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The acquisition of the phage-encoded superantigen ssa by scarlet fever-associated group A Streptococcus (Streptococcus pyogenes , GAS) is found in North Asia. Nonetheless, the impact of acquiring ssa by GAS in invasive infections is unclear. This study initially analyzed the prevalence of ssa + GAS among isolates from sterile tissues and blood. Among 220 isolates in northern Taiwan, the prevalence of ssa + isolates increased from 1.5% in 2008–2010 to 40% in 2017–2019. Spontaneous mutations in covR / covS , which result in the functional loss of capacity to phosphorylate CovR, are frequently recovered from GAS invasive infection cases. Consistent with this, Phostag western blot results indicated that among the invasive infection isolates studied, 10% of the ssa + isolates lacked detectable phosphorylated CovR. Transcription of ssa is upregulated in the covS mutant. Furthermore, in emm 1 and emm 12 covS mutants, ssa deletion significantly reduced their capacity to grow in human whole blood. Finally, this study showed that the ssa gene could be transferred from emm 12-type isolates to the emm 1-type wild-type strain and covS mutants through phage infection and lysogenic conversion. As the prevalence of ssa + isolates increased significantly, the role of streptococcal superantigen in GAS pathogenesis, particularly in invasive covR/covS mutants, should be further analyzed. [ABSTRACT FROM AUTHOR]

Background: Head-to-head comparison of clinical effectiveness between dulaglutide and liraglutide in Asia is limited. This study was aimed to assess the real-world comparative effectiveness of dulaglutide versus liraglutide. Methods: We conducted a retrospective cohort study by utilizing multi-institutional electronic medical records to identify real-world type 2 diabetes patients treated with dulaglutide or liraglutide during 2016–2018 in Taiwan and followed up until 2019. Effectiveness outcomes were assessed at every 3 months in the 1-year follow-up. Propensity score techniques were applied to enhance between-group comparability. Significant differences in changes of effectiveness outcomes between treatment groups during the follow-up were examined and further analyzed using mixed-model repeated-measures approaches. Results: A total of 1512 subjects receiving dulaglutide and 1513 subjects receiving liraglutide were identified. At 12 months, significant HbA1c changes from baseline were found in both treatments (dulaglutide: − 1.06%, p < 0.001; liraglutide: − 0.83%, p < 0.001), with a significant between-group difference (− 0.23%, 95% confidence interval − 0.38 to − 0.08%, p < 0.01). Both treatments yielded significant declines in weight, alanine aminotransferase level, and estimated glomerular filtration rate from baseline (dulaglutide: − 1.14 kg, − 3.08 U/L and − 2.08 mL/min/1.73 m2, p < 0.01; liraglutide: − 1.64 kg, − 3.65 U/L and − 2.33 mL/min/1.73 m2, p < 0.001), whereas only dulaglutide yielded a significant systolic blood pressure reduction (− 2.47 mmHg, p < 0.001). Between-group differences in changes of weight, blood pressure, and liver and renal functions at 12 months were not statistically significant. Conclusions: In real-world T2D patients, dulaglutide versus liraglutide was associated with better glycemic control and comparable effects on changes of weight, blood pressure, and liver and renal functions. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis , kills over 1 million people worldwide annually. Development of drug resistance (DR) in the pathogen is a major challenge for TB control. We conducted whole-genome analysis of seven Taiwan M. tuberculosis isolates: One drug susceptible (DS) and five DR Beijing lineage isolates and one DR Euro-American lineage isolate. Developing a new method for DR mutation identification and applying it to the next-generation sequencing (NGS) data from the 6 Beijing lineage isolates, we identified 13 known and 6 candidate DR mutations and provided experimental support for 4 of them. We assembled the genomes of one DS and two DR Beijing lineage isolates and the Euro-American lineage isolate using NGS data. Moreover, using both PacBio and NGS sequencing data, we obtained a high-quality assembly of an extensive DR Beijing lineage isolate. Comparative analysis of these five newly assembled genomes and two published complete genomes revealed a large number of genetic changes, including gene gains and losses, indels and translocations, suggesting rapid evolution of M. tuberculosis. We found the MazEF toxin–antitoxin system in all the seven isolates studied and several interesting mutations in MazEF proteins. Finally, we used the four assembled Beijing lineage genomes to construct a high-quality Beijing lineage reference genome that is DS and contains all the genes in the four genomes. It contains 212 genes not found in the standard reference H37Rv, which is Euro-American. It is therefore a better reference than H37Rv for the Beijing lineage, the predominant lineage in Asia. [ABSTRACT FROM AUTHOR]

