A Study to Evaluate Accuracy and Validity of the EFAI Computer-Aided Bone Age Diagnosis System Compared With Qualified Physicians.

Study Objectives: In previous research, we built a deep neural network model based on Inception-Resnet-v2 to predict bone age (EFAI-BAA). The primary objective of the study was to determine if the EFAI-BAA was substantially concordant with the qualified physicians in assessing bone ages. The secondary objective of the study was to determine if the EFAI-BAA was no different in the clinical rating (advanced, normal, or delayed) with the qualified physicians. Method: This was a retrospective study. The left-hand X-ray images of male subjects aged 3-16 years old and female subjects aged 2-15 years old were collected from China Medical University Hospital (CMUH) and Asia University Hospital (AUH) retrospectively since the trial began until the included image amount reached 368. This was a blinded study. The qualified physicians who ran, read, and interpreted the tests were blinded to the values assessed by the other qualified physicians and the EFAI-BAA. Results: The concordance correlation coefficient (CCC) between the EFAI-BAA (EFAI-BAA), the evaluation of bone age by physician in Kaohsiung Veterans General Hospital (KVGH), Taichung Veterans General Hospital (TVGH2), and in Taipei Tzu Chi Hospital (TZUCHI-TP) was 0.9828 (95% CI: 0.9790-0.9859, p-value = 0.6782), 0.9739 (95% CI: 0.9681-0.9786, p-value = 0.0202), and 0.9592 (95% CI: 0.9501-0.9666, p-value = 0.4855), respectively. Conclusion: There was a consistency of bone age assessment between the EFAI-BAA and each one of the three qualified physicians (CCC = 0.9). As the significant difference in the clinical rating was only found between the EFAI-BAA and the qualified physician in TVGH2, the performance of the EFAI-BAA was considered similar to the qualified physicians.

Association of Metabolic Syndrome with Aerobic Exercise and LPL rs3779788 Polymorphism in Taiwan Biobank Individuals.

PURPOSE: The Lipoprotein lipase (LPL) gene is a significant contributor to dyslipidemia. It has shown associations with several conditions including atherosclerosis, obesity, and metabolic syndrome (MetS). We assessed the interactive association between MetS and rs3779788 of the LPL gene based on aerobic exercise. MATERIALS AND METHODS: Data were available for 7532 Taiwan Biobank (TWB) participants recruited between 2008 and 2016. We used multiple logistic regression to determine the odds ratios (OR) for MetS and their 95% confident intervals (C.I.). Potential variables included LPL rs3779788, aerobic exercise, sex, age, education, marital status, body mass index (BMI), smoking, alcohol consumption, midnight snacking, vegetarian diet, coffee, dietary fat, and tea drinking. RESULTS: Aerobic exercise was protective against MetS (OR, 0.858; 95% C.I., 0.743-0.991). Compared to CC/CT genotype, the OR for developing MetS was 0.875, (95% C.I., 0.571-1.341) in TT individuals. The test for interaction was significant for the rs3779788 variant and aerobic exercise (p = 0.0484). In our group analyses, the OR for MetS was 0.841 (95% C.I., 0.727-0.974) in CC/CT and 4.076 (95% C.I., 1.158-14.346) in TT individuals who did aerobic exercise compared to those who did not. CONCLUSION: Our study indicated that aerobic exercise improved metabolic syndrome in Taiwanese adults with rs3779788 CC/CT genotype relative to those with TT genotype.

Usefulness of multi-labelling artificial intelligence in detecting rhythm disorders and acute ST-elevation myocardial infarction on 12-lead electrocardiogram.

