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Tsan-Min Wang,1 Yi-Liang Lee,2,3 Chi-Hsiang Chung,1,4,5 Chien-An Sun,6,7 Chieh-Yi Kang,8 Gwo-Jang Wu,1,2,9 Wu-Chien Chien1,4,5,10 1Department of Medical Research, Tri-Service General Hospital, Taipei, 11490, Taiwan; 2Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China; 3Department of Obstetrics and Gynecology, Kang Ning Hospital, Taipei, Taiwan, Republic of China; 4School of Public Health, National Defense Medical Center, Taipei, 11490, Taiwan; 5Taiwanese Injury Prevention and Safety Promotion Association (TIPSPA), Taipei, 11490, Taiwan; 6Department of Public Health, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan, Republic of China; 7Big Data Research Center, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan, Republic of China; 8Department of Obstetrics & Gynecology, Chi Mei Medical Center Gynecologic Oncologist Division, Tainan City, Taiwan, Republic of China; 9Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, 11490, Taiwan; 10Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, 11490,TaiwanCorrespondence: Wu-Chien Chien; Gwo-Jang Wu, Email chienwu@ndmctsgh.edu.tw; gwojang@yahoo.comObjective: A multitude of previous studies has substantiated that endometriosis correlated highly with psychiatric health. This study aims to investigate the association between endometriosis and psychiatric health.Methods: Utilizing the National Health Insurance Research Database of Taiwan, 100,770 enrolled participants, including 20,154 patients with endometriosis and 80,616 in the control group (1:4), matched for age, and index date from Taiwan’s Longitudinal Health Insurance Database between January 1, 2000, and December 31, 2015. The Cox proportional regression model was used to compare the risk of mental disorders during the 16 years of follow-up after adjusting for confounding factors.Results: Of the study patients, 4083 (20.26%) developed mental disorders; 9225 of the 80,616 controls (11.44%) developed mental disorders. The Cox regression demonstrated that, after adjusting for age, monthly income, urbanization level, etc., people with endometriosis are more likely to suffer from mental disorders compared to those without endometriosis (hazard ratio [HR]=2.131; 95% confidence interval [CI]= 1.531– 2.788; p< 0.001). The result illustrated that women over 40 years old had a more significant risk.Conclusion: Compared to people without endometriosis, this study provides evidence that patients with endometriosis are at a 2.131-fold higher risk of developing mental disorders, especially in elder women. Regular psychiatric follow-up might be needed for those patients.Keywords: endometriosis, mental disorders, national health insurance research database, cohort study, Taiwan, women

Tsan-Min Wang,1,2 Cheng-Hao Chou,1,2 Yi-Liang Lee,3,4 Chi-Hsiang Chung,1,5,6 Yao-Ching Huang,1,7 Xiao-Cheng Lai,8 Chien-An Sun,9,10 Chieh-Yi Kang,11 Gwo-Jang Wu,1,3,12 Wu-Chien Chien1,5,6,8 1Department of Medical Research, Tri-Service General Hospital, Taipei, Taiwan; 2Taipei Municipal Jianguo High School, Taipei, Taiwan; 3Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China; 4Department of Obstetrics and Gynecology, Kang Ning Hospital, Taipei, Taiwan, Republic of China; 5School of Public Health, National Defense Medical Center, Taipei, Taiwan; 6Taiwanese Injury Prevention and Safety Promotion Association (TIPSPA), Taipei, Taiwan; 7Department of Chemical Engineering and Biotechnology, National Taipei University of Technology (Taipei Tech), Taipei, Taiwan; 8Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; 9Department of Public Health, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan, Republic of China; 10Big Data Research Center, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan, Republic of China; 11Chi Mei Medical Center Gynecologic Oncologist Division, Department of Obstetrics & Gynecology, Tainan City, Taiwan, Republic of China; 12Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, TaiwanCorrespondence: Gwo-Jang Wu; Chieh-Yi Kang, Email gwojang@yahoo.com; albert0113@yahoo.com.twObjective: Previous studies have shown an increased in psychiatric disorders in women with disorders associated with hyperandrogenism, but few nationwide cohorts have studied this phenomenon. Therefore, this study is aimed to examine the association between the clinical manifestations of hyperandrogenism and subsequent psychiatric disorders.Methods: Based on the National Health Insurance Research Database, 49,770 enrolled participants were matched for age and index date between January 1, 2000, and December 31, 2015. Hirsutism, polycystic ovary syndrome, and acne are characterized by hyperandrogenism. After adjusting for confounding factors, we used Cox proportional analysis to compare the risk of psychiatric disorders during the 16 years of follow-up.Results: Of all the participants, 1319 (13.25%) had psychiatric disorders in the study group, whereas only 3900(9.80%) had psychiatric disorders in the control group. After adjusting for age, and monthly income, the Cox regression analysis showed that the study patients were more likely to develop psychiatric disorders (hazard ratio [HR]: 2.004, 95% confidence interval [CI] = 1.327– 2.724, P < 0.001). The results demonstrated that women aged 20– 29 years had a more significant risk.Conclusion: Women with clinical characteristics of hyperandrogenism have a higher risk of developing psychiatric disorders, especially those aged 20– 29 years.Keywords: hyperandrogenism, psychiatric disorders, national health insurance research database, cohort study, women, Taiwan