Tinnitus and hearing impairment are prevalent among headache patients. This study aims to investigate the risk of tinnitus, sensorineural hearing impairment, and sudden deafness in patients with non-migraine headache. Participants included 43 294 patients with non-migraine headache (non-migraine headache cohort) and 173 176 patients with no headache of any type (control cohort) frequency-matched with respect to 10-year age interval and sex from the Longitudinal Health Insurance Database 2005 of the Taiwan National Health Insurance Research Database. The mean age of the non-migraine headache cohort was 28.4 ± 14.9 years, and 58.5% of this cohort was male. The incidence rates of tinnitus, sensorineural hearing impairment, and sudden deafness were compared between cohorts using the Kaplan–Meier method with the log-rank test. A Cox proportional hazard model was used to examine the association of tinnitus, sensorineural hearing impairment, and sudden deafness with non-migraine headache, with adjustment for all covariates. The combined risk of either tinnitus, sensorineural hearing impairment, or sudden deafness was higher in the non-migraine headache cohort than in the control cohort (adjusted odds ratio [aHR], 2.73; 95% confidence interval [95% CI], 2.62–2.84; p < 0.0001). Subgroup analysis showed that patients in the non-migraine headache cohort were at significantly higher risk of developing tinnitus (aHR, 3.05; 95% CI, 2.91–3.19; p < 0.0001), sensorineural hearing impairment (aHR, 1.89; 95% CI, 1.74–2.05; p < 0.0001), and sudden deafness (aHR, 2.14; 95% CI, 1.77–2.59; p < 0.0001) than were controls. In this population-based study, the risks of tinnitus, sensorineural hearing impairment, and sudden deafness were found to be significantly higher in patients with non-migraine headache than in those without headache. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the association between tonsillitis and the risk of newly diagnosed ankylosing spondylitis (AS). Methods: We used 2003–2012 data from Taiwan’s National Health Insurance Research Database to conduct this nationwide, population-based, case-control study. We identified AS patients newly diagnosed between 2005 to 2012 as the study group and selected age, sex and index-year matched (1:6) non-AS individuals as controls. The association between tonsillitis and risk of newly diagnosed AS was determined by calculating odds ratios (ORs) with 95% confidence intervals (CIs) using conditional logistic regression analysis. Results: We identified 37,002 newly diagnosed AS cases and 222,012 matched non-AS controls. Patients with AS were more likely to have tonsillitis (aOR 1.46, 95% CI 1.43–1.50), appendicitis (aOR 1.29, 95% CI 1.13–1.48) and periodontitis (aOR 1.35, 95% CI 1.31–1.38) than non-AS control subjects. The association between tonsillitis and AS was consistent using varying definitions for tonsillitis, and we further found that a high frequency of visits for tonsillitis, a high medical cost for tonsillitis and a long interval between diagnosis were associated with newly diagnosed AS in a dose-response manner. Furthermore, the association between tonsillitis and AS appeared to be stronger in females (aOR 1.59, 95% CI 1.53–1.65) than those in males (aOR 1.39, 95% CI 1.35–1.44). Conclusions: The present study revealed an association between AS risk and prior tonsillitis and indicates the need for vigilance of AS-associated symptoms in patients who had been diagnosed with tonsillitis, particularly in females. [ABSTRACT FROM AUTHOR]

Numerical simulation has been widely applied to the assessment of debris flow hazards. In East Asia and especially Taiwan, the most widely used numerical programs are FLO-2D and Debris-2D. Although these two programs are applied to the same engineering tasks, they are different in many aspects. These two programs were compared according to their fundamental theories, input and output data, computational algorithms and results. Using both programs, the simulations of a real debris flow with abundant granular material induced by landslides at Xinfa village in southern Taiwan are performed for comparison. The simulation results show that Debris-2D gives better assessment in hazard area delineating and flow depth predicting. Therefore, Debris-2D is better for simulation of granular debris flows. [ABSTRACT FROM AUTHOR]

