Impact of Healthy Lifestyle Factors on Life Expectancy and Lifetime Health Care Expenditure: Nationwide Cohort Study.

BACKGROUND: The association between lifestyle risk factors and the risk of mortality and chronic diseases has been established, while limited research has explored the impact of healthy lifestyle factors on lifetime health care expenditure using longitudinal individual data. OBJECTIVE: We aimed to determine the individual and combined effects of 5 healthy lifestyle factors on life expectancy and lifetime health care expenditure in Taiwan. METHODS: Using data from the National Health Interview Survey cohort, 5 healthy lifestyle behaviors were defined and analyzed: nonsmoking, avoiding excessive alcohol consumption, engaging in sufficient physical activity, ensuring sufficient fruit and vegetable intake, and maintaining a normal weight. We used a rolling extrapolation algorithm that incorporated inverse probability of treatment weighting to estimate the life expectancy and lifetime health care expenditure of the study populations with and without healthy lifestyle factors. RESULTS: A total of 19,893 participants aged ≥30 (mean age 48.8, SD 13.4) years were included, with 3815 deaths recorded during a median follow-up period of 15.6 years. The life expectancy and per capita estimated lifetime health care expenditures for the overall study population were 35.32 years and US $58,560, respectively. Multivariable-adjusted hazard ratios for all-cause mortality in participants adhering to all 5 healthy lifestyle factors, compared with those adhering to none, were 0.37 (95% CI 0.27-0.49). We found significant increases in life expectancy for nonsmokers (2.31 years; 95% CI 0.04-5.13; P=.03), those with sufficient physical activity (1.85 years; 95% CI 0.25-4.34; P=.02), and those with adequate fruit and vegetable intake (3.25 years; 95% CI 1.29-6.81; P=.01). In addition, nonsmokers experienced a significant reduction in annual health care expenditure (-9.78%; 95% CI -46.53% to -1.45%; P=.03), as did individuals maintaining optimal body weight (-18.36%; 95% CI -29.66% to -8.57%; P=.01). Overall, participants adhering to all 5 healthy lifestyle behaviors exhibited a life gain of 7.13 years (95% CI 1.33-11.11; P=.02) compared with those adhering to one or none, with a life expectancy of 29.19 years (95% CI 25.45-33.62). Furthermore, individuals adopting all 5 healthy lifestyle factors experienced an average annual health care expenditure reduction of 28.12% (95% CI 4.43%-57.61%; P=.02) compared with those adopting one or none. CONCLUSIONS: Adopting a healthy lifestyle is associated with a longer life expectancy and a reduction of health care expenditure in Taiwanese adults. This contributes to a more comprehensive understanding of the impact of healthy lifestyle factors on the overall health and economic burden.

Discrepancies in dengue burden estimates: a comparative analysis of reported cases and global burden of disease study, 2010-2019.

BACKGROUND: Dengue is a significant mosquito-borne disease. Several studies have utilized estimates from the Global Burden of Disease (GBD) study to assess the global, regional or national burden of dengue over time. However, our recent investigation suggests that GBD's estimates for dengue cases in Taiwan are unrealistically high. The current study extends the scope to compare reported dengue cases with GBD estimates across 30 high-burden countries and territories, aiming to assess the accuracy and interpretability of the GBD's dengue estimates. METHODS: Data for this study were sourced from the GBD 2019 study and various national and international databases documenting reported dengue cases. The analysis targeted the top 30 countries and territories with the highest 10-year average of reported cases from 2010 to 2019. Discrepancies were quantified by computing absolute differences and ratios between the 10-year average of reported cases and GBD estimates. Coefficients of variation (CV) and estimated annual percentage changes (EAPCs) were calculated to assess variations and trends in the two data sources. RESULTS: Significant discrepancies were noted between reported data and GBD estimates in the number of dengue cases, incidence rates, and EAPCs. GBD estimates were substantially higher than reported cases for many entities, with the most notable differences found in China (570.0-fold), India (303.0-fold), Bangladesh (115.4-fold), Taiwan (85.5-fold) and Indonesia (23.2-fold). Furthermore, the GBD's estimates did not accurately reflect the extensive yearly fluctuations in dengue outbreaks, particularly in non-endemic regions such as Taiwan, China and Argentina, as evidenced by high CVs. CONCLUSIONS: This study reveals substantial discrepancies between GBD estimates and reported dengue cases, underscoring the imperative for comprehensive analysis in areas with pronounced disparities. The failure of GBD estimates to represent the considerable annual fluctuations in dengue outbreaks highlights the critical need for improvement in disease burden estimation methodologies for dengue.