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

Tien-Yu Chen,1– 3,&ast; Vincent Yi-Fong Su,4,5,&ast; Chung-Hsin Lee,6 Chi-Hsiang Chung,7– 9 Chia-Kuang Tsai,3,10 Chung-Kan Peng,3,11 Hsiao-Ching Lai,1 Wu-Chien Chien,7– 9,12 Nian-Sheng Tzeng1,13 1Department of Psychiatry, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan; 2Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan; 3Sleep Medicine Center, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan; 4Department of Internal Medicine, Taipei City Hospital, Taipei, Taiwan; 5Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan; 6Department of Neurosurgery, Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan; 7Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 8School of Public Health, National Defense Medical Center, Taipei, Taiwan; 9Taiwanese Injury Prevention and Safety Promotion Association, Taipei, Taiwan; 10Department of Neurology, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan; 11Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan; 12Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; 13Student Counseling Center, National Defense Medical Center, Taipei, Taiwan&ast;These authors contributed equally to this workCorrespondence: Wu-Chien ChienDepartment of Medical Research, Tri-Service General Hospital, National Defense Medical Center, 7115R, No. 325, Section 2, Cheng-Kung Road, Neihu District, Taipei, 11490, TaiwanTel +886 2-87923311, Ext. 19189Fax +886 2-87927235Email chienwu@mail.ndmctsgh.edu.twNian-Sheng TzengDepartment of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, 325, Section 2, Cheng-Kung Road, Neihu District, Taipei City, 11490, TaiwanTel +886 2-87927299Fax +886 2-87927221Email pierrens@mail.ndmctsgh.edu.twPurpose: Asthma, which is caused by inflammation of the airways, affects the sensitivity of nerve endings. Narcolepsy is a chronic sleep disorder that may be caused by autoimmunity. Recent studies have reported a positive association between narcolepsy and asthma. We aimed to examine the association between asthma and narcolepsy and determine the effects of therapeutic corticosteroid or bronchodilator use.Materials and Methods: We conducted a nationwide population-based, nested case-control study using Taiwan’s National Health Insurance Research Database (NHIRD) between 2000 and 2013. Subjects with narcolepsy (ICD-9-CM code 347) were enrolled, with 1:3 estimated propensity score-matched controls based on sex, age, and index year. The association between narcolepsy and asthma was assessed using multiple logistic regression analyses. The covariates included sex, age, monthly insurance premiums, geographical area of residence, urbanization level of residence, level of care, and presence of diseases related to immune response and central nervous system. The effects of corticosteroid and bronchodilator use were also analyzed.Results: Overall, 2008 subjects were identified from the NHIRD (502 patients with narcolepsy and 1506 controls). The participants with narcolepsy had almost three times the level of previous asthma diagnosis than controls. Compared to those without asthma, patients with asthma had an adjusted odds ratio (OR) of 3.181 for narcolepsy comorbidity (95% confidence interval [CI]: 2.048– 4.941, p< 0.001). The use of inhaled corticosteroids was associated with a lower risk of narcolepsy comorbidity, with an adjusted OR of 0.465 (95% CI, 0.250– 0.634; p< 0.001), in patients with asthma when compared to those without treatment.Conclusion: This study demonstrated a significantly higher level of previous asthma diagnosis in patients with narcolepsy. The use of inhaled corticosteroids was associated with a lower risk of narcolepsy comorbidity in asthma patients, compared to those without treatment.Keywords: asthma, narcolepsy, corticosteroid, bronchodilators

Yi-Jen Huang,1,2 Senyeong Kao,1,3 Li-Ting Kao,1,3– 5 Chih-Feng Chian,6 Chi-Hsiang Chung,3,7 Wu-Chien Chien,1,3,7,* Kwua-Yun Wang1,8,9,* 1Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; 2Department of Nursing, University of Kang Ning, Taipei, Taiwan; 3School of Public Health, National Defense Medical Center, Taipei, Taiwan; 4Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan; 5School of Pharmacy, National Defense Medical Center, Taipei, Taiwan; 6Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri‐Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 7Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 8School of Nursing, National Defense Medical Center, Taipei, Taiwan; 9Department of Nursing, Taipei Veterans General Hospital, Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Wu-Chien ChienDepartment of Medical Research, Tri-Service General Hospital, National Defense Medical Center, 7115R, No. 325, Section 2, Cheng-Kung Road, Neihu District, Taipei City, 11490, Taiwan, Republic of ChinaTel +886-2-87923311, Ext. 19189Fax +886-2-87927235Email chienwu@ndmctsgh.edu.twKwua-Yun WangGraduate Institute of Life Sciences, National Defense Medical Center, 9314R, No. 161, Section 6, Min-Chuan East Road, Neihu District, Taipei City, 11490, TaiwanTel +886-2-87923100 ext.18766Email kywang7@vghtpe.gov.twPurpose: The role of statins as anti-inflammatory drugs in chronic obstructive pulmonary disease (COPD) is controversial. This study aimed to determine the efficacy of statins used with or without corticosteroids in COPD patients.Patients and Methods: This was a retrospective cohort study and used the two million outpatients and inpatients in Taiwan’s Longitudinal Health Insurance Database covering 2000 to 2015. A total of 92,460 patients were identified in this study. We divided COPD patients into four groups by auditing each patient’s medication (statins used or not; corticosteroids used or not) and used Cox regression to analyze and compare the effects of statins in COPD patients with or without corticosteroids.Results: In terms of all COPD patients, our findings were consistent with previous studies showing that statins decreased COPD-related hospitalization and mortality rates. However, the beneficial effects were only observed in younger patients or those not taking corticosteroids in further analysis. Statins significantly decreased hospitalization and mortality rates in the non-corticosteroids groups. The hazard ratios increased with age and were not statistically significant for patients > 70 years old. Statins did not significantly decrease ED visits, hospitalization, and mortality in corticosteroids groups.Conclusion: Statins decreased hospitalization and mortality rates in COPD patients not taking corticosteroids but were not efficacious in patients on corticosteroids therapy. Furthermore, the beneficial effects of statins gradually decreased with patient age. Based on the findings, statins used in COPD patients may need to consider the patient age and corticosteroids used or not.Keywords: COPD, exacerbation, statins, corticosteroids, mortality