Background: Genotype I (GI) Japanese encephalitis virus (JEV) that replaced GIII virus has become the dominant circulating virus in Asia. Currently, all registered live and inactivated JEV vaccines are derived from genotype III viruses. In Taiwan, the compulsory JEV vaccination policy recommends that children receives four doses of formalin-inactivated Nakayama (GIII) JEV vaccine. Methodology/Principal Findings: To evaluate the influence of genotype replacement on the post-vaccination viral neutralizing ability by GIII and GI viruses, the small panel of vaccinated-children serum specimens was assembled, and the reciprocal 50% plaque-reduction neutralizing antibody titers (PRNT50) were measured against Nakayama vaccine strain, CJN GIII human brain isolate and TC2009-1 GI mosquito isolate. The seropositivity rate (PRNT50≥1∶10) and geometric mean titers (GMT) against the TC2009-1 virus were the lowest among the three viruses. The protective threshold against the CJN and TC2009-1 viruses could only be achieved when the GMT against Nakayama virus was ≥1∶20 or ≥1∶80, respectively. Using undiluted vaccinees' sera, the enhancement of JEV infection in K562 cells was observed in some low or non-neutralizing serum specimens. Conclusions/Significance: Our preliminary study has shown that neutralizing antibodies, elicited by the mouse brain-derived and formalin-inactivated JEV Nakayama vaccine among a limited number of vaccinees, have reduced neutralizing capacity against circulating GI virus, but more detailed studies are needed to address the potential impact on the future vaccine policy. Author Summary: Genotype I (GI) Japanese encephalitis virus (JEV) that replaced GIII virus has become the dominant circulating virus in Asia; however, all available JEV vaccines are derived from genotype III viruses, and no study has been conducted on the cross-neutralization and protection elicited by GIII JEV vaccines against GI viruses using vaccinated children's serum specimens collected from the general population. Genotype I virus was first detected in Taiwan in 2008, and became the dominant circulating JEV, and was island-wide within a year. In the present study, the small panel of GIII virus vaccinated-children serum specimens were not only showed lower strain-specific neutralization against GI virus as compared to the GIII vaccine and human isolates but also observed the enhancement of GI virus infection in K562 cells in some low or non-neutralizing serum specimens. These preliminary results indicated the reduced neutralization potency due to genotype replacement should be closely monitored in the JE epidemic/endemic regions in the future. [ABSTRACT FROM AUTHOR]

Dengue fever is the most serious vector-borne disease in Asia. There are still no dengue vaccines or therapeutic drugs, and vector-mosquito control is the main prevention and treatment method. The prevention and control of dengue-fever vector mosquitoes in Taiwan is still dominated by larval control. However, the removal of the source of mosquito-borne diseases has not been fully implemented, and the removal process of vector-borne mosquitoes cannot keep up with their breeding rate. In addition, chemical agents used in the elimination of pathogenic mosquitoes may cause mosquito resistance and environmental pollution. Therefore, it is important to develop new prevention and control technologies. This study is dedicated to the development of a mosquito trapping optical system with high efficiency and low glare that is safe for humans. The system is mainly equipped with ultraviolet light-emitting diodes (UV-LED), a freeform-surfaced optical reflector, and a photocatalyst. The reflector can lead light downward for the protection of user eyes, and expand the range of trapping mosquitoes to 225 π m2. Based on practical experiments, captured mosquitoes increased by about 450% through the proposed system compared to conventional traps using UV LED. In addition, the proposed system is shown to be 45% more enhanced in trapping capability after a photocatalyst (titanium dioxide) coating is applied to its reflector. [ABSTRACT FROM AUTHOR]

Abstract: Metropolitan Taipei, which is located in the subtropical area, is characterized by high population and automobile densities. For convenience, most primary schools are located near major roads. This study explores the exposure of acid aerosols for schoolchildren in areas in Taipei with different traffic densities. Acid aerosols were collected by using a honeycomb denuder filter pack sampling system (HDS). Experimental results indicated that the air pollutants were significantly correlated with traffic densities. The ambient air NO2, SO2, HNO3, NO3 −, SO4 2−, and aerosol acidity concentrations were 31.3 ppb, 4.7 ppb, 1.3 ppb, 1.9 μg m−3, 18.5 μg m−3, and 49.5 nmol m−3 in high traffic density areas, and 6.1 ppb, 1.8 ppb, 0.9 ppb, 0.7 μg m−3, 8.8 μg m−3 and 14.7 nmol m−3 in low traffic density areas. The exposure levels of acid aerosols for schoolchildren would be higher than the measurements because the sampling height was 5 m above the ground. The SO2 levels were low (0.13–8.03 ppb) in the metropolitan Taipei. However, the SO4 2− concentrations were relatively high, and might be attributed to natural emissions of sulfur-rich geothermal sources. The seasonal variations of acid aerosol concentrations were also observed. The high levels of acidic particles in spring time may be attributed to the Asian dust storm and low height of the mixture layer. We conclude that automobile contributed not only the primary pollutants but also the secondary acid aerosols through the photochemical reaction. Schoolchildren were exposed to twice the acid aerosol concentrations in high traffic density areas compared to those in low traffic density areas. The incidence of allergic rhinitis of schoolchildren in the high traffic density areas was the highest in spring time. Accompanied by high temperature variation and high levels of air pollution in spring, the health risk of schoolchildren had been observed. [Copyright &y& Elsevier]