Low-Dose Versus Standard-Dose Alteplase in Bridging Therapy for Large Vessel Stroke: A Systematic Review and Meta-Analysis.

INTRODUCTION The efficacy and safety of low- and standard-dose alteplase for acute ischemic stroke (AIS) have not been consistently compared in previous studies. Nevertheless, the distinctions in the effects of low- and standard-dose alteplase, particularly within the context of bridging therapy (BT) for large vessel occlusion (LVO), warrant further exploration. This study compared clinical outcomes between BT with low- and standard-dose alteplase in patients with LVO-related AIS. METHODS We performed a search for randomized controlled trials and prospective or retrospective cohort studies investigating the clinical outcomes of BT in AIS in the PubMed, Embase, and Cochrane Library databases from inception to November 2022. The outcomes of interest were 90-day functional independence, successful recanalization, symptomatic intracerebral hemorrhage (sICH) and mortality; these outcomes were compared between patients who received BT with low- (primarily 0.6 mg/kg) and standard-dose alteplase (0.9 mg/kg). We used the standard-dose group as the reference and calculated the odds ratio (OR) and its 95% confidence interval (CI) from the raw numbers. Meta-analysis and ethnicity-based subgroup analysis (Asian and non-Asian) were performed. RESULTS Five observational studies, published after 2017 and including 408 patients, were included. The meta-analysis results demonstrated that compared with BT with standard-dose alteplase, BT with low-dose alteplase did not improve 90-day functional independence (odds ratio, [OR] 1.02; 95% confidence interval [CI], 0.58-1.80). Nevertheless, BT with low-dose alteplase was associated with a comparable successful recanalization rate (OR, 1.35; 95% CI, 0.68-2.67) and similar sICH incidence (OR 0.36; 95% CI, 0.10-1.36), and mortality (OR, 0.64; 95% CI, 0.27-1.54) compared with BT with standard-dose alteplase; however, the above three results were nonsignificant. In the ethnicity-based subgroup analyses, no differences were noted between Asian and non-Asian participants. CONCLUSIONS In patients with LVO-related AIS, BT with low- or standard-dose alteplase may provide similar efficacy, with no significant differences in sICH incidence and mortality. Additional well-designed prospective studies are required to confirm this result.

Quantifying the potential effects of air pollution reduction on population health and health expenditure in Taiwan.

Air pollution, particularly ambient fine particulate matter (PM2.5) pollution, poses a significant risk to public health, underscoring the importance of comprehending the long-term impact on health burden and expenditure at national and subnational levels. Therefore, this study aims to quantify the disease burden and healthcare expenditure associated with PM2.5 exposure in Taiwan and assess the potential benefits of reducing pollution levels. Using a comparative risk assessment framework that integrates an auto-aggressive integrated moving average model, we evaluated the avoidable burden of cardiopulmonary diseases (including ischemic heart disease, stroke, chronic obstructive pulmonary disease, lung cancer, and diabetes mellitus) and related healthcare expenditure under different air quality target scenarios, including status quo and target scenarios of 15, 10, and 5 µg/m3 reduction in PM2.5 concentration. Our findings indicate that reducing PM2.5 exposure has the potential to significantly alleviate the burden of multiple diseases. Comparing the estimated attributable disease burden and healthcare expenditure between reference and target scenarios from 2022 to 2050, the avoidable disability-adjusted life years were 0.61, 1.83, and 3.19 million for the 15, 10, and 5 µg/m3 target scenarios, respectively. Correspondingly, avoidable healthcare expenditure ranged from US$ 0.63 to 3.67 billion. We also highlighted the unequal allocation of resources and the need for policy interventions to address health disparities due to air pollution. Notably, in the 5 µg/m3 target scenario, Kaohsiung City stands to benefit the most, with 527,368 disability-adjusted life years avoided and US$ 0.53 billion saved from 2022 to 2050. Our findings suggest that adopting stricter emission targets can effectively reduce the health burden and associated healthcare expenditure in Taiwan. Overall, this study provides policymakers in Taiwan with valuable insights for mitigating the negative effects of air pollution by establishing a comprehensive framework for evaluating the co-benefits of air pollution reduction on healthcare expenditure and disease burden.