Yao-Ching Huang,1 Wu-Chien Chien,2– 5,* Chi-Hsiang Chung,2– 4 Hsin-An Chang,6,7 Yu-Chen Kao,6,8 Fang-Jung Wan,6 Shi-Hao Huang,1 Ren-Jei Chung,1,* Richard S Wang,9 Bing-Long Wang,2,* Nian-Sheng Tzeng,7,8,* Chien-An Sun10,11 1Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, Taiwan; 2School of Public Health, National Defense Medical Center, Taipei, Taiwan; 3Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 4Taiwanese Injury Prevention and Safety Promotion Association, Taipei, Taiwan; 5Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; 6Department of Psychiatry, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan; 7Student Counseling Center, National Defense Medical Center, Taipei, Taiwan; 8Department of Psychiatry, Tri-Service General Hospital, Song-Shan Branch, National Defense Medical Center, Taipei, Taiwan; 9Program of Data Analytic and Business Computing, Stern School of Business, New York University, USA; 10Department of Public Health, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan; 11Big Data Research Center, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan*These authors contributed equally to this workCorrespondence: Nian-Sheng TzengDepartment of Psychiatry, School of Medicine, Tri-Service General Hospital, National Defense Medical Center, 325, Section 2, Cheng-Gung Road, Nei-Hu District, Taipei, Taiwan, Republic of ChinaTel +886-2-87923311 Ext 17484Fax +886-2-87927221Email pierrens@mail.ndmctsgh.edu.twBing-Long WangDepartment of Public Health, National Defense Medical Center, 116, Section 6, Minchuan E. Road, Nei-Hu District, Taipei, Taiwan, Republic of ChinaTel +886-980-794951Email billwang1203@gmail.comBackground: Multiple sclerosis (MS) is a demyelinating disease that can damage neurons in the brain and spinal cord and is associated with several psychiatric disorders. However, few studies have evaluated the risk of psychiatric disorders in patients with MS by using a nationwide database. This study investigated the association between MS and the risk of psychiatric disorders.Methods: Using data from the Taiwan National Health Insurance Research Database from 2000 to 2015, we identified 1066 patients with MS. After adjustment for confounding factors, Fine and Gray’s competing risk model was used to compare the risk of psychiatric disorders during 15 years of follow-up.Results: Of the patients with MS, 531 (4622.86 per 105 person years) developed psychiatric disorders; by contrast, 891 of the 3198 controls (2485.31 per 105 person years) developed psychiatric disorders. Fine and Gray’s competing risk model revealed an adjusted hazard ratio (HR) of 5.044 (95% confidence interval = 4.448– 5.870, p < 0.001) after adjustment for all the covariates. MS was associated with depression, anxiety, bipolar disorder, sleep disorders, schizophrenia, schizophreniform disorder, and other psychotic disorders (adjusted HR: 12.464, 4.650, 6.987, 9.103, 2.552, 2.600, 2.441, and 2.574, respectively; all p < 0.001). Some disease-modifying drugs were associated with a lower risk of anxiety or depression.Conclusion: Patients with MS were determined to have a higher risk of developing a wide range of psychiatric disorders.Keywords: multiple sclerosis, psychiatric disorders, depression, anxiety

Shih-Chun Hsing,1,2 Yo-Ting Jin,3,4 Nian-Sheng Tzeng,5,6 Chi-Hsiang Chung,7– 9 Tien-Yu Chen,5,10,11 Hsin-An Chang,5,6 Yu-Chen Kao,5,12 Wu-Chien Chien4,7– 9 1Center for Healthcare Quality Management, Cheng Hsin General Hospital, Taipei, Taiwan; 2Department of Health Care Management, College of Health Technology, National Taipei University of Nursing and Heath Sciences, Taipei, Taiwan, Republic of China; 3Department of Nursing, Hsin Sheng Junior College of Medical Care and Management, Taoyuan, Taiwan; 4Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; 5Department of Psychiatry, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan; 6Student Counseling Center, National Defense Medical Center, Taipei, Taiwan; 7Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 8School of Public Health, National Defense Medical Center, Taipei, Taiwan; 9Taiwanese Injury Prevention and Safety Promotion Association, Taipei, Taiwan; 10Department of Psychiatry, Tri-Service General Hospital, Keelung Branch, National Defense Medical Center, Taipei, Taiwan; 11Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan; 12Department of Psychiatry, Tri-Service General Hospital, Song-Shan Branch, National Defense Medical Center, Keelung, TaiwanCorrespondence: Nian-Sheng TzengDepartment of Psychiatry, School of Medicine, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, No. 325, Section 2, Cheng-Gung Road, Nei-Hu District, Taipei, TaiwanTel +886 2-87923311, ext. 17484Fax +886-2-87927221Email pierrens@mail.ndmctsgh.edu.twWu-Chien ChienDepartment of Medical Research, Tri-Service General Hospital, National Defense Medical Center, 7115R, No. 325, Section 2, Cheng-Gung Road, Nei-Hu District, Taipei, TaiwanTel +886 2-87923311, ext. 19189Fax +886 2-87927235Email chienwu@ndmctsgh.edu.twBackground: To examine the association between the usage of agomelatine in patients with major depressive disorder and the usage of sedative-hypnotics.Methods: This population-based, cross-sectional study used Taiwan’s National Health Insurance Research Database (NHIRD) between 2012 and 2015. The agomelatine-only group and matched control (1:3) with the usage of other antidepressants were enrolled. The association between the usage of the agomelatine and other antidepressants and the usage of sedative-hypnotics in the patients were also assessed.Results: A total of 7961 subjects were enrolled comprising 1985 with the usage of agomelatine only, and 5976 with other antidepressants. In the present study, a total of 3322 subjects who used the sedative-hypnotics were recorded, with 811 (40.86%) from the agomelatine-only group and 2511 (42.02%) from the non-agomelatine group, which have used sedative-hypnotics. After adjusting for covariates, the odds ratio (OR) of the usage of sedative-hypnotics in the agomelatine only-group was 0.892 (95% CI: 0.306– 1.601, p = 0.533), in comparison to the controls, and the relative risk (RR) of the usage of sedative-hypnotics in the agomelatine only-group was 0.892 0.910 (95% CI: 0.312– 1.633, p = 0.452), in comparison to the controls. No matter as to whether the treatment duration was < 30 days or ≧ 30 days of agomelatine treatment was not associated with the increased usage of the sedative-hypnotics. The OR or RR for usage of the sedative-hypnotics was associated with the Charlson Comorbidity Index (CCI) scores as 2, 3, and ≧ 4, and the medical care from the medical center and regional hospital.Conclusion: Patients with the agomelatine-only group were not associated with the usage of sedative-hypnotics in comparison to the group using other antidepressants.Keywords: agomelatine, insomnia, antidepressant, major depressive disorder, National Health Insurance Research Database

