo Lee,1 Eunju Lee1 1Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 2PyeongChang Health Center & County Hospital, Gangwon-Do, 3Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 4Geriatric Center, Seoul National University Bundang Hospital, Gyeonggi-Do, 5Goldman Urology Clinic, Seoul, Republic of Korea *These authors contributed equally to this work Purpose: It is important to define lean muscle mass when diagnosing sarcopenia, but there is still controversy on the clinical implication of sarcopenia derived by height, weight, and body mass index (BMI) adjusted muscle mass indices. We aimed to evaluate the longitudinal clinical relevance of 3 sarcopenia definitions in the Korean population. Patients and methods: We conducted comprehensive geriatric assessments for 1,379 community-dwelling older participants in the Aging Study of PyeongChang Rural Area (ASPRA) cohort and followed them up prospectively for death, institutionalization, and disability every 3 months. Sarcopenia was defined using the Asian Working Group consensus algorithm, combining grip strength, gait speed, and muscle mass.Results: Among 1,343 participants (mean age: 76 years, 741 women) analyzed, there were 29 deaths and 89 institutionalizations during 22.0 ± 8.3 months follow-up (mean ± SD). All three muscle indices correlated to age and sex. All sarcopenia criteria with muscle mass indices of height, weight, and body mass index (BMI) adjustment significantly predicted death or institutionalization. However, when adjusted for age and sex, only the sarcopenia criteria with muscle mass index of height adjustment were significantly associated with major adverse health outcomes.Conclusion: Adjusting age and gender, the sarcopenia definition from the quintile-based muscle index of height adjustment could predict death or institutionalization in Korean community-dwelling older adults. Keywords: cohort studies, frailty, geriatric assessment, muscle index, muscle mass, muscles, sarcopenia

Ye-Seul Lee,1 Won-Mo Jung,1 Hyunchul Jang,2 Sanghyun Kim,2 Sun-Yong Chung,3 Younbyoung Chae1 1Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul, 2Mibyeong Research Center, Korean Institute of Oriental Medicine, Daejeon, 3Department of Neuropsychiatry, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea Objectives: Recently, there has been increasing interest in preventing and managing diseases both inside and outside medical institutions, and these concerns have supported the development of the individual Personal Health Record (PHR). Thus, the current study created a mobile platform called “Mind Mirror” to evaluate psychological and physical conditions and investigated whether PHRs would be a useful tool for assessment of the dynamic relationship between the emotional and physical conditions of an individual.Methods: Mind Mirror was used to collect 30 days of observational data about emotional valence and the physical states of pain and fatigue from 20 healthy participants, and these data were used to analyze the dynamic relationship between emotional and physical conditions. Additionally, based on the cross-correlations between these three parameters, a multilevel multivariate regression model (mixed linear model [MLM]) was implemented.Results: The strongest cross-correlation between emotional and physical conditions was at lag 0, which implies that emotion and body condition changed concurrently. In the MLM, emotional valence was negatively associated with fatigue (β =-0.233, P

Hye-Jin Moon,1,* Yongmin Chang,2,* Yeong Seon Lee,1 Huijin Song,3 Hyuk Won Chang,4 Jeonghun Ku,5 Richard P Allen,6 Christopher J Earley,6 Yong Won Cho1 1Department of Neurology, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Republic of Korea; 2Department of Molecular Medicine, 3Department of Medical and Biological Engineering, Kyungpook National University and Hospital, Daegu, Republic of Korea; 4Department of Radiology, 5Department of Biomedical Engineering, School of Medicine, Keimyung University, Daegu, Republic of Korea; 6Department of Neurology, Johns Hopkins University, Hopkins Bayview Medical Center, Baltimore, MD, USA *These authors contributed equally to this work Purpose: Magnetic resonance imaging relaxometry studies differed on the relaxometry methods and their approaches to determining the regions of interest (ROIs) in restless legs syndrome (RLS) patients. These differences could account for the variable and inconsistent results found across these studies. The aim of this study was to assess the relationship between the different relaxometry methods and different ROI approaches using each of these methods on a single population of controls and RLS subjects. Methods: A 3.0-T magnetic resonance imaging with the gradient-echo sampling of free induction decay and echo pulse sequence was used. The regional brain “iron concentrations” were determined using three relaxometry metrics (R2, R2*, and R2') through two different ROI methods. The substantia nigra (SN) was the primary ROI with red nucleus, caudate, putamen, and globus pallidus as the secondary ROIs. Results: Thirty-seven RLS patients and 40 controls were enrolled. The iron concentration as determined by R2 did not correlate with either of the other two methods, while R2* and R2' showed strong correlations, particularly for the substantia nigra and red nucleus. In the fixed-shape ROI method, the RLS group showed a lower iron index compared to the control group in the substantia nigra and several other regions. With the semi-automated ROI method, however, only the red nucleus showed a significant difference between the two groups. Conclusion: Both the relaxometry and ROI determination methods significantly influenced the outcome of studies that used these methods to estimate regional brain iron concentrations. Keywords: restless legs syndrome, relaxometry, region of interest, substantia nigra, iron