Aims: To develop an artificial intelligence-based approach with multi-labelling capability to identify both ST-elevation myocardial infarction (STEMI) and 12 heart rhythms based on 12-lead electrocardiograms (ECGs). Methods and results: We trained, validated, and tested a long short-term memory (LSTM) model for the multi-label diagnosis of 13 ECG patterns (STEMI + 12 rhythm classes) using 60 537 clinical ECGs from 35 981 patients recorded between 15 January 2009 and 31 December 2018. In addition to the internal test above, we conducted a real-world external test, comparing the LSTM model with board-certified physicians of different specialties using a separate dataset of 308 ECGs covering all 13 ECG diagnoses. In the internal test, the area under the curves (AUCs) of the LSTM model in classifying the 13 ECG patterns ranged between 0.939 and 0.999. For the external test, the LSTM model for multi-labelling of the 13 ECG patterns evaluated by AUC was 0.987 ± 0.021, which was superior to those of cardiologists (0.898 ± 0.113, P < 0.001), emergency physicians (0.820 ± 0.134, P < 0.001), internists (0.765 ± 0.155, P < 0.001), and a commercial algorithm (0.845 ± 0.121, P < 0.001). Of note, the LSTM model achieved an accuracy of 0.987, AUC of 0.997, and precision, recall, and F 1 score of 0.952, 0.870, and 0.909, respectively, in detecting STEMI. Conclusions: We demonstrated the usefulness of an LSTM model in the multi-labelling detection of both rhythm classes and STEMI in competitive testing against board-certified physicians. This AI tool exceeding the cardiologist-level performance in detecting STEMI and rhythm classes on 12-lead ECG may be useful in prioritizing chest pain triage and expediting clinical decision-making in healthcare.

Combination of Exercise and Vegetarian Diet: Relationship with High Density-Lipoprotein Cholesterol in Taiwanese Adults Based on MTHFR rs1801133 Polymorphism.

We examined the association between high-density lipoprotein cholesterol (HDL-C), and exercise and vegetarian diets, in Taiwanese adults, based on the Methylenetetrahydrofolate reductase (MTHFR) rs1801133 polymorphism. Using regression models, we analyzed historical data collected from 9255 Taiwan Biobank (TWB) participants from 2008 through 2015. Exposure to exercise was associated with higher HDL-C (ß = 1.0508 and 1.4011 for GG and GA + AA individuals, respectively), whereas a vegetarian diet was associated with lower HDL-C (ß = -6.2793 and -4.6359 for those with GG and GA + AA genotype, respectively). We found an interaction between exercise and diet among GG individuals (p = 0.0101). Compared with no exercise/no vegetarian diet, vegetarian diet/no exercise was associated with a 5.1514 mg/dl reduction in HDL-C among those with GG genotype (ß = -5.1514, p < 0.0001) and a 4.8426 mg/dl reduction (ß = -4.8426, p < 0.0001) among those with GA + AA genotype. Vegetarian diets in combination with exercise predicted a 6.5552 mg/dl reduction in HDL-C among GG individuals (ß = -6.5552) and a 2.8668 mg/dl reduction among GA + AA individuals (p < 0.05). These findings demonstrated that vegetarian diet alone was associated with lower HDL-C, no matter the rs1801133 genotype. However, the inclusion of regular exercise predicted much lower levels among GG individuals, whereas levels among GA + AA individuals were relatively higher.

The Impact of Aerobic Exercise and Badminton on HDL Cholesterol Levels in Taiwanese Adults.

Elevated levels of high-density lipoprotein cholesterol (HDL-C) have been associated with a decreased risk of coronary heart disease (CHD). An active lifestyle is necessary to improve HDL-C, including (but not limited to) physical exercise. Research on the association between badminton, an intermittent exercise, and HDL-C is limited. We investigated the impact of aerobic exercise and badminton on HDL-C levels in Taiwanese adults. The sociodemographic data of 7543 participants, comprising 3472 men and 4071 women aged between 30 and 70 years, were retrieved from the Taiwan Biobank. The participants were grouped into three exercise categories-no exercise, aerobic exercise, and badminton exercise. The HDL-C levels were compared using an analysis of variance (ANOVA). Multivariate linear regression models were used to determine the associations between HDL and exercise. Comparing the other two groups to the no-exercise group, the individuals who were engaged in aerobic and badminton exercise were significantly associated with higher HDL-C levels (ß = 1.4077; p < 0.0001 and ß = 5.6052; p = 0.0079, respectively). Aerobic exercise and badminton were also associated with higher HDL-C levels among carriers of the lipoprotein lipase (LPL) rs328 genotypes. Aerobic exercise and regular badminton were associated with higher levels of HDL-C, with the badminton group being more significant.