Yueh-Er Chiou,1,2 Wu-Chien Chien,3– 5,* Chi-Hsiang Chung,3,4,6 Hsin-An Chang,7,8 Yu-Chen Kao,7,9 Pei-Kwei Tsay,10,* Nian-Sheng Tzeng7,8,* 1Department of Nursing, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; 2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; 3Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 4School of Public Health, National Defense Medical Center, Taipei, Taiwan; 5Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; 6Taiwanese Injury Prevention and Safety Promotion Association, Taipei, Taiwan; 7Department of Psychiatry, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan; 8Student Counseling Center, National Defense Medical Center, Taipei, Taiwan; 9Department of Psychiatry, Tri-Service General Hospital, Song-Shan Branch, National Defense Medical Center, Taipei, Taiwan; 10Department of Public Health and Center of Biostatistics, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan*These authors contributed equally to this workCorrespondence: Pei-Kwei TsayDepartment of Public Health and Center of Biostatistics, College of Medicine, Chang Gung University, Tao-Yuan 333, TaiwanTel +886-3-211-8800 # 5068 (PKT)Email Tsay@mail.cgu.edu.twNian-Sheng TzengJoint Program for Geriatric Psychiatry and Psychosomatic Medicine, Department of Psychiatry, School of Medicine, Tri-Service General Hospital, National Defense Medical Center, 325, Section 2, Cheng-Gung Road, Nei-Hu District, Taipei, Taiwan, Republic of ChinaTel +886-2-87923311, Ext 17484Fax +886-2-87927221Email pierrens@mail.ndmctsgh.edu.twBackground: Herbal medicine containing aristolochic acids (HMCAA) was used for inflammatory and infectious diseases. This study aimed to investigate the association between the usage of HMCAA and the risk of dementia.Methods: A total of 199 new users of HMCAA were enrolled, along with 597 controls without the usage of HMCAA, at a ratio of 1:3 – matched by age, sex, and comorbidity, between 2000 and 2003 – from the National Health Research Institutes Database (NHRID) of Taiwan, which contains two million randomly sampled subjects, in this cohort study. We used Fine and Gray’s survival analysis (competing with mortality) to compare the risk of developing dementia during a 15-year follow-up period (2000– 2015).Results: In general, HMCAA was not significantly associated with dementia (adjusted subdistribution hazard ratio [SHR] = 0.861, 95% confidence interval [CI] = 0.484– 1.532, p = 0.611) for the HMCAA-cohort, although differential risk was observed among the groups at risk. The patients with usage of HMCAA aged ≧ 85 years were associated with a higher risk in dementia (adjusted SHR: 6.243, 95% CI=1.258– 21.084, p = 0.001), in comparison to those aged 50– 54 years. Furthermore, the patients with usage of HMCAA that had cerebrovascular accidents were associated with an increased risk of dementia.Conclusion: The usage of HMCAA was associated with the risk of developing dementia in the patients aged ≧ 85 years.Keywords: herbal medicine containing aristolochic acids, traditional Chinese herbal medicines, dementia

Chuan-Chi Yang,1,2 Wu-Chien Chien,3–5 Chi-Hsiang Chung,3,4,6 Yia-Ping Liu,2,7–9 Chin-Bin Yeh,2 Kuang-Huei Chen,1 Szu-Nian Yang,1,9,10 Hsin-An Chang,2,11 Yu-Chen Kao,2,12 Wan-Chun Lu,2 Nian-Sheng Tzeng2,11 1Department of Psychiatry, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan, ROC; 2Department of Psychiatry, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan, ROC; 3Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC; 4School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC; 5Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC; 6Taiwanese Injury Prevention and Safety Promotion Association, Taipei, Taiwan, ROC; 7Department of Psychiatry, Chen-Hsin General Hospital, Taipei, Taiwan, ROC; 8Institute of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan, ROC; 9Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, ROC; 10Headquarters, Tri-Service General Hospital, Beitou Branch, National Defense Medical Center, Taipei, Taiwan, ROC; 11Student Counseling Center, National Defense Medical Center, Taipei, Taiwan, ROC; 12Department of Psychiatry, Tri-Service General Hospital, Song-Shan Branch, National Defense Medical Center, Taipei, Taiwan, ROCCorrespondence: Nian-Sheng TzengDepartment of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, 325, Chung-Gung Road, Sec 2, Nei-Hu District 114, Taipei, Taiwan, ROCTel +886-2-87927299 ext 13674Email pierrens@mail.ndmctsgh.edu.twBackground: The associations between the human immunodeficiency virus (HIV) and dementias are as yet to be studied in Taiwan. The aim of this study is to clarify as to whether HIV infections are associated with the risk of dementia.Methods: A total of 1,261 HIV-infected patients and 3,783 controls (1:3) matched for age and sex were selected between January 1 and December 31, 2000 from Taiwan’s National Health Insurance Research Database (NHIRD). Fine and Gray’s survival analysis (competing with mortality) analyzed the risk of dementias during the 15-year follow up. The association between the highly active antiretroviral therapy (HAART) and dementia was analyzed by stratifying the HAART status among the HIV subjects.Results: During the follow-up period, 25 in the HIV group (N= 1,261) and 227 in the control group (N= 3,783) developed dementia (656.25 vs 913.15 per 100,000 person-years). Fine and Gray’s survival analysis revealed that the HIV patients were not associated with an increased risk of dementia, with the adjusted hazard ratio (HR) as 0.852 (95% confidence interval [CI]: 0.189–2.886, p=0.415) after adjusting for sex, age, comorbidities, geographical region, and the urbanization level of residence. There was no significant difference between the two groups of HIV-infected patients with or without HAART in the risk of dementia.Conclusion: This study found that HIV infections, either with or without HAART, were not associated with increased diagnoses of neurodegenerative dementias in patients older than 50 in Taiwan.Keywords: human immunodeficiency virus, highly active antiretroviral therapy, dementia, National Health Insurance Research Database, cohort study

Tzu-Yi Wu,1 Chia-Hua Chung,2 Chia-Ni Lin,3 Jing-Shiang Hwang,2 Jung-Der Wang3,4 1Institute of Economics, Academia Sinica, Taipei, Taiwan; 2Institute of Statistical Science, Academia Sinica, Taipei, Taiwan; 3Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 4Department of Occupational and Environmental Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan Background: The mortality rates for different cancers are no longer an efficient tool for making national policy. The purpose of this study were to quantify the lifetime risks, life expectancies (LEs) after diagnosis, expected years of life lost (EYLL), and lifetime health care expenditures for 19 major cancers in Taiwan. Methods: A total of 831,314 patients with 19 pathologically proven cancers were abstracted from the Taiwan Cancer Registry from 1998 to 2012. They were linked to the National Mortality Registry (1998–2014) and National Health Insurance reimbursement database (1998–2013) for survival and health care costs. We estimated the cumulative incidence rate for ages 0–79 years and the lifetime survival function for patients with different cancer sites. The EYLL was calculated by subtracting the LE of each cancer cohort from that of the age- and sex-matched referents simulated from national life tables. The estimated lifetime cost was calculated by adding up the product of survival probability and mean cost at the corresponding duration-to-date after adjustment for the inflation to the year of 2013. Results: There were 5 cancers with a lifetime risk exceeding 4%: colorectal, liver, lung, and prostate in males, and breast and colorectal in females. Cancers with EYLL of >10 years were: esophageal, intrahepatic bile ducts, liver, pancreas, oral, nasopharyngeal, leukemia, lung, and gallbladder, extrahepatic bile ducts and biliary tract in males, and intrahepatic bile ducts, pancreas, nasopharyngeal, lung, esophageal, leukemia, liver, gallbladder, extrahepatic bile ducts and biliary tract, ovary, and stomach in females. Cancers with lifetime health care expenditures exceeding US$50,000 to the National Health Insurance were as follows: leukemia, kidney, testis, renal pelvis and ureter in males, and renal pelvis and ureter, leukemia, breast, urinary bladder, kidney, ovary, and nasopharyngeal in females. All these impacts should be considered in health policy decisions. Conclusion: The impacts of cancer in Taiwan are very large. Future studies must consider both quality of life and the entire impact from societal perspectives. Keywords: health impacts, incidence rate, expected years of life lost, cancer prevention