Jun Won Kim,1,2 KounSeok Lee,3 Young Sik Lee,4 Doug Hyun Han,4 Kyung Joon Min,4 Sung Hwan Song,5 Ga Na Park,6 Ju Young Lee,1 Jae Ock Kim5 1Division of Child and Adolescent Psychiatry, Department of Neuropsychiatry, College of Medicine, Seoul National University, Seoul, South Korea; 2Department of Psychiatry, Graduate School, Chung-Ang University, Seoul, South Korea; 3Department of Psychiatry, Samsung Medical Center, Seoul, South Korea; 4Department of Psychiatry, Chung-Ang University, College of Medicine, Seoul, South Korea; 5Department of Psychiatry, Gongju National Hospital, Gongju, South Korea; 6Department of Special Education, Graduate School, Dankook University, Jukjeon, South Korea Purpose: Low socioeconomic status is an important risk factor for child psychiatric problems. Low socioeconomic status is also associated with psychiatric problems later in life. We investigated the effects of group bullying on clinical characteristics and psychopathology in elementary school students using child-welfare facilities.Methods: Three hundred and fifty-eight elementary school students using child-welfare facilities were recruited. The School Bullying Self Rating Questionnaire was used to assess group bullying. To evaluate related psychopathology, the Children’s Problem-Behavior Screening Questionnaire, the Children’s Depression Inventory, the Beck Anxiety Inventory, the Suicidal Ideation Questionnaire, Young’s Internet Addiction Scale, and Conners–Wells’ Adolescent Self-Report Scale were applied. Samples were classified according to school grade (lower or upper), and each group’s characteristics were compared as they related to bullying victims versus non-victims.Results: The prevalence rate of group bullying was 22% in the lower-grade group and 12% in the higher-grade group. Bullying victims in lower grades reported high somatization, depressive symptoms, Internet addiction, and attention deficit hyperactivity disorder tendencies, whereas those in upper grades reported cognitive problems, symptoms of depression and anxiety, suicidal ideation, Internet addiction, and attention deficit hyperactivity disorder tendencies. Somatization and depressive symptoms were significant predictors of bullying in the lower-grade group, and anxiety was a significant predictor of bullying in the upper-grade group.Conclusion: This study demonstrated that elementary school students using child-welfare facilities might have an increased risk of being bullied and that bullying victims may have different psychopathologies depending on their ages. Keywords: socioeconomic status, somatization, depression, anxiety

Young Il Jeong,1,* Kyu Don Chung,2,* Da Hye Kim,3 Yoon Hyuk Kim,4 Yeon Soo Lee,5 Ki Choon Choi31Cancer Center, Chonnam National University Hwasun Hospital, Hwasun, South Korea; 2Department of Anesthesiology and Pain Medicine, Catholic University, Seoul, South Korea; 3Grassland and Forage Research Center, Rural Development Administration, Cheonan, South Korea; 4Department of Mechanical Engineering, Kyung Hee University, Seoul, South Korea; 5Department of Biomedical Engineering, Catholic University of Daegu, Daegu, South Korea*These authors equally contributed to this workPurpose: All-trans retinoic acid (RA)-incorporated nanoparticles were prepared using deoxycholic acid-conjugated dextran (DexDA). Anticancer activity of RA-incorporated DexDA nanoparticles were tested in vitro and in vivo.Methods: RA-incorporated nanoparticles were prepared by dialysis. Antiproliferative and anti-invasive potential of RA-incorporated nanoparticles were studied using CT26 colorectal carcinoma cells.Results: RA-incorporated nanoparticles have small particle sizes of around 70–300 nm and spherical shapes. The higher drug-feeding ratio and higher substitution degree of deoxycholic acid in the conjugates resulted in higher drug contents, lower loading efficiency, and larger particle size. RA release rate became slower at higher drug contents and higher substitution degree of deoxycholic acid in the DexDA conjugates. The antiproliferation activity, anti-invasive activity, and matrix metalloproteinase 2 expression of RA-incorporated nanoparticles against CT26 cells in vitro was similar to RA. However, RA-incorporated nanoparticles had superior antimetastatic activity in an animal pulmonary metastatic model of CT26 cells compared to RA itself.Conclusion: RA-incorporated nanoparticles showed similar anticancer activity in vitro and superior antimetastatic activity in vivo in a pulmonary metastatic model of CT26 cells. We suggest that RA-incorporated nanoparticles are promising vehicles for efficient delivery of RA.Keywords: nanoparticle, dextran, deoxycholic acid, retinoic acid, cancer cell invasion