Cardiovascular Disease Burden Attributable to High Body Mass Index in Taiwan.

Background: Studies on disease burden in Taiwan are lacking. We aimed to quantify the burden of cardiovascular disease (CVD) attributable to high body mass index (BMI) in Taiwan. Methods: Using a comparative risk assessment approach from the Global Burden of Disease study, we estimated the population attributable fraction (PAF), attributable CVD burden, and disability-adjusted life years (DALYs) according to sex, age, and area of residence in Taiwan. The BMI distribution for the population was obtained from the National Health Interview Survey in 2013. CVD was defined as an ischemic heart disease or stroke. Results: The attributable PAF for CVD from high BMI was 18.0% (19.6% in men and 15.6% in women), and it was highest (42.7%) in those aged 25-30 years. Adults aged 60-65 years had the highest absolute DALYs (11,546). The average relative age-standardized attributable burden was 314 DALYs per 100,000 person-years, and it was highest in those aged 75-80 years (1,407 DALYs per 100,000 person-years). Those living in Taitung County had the highest PAF of 21.9% and the highest age-standardized attributable burden (412 DALYs). Conclusions: In Taiwan, an 18% reduction in CVDs could be achieved if obesity/overweight was prevented. Prevention was most effective in early adulthood. The absolute CVD burden from obesity/overweight was highest in middle-aged men, and the relative burden was highest in older adults. Resource allocation in targeted populations and specific areas to eliminate CVD and health inequities is urgently required.

Perceptions towards the COVID-19 Pandemic during Different Lockdown Levels among International Students in Taiwan.

International students face many impediments under the COVID-19 pandemic. The objectives of this study are to assess the association between the perceptions of international students and the lockdown policy for COVID-19. In 2021, three different levels of lockdown policy were enforced, including level I from January to April, level III from May to July, and level II from August to December. We conducted three surveys for international graduate students using a validated questionnaire during the different lockdown levels. We collected 185, 119, and 83 valid questionnaires in level I, II, and III, respectively. There were linear trends in the correlations of lockdown policy with the knowledge (p = 0.052), attitudes (p = 0.002), and practices (p < 0.001) of COVID-19. In brief, the stricter the lockdown policy, the better the students adhered to sufficient knowledge, positive attitudes, and healthy practices. Furthermore, there were significant linear correlations of lockdown policy with the transportation, school study, leisure, family life, and diet behavior. In conclusion, lockdown policy had important impacts on the knowledge, attitudes, practices, and daily lives of international students. The findings indicated that the lockdown system and its corresponding measures appear to affect perceptions in a positive way.

SeqCP: A sequence-based algorithm for searching circularly permuted proteins.

Circular permutation (CP) is a protein sequence rearrangement in which the amino- and carboxyl-termini of a protein can be created in different positions along the imaginary circularized sequence. Circularly permutated proteins usually exhibit conserved three-dimensional structures and functions. By comparing the structures of circular permutants (CPMs), protein research and bioengineering applications can be approached in ways that are difficult to achieve by traditional mutagenesis. Most current CP detection algorithms depend on structural information. Because there is a vast number of proteins with unknown structures, many CP pairs may remain unidentified. An efficient sequence-based CP detector will help identify more CP pairs and advance many protein studies. For instance, some hypothetical proteins may have CPMs with known functions and structures that are informative for functional annotation, but existing structure-based CP search methods cannot be applied when those hypothetical proteins lack structural information. Despite the considerable potential for applications, sequence-based CP search methods have not been well developed. We present a sequence-based method, SeqCP, which analyzes normal and duplicated sequence alignments to identify CPMs and determine candidate CP sites for proteins. SeqCP was trained by data obtained from the Circular Permutation Database and tested with nonredundant datasets from the Protein Data Bank. It shows high reliability in CP identification and achieves an AUC of 0.9. SeqCP has been implemented into a web server available at: http://pcnas.life.nthu.edu.tw/SeqCP/.