BackgroundTo determine genomic alterations in head and neck squamous cell carcinoma (HNSCC) using formalin-fixed, paraffin-embedded (FFPE) tumors obtained through routine clinical practice, selected cancer-related genes were evaluated and compared with alterations seen in frozen tumors obtained through research studies.Patients and methodsDNA samples obtained from 252 FFPE HNSCC were analyzed using next-generation sequencing-based (NGS) clinical assay to determine sequence and copy number variations in 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer. Human papillomavirus (HPV) status was determined by presence of the HPV DNA sequence in all samples and corroborated with high-risk HPV in situ hybridization (ISH) and p16 immunohistochemical (IHC) staining in a subset of tumors. Sequencing data from 399 frozen tumors in The Cancer Genome Atlas and University of Chicago public datasets were analyzed for comparison.ResultsAmong 252 FFPE HNSCC, 84 (33%) were HPV positive and 168 (67%) were HPV negative by sequencing. A subset of 40 tumors with HPV ISH and p16 IHC results showed complete concordance with NGS-derived HPV status. The most common genes with genomic alterations were PIK3CA and PTEN in HPV-positive tumors and TP53 and CDKN2A/B in HPV-negative tumors. In the pathway analysis, the PI3K pathway in HPV-positive tumors and DNA repair-p53 and cell cycle pathways in HPV-negative tumors were frequently altered. The HPV-positive oropharynx and HPV-positive nasal cavity/paranasal sinus carcinoma shared similar mutational profiles.ConclusionThe genomic profile of FFPE HNSCC tumors obtained through routine clinical practice is comparable with frozen tumors studied in research setting, demonstrating the feasibility of comprehensive genomic profiling in a clinical setting. However, the clinical significance of these genomic alterations requires further investigation through application of these genomic profiles as integral biomarkers in clinical trials.

BackgroundA germline mutation in the 3'-untranslated region of KRAS (rs61764370, KRAS-variant: TG/GG) has previously been associated with altered patient outcome and drug resistance/sensitivity in various cancers. We examined the prognostic and predictive significance of this variant in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).Patients and methodsWe conducted a retrospective study of 103 HNSCCs collected from three completed clinical trials. KRAS-variant genotyping was conducted for these samples and 8 HNSCC cell lines. p16 expression was determined in a subset of 26 oropharynx tumors by immunohistochemistry. Microarray analysis was also utilized to elucidate differentially expressed genes between KRAS-variant and non-variant tumors. Drug sensitivity in cell lines was evaluated to confirm clinical findings.ResultsKRAS-variant status was determined in 95/103 (92%) of the HNSCC tumor samples and the allelic frequency of TG/GG was 32% (30/95). Three of the HNSCC cell lines (3/8) studied had the KRAS-variant. No association between KRAS-variant status and p16 expression was observed in the oropharynx subset (Fisher's exact test, P = 1.0). With respect to patient outcome, patients with the KRAS-variant had poor progression-free survival when treated with cisplatin (log-rank P = 0.002). Conversely, KRAS-variant patients appeared to experience some improvement in disease control when cetuximab was added to their platinum-based regimen (log-rank P = 0.04).ConclusionsThe TG/GG rs61764370 KRAS-variant is a potential predictive biomarker for poor platinum response in R/M HNSCC patients.Clinical trial registration numbersNCT00503997, NCT00425750, NCT00003809.

This paper presents a Spatio-Temporal Road Inference for a KEeping NETwork (StrikeNet), aimed at enhancing Road Lane Reconstruction (RLR) and lateral motion control in Autonomous Vehicles (AV) using deep neural networks. Accurate road lane model coefficients are essential for an effective Lane Keeping System (LKS), but the traditional vision system often fails in situations where lane markers are absent or faint and cannot be properly recognized. To overcome this, a driving dataset was restructured, combining road information from a vision system and forward images for spatial training of RLR. Sequential spatial learning outputs were then processed with in-vehicle sensor data for temporal inference via Long Short-Term Memory (LSTM). The StrikeNet was rigorously tested in both typical and uncertain driving environments. Comprehensive statistical and visualization analyses were conducted to evaluate the performance of various RLR methods and lateral motion control strategies. Remarkably, the RLR demonstrated its capability to derive reliable road coefficients even in the absence of lane markers. Upon performance comparison with four alternative techniques, our method yields the lowest error and variance between human steering inputs and the control input. Specifically, under high and low lane quality conditions, the proposed method maximally reduced the control input error by up to 72% and 66%, respectively, and decreased the variance by 54% and 94%, respectively. The findings highlight StrikeNet’s effectiveness in bolstering the fail-operational performance, and reliability of lane-keeping or lane departure warning systems in autonomous driving, thereby enhancing control continuity and mitigating path deviation-induced traffic accidents.

Taiwan produces a total of about 46,000 metric tons of lemons, and its processing by-product, lemon peel, is rich in pectin. Proper utilization of vegetable and fruit processing waste increases the value of lemons and also achieves the purpose of friendly and sustainable environmental protection. To promote the applications in industries, ultrasound assisted extraction (UAE) and microwave assisted extraction (MAE) of pectin from lemon peel was performed and the effects of both on the yield (%), physiological, and chemical properties of lemon pectin were explored and evaluated in the present study. In addition, the response surface methodology (RSM) was also applied to optimize the extraction conditions, and the extraction was carried out with the central composite design (CCD) of three factors: UAE: time (X1, 60∼110.5 min), pH (X2, 1.0 ∼3.0), and temperature (X3, 20.8∼80.2 °C); MAE: time (X1, 1.5∼6.5 min), pH (X2, 1.0∼3.0), and wattage (X3, 113.6∼786.4 W). The results showed that the specific optimized conditions for UAE were 60 min, pH 1.0, and 55 °C. The optimal conditions for MAE were 4 min, pH 1.0, and 450 W; the optimal yields of lemon peel pectin were 37.9 % and 41.4 % respectively.