Vegetarian Diets along with Regular Exercise: Impact on High-Density Lipoprotein Cholesterol Levels among Taiwanese Adults.

Background and objectives: High-density lipoprotein cholesterol (HDL-C) is important for improving risk estimates of atherosclerotic cardiovascular disease. We investigated the effect of omnivore and diverse vegetarian diets in connection with exercise on HDL-C. Materials and Methods: Historical data of 9588 biobank participants (4025 exercisers and 5563 non-exercisers) aged 30-70 years were categorized as omnivores (n = 8589), former vegetarians (n = 544), lacto-ovo vegetarians (n = 417), and strict vegetarians (n = 38). We used multiple linear regression for analyses. Results: HDL-C levels were higher in exercisers compared to non-exercisers. Compared with omnivores, strict vegetarians had decreased levels of HDL-C (ß = -5.705; p = 0.001) followed by lacto-ovo vegetarians (ß = -3.900; p < 0.001) and former vegetarians (ß = -0.329; p = 0.475). The test for trend was significant (p < 0.001). After categorization by exercise modalities, the ß-value was -13.984 for strict vegetarians, -4.419 for lacto-ovo vegetarians, and -1.864 for former vegetarians, respectively (p < 0.05). There was an interaction between diet and exercise (p = 0.009). Omnivores who exercised regularly had significantly higher HDL-C, whereas strict vegetarians who exercised regularly had significantly lower HDL-C. Conclusions: In summary, strict vegetarian diets in conjunction with regular exercise might not serve as healthful behaviors to be implemented in everyday life considering the negative impact on HDL-C.

Blood-Based SOX2-Promoter Methylation in Relation to Exercise and PM2.5 Exposure among Taiwanese Adults.

Increased ventilation during exercise in polluted areas could trigger airway inflammation. We evaluated blood DNA methylation of the SOX2-promoter region in relation to exercise and PM2.5 in Taiwanese adults. Data of 948 participants aged 30-70 years were retrieved from the Taiwan Biobank Database (2008-2015) and the Air Quality Monitoring Database (2006-2011). PM2.5 was positively associated with SOX2-promoter methylation (ß = 0.000216; p < 0.0001). The interaction between PM2.5 and exercise on SOX2-promoter methylation was significant (p = 0.0146). After stratification by exercise habits, PM2.5 was positively associated with SOX2 methylation in only individuals who did regular exercise (ß = 0.0003490; p < 0.0001). After stratification by exercise habits and residential areas, SOX2-promoter methylation levels in those who lived in the southern area were higher for both the regular exercise (ß = 0.00272; p = 0.0172) and no regular exercise groups (ß = 0.002610 and p = 0.0162). SOX2-promoter methylation levels in those who lived in the northern area and did regular exercise were lower; ß = -0.00314 (p = 0.0036). In conclusion, PM2.5 was positively associated with SOX2-promoter methylation in participants who did regular exercise. Living in the southern area was positively associated with SOX2-promoter methylation regardless of exercise habits.

Interaction of Osteoarthritis and BMI on Leptin Promoter Methylation in Taiwanese Adults.

Leptin (LEP) regulates glucose metabolism and energy storage in the body. Osteoarthritis (OA) is associated with the upregulation of serum LEP. LEP promoter methylation is associated with obesity. So far, few studies have explored the association of BMI and OA with LEP methylation. We assessed the interaction between body mass index (BMI) and OA on LEP promoter methylation. Data of 1114 participants comprising 583 men and 558 women, aged 30-70 years were retrieved from the Taiwan Biobank Database (2008-2015). Osteoarthritis was self-reported and cases were those who reported having ever been clinically diagnosed with osteoarthritis. BMI was categorized into underweight, normal weight, overweight, and obesity. The mean LEP promoter methylation level in individuals with osteoarthritis was 0.5509 ± 0.00437 and 0.5375 ± 0.00101 in those without osteoarthritis. The interaction between osteoarthritis and BMI on LEP promoter methylation was significant (p-value = 0.0180). With normal BMI as the reference, the mean LEP promoter methylation level was significantly higher in obese osteoarthritic individuals (ß = 0.03696, p-value = 0.0187). However, there was no significant association between BMI and LEP promoter methylation in individuals without osteoarthritis, regardless of BMI. In conclusion, only obesity was significantly associated with LEP promoter methylation (higher levels) specifically in osteoarthritic patients.