Lifetime exposure to PM2.5 air pollution and disability-adjusted life years due to cardiopulmonary disease: A modeling study based on nationwide longitudinal data.

BACKGROUND: As knowledge of the health risks of PM2.5 has grown, the focus of PM2.5-related health impact assessments has evolved from simple risk models to burden-of-disease estimates. We proposed an ecological approach to directly estimate the impacts of lifetime exposure to PM2.5 on expected health losses due to cardiopulmonary diseases for older adult populations in Taiwan. METHODS: We created study cohorts of 3.5 million older people living in 350 townships in Taiwan. We used a weighted regression model, with adjustments of area characteristic variables, to directly estimate the impacts of lifetime mean PM2.5 exposure on health losses among the 350 cohorts. Potential avoidable disability-adjusted life years (DALYs) by assuming that ambient PM2.5 met the air quality standard was estimated. RESULTS: Each 10 µg/m3 increase in lifetime mean exposure to PM2.5 for an individual corresponded to an increment of 0.25 (95 % confidence interval (CI): 0.18-0.32) DALYs due to cardiopulmonary diseases, after adjusting for a wide range of ecological covariates. We estimated that 611.8 (95 % CI: 440.4-783.2) DALYs per 1000 older adult population could potentially be avoided by achieving air quality standards of WHO in Taiwan. CONCLUSIONS: Reducing PM2.5 pollution in Taiwan associated with significant health co-benefits, providing important implications for public health and environmental management.

Updating the Insecticide Resistance Status of Aedes aegypti and Aedes albopictus in Asia: A Systematic Review and Meta-Analysis.

BACKGROUND: Aedes aegypti and Aedes albopictus are two important vectors of several important arboviruses, including the dengue, chikungunya, and Zika viruses. Insecticide application is an important approach to reduce vector abundance during Aedes spp.-borne outbreaks in the absence of effective vaccines and treatments. However, insecticide overuse can result in the development of resistance, and careful monitoring of resistance markers is required. METHODS: This meta-analysis and systematic review explored the spatial and temporal patterns of insecticide resistance in Asia from 2000 to 2021. PubMed, Scopus, EbscoHost, and Embase were used to enhance the search capability. The random-effects model was applied for the 94 studies that met our inclusion criteria for qualitative synthesis and meta-analysis. RESULTS: Four major insecticides were studied (malathion, dichlorodiphenyltrichloroethane, permethrin, and deltamethrin). Dichlorodiphenyltrichloroethane resistance rates were high in both Ae. aegypti and Ae. albopictus (68% and 64%, respectively). Conversely, malathion resistance was less prevalent in Ae. aegypti (3%), and deltamethrin resistance was less common in Ae. albopictus (2%). Ae. aegypti displayed consistently high resistance rates (35%) throughout the study period, whereas the rate of insecticide resistance in Ae. albopictus increased from 5% to 12%. The rates of the major kdr mutations F1534C, V1016G, and S989P were 29%, 26%, and 22%, respectively. CONCLUSIONS: Insecticide resistance in both Ae. aegypti and Ae. albopictus is widespread in Asia, although the rates vary by country. Continuous monitoring of the resistance markers and modification of the control strategies will be important for preventing unexpected outbreaks. This systematic review and meta-analysis provided up-to-date information on insecticide resistance in dengue-endemic countries in Asia.

The Incidence of Contrast-Induced Nephropathy and the Need of Dialysis in Patients Receiving Angiography: A Systematic Review and Meta-Analysis.