Spine surgery is a prevalently performed procedure. Some authors have proposed an age-related surge in surgical and general complications. During spine surgery, patients are placed in positions that are not physiologic, would not be tolerated for prolonged periods by the patient in the awake state, and may lead to complications. Understanding these uncommon complications and their etiology is pivotal to prevention and necessary. The patient is a 76-year-old woman referred to the outpatient department of neurosurgery in February 2022 by her physiatrist with a chief complaint of chronic low back pain and numbness over the left leg. Lumbar spine magnetic resonance imaging revealed degenerative disc disease and posterior disc bulging at the levels of L2/3∼L5/S1 with compression of the thecal sac. After receiving anti-inflammatory medication, nerve block and caudal block, her symptoms persisted. She was referred to a neurosurgeon for surgical intervention. We diagnosed spinal stenosis with left L3 and L4 radiculopathy, and elective decompression surgery was scheduled a few days later. We performed discectomies at L2/3 and L3/4 and left unilateral laminectomy at L2 and L3 for bilateral decompression. Following an uneventful surgery, the patient was extubated, and her left leg pain improved, but pain over the right outer calf with drop foot developed. A second lumbar MRI the next day revealed no evidence of recurrent disc herniation or epidural hematoma. Then, she received nerve conduction velocity and needle electromyogram on postoperative day 2, and the studies indicated right common peroneal nerve entrapment neuropathy. After medication with steroids and foot splint use, right leg pain improved. However, weak dorsiflexion of the right ankle persisted. We referred this patient to a physiatrist and OPD for follow-up after discharge. Perioperative peripheral nerve injury (PPNI) is most commonly caused by peripheral nerve ischemia due to abnormal nerve lengthening or pressure and can be exacerbated by systemic hypotension. Any diseases affecting microvasculature and anatomical differences may contribute to nerve injury or render patients more susceptible to nerve injury. Prevention, early detection and intervention are paramount to reducing PPNI and associated adverse outcomes. The use of intraoperative neuromonitoring theoretically allows the surgical team to detect and intervene in impending PPNI during surgery.

The human genome is pervasively transcribed and produces a wide variety of long non-coding RNAs (lncRNAs), constituting the majority of transcripts across human cell types. Some specific nuclear lncRNAs have been shown to be important regulatory components acting locally. As RNA-chromatin interaction and Hi-C chromatin conformation data showed that chromatin interactions of nuclear lncRNAs are determined by the local chromatin 3D conformation, we used Hi-C data to identify potential target genes of lncRNAs. RNA-protein interaction data suggested that nuclear lncRNAs act as scaffolds to recruit regulatory proteins to target promoters and enhancers. Nuclear lncRNAs may therefore play a role in directing regulatory factors to locations spatially close to the lncRNA gene. We provide the analysis results through an interactive visualization web portal at https://fantom.gsc.riken.jp/zenbu/reports/#F6_3D_lncRNA.

This study aimed to assess the effects of hexavalent chromium on zebrafish (Danio rerio) embryo development. The zebrafish embryos were treated with solutions containing chromium at different concentrations (0.1, 1, 3.125, 6.25, 12.5, 50, and 100 µg/mL). The development of zebrafish embryos was estimated by the determination of survival rate, heart rate, and the measurement of larvae body length. Real time RT-PCR and Western blot were performed to assess the expression of apoptosis- and antioxidant-related genes. The results showed that the reduced survival rate of zebrafish embryos and larvae was associated with an increase in chromium concentration. The exposure of higher concentrations resulted in a decrease in body length of zebrafish larvae. In addition, a marked increase in heart rate was observed in the zebrafish larvae under chromium treatment, especially at high concentrations. The real-time RT-PCR analysis showed that the transcript expressions for cell-cycle-related genes (cdk4 and cdk6) and antioxidant-related genes (sod1 and sod2) were downregulated in the zebrafish embryos treated with chromium. Western blot analysis revealed the upregulation of Caspase 3 and Bax, while a downregulation was observed in Bcl2. These results indicated that hexavalent chromium induced changes in zebrafish embryo development by altering apoptosis- and antioxidant-related genes.

Abstract As society continues to age, it is becoming increasingly important to monitor drug use in the elderly. Social media data have been used for monitoring adverse drug reactions. The aim of this study was to determine whether social network studies (SNS) are useful sources of drug side effects information. We propose a method for utilizing SNS data to plot the known side effects of geriatric drugs in a dosing map. We developed a lexicon of drug terms associated with side effects and mapped patterns from social media data. We confirmed that well-known side effects may be obtained by utilizing SNS data. Based on these results, we propose a pharmacovigilance pipeline that can be extended to unknown side effects. We propose the standard analysis pipeline Drug_SNSMiner for monitoring side effects using SNS data and evaluated it as a drug prescription platform for the elderly. We confirmed that side effects may be monitored from the consumer’s perspective based on SNS data using only drug information. SNS data were deemed good sources of information to determine ADRs and obtain other complementary data. We established that these learning data are invaluable for AI requiring the acquisition of ADR posts on efficacious drugs.

This paper proposes a spatiotemporal architecture with a deep neural network (DNN) for road surface conditions and types classification using LiDAR for autonomous emergency braking (AEB) systems. It is known that LiDAR provides information on the reflectivity and number of point clouds depending on a road surface. Thus, this paper utilizes the characteristics of LiDAR and the vehicle’s speed obtained from in-vehicle sensors for classifying front road surface conditions for the AEB system application. First, we divided the front road area into four subregions to use spatial information from the vehicle’s speed. Second, we constructed feature vectors using each subregion’s reflectivity, number of point clouds, and in-vehicle information. Third, the DNN classifies road surface conditions and types for each subregion. Finally, the output of the DNN feeds into the spatiotemporal process to make the final classification reflecting vehicle speed and probability given by the outcomes of softmax functions of the DNN output layer. To validate the effectiveness of the proposed method, we performed a comparative study with five other algorithms. With the proposed DNN, we obtained the highest accuracy of 98.0% and 98.6% for two subregions near the vehicle. In addition, we implemented the proposed method on the NVIDIA Jetson TX2 board to confirm that it is applicable in real-time.