Effects of Regular Aerobic Exercise and Resistance Training on High-Density Lipoprotein Cholesterol Levels in Taiwanese Adults.

Increased levels of high-density lipoprotein cholesterol (HDL-C) can improve endothelial function. This may help reduce cardiovascular risks and mortality. Evidence has been provided on the association between cardiometabolic traits, such as HDL-C and exercise modalities. However, there is the absence of studies investigating this association in Taiwan. We assessed the relationship between exercise type and HDL-C among Taiwanese adults. Data were collected from Taiwan Biobank (TWB), a national biomedical research database that contains the genetic information of ethnic Taiwanese residents gathered from 2008 to 2016. We enrolled 24,856 participants aged 30 to 70 years who completed a questionnaire about their recent health behaviors including smoking, drinking, and exercise. Regular exercise was categorized as non-aerobic exercise (separated as weight training, ball game, and mixed exercise) and strict aerobic exercise. Linear regression models were used to assess the effects of exercise in a questionnaire-based manner. After multivariate adjustments, HDL-C was positively associated with aerobic (ß = 1.33748, p < 0.0001) and non-aerobic (ß = 2.56210; p < 0.0001) exercise. Positive associations were also found for resistance training (ß = 4.01828, p = 0.0020), ballgame (ß = 2.43815, p = 0.0001), and mixed exercise (ß = 2.47021, p < 0.0001). This study demonstrated that both aerobic and non-aerobic exercise have positive effects on HDL-C among Taiwanese adults. Among the non-aerobic exercise groups, resistance training had the greatest effect.

Association between Aerobic Exercise and High-Density Lipoprotein Cholesterol Levels across Various Ranges of Body Mass Index and Waist-Hip Ratio and the Modulating Role of the Hepatic Lipase rs1800588 Variant.

Changes in concentrations of high-density lipoprotein cholesterol (HDL-C) are modified by several factors. We examined the relationship between aerobic exercise and HDL-C among different categories of body mass index (BMI) and waist-hip ratio (WHR) and the impact of rs1800588 variant in the hepatic lipase (LIPC) gene. We analyzed data from 6184 men and 8353 women aged 30-70 years. Participants were grouped into two WHR categories: Normal (0 < WHR < 0.9 for men and 0 < WHR < 0.8 for women) and abnormal (WHR ≥ 0.9 for men and WHR ≥ 0.8 for women). The BMI categories were: Underweight (BMI < 18.5 kg/m2), normal weight (18.5 ≤ BMI < 24 kg/m2), overweight (24 ≤ BMI < 27 kg/m2), and obese (BMI ≥ 27 kg/m2). Multivariate linear regression models were used to investigate associations between HDL-C and exercise. Aerobic exercise was significantly associated with higher HDL-C (ß = 1.18325; p < 0.0001) when compared with no exercise. HDL-C was significantly lower in persons with abnormal compared to those with normal WHR (ß = -3.06689; p < 0.0001). Compared with normal weight, overweight and obese categories were associated with lower HDL-C, with ß values of -4.31095 and -6.44230, respectively (p < 0.0001). Unlike rs1800588 CT and TT genotypes, associations between aerobic exercise and HDL were not significant among CC carriers no matter their BMI or WHR.

Methylation at cg05575921 of a smoking-related gene (AHRR) in non-smoking Taiwanese adults residing in areas with different PM2.5 concentrations.