Objectives: The risk of dialysis following contrast exposure is unclear. We aimed to examine the overall risk of contrast induced nephropathy and the need of dialysis based on a systematic review with random-effects meta-analysis. Methods: We searched the electronic database including PubMed, Medline, Embase, and Cochrane Library from inception to 31 October, 2020 with predetermined search term to identify relevant studies. Observational studies investigating the association between contrast induced nephropathy after angiography and the need of dialysis were included, and summary risks were estimated. Two independent reviewers extracted the data, followed with random effects model to calculate the overall pooled incidence of contrast induced nephropathy and the need of dialysis after angiography. Subgroup-analysis and meta-regression were performed to assess heterogeneity of incidence across studies. Results: Of 2,243 identified articles, 259 met our inclusion criteria were included in the meta-analysis after screening. Pooled effect estimates had the following summary incidence proportion for contrast induced nephropathy after angiography: 9.06% (95% CI: 8.53-9.58%; derived from 120 studies) and 0.52% (95% CI: 0.37-0.70%; derived from 110 studies) for the need of dialysis, respectively. The stratified summary incidence proportion of contrast induced nephropathy after contrast administration via intra-arterial route was 9.60% (95% CI: 9.0-10.2%; derived from 106 studies) and was 0.6% (95% CI: 0.40-0.80%; derived from 100 studies) for the need of dialysis, respectively. Our meta-regressions found that the amount of contrast medium exposure was associated with contrast-induced nephropathy. Conclusion: The potential risk of dialysis needs to be communicated to patients undergoing procedures requiring contrast, especially via intra-arterial exposure. Systematic Review Registration: [https://reurl.cc/8Wrlry], identifier [CRD42020170702].

Long-term exposure to ambient fine particulate matter (PM2.5) and associations with cardiopulmonary diseases and lung cancer in Taiwan: a nationwide longitudinal cohort study.

BACKGROUND: Although a number of studies have reported on the health effects of fine particulate matter (PM2.5) exposure, particularly in North American and European countries as well as China, the evidence about intermediate to high levels of PM2.5 exposures is still limited. We aimed to investigate the associations between long-term exposure to PM2.5 and risk of cardiopulmonary disease incidence in Taiwan with intermediate levels of PM2.5 exposure. METHODS: A cohort of Taiwanese adults, who participated in the 2001, 2005, 2009 and 2013 National Health Interview Surveys, was followed through 2016 to identify cardiopulmonary disease onset. Exposure to PM2.5 was estimated by incorporating a widespread monitoring network of air quality monitoring stations and microsensors. We used time-dependent Cox regression models to examine the associations between the PM2.5 exposures and health outcomes, adjusting for individual characteristics and ecological covariates. The natural cubic spline functions were used to explore the non-linear effects of the PM2.5 exposure. RESULTS: A total of 62 694 adults from 353 towns were enrolled. Each 10-µg/m3 increase in 5-year average exposure to PM2.5 was associated with a 4.8% increased risk of incident ischaemic heart disease (95% CI: -3.3, 13.6), 3.9% increased risk of incident stroke (95% CI: -2.9, 11.1), 6.7% increased risk of incident diabetes (95% CI: 1.1, 12.7), 15.7% increased risk of incident lung cancer (95% CI: -0.9, 35.1) and 11.5% increased risk of incident chronic obstructive pulmonary disease (95% CI: -0.8, 25.2). The concentration-response curve showed that there was no statistical evidence of non-linearity for most of the disease outcomes except for ischaemic heart disease (P for non-linearity = 0.014). CONCLUSIONS: Long-term exposure to intermediate levels of ambient PM2.5 was associated with cardiopulmonary health outcomes. Our study adds value to future application and national burden of disease estimation in evaluating the health co-benefits from ambient air pollution reduction policy in Asian countries.

Efficacy of Osteoporosis Medications for Patients With Chronic Kidney Disease: An Updated Systematic Review and Network Meta-Analysis.