High-quality cardiopulmonary resuscitation (CPR) is a key element in out-of-hospital cardiac arrest (OHCA) resuscitation. Mechanical CPR devices have been developed to provide uninterrupted and high-quality CPR. Although human studies have shown controversial results in favor of mechanical CPR devices, their application in pre-hospital settings continues to increase. There remains scant data on the pre-hospital use of mechanical CPR devices in Asia. Therefore, we conducted a retrospective cohort study between September 2018 and August 2020 in an urban city of Taiwan to analyze the effects of mechanical CPR devices on the outcomes of OHCA; the primary outcome was attainment of return of spontaneous circulation (ROSC). Of 552 patients with OHCA, 279 received mechanical CPR and 273 received manual CPR, before being transferred to the hospital. After multivariate adjustment for the influencing factors, mechanical CPR was independently associated with achievement of any ROSC (OR = 1.871; 95%CI:1.195-2.930) and sustained (≥24 h) ROSC (OR = 2.353; 95%CI:1.427-3.879). Subgroup analyses demonstrated that mechanical CPR is beneficial in shorter emergency medical service response time (≤4 min), witnessed cardiac arrest, and non-shockable cardiac rhythm. These findings support the importance of early EMS activation and high-quality CPR in OHCA resuscitation.

We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA. We analyzed GWAS-data from Taiwan, Shanghai, and Shenyang (1472 cases; 1497 controls), as well as a separate study conducted in Xuanwei (152 cases; 522 controls) for additional analyses. We summarized genetic susceptibility using a polygenic risk score (PRS), which was the weighted sum of the risk-alleles from the 10 previously identified loci. We estimated associations between a PRS, coal use (ever/never), and lung adenocarcinoma with multivariable logistic regression models, and evaluated potential gene-environment interactions using likelihood ratio tests. There was a strong association between continuous PRS and lung adenocarcinoma among never coal users (Odds Ratio (OR) = 1.69 (95% Confidence Interval (CI) = 1.53, 1.87), p=1 × 10 - 26 ). This effect was attenuated among ever coal users (OR = 1.24 (95% CI: 1.03, 1.50), p = 0.02, p-interaction = 6 × 10 -3 ). We observed similar attenuation among coal users from Xuanwei. Our study provides evidence that genetic susceptibility to lung adenocarcinoma among never-smoking Asian women is weaker among coal users. These results suggest that lung cancer pathogenesis may differ, at least partially, depending on exposure to coal combustion products. Notably, these novel findings are among the few instances of sub-multiplicative gene-environment interactions in the cancer literature., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Chronic pain (CP) may increase the risk for major adverse cardiac and cerebrovascular events (MACCEs); however, this issue is still unclear in the Asian population. We conducted this study to delineate it., Design: From the Taiwan National Health Insurance Research Database, we identified 17,614 participants (<65 years) with CP and matched them by age and sex at a 1:2 ratio to participants without CP, who made up the comparison cohort. Several causes of CP and its underlying comorbidities were also analyzed., Outcome Measure: A comparison of MACCE occurring in the two cohorts was performed via follow-up until 2015., Results: The mean age (SD) was 50.2 (11.5) years and 50.4 (11.7) years in participants with and without CP, respectively. In both cohorts, the percentage of female participants was 55.5%. Common causes of CP were spinal disorders (23.9%), osteoarthritis (12.4%), headaches (11.0%), gout (10.2%), malignancy (6.2%), and osteoporosis (4.5%). After adjusting for hypertension, diabetes, chronic obstructive pulmonary disease, renal diseases, hyperlipidemia, liver diseases, dementia, and depression, participants with CP had a higher risk for MACCE than those without CP (adjusted hazard ratio [AHR] = 1.3, 95% confidence interval [CI] = 1.3 - 1.4). After conducting subgroup analyses, an increased risk was also found for all-cause mortality (AHR = 1.4, 95% CI = 1.1 - 1.8), acute myocardial infarction (AHR = 1.2, 95% CI = 1.0 - 1.4), and stroke (AHR = 1.3, 95% CI = 1.3 - 1.4)., Conclusions: CP is associated with increased occurrence of MACCE. Early detection and interventions for CP are suggested., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)