BACKGROUND: DNA methylation is associated with cancer, metabolic, neurological, and autoimmune disorders. Hypomethylation of aryl hydrocarbon receptor repressor (AHRR) especially at cg05575921 is associated with smoking and lung cancer. Studies on the association between AHRR methylation at cg05575921 and sources of polycyclic aromatic hydrocarbon (PAH) other than smoking are limited. The aim of our study was to assess the pattern of blood DNA methylation at cg05575921 in non-smoking Taiwanese adults living in areas with different PM2.5 levels. METHODS: Data on blood DNA methylation, smoking, and residence were retrieved from the Taiwan Biobank dataset (2008-2015). Current and former smokers, as well as individuals with incomplete information were excluded from the current study. The final analysis included 708 participants (279 men and 429 women) aged 30-70 years. PM2.5 levels have been shown to increase as one moves from the northern through central towards southern Taiwan. Based on this trend, the study areas were categorized into northern, north-central, central, and southern regions. RESULTS: Living in PM2.5 areas was associated with lower methylation levels: compared with the northern area (reference area), living in north-central, central, and southern areas was associated with lower methylation levels at cg05575921. However, only methylation levels in those living in central and southern areas were significant (ß = - 0.01003, P = 0.009 and ß = - 0.01480, P < 0.001, respectively. Even though methylation levels in those living in the north-central area were not statistically significant, the test for linear trend was significant (P < 0.001). When PM2.5 was included in the regression model, a unit increase in PM2.5 was associated with 0.00115 (P < 0.001) lower cg05575921 methylation levels. CONCLUSION: Living in PM2.5 areas was inversely associated with blood AHRR methylation levels at cg05575921. The methylation levels were lowest in participants residing in southern followed by central and north-central areas. Moreover, when PM2.5 was included in the regression model, it was inversely associated with methylation levels at cg05575921. Blood methylation at cg05575921 (AHRR) in non-smokers might indicate different exposures to PM2.5 and lung cancer which is a PM2.5-related disease.

Genetic and Non-Genetic Factor-Adjusted Association between Coffee Drinking and High-Density Lipoprotein Cholesterol in Taiwanese Adults: Stratification by Sex.

Low high-density lipoprotein cholesterol (HDL-C) is a major risk factor for cardiovascular diseases (CVDs), the leading cause of global mortality. We aimed to determine the effect of coffee drinking and sex and their interaction, as well as rs1800588 and rs1800775 polymorphisms on HDL-C levels in Taiwanese adults. Data of 4262 men and 4813 women, aged 30-70 years, were retrieved from Taiwan Biobank. The interaction between sex and coffee drinking on HDL-C was significant (p = 0.0452). Coffee consumption was significantly associated with higher HDL-C levels in only women (ß = 0.81679; p = 0.0246). However, rs1800588 and rs1800775 variants were significantly associated with HDL-C in both sexes. In women, ß-values were 0.99080; p = 0.0059 and 3.16277; p < 0.0001 for rs1800588 CT and TT genotypes, respectively and -1.80954; p < 0.0001 and -2.81512; p < 0.0001 for rs1800775 AC and CC genotypes, respectively. In men, ß-values were 1.32430; p < 0.0001 and 3.24976; p < 0.0001 for rs1800775 CT and TT genotypes, respectively and -1.96232; p < 0.0001 and -2.71536, p < 0.0001 for the AC and CC genotypes, respectively. In conclusion, coffee drinking was significantly associated with higher high-density lipoprotein (HDL) levels in women but not men after adjusting for confounders including rs1800588 (LIPC) and rs1800775 (CETP) variants.

SOX2 promoter hypermethylation in non-smoking Taiwanese adults residing in air pollution areas.