Background: Chronic kidney disease (CKD) is associated with bone and mineral metabolism. In this study we evaluated the comparative efficacies and safety of osteoporosis medications in patients with CKD or a history of kidney transplantation, and make recommendations for the best choice of osteoporosis treatment among patients with CKD or a history of kidney transplantation. Methods: We systemically searched for randomized controlled trials published in PubMed, Embase, and Cochrane databases up to June 2020. Network-meta analysis was used to compare the relative effectiveness of different treatments. A random-effects model was used when heterogeneity was expected. The safety of different treatments was also evaluated in terms of reported major adverse events. Results: A total of 17 studies with data from 10,214 patients who had stage 2-5 CKD, were receiving dialysis, or had a history of kidney transplantation were included in the network meta-analysis. Treatment with teriparatide, denosumab, alendronate, and raloxifene were all associated with a significantly reduced risk of fractures compared to treatment with placebos [teriparatide: odds ratio (OR) = 0.19, 95% confidence interval (CI): 0.10-0.35; denosumab: OR = 0.40, 95% CI: 0.27-0.58; alendronate: OR = 0.61, 95% CI: 0.40-0.92; raloxifene: OR = 0.52, 95% CI: 0.41-0.67]. The rank probability and the surface under the cumulative ranking (SUCRA) values suggested that teriparatide ranked the highest for improvement in vertebral bone mineral density (BMD) (SUCRA = 97.8%), whereas denosumab ranked the highest for improvement in femoral neck BMD (SUCRA = 88.3%). Conclusion: Teriparatide and denosumab seem to be the most effective treatments for preventing bone loss and reducing the risk of fracture in our network comparison. However, because of the limitations and potential biases in the reviewed studies, there is still some uncertainty about the best treatment options for osteoporosis in patients with CKD or a history of kidney transplantation. Systematic Review Registration: [PROSPERO], identifier [CRD42020209830].

County-Wide Mortality Assessments Attributable to PM2.5 Emissions from Coal Consumption in Taiwan.

Over one-third of energy is generated from coal consumption in Taiwan. In order to estimate the health impact assessment attributable to PM2.5 concentrations emitted from coal consumption in Taiwan. We applied a Gaussian trajectory transfer-coefficient model to obtain county-wide PM2.5 exposures from coal consumption, which includes coal-fired power plants and combined heat and power plants. Next, we calculated the mortality burden attributable to PM2.5 emitted by coal consumption using the comparative risk assessment framework developed by the Global Burden of Disease study. Based on county-level data, the average PM2.5 emissions from coal-fired plants in Taiwan was estimated at 2.03 ± 1.29 (range: 0.32-5.64) µg/m3. With PM2.5 increments greater than 0.1 µg/m3, there were as many as 16 counties and 66 air quality monitoring stations affected by coal-fired plants and 6 counties and 18 monitoring stations affected by combined heat and power plants. The maximum distances affected by coal-fired and combined heat and power plants were 272 km and 157 km, respectively. Our findings show that more counties were affected by coal-fired plants than by combined heat and power plants with significant increments of PM2.5 emissions. We estimated that 359.6 (95% CI: 334.8-384.9) annual adult deaths and 124.4 (95% CI: 116.4-132.3) annual premature deaths were attributable to PM2.5 emitted by coal-fired plants in Taiwan. Even in six counties without power plants, there were 75.8 (95% CI: 60.1-91.5) deaths and 25.8 (95%CI: 20.7-30.9) premature deaths annually attributable to PM2.5 emitted from neighboring coal-fired plants. This study presents a precise and effective integrated approach for assessing air pollution and the health impacts of coal-fired and combined heat and power plants.

Global burden of tuberculosis attributable to cancer in 2019: Global, regional, and national estimates.

BACKGROUND: Cancer is an independent risk factor for tuberculosis (TB). The global burden of incident TB attributable to cancer has never been explored. We aimed to evaluate the cancer-attributable burden of TB. METHODS: We estimated the population attributable fraction (PAF) by Levin's formula. The cancer prevalence rates were derived from the Institute for Health Metrics and Evaluation. The relative risk of TB in cancer patients was estimated by using the National Health Insurance Research Database in Taiwan. The global burden of incidence TB attributable to cancer was the weighted sum of PAFs multiplied by the incidence of TB retrieved from the World Health Organization. RESULTS: Worldwide, the total of incident TB cases attributable to cancer was 115,478 cases with a 95% confidence interval (CI), 110,482-123,007, in 2019. The global PAF of TB due to cancer was 1.85% (95% CI, 1.77-1.97%). The three countries with the highest PAFs were Greenland (7.77%), Canada (7.75%), and the United States of America (6.79%), while the three countries with the highest attributable TB cases due to cancer were China (25,240), India (21,629), and Indonesia (13,917). Cancer of respiratory system contributed to 60,257 of TB cases. CONCLUSIONS: This study comprehensively explored the impact of cancer on the global burden of TB. Efforts to reduce cancer risk, delay the occurrence of cancer, or treat latent TB infection in the cancer population could potentially reduce the burden of TB and rely on formulating integrated strategies.