We address the challenge of identifying meaningful communities by proposing a model based on convex game theory and a measure of community strength. Many existing community detection methods fail to provide unique solutions, and it remains unclear how the solutions depend on initial conditions. Our approach identifies strong communities with a hierarchical structure, visualizable as a dendrogram, and computable in polynomial time using submodular function minimization. This framework extends beyond graphs to hypergraphs or even polymatroids. In the case when the model is graphical, a more efficient algorithm based on the max-flow min-cut algorithm can be devised. Though not achieving near-linear time complexity, the pursuit of practical algorithms is an intriguing avenue for future research. Our work serves as the foundation, offering an analytical framework that yields unique solutions with clear operational meaning for the communities identified.

Background: Cells are sensitive to changes in gravity, especially the cytoskeletal structures that determine cell morphology. The aim of this study was to assess the effects of simulated microgravity (SMG) on 3T3 cell morphology, as demonstrated by a characterization of the morphology of cells and nuclei, alterations of microfilaments and microtubules, and changes in cycle progression. Methods: 3T3 cells underwent induced SMG for 72 h with Gravite®, while the control group was under 1G. Fluorescent staining was applied to estimate the morphology of cells and nuclei and the cytoskeleton distribution of 3T3 cells. Cell cycle progression was assessed by using the cell cycle app of the Cytell microscope, and Western blot was conducted to determine the expression of the major structural proteins and main cell cycle regulators. Results: The results show that SMG led to decreased nuclear intensity, nuclear area, and nuclear shape and increased cell diameter in 3T3 cells. The 3T3 cells in the SMG group appeared to have a flat form and diminished microvillus formation, while cells in the control group displayed an apical shape and abundant microvilli. The 3T3 cells under SMG exhibited microtubule distribution surrounding the nucleus, compared to the perinuclear accumulation in control cells. Irregular forms of the contractile ring and polar spindle were observed in 3T3 cells under SMG. The changes in cytoskeleton structure were caused by alterations in the expression of major cytoskeletal proteins, including β-actin and α-tubulin 3. Moreover, SMG induced 3T3 cells into the arrest phase by reducing main cell cycle related genes, which also affected the formation of cytoskeleton structures such as microfilaments and microtubules. Conclusions: These results reveal that SMG generated morphological changes in 3T3 cells by remodeling the cytoskeleton structure and downregulating major structural proteins and cell cycle regulators.

Abstract Background Fluid assessment is challenging, and fluid overload poses a significant problem among dialysis patients, with pulmonary oedema being the most serious consequence. Our study aims to develop a simple objective fluid assessment strategy using lung ultrasound (LUS) and artificial intelligence (AI) to assess the fluid status of dialysis patients. Methods This was a single-centre study of 76 hemodialysis and peritoneal dialysis patients carried out between July 2020 to May 2022. The fluid status of dialysis patients was assessed via a simplified 8-point LUS method using a portable handheld ultrasound device (HHUSD), clinical examination and bioimpedance analysis (BIA). The primary outcome was the performance of 8-point LUS using a portable HHUSD in diagnosing fluid overload compared to physical examination and BIA. The secondary outcome was to develop and validate a novel AI software program to quantify B-line count and assess the fluid status of dialysis patients. Results Our study showed a moderate correlation between LUS B-line count and fluid overload assessed by clinical examination (r = 0.475, p

A historical investigation is a kind of inquiry-based learning, aiming to guide students’ reading and analyzing processes of historical text to enhance the historical thinking. For this reason, a Digital Humanities Research Platform for Mr. Lo Chia-Lun’s Writings (DHRP-MLCLW) with Perspective Change and Chronological Division Tool (PCCDT) is used for assisting senior high school students in inquiry-based learning activities of history course. It is expected to help learners understand historical investigation issues from different perspectives and aspects as well as enhance learners’ understanding and inquiry abilities of interpreting historical text and context. With a pre-experimental research design, a total of 13 Grade 10 students in a senior high school in Taipei City, Taiwan, were recruited as the research participants for DHRP-MLCLW with PCCDT supported history inquiry course to examine whether learners significantly promote inquiry-based learning performance and to investigate students’ learning satisfaction. Furthermore, lag sequential analysis (LSA) is applied to explore the effective behavior transition mode of learners with high learning performance. Semi-structured interview is also utilized for understanding learners’ perception and suggestions about using the DHRP-MLCLW with PCCDT for history inquiry course. The research results show that DHRP-MLCLW with PCCDT supported history inquiry course could effectively enhance learners’ learning performance and led to highly positive learning satisfaction. Moreover, the LSA results reveal that compared with the learners with low learning performance, the behavioral patterns among those with high learning performance using the DHRP-MLCLW with PCCDT for inquiry-based historical investigation better reflect the spirit of inquiry-based learning.

In recent years, many university libraries have begun to develop scholar repositories or academic hubs that can present institutional research results from an author’s perspective instead of the perspective of articles used in the most current institutional repository systems. Accordingly, National Chengchi University Library reshaped the original institutional repository system as an integrated platform called NCCU Academic Hub with a broader range of researcher information, multiple and visualized functions, and an author’s perspective on researcher information for more effectively spreading academic research outcomes. In order to understand the user behavior of this platform, this study used xAPI to record the users’ operation historical processes, and through user behavior analysis, we hope to understand the behavior characteristics and behavior transfer patterns of users in general, users in different regions, and users with high or low download frequency of papers. The analysis is valuable for understanding how users operate the platform, how to improve the service model of this platform, and how to optimize the web pages and functional design of this platform.

Abstract Purpose Ataxia telangiectasia mutated (ATM) is a key mediator of the DNA damage response, and several ATM inhibitors (ATMi) are currently undergoing early phase clinical trials for the treatment of cancer. A radiolabelled ATMi to determine drug pharmacokinetics could assist patient selection in a move towards more personalised medicine. The aim of this study was to synthesise and investigate the first 18F-labelled ATM inhibitor [18F]1 for non-invasive imaging of ATM protein and ATMi pharmacokinetics. Methods Radiofluorination of a confirmed selective ATM inhibitor (1) was achieved through substitution of a nitro-precursor with [18F]fluoride. Uptake of [18F]1 was assessed in vitro in H1299 lung cancer cells stably transfected with shRNA to reduce expression of ATM. Blocking studies using several non-radioactive ATM inhibitors assessed binding specificity to ATM. In vivo biodistribution studies were performed in wild-type and ATM-knockout C57BL/6 mice using PET/CT and ex vivo analysis. Uptake of [18F]1 in H1299 tumour xenografts was assessed in BALB/c nu/nu mice. Results Nitro-precursor 2 was synthesised with an overall yield of 12%. Radiofluorination of 2 achieved radiochemically pure [18F]1 in 80 ± 13 min with a radiochemical yield of 20 ± 13% (decay-corrected) and molar activities up to 79.5 GBq/μmol (n = 11). In vitro, cell-associated activity of [18F]1 increased over 1 h, and retention of [18F]1 dropped to 50% over 2 h. [18F]1 uptake did not correlate with ATM expression, but could be reduced significantly with an excess of known ATM inhibitors, demonstrating specific binding of [18F]1 to ATM. In vivo, fast hepatobiliary clearance was observed with tumour uptake ranging 0.13–0.90%ID/g after 1 h. Conclusion Here, we report the first radiofluorination of an ATM inhibitor and its in vitro and in vivo biological evaluations, revealing the benefits but also some limitations of 18F-labelled ATM inhibitors.