BACKGROUND: Both SOX2 promoter methylation and air pollution have been associated with lung cancer risk. However, little has been done to assess SOX2 promoter methylation in individuals living in air pollution areas. The aim of this study was to investigate SOX2 promoter methylation in non-smoking Taiwanese adults living in areas with different levels of air pollution especially particulate matter with diameter < 2.5 µm (PM2.5). METHODS: A total of 1142 individuals aged 30-70 years were recruited. Data on SOX2 methylation, residence, age, and exposure to second-hand smoke (SHS) among others were extracted from the Taiwan Biobank dataset (2008-2015). After excluding former and current smokers, alongside those with incomplete information, a total of 461 non-smokers comprising 176 men and 285 women were included in the study. Participants' residences were grouped under northern and central/southern areas because air pollution (PM2.5) is lower in northern compared to central and southern areas. RESULTS: The methylation levels in men (0.16310 ± 0.01230) and women (0.15740 ± 0.01240) were significantly different (P < .0001). In both sexes, the SOX2 promoter region was shown to be significantly hypermethylated in central and southern areas compared with the northern areas. The regression coefficient (ß) was 0.00331 (P = 0.0257) in men and 0.00514 (P < .0001) in women. CONCLUSION: SOX2 was significantly hypermethylated in both men and women residing in central and southern areas. The consistency in the results for both sexes shows that SOX2 promoter methylation could serve as a potential biomarker for industrial air pollution exposure. Moreover, it might reflect predisposition to cancer. Hence, healthy non-smokers at precancerous stages who have not been clinically diagnosed could be identified.

The Impact of Aerobic Exercise and Badminton on HDL Cholesterol Levels in Adult Taiwanese.

Elevated levels of high-density lipoprotein cholesterol (HDL-C) have been associated with a decreased risk of coronary heart disease (CHD). An active lifestyle is necessary in order to improve lipid HDL-C, including (but not limited to) physical exercise. Research on the association between badminton, an intermittent exercise, and HDL-C is limited. We investigated the impact of aerobic exercise and badminton on HDL-C levels in Taiwanese adults. The sociodemographic data of 7797 participants comprising 3559 men and 4238 women aged between 30 to 70 years were retrieved from the Taiwan Biobank. The participants were grouped into three exercise categories-no exercise, aerobic exercise, and badminton exercise. The HDL-C levels were compared using an analysis of variance (ANOVA). The multivariate linear regression models were used to determine the associations between HDL and exercise. Comparing the other two groups to the no-exercise group, the individuals who were engaged in aerobic and badminton exercise were significantly associated with a higher HDL-C (ß =1.3154; p <0.0001 and ß = 6.5954; p = 0.0027, respectively). Aerobic exercise and badminton were also associated with higher HDL-C levels among carriers of the lipoprotein lipase (LPL) rs328 genotypes. Aerobic exercise and regular badminton were associated with higher levels of HDL-C, with the badminton group being more significant.

Body mass index modulates the association between CDKAL1 rs10946398 variant and type 2 diabetes among Taiwanese women.

CDKAL1 rs10946398 is a type 2 diabetes (T2D)-associated variant. It is a new body mass index (BMI)-associated variant in Asian populations. We investigated the association between rs10946398 and T2D among 9908 participants aged 30-70 years based on BMI: normal weight; 18.5 ≤ BMI < 24 kg/m2, overweight; 24 ≤ BMI < 27 kg/m2, and obesity; BMI ≥27 kg/m2. The CC genotype conferred a higher risk of T2D than the CA genotype. The odds ratios (ORs) were 1.83; 95% confidence interval (CI) 1.49-2.26 and 1.20; 95% CI 1.02-1.40, respectively. The C allele was the significant risk allele compared with A allele (OR = 1.32; 95% CI 1.19-1.47). For normal, overweight and obese participants with CC genotype, the ORs were respectively 1.69; 95% CI 1.02-2.81, 2.34; 95% CI 1.50-3.66, and 1.58; 95% CI 1.02-2.45 among men and 1.22; 95% CI 0.67-2.22, 2.42; 95% CI 1.30-4.52, and 2.3; 95% CI 1.19-4.50 among women. The C allele ORs were higher in obese and overweight women. In conclusion, the rs10946398 CC/CA genotypes, as well as the C allele increased the risk of T2D. The ORs were higher in women who were overweight and obese than in those with normal weight. Nonetheless, significant results were prominent only among those with CC genotype and C allele.