Discovering the Ultimate Limits of Protein Secondary Structure Prediction.

Secondary structure prediction (SSP) of proteins is an important structural biology technique with many applications. There have been ~300 algorithms published in the past seven decades with fierce competition in accuracy. In the first 60 years, the accuracy of three-state SSP rose from ~56% to 81%; after that, it has long stayed at 81-86%. In the 1990s, the theoretical limit of three-state SSP accuracy had been estimated to be 88%. Thus, SSP is now generally considered not challenging or too challenging to improve. However, we found that the limit of three-state SSP might be underestimated. Besides, there is still much room for improving segment-based and eight-state SSPs, but the limits of these emerging topics have not been determined. This work performs large-scale sequence and structural analyses to estimate SSP accuracy limits and assess state-of-the-art SSP methods. The limit of three-state SSP is re-estimated to be ~92%, 4-5% higher than previously expected, indicating that SSP is still challenging. The estimated limit of eight-state SSP is 84-87%. Several proposals for improving future SSP algorithms are made based on our results. We hope that these findings will help move forward the development of SSP and all its applications.

CirPred, the first structure modeling and linker design system for circularly permuted proteins.

BACKGROUND: This work aims to help develop new protein engineering techniques based on a structural rearrangement phenomenon called circular permutation (CP), equivalent to connecting the native termini of a protein followed by creating new termini at another site. Although CP has been applied in many fields, its implementation is still costly because of inevitable trials and errors. RESULTS: Here we present CirPred, a structure modeling and termini linker design method for circularly permuted proteins. Compared with state-of-the-art protein structure modeling methods, CirPred is the only one fully capable of both circularly-permuted modeling and traditional co-linear modeling. CirPred performs well when the permutant shares low sequence identity with the native protein and even when the permutant adopts a different conformation from the native protein because of three-dimensional (3D) domain swapping. Linker redesign experiments demonstrated that the linker design algorithm of CirPred achieved subangstrom accuracy. CONCLUSIONS: The CirPred system is capable of (1) predicting the structure of circular permutants, (2) designing termini linkers, (3) performing traditional co-linear protein structure modeling, and (4) identifying the CP-induced occurrence of 3D domain swapping. This method is supposed helpful for broadening the application of CP, and its web server is available at http://10.life.nctu.edu.tw/CirPred/ and http://lo.life.nctu.edu.tw/CirPred/ .

The influence of dataset homology and a rigorous evaluation strategy on protein secondary structure prediction.

The secondary structure prediction (SSP) of proteins has long been an essential structural biology technique with various applications. Despite its vital role in many research and industrial fields, in recent years, as the accuracy of state-of-the-art secondary structure predictors approaches the theoretical upper limit, SSP has been considered no longer challenging or too challenging to make advances. With the belief that the substantial improvement of SSP will move forward many fields depending on it, we conducted this study, which focused on three issues that have not been noticed or thoroughly examined yet but may have affected the reliability of the evaluation of previous SSP algorithms. These issues are all about the sequence homology between or within the developmental and evaluation datasets. We thus designed many different homology layouts of datasets to train and evaluate SSP prediction models. Multiple repeats were performed in each experiment by random sampling. The conclusions obtained with small experimental datasets were verified with large-scale datasets using state-of-the-art SSP algorithms. Very different from the long-established assumption, we discover that the sequence homology between query datasets for training, testing, and independent tests exerts little influence on SSP accuracy. Besides, the sequence homology redundancy between or within most datasets would make the accuracy of an SSP algorithm overestimated, while the redundancy within the reference dataset for extracting predictive features would make the accuracy underestimated. Since the overestimating effects are more significant than the underestimating effect, the accuracy of some SSP methods might have been overestimated. Based on the discoveries, we propose a rigorous procedure for developing SSP algorithms and making reliable evaluations, hoping to bring substantial improvements to future SSP methods and benefit all research and application fields relying on accurate prediction of protein secondary structures.