BackgroundStudies have investigated the effects of achievement goals on learning interests and mathematics performance above the elementary-school level. However, few studies have explored this topic among kindergarteners based on sound theoretical frameworks.MethodsThrough the enrollment of 15 kindergarten teachers and 180 kindergarteners, this study re-validated newly developed measurements of kindergarteners’ achievement goals and learning interests and used these measures to further clarify the effects of achievement goals on learning interests and mathematics performances using structural equation modeling.ResultsThe results indicate that (1) task-approach goals have positive effects on situational interest and advanced arithmetic performance, whereas task-avoidance goals have positive effects on individual interest. (2) Self-based goals have null effects on most learning interests and mathematics performance, but they have significant negative effects on numbering and counting performance. However, most of these null effects represent negative tendencies. (3) Other-approach goals have positive effects on situational interest and basic arithmetic performance, whereas other-avoidance goals have null effects on these outcomes but have an almost significant positive effect on numbering and counting performance. (4) Task-based goals and self-approach goals are generally beneficial for learning interests and mathematics performance.ConclusionThese results suggest that task-based goals and other-approach goals may be implemented with consideration of the potential long-term detrimental effects of social comparison on learning outcomes. Furthermore, possible negative effects of self-based goals must be monitored to prevent them from undermining learning outcomes. This study revealed consistent, inconsistent, and new evidence that, respectively, verifies, complements, and contradicts findings on the learning outcomes of students above the elementary-school level.

Background: Degenerative rotator cuff tears and osteoarthritis (OA) are associated with differences in coronal plane scapular morphology, with particular focus on the effect of the critical shoulder angle (CSA) on shoulder biomechanics. The effect, if any, of axial plane scapular morphology is less well established. We have noticed wide disparity of axial coracoid tip position in relation to the face of the glenoid and sought to investigate the significance of this through measurement of the critical coracoid process angle (CCPA), which incorporates coracoid tip position and glenoid version. Methods: CCPA, CSA, and glenoid retroversion were measured by three independent reviewers from the cross-sectional two-dimensional computed tomography (CT) and magnetic resonance imaging of 160 patients in four equal and matched case-control groups: (1) a control group of patients with a radiologically normal shoulder and no history of shoulder symptoms who had a CT thorax for another reason, (2) patients with primary OA with Walch type-A glenoid wear pattern on CT scan, (3) patients with type-B glenoid primary OA, and (4) patients with magnetic resonance imaging–proven atraumatic tears of the posterosuperior rotator cuff. Results: Interobserver agreement was excellent for all measured parameters. The median CCPA was significantly lower in the type-B OA group (9.3˚) than that in controls (18.7˚), but not significantly different in the other study groups. There was a trend toward greater glenoid retroversion in the type-B OA group, but receiver operating characteristic curve analysis demonstrated the CCPA to be by far the most powerful discriminator for type-B OA. The optimal cutoff value was calculated for the CCPA at 14.3˚ with a sensitivity of 93% and specificity of 90% for type-B OA. Compared with controls, the CSA was significantly higher in the rotator cuff tear group and lower in both OA groups, but did not differentiate between type-A and type-B OA. Conclusion: Combined with a lower CSA, a lower CCPA (

Background: According to the World Health Organization (WHO), as of April 9, 2022, there had been 494,587,638 confirmed COVID-19 cases and 6,170,283 deaths reported worldwide. In Hong Kong, in recent outbreak, ~55% of confirmed cases were residential care home (RCH) residents and >800 staff were infected. In 2016, ~15% of people aged ≥80 years were living in residential care homes. Objectives: To assess healthcare worker (HCW) knowledge level and attitudes about PPE use in residential care homes. Methods: This cross-sectional study, included participants who worked in the residential care homes, registered as healthcare workers (HCWs). HCWs who were part-time staff or worked

Abstract We demonstrate a simple and compact approach to laser cool and trap atoms based on laser-induced thermal ablation (LITA) of a pure solid granule. A rapid thermalisation of the granule leads to a fast recovery of the ultra-high vacuum condition required for a long trapping lifetime of the cold gas. We give a proof-of-concept of the technique, performing a magneto-optical trap on the 461 nm $$^1S_0\rightarrow \,^1P_1$$ 1 S 0 → 1 P 1 transition of strontium. We get up to 3.5 million of cold strontium-88 atoms with a trapping lifetime of more than 4 s. The lifetime is limited by the pressure of the strontium-free residual background vapour. We also implement an original configuration of permanent magnets to create the quadruple magnetic field of the magneto-optical trap. The LITA technique can be generalized to other atomic elements such as transition metals and lanthanide atoms, and shows a strong potential for applications in quantum technologies ranging from quantum computing to precision measurements such as outdoor inertial sensing.

The purpose of this study is to investigate the reciprocal longitudinal effects between mobile phone dependence and school adaptation among Korean adolescents, controlling for sociodemographic characteristics. An autoregressive cross-lagged model was applied to a data set from a sample of 1659 adolescents from the Korean Children and Youth Panel Survey conducted by the National Youth Policy Institute. We found that the positive autoregressive effects of mobile phone dependence and school adaptation were statistically significant over the study period. Results from the cross-lagged analyses demonstrated a unidirectional relationship between two variables: Superior school adaptation decreased mobile phone dependence, but mobile phone dependence did not affect school adaptation. Thus, we identified the causal direction and reciprocal relationship between mobile phone dependence and school adaptation. Girls were found to have a higher level of mobile phone dependence than boys did. Furthermore, the higher the household income, the better adolescents adapted to school. Child abuse and neglect played a role in increasing mobile phone dependence and negatively affected school adaptation.