A secondary structure-based position-specific scoring matrix applied to the improvement in protein secondary structure prediction.

Protein secondary structure prediction (SSP) has a variety of applications; however, there has been relatively limited improvement in accuracy for years. With a vision of moving forward all related fields, we aimed to make a fundamental advance in SSP. There have been many admirable efforts made to improve the machine learning algorithm for SSP. This work thus took a step back by manipulating the input features. A secondary structure element-based position-specific scoring matrix (SSE-PSSM) is proposed, based on which a new set of machine learning features can be established. The feasibility of this new PSSM was evaluated by rigid independent tests with training and testing datasets sharing <25% sequence identities. In all experiments, the proposed PSSM outperformed the traditional amino acid PSSM. This new PSSM can be easily combined with the amino acid PSSM, and the improvement in accuracy was remarkable. Preliminary tests made by combining the SSE-PSSM and well-known SSP methods showed 2.0% and 5.2% average improvements in three- and eight-state SSP accuracies, respectively. If this PSSM can be integrated into state-of-the-art SSP methods, the overall accuracy of SSP may break the current restriction and eventually bring benefit to all research and applications where secondary structure prediction plays a vital role during development. To facilitate the application and integration of the SSE-PSSM with modern SSP methods, we have established a web server and standalone programs for generating SSE-PSSM available at http://10.life.nctu.edu.tw/SSE-PSSM.

Enhancing Data Linkage to Break the Chain of COVID-19 Spread: The Taiwan Experience.

Digital technology has been widely used in health care systems and disease management, as well as in controlling the spread of COVID-19. As one of the most successful countries in combating the COVID-19 pandemic, Taiwan has successfully used digital technology to strengthen its efforts in controlling the COVID-19 pandemic. Taiwan has a well-established National Health Insurance System (NHIS), which provides a great opportunity to develop a nationwide data linkage model in an agile manner. Here we provide an overview of the application of data linkage models for strategies in combating COVID-19 in Taiwan, including NHIS centralized data linkage systems and "from border to community" information-driven data linkage systems during the COVID-19 pandemic. Furthermore, we discuss the dual role of digital technologies in being an "enabler" and a "driver" in early disease prevention. Lastly, Taiwan's experience in applying digital technology to enhance the control of COVID-19 potentially highlights lessons learned and opportunities for other countries to handle the COVID-19 situation better.

Do Orthopedic Surgeons or Neurosurgeons Detect More Hip Disorders in Patients with Hip-Spine Syndrome? A Nationwide Database Study.

Background: Disorders of the hip and lumbar spine can create similar patterns of pain and dysfunction. It is unknown whether all surgeons, regardless of orthopedic or neurosurgery training, investigate and diagnose concurrent hip and spine pathology at the same rate. Methods: Data were retrieved from Taiwan's National Health Insurance Research Database (NHIRD). Enrolled patients were stratified into hip and spine surgery at the same admission (Both), hip surgery before spine surgery (HS), or spine surgery before hip surgery (SH). The SH group was further subdivided based on whether spine surgery was performed by an orthopedic surgeon (OS) or neurosurgeon (NS), and differences in preoperative radiographic examinations and diagnoses were collected and analyzed. Results: In total, 1824 patients received lumbar spine surgery within 1 year before or after hip replacement surgery. Of these, 103 patients had spine and hip surgery in the same admission (Both), 1290 patients had spine surgery before hip surgery (SH), and 431 patients had hip surgery before spine surgery (HS). In the SH group, patients were categorized into spine surgery by orthopedic surgeons (OS) (n = 679) or neurosurgeons (NS) (n = 522). In the SH group, orthopedic surgeons investigated hip pathology with X-rays more often (52.6% vs. 38.1%, p < 0.001) and diagnosed more cases of hip disease (43.6% vs. 28.9%, p < 0.001) than neurosurgeons. Conclusions: Of patients in Taiwan's NHIRD who had concurrent surgical degenerative hip and lumbar spine disorders who had spine surgery before hip surgery, orthopedic surgeons obtained hip images and made hip-related diagnoses more frequently than did neurosurgeons.